Collagenase Enzymatic Fasciotomy for Dupuytren Contracture in Patients on Chronic Immunosuppression

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Collagenase Enzymatic Fasciotomy for Dupuytren Contracture in Patients on Chronic Immunosuppression

The incidence of Dupuytren disease increases with advancing age,1 as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.7 The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.8 Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.6 The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.9 In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.10 A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.6 Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,6 the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,6 except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

 

 

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.6 No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.6 Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent11 and may become evident in patients receiving low doses over prolonged periods. Skin atrophy12 and delayed wound healing9 are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.13 It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.14 Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.15

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.6 More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.16 This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.

References

1.    Loos B, Puschkin V, Horch RE. 50 years experience with Dupuytren’s contracture in the Erlangen University Hospital—a retrospective analysis of 2919 operated hands from 1956 to 2006. BMC Musculoskelet Disord. 2007;8:60.

2.    Coert JH, Nérin JP, Meek MF. Results of partial fasciectomy for Dupuytren disease in 261 consecutive patients. Ann Plast Surg. 2006;57(1):13-17.

3.    Sennwald GR. Fasciectomy for treatment of Dupuytren’s disease and early complications. J Hand Surg Am. 1990;15(5):755-761.

4.    Badalamente MA, Hurst LC. Enzyme injection as nonsurgical treatment of Dupuytren’s disease. J Hand Surg Am. 2000;25(4):629-636.

5.      Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren’s disease. J Hand Surg Am. 2002;27(5):788-798.

6.    Hurst LC, Badalamente MA, Hentz VR, et al; CORD I Study Group. Injectable collagenase Clostridium histolyticum for Dupuytren’s contracture. N Engl J Med. 2009;361(10):968-979.

7.    Mookhtiar KA, Van Wart HE. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1992;1:116-126.

8.    Watanabe K. Collagenolytic proteases from bacteria. Appl Microbiol Biotechnol. 2004;63(5):520-526.

9.    Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013;206(3):410-417.

10. Denkler K. Surgical complications associated with fasciectomy for Dupuytren’s disease: a 20-year review of the English literature. Eplasty. 2010;10:e15.

11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11(6):954-963.

12. Oikarinen A, Autio P. New aspects of the mechanism of corticosteroid-induced dermal atrophy. Clin Exp Dermatol. 1991;16(6):416-419.

13. Makinodan T, Santos GW, Quinn RP. Immunosuppressive drugs. Pharmacol Rev. 1970;22(2):189-247.

14. Röllinghoff M, Schrader J, Wagner H. Effect of azathioprine and cytosine arabinoside on humoral and cellular immunity in vitro. Clin Exp Immunol. 1973;15(2):261-269.

15. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102(2):322-328.

16. Desai SS, Hentz VR. Collagenase Clostridium histolyticum for Dupuytren’s contracture. Expert Opin Biol Ther. 2010;10(9):1395-1404.

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Author and Disclosure Information

Michael J. Waters, BMBS, B. Physio, Mark R. Belsky, MD, Philip E. Blazar, MD, Matthew I. Leibman, MD, and David E. Ruchelsman, MD

Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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The American Journal of Orthopedics - 44(11)
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518-521
Legacy Keywords
american journal of orthopedics, AJO, original study, study, collagenase enzymatic fasciotomy, dupuytren contracture, chronic immunosuppression, hand, dupuytren, disease, therapy, therapies, joints, waters, belsky, blazar, leibman, ruchelsman
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Author and Disclosure Information

Michael J. Waters, BMBS, B. Physio, Mark R. Belsky, MD, Philip E. Blazar, MD, Matthew I. Leibman, MD, and David E. Ruchelsman, MD

Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

Author and Disclosure Information

Michael J. Waters, BMBS, B. Physio, Mark R. Belsky, MD, Philip E. Blazar, MD, Matthew I. Leibman, MD, and David E. Ruchelsman, MD

Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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Article PDF

The incidence of Dupuytren disease increases with advancing age,1 as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.7 The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.8 Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.6 The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.9 In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.10 A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.6 Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,6 the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,6 except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

 

 

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.6 No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.6 Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent11 and may become evident in patients receiving low doses over prolonged periods. Skin atrophy12 and delayed wound healing9 are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.13 It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.14 Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.15

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.6 More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.16 This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.

The incidence of Dupuytren disease increases with advancing age,1 as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.7 The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.8 Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.6 The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.9 In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.10 A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.6 Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,6 the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,6 except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

 

 

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.6 No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.6 Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent11 and may become evident in patients receiving low doses over prolonged periods. Skin atrophy12 and delayed wound healing9 are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.13 It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.14 Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.15

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.6 More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.16 This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.

References

1.    Loos B, Puschkin V, Horch RE. 50 years experience with Dupuytren’s contracture in the Erlangen University Hospital—a retrospective analysis of 2919 operated hands from 1956 to 2006. BMC Musculoskelet Disord. 2007;8:60.

2.    Coert JH, Nérin JP, Meek MF. Results of partial fasciectomy for Dupuytren disease in 261 consecutive patients. Ann Plast Surg. 2006;57(1):13-17.

3.    Sennwald GR. Fasciectomy for treatment of Dupuytren’s disease and early complications. J Hand Surg Am. 1990;15(5):755-761.

4.    Badalamente MA, Hurst LC. Enzyme injection as nonsurgical treatment of Dupuytren’s disease. J Hand Surg Am. 2000;25(4):629-636.

5.      Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren’s disease. J Hand Surg Am. 2002;27(5):788-798.

6.    Hurst LC, Badalamente MA, Hentz VR, et al; CORD I Study Group. Injectable collagenase Clostridium histolyticum for Dupuytren’s contracture. N Engl J Med. 2009;361(10):968-979.

7.    Mookhtiar KA, Van Wart HE. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1992;1:116-126.

8.    Watanabe K. Collagenolytic proteases from bacteria. Appl Microbiol Biotechnol. 2004;63(5):520-526.

9.    Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013;206(3):410-417.

10. Denkler K. Surgical complications associated with fasciectomy for Dupuytren’s disease: a 20-year review of the English literature. Eplasty. 2010;10:e15.

11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11(6):954-963.

12. Oikarinen A, Autio P. New aspects of the mechanism of corticosteroid-induced dermal atrophy. Clin Exp Dermatol. 1991;16(6):416-419.

13. Makinodan T, Santos GW, Quinn RP. Immunosuppressive drugs. Pharmacol Rev. 1970;22(2):189-247.

14. Röllinghoff M, Schrader J, Wagner H. Effect of azathioprine and cytosine arabinoside on humoral and cellular immunity in vitro. Clin Exp Immunol. 1973;15(2):261-269.

15. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102(2):322-328.

16. Desai SS, Hentz VR. Collagenase Clostridium histolyticum for Dupuytren’s contracture. Expert Opin Biol Ther. 2010;10(9):1395-1404.

References

1.    Loos B, Puschkin V, Horch RE. 50 years experience with Dupuytren’s contracture in the Erlangen University Hospital—a retrospective analysis of 2919 operated hands from 1956 to 2006. BMC Musculoskelet Disord. 2007;8:60.

2.    Coert JH, Nérin JP, Meek MF. Results of partial fasciectomy for Dupuytren disease in 261 consecutive patients. Ann Plast Surg. 2006;57(1):13-17.

3.    Sennwald GR. Fasciectomy for treatment of Dupuytren’s disease and early complications. J Hand Surg Am. 1990;15(5):755-761.

4.    Badalamente MA, Hurst LC. Enzyme injection as nonsurgical treatment of Dupuytren’s disease. J Hand Surg Am. 2000;25(4):629-636.

5.      Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren’s disease. J Hand Surg Am. 2002;27(5):788-798.

6.    Hurst LC, Badalamente MA, Hentz VR, et al; CORD I Study Group. Injectable collagenase Clostridium histolyticum for Dupuytren’s contracture. N Engl J Med. 2009;361(10):968-979.

7.    Mookhtiar KA, Van Wart HE. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1992;1:116-126.

8.    Watanabe K. Collagenolytic proteases from bacteria. Appl Microbiol Biotechnol. 2004;63(5):520-526.

9.    Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013;206(3):410-417.

10. Denkler K. Surgical complications associated with fasciectomy for Dupuytren’s disease: a 20-year review of the English literature. Eplasty. 2010;10:e15.

11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11(6):954-963.

12. Oikarinen A, Autio P. New aspects of the mechanism of corticosteroid-induced dermal atrophy. Clin Exp Dermatol. 1991;16(6):416-419.

13. Makinodan T, Santos GW, Quinn RP. Immunosuppressive drugs. Pharmacol Rev. 1970;22(2):189-247.

14. Röllinghoff M, Schrader J, Wagner H. Effect of azathioprine and cytosine arabinoside on humoral and cellular immunity in vitro. Clin Exp Immunol. 1973;15(2):261-269.

15. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102(2):322-328.

16. Desai SS, Hentz VR. Collagenase Clostridium histolyticum for Dupuytren’s contracture. Expert Opin Biol Ther. 2010;10(9):1395-1404.

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Collagenase Enzymatic Fasciotomy for Dupuytren Contracture in Patients on Chronic Immunosuppression
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Open Carpal Tunnel Release With Use of a Nasal Turbinate Speculum

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Open Carpal Tunnel Release With Use of a Nasal Turbinate Speculum

Carpal tunnel syndrome (CTS) is a disorder characterized by entrapment of the median nerve at the wrist, which may lead to symptoms of pain, paresthesia, and, ultimately, thenar muscle atrophy. Surgical intervention is indicated with persistent or progressive symptoms despite nonoperative management. Timely surgical decompression aims to halt progression of this disorder and prevent permanent peripheral nerve injury.

Carpal tunnel release (CTR) is the most common hand and wrist surgery in the United States, with about 400,000 operations performed annually.1,2 Several methods of decompressing the carpal tunnel have been described.3 These include standard open CTR (OCTR), mini-open approaches, and various endoscopic techniques. OCTR was initially described by Sir James Learmonth in 1933,4 and it remains the gold-standard surgical treatment for patients with symptomatic CTS. Uniform excellent results with high patient satisfaction and low complication rates have been reported in several series.5-9 Common to all techniques is complete proximal-to-distal division of the transverse carpal ligament (TCL). Magnetic resonance imaging studies have shown that TCL transection and the resulting diastasis between the radial and ulnar leaflets cause a significant increase in the volume of the carpal tunnel, leading to decreased pressure.10,11

Endoscopic CTR (ECTR) techniques were developed in an effort to reduce complications, scar sensitivity, and pillar pain and facilitate more rapid return to work.12-17 Outcome studies have demonstrated that both open and endoscopic releases yield patient-reported subjective improvements over preoperative symptoms.18-22 A randomized, controlled trial by Trumble and colleagues23 in 2002 found that ECTR led to improved patient outcomes in the early postoperative period (first 3 months), though differences in outcomes were reduced at final follow-up. More recently (2007), a Cochrane review of 33 trials concluded there was no strong evidence favoring use of alternative techniques over OCTR.3 Further, OCTR has been found to be technically less demanding and associated with decreased complications and costs.24

Indications

The benefit of median nerve decompression at the wrist for CTS is clear.6,7 Indications for surgery in patients with CTS include persistent symptoms despite nonoperative treatment, objective sensory disturbance or motor weakness, and thenar atrophy. Symptomatic response to corticosteroid injection is predictive of success after carpal tunnel surgery.25 More than 87% of patients who gain symptomatic relief from corticosteroid injection have an excellent surgical outcome.

Technique

OCTR allows direct visualization of the TCL and the distal volar forearm fascia (DVFF) and evaluation for the presence of anomalous branching patterns of the median nerve. OCTR traditionally was performed through a 4- to 5-cm longitudinal incision extending from the wrist crease proximally to the Kaplan cardinal line distally. The mini-open technique is identical with the exception of incision length. We routinely use a 2.5- to 3-cm incision. Regardless of incision length, each OCTR should proceed through the same reproducible steps.

We perform OCTR under tourniquet control. Choice of anesthesia is surgeon and patient preference. We prefer local anesthesia with conscious sedation. After conscious sedation is administered, we infiltrate the carpal tunnel and surrounding subcutaneous tissue with 10 mL of a 50:50 mixture of 0.5% bupivacaine and 1% lidocaine without epinephrine.

A 2.5- to 3-cm longitudinal incision is made along the axis of the radial border of the ring finger from the Kaplan cardinal line26 and extending about 3 cm proximally toward the wrist flexion crease ulnar to the palmaris longus if present (Figure 1).

After the skin is incised longitudinally, the subcutaneous fat is mobilized and cutaneous sensory branches identified and protected. The underlying superficial palmar fascia is incised in line with the skin incision. The underlying midportion of the TCL is now visualized.

Transverse Carpal Ligament Release

Occasionally, the investing fascia along the ulnar edge of the thenar musculature is mobilized radialward (if the thenar musculature is well developed) to visualize the proximal limb of the TCL. Injury to any anomalous motor branch of the median nerve is avoided by directly visualizing and then incising the TCL (Figure 2). The TCL is incised along its ulnar border just radial to the hook of hamate from distal to proximal in line with the radial border of the ring finger. Staying near the ulnar attachment of the TCL keeps the plane of ligament division farther away from the median nerve and its recurrent motor branches. Although the ulnar neurovascular bundle typically resides ulnar to the hook of hamate in the canal of Guyon, the surgeon must be aware that it can be located radial to the hook in some instances.27,28 In the elderly, the ulnar artery may be tortuous and enter the field and require retraction. The TCL is incised distally until the sentinel fat pad, which marks the superficial palmar arterial arch, is visualized. This bed of adipose tissue marks the distal edge of the TCL.29

 

 

Proximally, subcutaneous tissues above the proximal limb of the TCL and DVFF are mobilized to about 2 cm proximal to the wrist flexion crease to create a plane for the fine long nasal turbinate speculum. The nasal turbinate speculum is then inserted into this plane above the proximal limb of the TCL and DVFF (Figure 3). Once inserted to the level of the confluence of the TCL and the DVFF, the speculum is opened.

Topside visualization is now encountered with the ulnar neurovascular bundle protected by the ulnar blade of the speculum. A long-handle scalpel is used to incise the TCL and the DVFF under direct visualization from proximal to distal in line with the previously completed distal release (Figure 4). As the nasal turbinate speculum is stretching the TCL and putting it under tension, the TCL can be heard splitting as it is being incised. Once the TCL and the DVFF are divided, the speculum is slowly closed and removed. Wide diastasis of the radial and ulnar leaflets of the TCL and the DVFF is directly visualized. Complete decompression of the median nerve from the distal forearm fascia to the superficial palmar arch is confirmed.

Adhesions between the undersurface of the radial leaflet and the flexor tendons and median nerve are mobilized. The median nerve is assessed for “hourglass” morphology or atrophy. The flexor tendons can be swept radialward with a free elevator to inspect the floor of the carpal tunnel. Flexor tenosynovectomy is not routinely performed. The incision is closed with interrupted simple sutures using 4-0 nylon.

Study Results

This study was conducted at Hand Surgery PC, Newton-Wellesley Hospital, Tufts University School of Medicine. Over a 10-month interval, 101 consecutive mini-OCTRs (63 right hands, 38 left hands) were performed with this proximal release modification in 88 patients (51 females, 37 males) by Dr. Ruchelsman and Dr. Belsky (Table). CTRs performed in the setting of wrist and/or carpal trauma were excluded. Mean age was 62.8 years. Mean follow-up was 11.3 weeks (~3 months). For isolated cases of CTR, mean tourniquet time was 16 minutes. CTS symptoms were relieved in all patients with a high degree of satisfaction as measured with history and examination findings at follow-up visits. There were no major complications (eg, infection, neural or vascular damage, severe residual pain). Four patients reported minor residual numbness in the fingers at latest follow-up but nevertheless had major improvement over preoperative baseline. These 4 patients had preoperative electromyograms or nerve conduction studies documenting the extent of their disease. There was 1 case of minor wound complication. Three weeks after surgery, the patient had a 1-cm wound opening, which closed with local wound care. The patient did not develop any drainage, infection, bleeding, or neurologic symptoms.

Discussion

Open release of the TCL—the gold standard of surgical treatment for CTS—produces reliable symptom relief in the vast majority of patients.25,30 Given that the most common complication of carpal tunnel surgery is incomplete release of the TCL,31,32 this technique, which uses a nasal turbinate speculum to better visualize the median nerve, could potentially reduce the reoperation rate. The nasal turbinate speculum allows the surgeon to see the confluence of the TCL and the DVFF. In addition, as the complete release can be visualized, there is minimal chance of injury.

The 2007 Cochrane review3 found no strong evidence supporting replacing OCTR with endoscopic techniques. Previous investigators have questioned the utility of ECTR given that it is higher in cost and more resource-intensive than OCTR1,33,34 and is associated with higher rates of certain complications.5,22,35-37 A 2004 meta-analysis of 13 randomized, controlled trials found a higher rate of reversible nerve damage with an odds ratio of 3.1 for ECTR versus OCTR.35 A more recent (2006) review of more than 80 studies found transient neurapraxias in 1.45% of ECTR cases and 0.25% of OCTR cases.5 The same study reported overall complication rates (reversible and major neurovascular structural injuries) of 0.74% for OCTR and 1.63% for ECTR (P < .005). Another limitation of ECTR is that endoscopic techniques require a higher degree of surgical skill, which makes teaching residents and fellows more challenging.

The novel nasal turbinate speculum technique presented here is easily reproducible and allows first-time surgeons to visualize all important structures. Given that this technique does not require an endoscope or an endoscope-viewing tower, it is likely more cost-effective and requires less time for turnover between cases. Patients obtain good relief of their CTS symptoms with this technique, and most return to their daily activities within weeks after operation.

References

1.    Ono S, Clapham PJ, Chung KC. Optimal management of carpal tunnel syndrome. Int J Gen Med. 2010;3(4):255-261.

2.    Concannon MJ, Brownfield ML, Puckett CL. The incidence of recurrence after endoscopic carpal tunnel release. Plast Reconstr Surg. 2000;105(5):1662-1665.

3.    Scholten RJ, Mink van der Molen A, Uitdehaag BM, Bouter LM, de Vet HC. Surgical treatment options for carpal tunnel syndrome. Cochrane Database Syst Rev. 2007;(4):CD003905.

4.    In memoriam Sir James Learmonth, K.C.V.O., C.B.E., hon. F.R.C.S. (1895-1967). Ann R Coll Surg Engl. 1967;41(5):438-439.

5.    Benson LS, Bare AA, Nagle DJ, Harder VS, Williams CS, Visotsky JL. Complications of endoscopic and open carpal tunnel release. Arthroscopy. 2006;22(9):919-924, 924.e1-e2.

6.    Jarvik JG, Comstock BA, Kliot M, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009;374(9695):1074-1081.

7.    Verdugo RJ, Salinas RA, Castillo JL, et al. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2008;(4):CD001552.

8.    Garland H, Langworth EP, Taverner D, et al. Surgical treatment for the carpal tunnel syndrome. Lancet. 1964;1(7343):1129-1130.

9.    Gerritsen AA, de Vet HC, Scholten RJ, et al. Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial. JAMA. 2002;288(10):1245-1251.

10.  Gelberman RH, Hergenroeder PT, Hargens AR, et al. The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am. 1981;63(3):380-383.

11.  Sucher BM. Myofascial manipulative release of carpal tunnel syndrome: documentation with magnetic resonance imaging. J Am Osteopath Assoc. 1993;93(12):1273-1278.

12.  Pereira EE, Miranda DA, Sere I, et al. Endoscopic release of the carpal tunnel: a 2-portal-modified technique. Tech Hand Up Extrem Surg. 2010;14(4):263-265.

13.  Louis DS, Greene TL, Noellert RC. Complications of carpal tunnel surgery. J Neurosurg. 1985;62(3):352-356.

14.  Mirza MA, King ET Jr, Tanveer S. Palmar uniportal extrabursal endoscopic carpal tunnel release. Arthroscopy. 1995;11(1):82-90.

15.  Brown MG, Keyser B, Rothenberg ES. Endoscopic carpal tunnel release. J Hand Surg Am. 1992;17(6):1009-1011.

16.  Agee JM, McCarroll HR Jr, Tortosa RD, et al. Endoscopic release of the carpal tunnel: a randomized prospective multicenter study. J Hand Surg Am. 1992;17(6):987-995.

17.  Okutsu I, Ninomiya S, Takatori Y, et al. Endoscopic management of carpal tunnel syndrome. Arthroscopy. 1989;5(1):11-18.

18.  Ghaly RF, Saban KL, Haley DA, et al. Endoscopic carpal tunnel release surgery: report of patient satisfaction. Neurol Res. 2000;22(6):551-555.

19.  Lee WP, Plancher KD, Strickland JW. Carpal tunnel release with a small palmar incision. Hand Clin. 1996;12(2):271-284.

20.  Biyani A, Downes EM. An open twin incision technique of carpal tunnel decompression with reduced incidence of scar tenderness. J Hand Surg Br. 1993;18(3):331-334.

21.  Brown RA, Gelberman RH, Seiler JG 3rd, et al. Carpal tunnel release. A prospective, randomized assessment of open and endoscopic methods. J Bone Joint Surg Am. 1993;75(9):1265-1275.

22.  Chow JC. Endoscopic release of the carpal ligament for carpal tunnel syndrome: 22-month clinical result. Arthroscopy. 1990;6(4):288-296.

23.  Trumble TE, Diao E, Abrams RA, et al. Single-portal endoscopic carpal tunnel release compared with open release: a prospective, randomized trial. J Bone Joint Surg Am. 2002;84(7):1107-1115.

24.  Gerritsen AA, Uitdehaag BM, van Geldere D, et al. Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome. Br J Surg. 2001;88(10):1285-1295.

25.  Edgell SE, McCabe SJ, Breidenbach WC, et al. Predicting the outcome of carpal tunnel release. J Hand Surg Am. 2003;28(2):255-261.

26.  Vella JC, Hartigan BJ, Stern PJ. Kaplan’s cardinal line. J Hand Surg Am. 2006;31(6):912-918.

27.  Kwon JY, Kim JY, Hong JT, et al. Position change of the neurovascular structures around the carpal tunnel with dynamic wrist motion. J Korean Neurosurg Soc. 2011;50(4):377-380.

28.  Netscher D, Polsen C, Thornby J, et al. Anatomic delineation of the ulnar nerve and ulnar artery in relation to the carpal tunnel by axial magnetic resonance imaging scanning. J Hand Surg Am. 1996;21(2):273-276.

29.  Madhav TJ, To P, Stern PJ. The palmar fat pad is a reliable intraoperative landmark during carpal tunnel release. J Hand Surg Am. 2009;34(7):1204-1209.

30.  Kulick MI, Gordillo G, Javidi T, et al. Long-term analysis of patients having surgical treatment for carpal tunnel syndrome. J Hand Surg Am. 1986;11(1):59-66.

31.  Bland JD. Treatment of carpal tunnel syndrome. Muscle Nerve. 2007;36(2):167-171.

32.  MacDonald RI, Lichtman DM, Hanlon JJ, et al. Complications of surgical release for carpal tunnel syndrome. J Hand Surg Am. 1978;3(1):70-76.

33.  Atroshi I, Larsson GU, Ornstein E, Hofer M, Johnsson R, Ranstam J. Outcomes of endoscopic surgery compared with open surgery for carpal tunnel syndrome among employed patients: randomised controlled trial. BMJ. 2006;332(7556):1473.

34.  Ferdinand RD, MacLean JG. Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment. J Bone Joint Surg Br. 2002;84(3):375-379.

35.  Thoma A, Veltri K, Haines T, et al. A meta-analysis of randomized controlled trials comparing endoscopic and open carpal tunnel decompression. Plast Reconstr Surg. 2004;114(5):1137-1146.

36.  Murphy RX Jr, Jennings JF, Wukich DK. Major neurovascular complications of endoscopic carpal tunnel release. J Hand Surg Am. 1994;19(1):114-118.

37.  Palmer DH, Paulson JC, Lane-Larsen CL, et al. Endoscopic carpal tunnel release: a comparison of two techniques with open release. Arthroscopy. 1993;9(5):498-508.

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american journal of orthopedics, AJO, orthopedic technologies and techniques, technology, technique, carpal tunnel release, carpal, nasal turbinate speculum, transverse carpal ligament, TCL, nerve, injury, CTR, wrist, ligament, muppavarapu, rajaee, ruchelsman, belsky
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Raghuveer C. Muppavarapu, MD, Sean S. Rajaee, MD, David E. Ruchelsman, MD, and Mark R. Belsky, MD

Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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Article PDF

Carpal tunnel syndrome (CTS) is a disorder characterized by entrapment of the median nerve at the wrist, which may lead to symptoms of pain, paresthesia, and, ultimately, thenar muscle atrophy. Surgical intervention is indicated with persistent or progressive symptoms despite nonoperative management. Timely surgical decompression aims to halt progression of this disorder and prevent permanent peripheral nerve injury.

Carpal tunnel release (CTR) is the most common hand and wrist surgery in the United States, with about 400,000 operations performed annually.1,2 Several methods of decompressing the carpal tunnel have been described.3 These include standard open CTR (OCTR), mini-open approaches, and various endoscopic techniques. OCTR was initially described by Sir James Learmonth in 1933,4 and it remains the gold-standard surgical treatment for patients with symptomatic CTS. Uniform excellent results with high patient satisfaction and low complication rates have been reported in several series.5-9 Common to all techniques is complete proximal-to-distal division of the transverse carpal ligament (TCL). Magnetic resonance imaging studies have shown that TCL transection and the resulting diastasis between the radial and ulnar leaflets cause a significant increase in the volume of the carpal tunnel, leading to decreased pressure.10,11

Endoscopic CTR (ECTR) techniques were developed in an effort to reduce complications, scar sensitivity, and pillar pain and facilitate more rapid return to work.12-17 Outcome studies have demonstrated that both open and endoscopic releases yield patient-reported subjective improvements over preoperative symptoms.18-22 A randomized, controlled trial by Trumble and colleagues23 in 2002 found that ECTR led to improved patient outcomes in the early postoperative period (first 3 months), though differences in outcomes were reduced at final follow-up. More recently (2007), a Cochrane review of 33 trials concluded there was no strong evidence favoring use of alternative techniques over OCTR.3 Further, OCTR has been found to be technically less demanding and associated with decreased complications and costs.24

Indications

The benefit of median nerve decompression at the wrist for CTS is clear.6,7 Indications for surgery in patients with CTS include persistent symptoms despite nonoperative treatment, objective sensory disturbance or motor weakness, and thenar atrophy. Symptomatic response to corticosteroid injection is predictive of success after carpal tunnel surgery.25 More than 87% of patients who gain symptomatic relief from corticosteroid injection have an excellent surgical outcome.

Technique

OCTR allows direct visualization of the TCL and the distal volar forearm fascia (DVFF) and evaluation for the presence of anomalous branching patterns of the median nerve. OCTR traditionally was performed through a 4- to 5-cm longitudinal incision extending from the wrist crease proximally to the Kaplan cardinal line distally. The mini-open technique is identical with the exception of incision length. We routinely use a 2.5- to 3-cm incision. Regardless of incision length, each OCTR should proceed through the same reproducible steps.

We perform OCTR under tourniquet control. Choice of anesthesia is surgeon and patient preference. We prefer local anesthesia with conscious sedation. After conscious sedation is administered, we infiltrate the carpal tunnel and surrounding subcutaneous tissue with 10 mL of a 50:50 mixture of 0.5% bupivacaine and 1% lidocaine without epinephrine.

A 2.5- to 3-cm longitudinal incision is made along the axis of the radial border of the ring finger from the Kaplan cardinal line26 and extending about 3 cm proximally toward the wrist flexion crease ulnar to the palmaris longus if present (Figure 1).

After the skin is incised longitudinally, the subcutaneous fat is mobilized and cutaneous sensory branches identified and protected. The underlying superficial palmar fascia is incised in line with the skin incision. The underlying midportion of the TCL is now visualized.

Transverse Carpal Ligament Release

Occasionally, the investing fascia along the ulnar edge of the thenar musculature is mobilized radialward (if the thenar musculature is well developed) to visualize the proximal limb of the TCL. Injury to any anomalous motor branch of the median nerve is avoided by directly visualizing and then incising the TCL (Figure 2). The TCL is incised along its ulnar border just radial to the hook of hamate from distal to proximal in line with the radial border of the ring finger. Staying near the ulnar attachment of the TCL keeps the plane of ligament division farther away from the median nerve and its recurrent motor branches. Although the ulnar neurovascular bundle typically resides ulnar to the hook of hamate in the canal of Guyon, the surgeon must be aware that it can be located radial to the hook in some instances.27,28 In the elderly, the ulnar artery may be tortuous and enter the field and require retraction. The TCL is incised distally until the sentinel fat pad, which marks the superficial palmar arterial arch, is visualized. This bed of adipose tissue marks the distal edge of the TCL.29

 

 

Proximally, subcutaneous tissues above the proximal limb of the TCL and DVFF are mobilized to about 2 cm proximal to the wrist flexion crease to create a plane for the fine long nasal turbinate speculum. The nasal turbinate speculum is then inserted into this plane above the proximal limb of the TCL and DVFF (Figure 3). Once inserted to the level of the confluence of the TCL and the DVFF, the speculum is opened.

Topside visualization is now encountered with the ulnar neurovascular bundle protected by the ulnar blade of the speculum. A long-handle scalpel is used to incise the TCL and the DVFF under direct visualization from proximal to distal in line with the previously completed distal release (Figure 4). As the nasal turbinate speculum is stretching the TCL and putting it under tension, the TCL can be heard splitting as it is being incised. Once the TCL and the DVFF are divided, the speculum is slowly closed and removed. Wide diastasis of the radial and ulnar leaflets of the TCL and the DVFF is directly visualized. Complete decompression of the median nerve from the distal forearm fascia to the superficial palmar arch is confirmed.

Adhesions between the undersurface of the radial leaflet and the flexor tendons and median nerve are mobilized. The median nerve is assessed for “hourglass” morphology or atrophy. The flexor tendons can be swept radialward with a free elevator to inspect the floor of the carpal tunnel. Flexor tenosynovectomy is not routinely performed. The incision is closed with interrupted simple sutures using 4-0 nylon.

Study Results

This study was conducted at Hand Surgery PC, Newton-Wellesley Hospital, Tufts University School of Medicine. Over a 10-month interval, 101 consecutive mini-OCTRs (63 right hands, 38 left hands) were performed with this proximal release modification in 88 patients (51 females, 37 males) by Dr. Ruchelsman and Dr. Belsky (Table). CTRs performed in the setting of wrist and/or carpal trauma were excluded. Mean age was 62.8 years. Mean follow-up was 11.3 weeks (~3 months). For isolated cases of CTR, mean tourniquet time was 16 minutes. CTS symptoms were relieved in all patients with a high degree of satisfaction as measured with history and examination findings at follow-up visits. There were no major complications (eg, infection, neural or vascular damage, severe residual pain). Four patients reported minor residual numbness in the fingers at latest follow-up but nevertheless had major improvement over preoperative baseline. These 4 patients had preoperative electromyograms or nerve conduction studies documenting the extent of their disease. There was 1 case of minor wound complication. Three weeks after surgery, the patient had a 1-cm wound opening, which closed with local wound care. The patient did not develop any drainage, infection, bleeding, or neurologic symptoms.

Discussion

Open release of the TCL—the gold standard of surgical treatment for CTS—produces reliable symptom relief in the vast majority of patients.25,30 Given that the most common complication of carpal tunnel surgery is incomplete release of the TCL,31,32 this technique, which uses a nasal turbinate speculum to better visualize the median nerve, could potentially reduce the reoperation rate. The nasal turbinate speculum allows the surgeon to see the confluence of the TCL and the DVFF. In addition, as the complete release can be visualized, there is minimal chance of injury.

The 2007 Cochrane review3 found no strong evidence supporting replacing OCTR with endoscopic techniques. Previous investigators have questioned the utility of ECTR given that it is higher in cost and more resource-intensive than OCTR1,33,34 and is associated with higher rates of certain complications.5,22,35-37 A 2004 meta-analysis of 13 randomized, controlled trials found a higher rate of reversible nerve damage with an odds ratio of 3.1 for ECTR versus OCTR.35 A more recent (2006) review of more than 80 studies found transient neurapraxias in 1.45% of ECTR cases and 0.25% of OCTR cases.5 The same study reported overall complication rates (reversible and major neurovascular structural injuries) of 0.74% for OCTR and 1.63% for ECTR (P < .005). Another limitation of ECTR is that endoscopic techniques require a higher degree of surgical skill, which makes teaching residents and fellows more challenging.

The novel nasal turbinate speculum technique presented here is easily reproducible and allows first-time surgeons to visualize all important structures. Given that this technique does not require an endoscope or an endoscope-viewing tower, it is likely more cost-effective and requires less time for turnover between cases. Patients obtain good relief of their CTS symptoms with this technique, and most return to their daily activities within weeks after operation.

Carpal tunnel syndrome (CTS) is a disorder characterized by entrapment of the median nerve at the wrist, which may lead to symptoms of pain, paresthesia, and, ultimately, thenar muscle atrophy. Surgical intervention is indicated with persistent or progressive symptoms despite nonoperative management. Timely surgical decompression aims to halt progression of this disorder and prevent permanent peripheral nerve injury.

Carpal tunnel release (CTR) is the most common hand and wrist surgery in the United States, with about 400,000 operations performed annually.1,2 Several methods of decompressing the carpal tunnel have been described.3 These include standard open CTR (OCTR), mini-open approaches, and various endoscopic techniques. OCTR was initially described by Sir James Learmonth in 1933,4 and it remains the gold-standard surgical treatment for patients with symptomatic CTS. Uniform excellent results with high patient satisfaction and low complication rates have been reported in several series.5-9 Common to all techniques is complete proximal-to-distal division of the transverse carpal ligament (TCL). Magnetic resonance imaging studies have shown that TCL transection and the resulting diastasis between the radial and ulnar leaflets cause a significant increase in the volume of the carpal tunnel, leading to decreased pressure.10,11

Endoscopic CTR (ECTR) techniques were developed in an effort to reduce complications, scar sensitivity, and pillar pain and facilitate more rapid return to work.12-17 Outcome studies have demonstrated that both open and endoscopic releases yield patient-reported subjective improvements over preoperative symptoms.18-22 A randomized, controlled trial by Trumble and colleagues23 in 2002 found that ECTR led to improved patient outcomes in the early postoperative period (first 3 months), though differences in outcomes were reduced at final follow-up. More recently (2007), a Cochrane review of 33 trials concluded there was no strong evidence favoring use of alternative techniques over OCTR.3 Further, OCTR has been found to be technically less demanding and associated with decreased complications and costs.24

Indications

The benefit of median nerve decompression at the wrist for CTS is clear.6,7 Indications for surgery in patients with CTS include persistent symptoms despite nonoperative treatment, objective sensory disturbance or motor weakness, and thenar atrophy. Symptomatic response to corticosteroid injection is predictive of success after carpal tunnel surgery.25 More than 87% of patients who gain symptomatic relief from corticosteroid injection have an excellent surgical outcome.

Technique

OCTR allows direct visualization of the TCL and the distal volar forearm fascia (DVFF) and evaluation for the presence of anomalous branching patterns of the median nerve. OCTR traditionally was performed through a 4- to 5-cm longitudinal incision extending from the wrist crease proximally to the Kaplan cardinal line distally. The mini-open technique is identical with the exception of incision length. We routinely use a 2.5- to 3-cm incision. Regardless of incision length, each OCTR should proceed through the same reproducible steps.

We perform OCTR under tourniquet control. Choice of anesthesia is surgeon and patient preference. We prefer local anesthesia with conscious sedation. After conscious sedation is administered, we infiltrate the carpal tunnel and surrounding subcutaneous tissue with 10 mL of a 50:50 mixture of 0.5% bupivacaine and 1% lidocaine without epinephrine.

A 2.5- to 3-cm longitudinal incision is made along the axis of the radial border of the ring finger from the Kaplan cardinal line26 and extending about 3 cm proximally toward the wrist flexion crease ulnar to the palmaris longus if present (Figure 1).

After the skin is incised longitudinally, the subcutaneous fat is mobilized and cutaneous sensory branches identified and protected. The underlying superficial palmar fascia is incised in line with the skin incision. The underlying midportion of the TCL is now visualized.

Transverse Carpal Ligament Release

Occasionally, the investing fascia along the ulnar edge of the thenar musculature is mobilized radialward (if the thenar musculature is well developed) to visualize the proximal limb of the TCL. Injury to any anomalous motor branch of the median nerve is avoided by directly visualizing and then incising the TCL (Figure 2). The TCL is incised along its ulnar border just radial to the hook of hamate from distal to proximal in line with the radial border of the ring finger. Staying near the ulnar attachment of the TCL keeps the plane of ligament division farther away from the median nerve and its recurrent motor branches. Although the ulnar neurovascular bundle typically resides ulnar to the hook of hamate in the canal of Guyon, the surgeon must be aware that it can be located radial to the hook in some instances.27,28 In the elderly, the ulnar artery may be tortuous and enter the field and require retraction. The TCL is incised distally until the sentinel fat pad, which marks the superficial palmar arterial arch, is visualized. This bed of adipose tissue marks the distal edge of the TCL.29

 

 

Proximally, subcutaneous tissues above the proximal limb of the TCL and DVFF are mobilized to about 2 cm proximal to the wrist flexion crease to create a plane for the fine long nasal turbinate speculum. The nasal turbinate speculum is then inserted into this plane above the proximal limb of the TCL and DVFF (Figure 3). Once inserted to the level of the confluence of the TCL and the DVFF, the speculum is opened.

Topside visualization is now encountered with the ulnar neurovascular bundle protected by the ulnar blade of the speculum. A long-handle scalpel is used to incise the TCL and the DVFF under direct visualization from proximal to distal in line with the previously completed distal release (Figure 4). As the nasal turbinate speculum is stretching the TCL and putting it under tension, the TCL can be heard splitting as it is being incised. Once the TCL and the DVFF are divided, the speculum is slowly closed and removed. Wide diastasis of the radial and ulnar leaflets of the TCL and the DVFF is directly visualized. Complete decompression of the median nerve from the distal forearm fascia to the superficial palmar arch is confirmed.

Adhesions between the undersurface of the radial leaflet and the flexor tendons and median nerve are mobilized. The median nerve is assessed for “hourglass” morphology or atrophy. The flexor tendons can be swept radialward with a free elevator to inspect the floor of the carpal tunnel. Flexor tenosynovectomy is not routinely performed. The incision is closed with interrupted simple sutures using 4-0 nylon.

Study Results

This study was conducted at Hand Surgery PC, Newton-Wellesley Hospital, Tufts University School of Medicine. Over a 10-month interval, 101 consecutive mini-OCTRs (63 right hands, 38 left hands) were performed with this proximal release modification in 88 patients (51 females, 37 males) by Dr. Ruchelsman and Dr. Belsky (Table). CTRs performed in the setting of wrist and/or carpal trauma were excluded. Mean age was 62.8 years. Mean follow-up was 11.3 weeks (~3 months). For isolated cases of CTR, mean tourniquet time was 16 minutes. CTS symptoms were relieved in all patients with a high degree of satisfaction as measured with history and examination findings at follow-up visits. There were no major complications (eg, infection, neural or vascular damage, severe residual pain). Four patients reported minor residual numbness in the fingers at latest follow-up but nevertheless had major improvement over preoperative baseline. These 4 patients had preoperative electromyograms or nerve conduction studies documenting the extent of their disease. There was 1 case of minor wound complication. Three weeks after surgery, the patient had a 1-cm wound opening, which closed with local wound care. The patient did not develop any drainage, infection, bleeding, or neurologic symptoms.

Discussion

Open release of the TCL—the gold standard of surgical treatment for CTS—produces reliable symptom relief in the vast majority of patients.25,30 Given that the most common complication of carpal tunnel surgery is incomplete release of the TCL,31,32 this technique, which uses a nasal turbinate speculum to better visualize the median nerve, could potentially reduce the reoperation rate. The nasal turbinate speculum allows the surgeon to see the confluence of the TCL and the DVFF. In addition, as the complete release can be visualized, there is minimal chance of injury.

The 2007 Cochrane review3 found no strong evidence supporting replacing OCTR with endoscopic techniques. Previous investigators have questioned the utility of ECTR given that it is higher in cost and more resource-intensive than OCTR1,33,34 and is associated with higher rates of certain complications.5,22,35-37 A 2004 meta-analysis of 13 randomized, controlled trials found a higher rate of reversible nerve damage with an odds ratio of 3.1 for ECTR versus OCTR.35 A more recent (2006) review of more than 80 studies found transient neurapraxias in 1.45% of ECTR cases and 0.25% of OCTR cases.5 The same study reported overall complication rates (reversible and major neurovascular structural injuries) of 0.74% for OCTR and 1.63% for ECTR (P < .005). Another limitation of ECTR is that endoscopic techniques require a higher degree of surgical skill, which makes teaching residents and fellows more challenging.

The novel nasal turbinate speculum technique presented here is easily reproducible and allows first-time surgeons to visualize all important structures. Given that this technique does not require an endoscope or an endoscope-viewing tower, it is likely more cost-effective and requires less time for turnover between cases. Patients obtain good relief of their CTS symptoms with this technique, and most return to their daily activities within weeks after operation.

References

1.    Ono S, Clapham PJ, Chung KC. Optimal management of carpal tunnel syndrome. Int J Gen Med. 2010;3(4):255-261.

2.    Concannon MJ, Brownfield ML, Puckett CL. The incidence of recurrence after endoscopic carpal tunnel release. Plast Reconstr Surg. 2000;105(5):1662-1665.

3.    Scholten RJ, Mink van der Molen A, Uitdehaag BM, Bouter LM, de Vet HC. Surgical treatment options for carpal tunnel syndrome. Cochrane Database Syst Rev. 2007;(4):CD003905.

4.    In memoriam Sir James Learmonth, K.C.V.O., C.B.E., hon. F.R.C.S. (1895-1967). Ann R Coll Surg Engl. 1967;41(5):438-439.

5.    Benson LS, Bare AA, Nagle DJ, Harder VS, Williams CS, Visotsky JL. Complications of endoscopic and open carpal tunnel release. Arthroscopy. 2006;22(9):919-924, 924.e1-e2.

6.    Jarvik JG, Comstock BA, Kliot M, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009;374(9695):1074-1081.

7.    Verdugo RJ, Salinas RA, Castillo JL, et al. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2008;(4):CD001552.

8.    Garland H, Langworth EP, Taverner D, et al. Surgical treatment for the carpal tunnel syndrome. Lancet. 1964;1(7343):1129-1130.

9.    Gerritsen AA, de Vet HC, Scholten RJ, et al. Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial. JAMA. 2002;288(10):1245-1251.

10.  Gelberman RH, Hergenroeder PT, Hargens AR, et al. The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am. 1981;63(3):380-383.

11.  Sucher BM. Myofascial manipulative release of carpal tunnel syndrome: documentation with magnetic resonance imaging. J Am Osteopath Assoc. 1993;93(12):1273-1278.

12.  Pereira EE, Miranda DA, Sere I, et al. Endoscopic release of the carpal tunnel: a 2-portal-modified technique. Tech Hand Up Extrem Surg. 2010;14(4):263-265.

13.  Louis DS, Greene TL, Noellert RC. Complications of carpal tunnel surgery. J Neurosurg. 1985;62(3):352-356.

14.  Mirza MA, King ET Jr, Tanveer S. Palmar uniportal extrabursal endoscopic carpal tunnel release. Arthroscopy. 1995;11(1):82-90.

15.  Brown MG, Keyser B, Rothenberg ES. Endoscopic carpal tunnel release. J Hand Surg Am. 1992;17(6):1009-1011.

16.  Agee JM, McCarroll HR Jr, Tortosa RD, et al. Endoscopic release of the carpal tunnel: a randomized prospective multicenter study. J Hand Surg Am. 1992;17(6):987-995.

17.  Okutsu I, Ninomiya S, Takatori Y, et al. Endoscopic management of carpal tunnel syndrome. Arthroscopy. 1989;5(1):11-18.

18.  Ghaly RF, Saban KL, Haley DA, et al. Endoscopic carpal tunnel release surgery: report of patient satisfaction. Neurol Res. 2000;22(6):551-555.

19.  Lee WP, Plancher KD, Strickland JW. Carpal tunnel release with a small palmar incision. Hand Clin. 1996;12(2):271-284.

20.  Biyani A, Downes EM. An open twin incision technique of carpal tunnel decompression with reduced incidence of scar tenderness. J Hand Surg Br. 1993;18(3):331-334.

21.  Brown RA, Gelberman RH, Seiler JG 3rd, et al. Carpal tunnel release. A prospective, randomized assessment of open and endoscopic methods. J Bone Joint Surg Am. 1993;75(9):1265-1275.

22.  Chow JC. Endoscopic release of the carpal ligament for carpal tunnel syndrome: 22-month clinical result. Arthroscopy. 1990;6(4):288-296.

23.  Trumble TE, Diao E, Abrams RA, et al. Single-portal endoscopic carpal tunnel release compared with open release: a prospective, randomized trial. J Bone Joint Surg Am. 2002;84(7):1107-1115.

24.  Gerritsen AA, Uitdehaag BM, van Geldere D, et al. Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome. Br J Surg. 2001;88(10):1285-1295.

25.  Edgell SE, McCabe SJ, Breidenbach WC, et al. Predicting the outcome of carpal tunnel release. J Hand Surg Am. 2003;28(2):255-261.

26.  Vella JC, Hartigan BJ, Stern PJ. Kaplan’s cardinal line. J Hand Surg Am. 2006;31(6):912-918.

27.  Kwon JY, Kim JY, Hong JT, et al. Position change of the neurovascular structures around the carpal tunnel with dynamic wrist motion. J Korean Neurosurg Soc. 2011;50(4):377-380.

28.  Netscher D, Polsen C, Thornby J, et al. Anatomic delineation of the ulnar nerve and ulnar artery in relation to the carpal tunnel by axial magnetic resonance imaging scanning. J Hand Surg Am. 1996;21(2):273-276.

29.  Madhav TJ, To P, Stern PJ. The palmar fat pad is a reliable intraoperative landmark during carpal tunnel release. J Hand Surg Am. 2009;34(7):1204-1209.

30.  Kulick MI, Gordillo G, Javidi T, et al. Long-term analysis of patients having surgical treatment for carpal tunnel syndrome. J Hand Surg Am. 1986;11(1):59-66.

31.  Bland JD. Treatment of carpal tunnel syndrome. Muscle Nerve. 2007;36(2):167-171.

32.  MacDonald RI, Lichtman DM, Hanlon JJ, et al. Complications of surgical release for carpal tunnel syndrome. J Hand Surg Am. 1978;3(1):70-76.

33.  Atroshi I, Larsson GU, Ornstein E, Hofer M, Johnsson R, Ranstam J. Outcomes of endoscopic surgery compared with open surgery for carpal tunnel syndrome among employed patients: randomised controlled trial. BMJ. 2006;332(7556):1473.

34.  Ferdinand RD, MacLean JG. Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment. J Bone Joint Surg Br. 2002;84(3):375-379.

35.  Thoma A, Veltri K, Haines T, et al. A meta-analysis of randomized controlled trials comparing endoscopic and open carpal tunnel decompression. Plast Reconstr Surg. 2004;114(5):1137-1146.

36.  Murphy RX Jr, Jennings JF, Wukich DK. Major neurovascular complications of endoscopic carpal tunnel release. J Hand Surg Am. 1994;19(1):114-118.

37.  Palmer DH, Paulson JC, Lane-Larsen CL, et al. Endoscopic carpal tunnel release: a comparison of two techniques with open release. Arthroscopy. 1993;9(5):498-508.

References

1.    Ono S, Clapham PJ, Chung KC. Optimal management of carpal tunnel syndrome. Int J Gen Med. 2010;3(4):255-261.

2.    Concannon MJ, Brownfield ML, Puckett CL. The incidence of recurrence after endoscopic carpal tunnel release. Plast Reconstr Surg. 2000;105(5):1662-1665.

3.    Scholten RJ, Mink van der Molen A, Uitdehaag BM, Bouter LM, de Vet HC. Surgical treatment options for carpal tunnel syndrome. Cochrane Database Syst Rev. 2007;(4):CD003905.

4.    In memoriam Sir James Learmonth, K.C.V.O., C.B.E., hon. F.R.C.S. (1895-1967). Ann R Coll Surg Engl. 1967;41(5):438-439.

5.    Benson LS, Bare AA, Nagle DJ, Harder VS, Williams CS, Visotsky JL. Complications of endoscopic and open carpal tunnel release. Arthroscopy. 2006;22(9):919-924, 924.e1-e2.

6.    Jarvik JG, Comstock BA, Kliot M, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009;374(9695):1074-1081.

7.    Verdugo RJ, Salinas RA, Castillo JL, et al. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2008;(4):CD001552.

8.    Garland H, Langworth EP, Taverner D, et al. Surgical treatment for the carpal tunnel syndrome. Lancet. 1964;1(7343):1129-1130.

9.    Gerritsen AA, de Vet HC, Scholten RJ, et al. Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial. JAMA. 2002;288(10):1245-1251.

10.  Gelberman RH, Hergenroeder PT, Hargens AR, et al. The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am. 1981;63(3):380-383.

11.  Sucher BM. Myofascial manipulative release of carpal tunnel syndrome: documentation with magnetic resonance imaging. J Am Osteopath Assoc. 1993;93(12):1273-1278.

12.  Pereira EE, Miranda DA, Sere I, et al. Endoscopic release of the carpal tunnel: a 2-portal-modified technique. Tech Hand Up Extrem Surg. 2010;14(4):263-265.

13.  Louis DS, Greene TL, Noellert RC. Complications of carpal tunnel surgery. J Neurosurg. 1985;62(3):352-356.

14.  Mirza MA, King ET Jr, Tanveer S. Palmar uniportal extrabursal endoscopic carpal tunnel release. Arthroscopy. 1995;11(1):82-90.

15.  Brown MG, Keyser B, Rothenberg ES. Endoscopic carpal tunnel release. J Hand Surg Am. 1992;17(6):1009-1011.

16.  Agee JM, McCarroll HR Jr, Tortosa RD, et al. Endoscopic release of the carpal tunnel: a randomized prospective multicenter study. J Hand Surg Am. 1992;17(6):987-995.

17.  Okutsu I, Ninomiya S, Takatori Y, et al. Endoscopic management of carpal tunnel syndrome. Arthroscopy. 1989;5(1):11-18.

18.  Ghaly RF, Saban KL, Haley DA, et al. Endoscopic carpal tunnel release surgery: report of patient satisfaction. Neurol Res. 2000;22(6):551-555.

19.  Lee WP, Plancher KD, Strickland JW. Carpal tunnel release with a small palmar incision. Hand Clin. 1996;12(2):271-284.

20.  Biyani A, Downes EM. An open twin incision technique of carpal tunnel decompression with reduced incidence of scar tenderness. J Hand Surg Br. 1993;18(3):331-334.

21.  Brown RA, Gelberman RH, Seiler JG 3rd, et al. Carpal tunnel release. A prospective, randomized assessment of open and endoscopic methods. J Bone Joint Surg Am. 1993;75(9):1265-1275.

22.  Chow JC. Endoscopic release of the carpal ligament for carpal tunnel syndrome: 22-month clinical result. Arthroscopy. 1990;6(4):288-296.

23.  Trumble TE, Diao E, Abrams RA, et al. Single-portal endoscopic carpal tunnel release compared with open release: a prospective, randomized trial. J Bone Joint Surg Am. 2002;84(7):1107-1115.

24.  Gerritsen AA, Uitdehaag BM, van Geldere D, et al. Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome. Br J Surg. 2001;88(10):1285-1295.

25.  Edgell SE, McCabe SJ, Breidenbach WC, et al. Predicting the outcome of carpal tunnel release. J Hand Surg Am. 2003;28(2):255-261.

26.  Vella JC, Hartigan BJ, Stern PJ. Kaplan’s cardinal line. J Hand Surg Am. 2006;31(6):912-918.

27.  Kwon JY, Kim JY, Hong JT, et al. Position change of the neurovascular structures around the carpal tunnel with dynamic wrist motion. J Korean Neurosurg Soc. 2011;50(4):377-380.

28.  Netscher D, Polsen C, Thornby J, et al. Anatomic delineation of the ulnar nerve and ulnar artery in relation to the carpal tunnel by axial magnetic resonance imaging scanning. J Hand Surg Am. 1996;21(2):273-276.

29.  Madhav TJ, To P, Stern PJ. The palmar fat pad is a reliable intraoperative landmark during carpal tunnel release. J Hand Surg Am. 2009;34(7):1204-1209.

30.  Kulick MI, Gordillo G, Javidi T, et al. Long-term analysis of patients having surgical treatment for carpal tunnel syndrome. J Hand Surg Am. 1986;11(1):59-66.

31.  Bland JD. Treatment of carpal tunnel syndrome. Muscle Nerve. 2007;36(2):167-171.

32.  MacDonald RI, Lichtman DM, Hanlon JJ, et al. Complications of surgical release for carpal tunnel syndrome. J Hand Surg Am. 1978;3(1):70-76.

33.  Atroshi I, Larsson GU, Ornstein E, Hofer M, Johnsson R, Ranstam J. Outcomes of endoscopic surgery compared with open surgery for carpal tunnel syndrome among employed patients: randomised controlled trial. BMJ. 2006;332(7556):1473.

34.  Ferdinand RD, MacLean JG. Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment. J Bone Joint Surg Br. 2002;84(3):375-379.

35.  Thoma A, Veltri K, Haines T, et al. A meta-analysis of randomized controlled trials comparing endoscopic and open carpal tunnel decompression. Plast Reconstr Surg. 2004;114(5):1137-1146.

36.  Murphy RX Jr, Jennings JF, Wukich DK. Major neurovascular complications of endoscopic carpal tunnel release. J Hand Surg Am. 1994;19(1):114-118.

37.  Palmer DH, Paulson JC, Lane-Larsen CL, et al. Endoscopic carpal tunnel release: a comparison of two techniques with open release. Arthroscopy. 1993;9(5):498-508.

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The American Journal of Orthopedics - 44(11)
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The American Journal of Orthopedics - 44(11)
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Open Carpal Tunnel Release With Use of a Nasal Turbinate Speculum
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Open Carpal Tunnel Release With Use of a Nasal Turbinate Speculum
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american journal of orthopedics, AJO, orthopedic technologies and techniques, technology, technique, carpal tunnel release, carpal, nasal turbinate speculum, transverse carpal ligament, TCL, nerve, injury, CTR, wrist, ligament, muppavarapu, rajaee, ruchelsman, belsky
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american journal of orthopedics, AJO, orthopedic technologies and techniques, technology, technique, carpal tunnel release, carpal, nasal turbinate speculum, transverse carpal ligament, TCL, nerve, injury, CTR, wrist, ligament, muppavarapu, rajaee, ruchelsman, belsky
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Excision of Symptomatic Spinous Process Nonunion in Adolescent Athletes

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Excision of Symptomatic Spinous Process Nonunion in Adolescent Athletes

Fractures of the spinous process of the lower cervical spine or upper thoracic spine are frequently referred to as clay-shoveler’s fractures. Originally reported by Hall1 in 1940, these fractures were described in workers in Australia who dug drains in clay soil and threw the clay overhead with long shovels. Occasionally, the mud would not release from the shovel, causing excess force to be transmitted to the supraspinous ligaments and resulting in a forceful avulsion fracture of one or multiple spinous processes. The few reports following the earliest description in the literature frequently describe the mechanism of injury as being athletic in nature.2-4 The forceful contraction of the paraspinal and trapezius muscles on the supraspinous ligaments and the resultant attachment to the spinous processes make this a not uncommon injury during athletics, especially with a flexed position of the neck and shoulders. The resultant fracture or apophyseal avulsion is painful and often necessitates a visit to the physician, with plain films, computed tomography (CT) scans, or magnetic resonance imaging (MRI) confirming the diagnosis.5

Treatment of these fractures has not been well described, but frequently a period of rest followed by physical therapy will allow a return to activity. We present a series of adolescent athletes who developed nonunion of the fracture of the T1 spinous process with continued symptoms, despite rest and conservative therapy, and who underwent surgical excision of the ununited fragment.

Materials and Methods

We obtained institutional review board permission for this study and searched the surgical database between 2006 and 2013 for patients who had undergone resection of a spinous process nonunion. We collected demographic data on the patients, evaluated the radiographic studies, and reviewed operative reports and follow-up patient data.

Results

Dr. Hedequist operated on 3 patients with a spinous process nonunion over the study time period. The average age of the patients was 14 years; the location of the spinous process fracture was the T1 vertebra in all patients. Two patients sustained the injury while playing hockey and 1 during wrestling. The average duration of symptoms prior to operation was 10 months; all patients had seen physicians without a diagnosis prior to evaluation at out institution. All patients had a trial of physical therapy before surgery, and all had been unable to return to sport after injury secondary to pain.

Examination of all patients revealed pain directly over the fracture site and accentuated by forward flexion of the neck and shoulders. Evaluation of injury plain films revealed a fracture fragment in 2 patients (Figure 1). All 3 patients underwent MRI and CT scans confirming the diagnosis. MRI confirmed areas of increased signal at the tip of the T1 spinous process, with inflammation in the supraspinous ligament directly at that region (Figure 2). The CT scans confirmed the presence of a bony fragment correlating with the tip of the T1 spinous process (Figure 3).

   

Surgery was performed under general endotracheal anesthesia via a midline incision over the affected area down to the spinous process. The supraspinous ligament was opened revealing an easily identified and definable ununited ossicle, which was removed without taking down the interspinous ligament. All 3 nonunions were noted to be atrophic with no evidence of surrounding inflammatory tissue or bursa. The residual end of the spinous process was smoothed down with a rongeur. Standard closure was performed. There were no surgical complications.

All patients had complete relief of pain at follow-up; 1 patient returned to full sports activity at 6 weeks and the other 2 returned to full sports activity at 3 months. There was no loss of cervical motion or trapezial strength at follow-up. All patients voiced satisfaction with the decision for surgical intervention.

Discussion

Clay-shoveler’s fracture is an injury well known to orthopedists. This fracture is thought to be caused by a forceful contraction of the thoracic paraspinal and trapezial muscles, causing an avulsion fracture with pain and frequently a “pop” experienced by the patient.1 Usually considered self-limiting injuries, treatment involves a period of rest and activity modification with occasional physical therapy. Return to sports has been reported with occasional pain but with patient satisfaction.3,5,6

Our series of patients represent a group of adolescent athletes who sustained spinous process fractures of the T1 vertebra and, despite a significant period of rest and activity modification, were unable to return to sports given their pain. The examination of these patients revealed focal tenderness at the tip of the spinous process. The diagnosis is made clinically, with radiographic studies confirming the diagnosis. In our series of patients, MRI was the original modality used to confirm injury to the area, with hyperintensity seen in the area of the supraspinous ligament and tip of the spinous process. CT confirmed the nonunion and presence of an ossicle in all patients. Surgical exposure of that area easily exposed the ununited ossicle, which was removed in all patients.

 

 

To our knowledge, this is the first report in the literature describing surgical excision of an ununited spinous process fracture in adolescent athletes. The original descriptive case series by Hall1 states “in the minds of surgeons who have seen many of these cases that early operative removal of the fragments is the proper routine treatment.” Since that original series, we have not found articles in the literature that support surgical removal; however, persistent symptoms after fracture are described.5 It is not surprising that these patients developed pain at the site of the fracture given the forces acting in that area. The trapezial and paraspinal muscles acting on that area are forceful and repetitive during activities, especially sports. All our patients had pain with attempts at activity and all had had a significant period of rest. In a recent article, this injury was described in adolescents without the patients having clear relief of symptoms despite a period of inactivity.5 While physical therapy is therapeutic in some patients experiencing pain, it can be a source of aggravation due to neck and shoulder motion and muscle contraction. It is not surprising that therapy would not help in most cases, as neck and shoulder motion and muscle contraction are the sources of continuing discomfort.

Clinical practice suggests that most patients with spinous process fractures will become pain-free; however, that is not universal. This series demonstrates that a small subset of patients with this injury will continue to have significant symptoms despite a period of rest. In those patients who desire a pain-free return to sports, we recommend consideration of surgical excision after confirmation of nonunion with radiographic studies. The inherent risks of surgical treatment are minimal with this procedure, and the benefits include return to pain-free sports activity, with the resultant physical and psychosocial benefits for adolescent athletes.

References

1.    Hall RDM. Clay-shoveler’s fracture. J Bone Joint Surg Am. 1940;22(1):63-75.

2.    Herrick RT. Clay-shoveler’s fracture in power-lifting. A case report. Am J Sports Med. 1981;9(1):29-30.

3.    Hetsroni I, Mann G, Dolev E, Morgenstern D, Nyska M. Clay shoveler’s fracture in a volleyball player. Phys Sportsmed. 2005;33(7):38-42.

4.    Kaloostian PE, Kim JE, Calabresi PA, Bydon A, Witham T. Clay-shoveler’s fracture during indoor rock climbing. Orthopedics. 2013;36(3):e381-e383.

5.    Yamaguchi KT Jr, Myung KS, Alonso MA, Skaggs DL. Clay-shoveler’s fracture equivalent in children. Spine. 2012;37(26):e1672-e1675.

6.    Kang DH, Lee SH. Multiple spinous process fractures of the thoracic vertebrae (clay-shoveler’s fracture) in a beginning golfer: a case report. Spine. 2009;34(15):e534-e537.

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Fractures of the spinous process of the lower cervical spine or upper thoracic spine are frequently referred to as clay-shoveler’s fractures. Originally reported by Hall1 in 1940, these fractures were described in workers in Australia who dug drains in clay soil and threw the clay overhead with long shovels. Occasionally, the mud would not release from the shovel, causing excess force to be transmitted to the supraspinous ligaments and resulting in a forceful avulsion fracture of one or multiple spinous processes. The few reports following the earliest description in the literature frequently describe the mechanism of injury as being athletic in nature.2-4 The forceful contraction of the paraspinal and trapezius muscles on the supraspinous ligaments and the resultant attachment to the spinous processes make this a not uncommon injury during athletics, especially with a flexed position of the neck and shoulders. The resultant fracture or apophyseal avulsion is painful and often necessitates a visit to the physician, with plain films, computed tomography (CT) scans, or magnetic resonance imaging (MRI) confirming the diagnosis.5

Treatment of these fractures has not been well described, but frequently a period of rest followed by physical therapy will allow a return to activity. We present a series of adolescent athletes who developed nonunion of the fracture of the T1 spinous process with continued symptoms, despite rest and conservative therapy, and who underwent surgical excision of the ununited fragment.

Materials and Methods

We obtained institutional review board permission for this study and searched the surgical database between 2006 and 2013 for patients who had undergone resection of a spinous process nonunion. We collected demographic data on the patients, evaluated the radiographic studies, and reviewed operative reports and follow-up patient data.

Results

Dr. Hedequist operated on 3 patients with a spinous process nonunion over the study time period. The average age of the patients was 14 years; the location of the spinous process fracture was the T1 vertebra in all patients. Two patients sustained the injury while playing hockey and 1 during wrestling. The average duration of symptoms prior to operation was 10 months; all patients had seen physicians without a diagnosis prior to evaluation at out institution. All patients had a trial of physical therapy before surgery, and all had been unable to return to sport after injury secondary to pain.

Examination of all patients revealed pain directly over the fracture site and accentuated by forward flexion of the neck and shoulders. Evaluation of injury plain films revealed a fracture fragment in 2 patients (Figure 1). All 3 patients underwent MRI and CT scans confirming the diagnosis. MRI confirmed areas of increased signal at the tip of the T1 spinous process, with inflammation in the supraspinous ligament directly at that region (Figure 2). The CT scans confirmed the presence of a bony fragment correlating with the tip of the T1 spinous process (Figure 3).

   

Surgery was performed under general endotracheal anesthesia via a midline incision over the affected area down to the spinous process. The supraspinous ligament was opened revealing an easily identified and definable ununited ossicle, which was removed without taking down the interspinous ligament. All 3 nonunions were noted to be atrophic with no evidence of surrounding inflammatory tissue or bursa. The residual end of the spinous process was smoothed down with a rongeur. Standard closure was performed. There were no surgical complications.

All patients had complete relief of pain at follow-up; 1 patient returned to full sports activity at 6 weeks and the other 2 returned to full sports activity at 3 months. There was no loss of cervical motion or trapezial strength at follow-up. All patients voiced satisfaction with the decision for surgical intervention.

Discussion

Clay-shoveler’s fracture is an injury well known to orthopedists. This fracture is thought to be caused by a forceful contraction of the thoracic paraspinal and trapezial muscles, causing an avulsion fracture with pain and frequently a “pop” experienced by the patient.1 Usually considered self-limiting injuries, treatment involves a period of rest and activity modification with occasional physical therapy. Return to sports has been reported with occasional pain but with patient satisfaction.3,5,6

Our series of patients represent a group of adolescent athletes who sustained spinous process fractures of the T1 vertebra and, despite a significant period of rest and activity modification, were unable to return to sports given their pain. The examination of these patients revealed focal tenderness at the tip of the spinous process. The diagnosis is made clinically, with radiographic studies confirming the diagnosis. In our series of patients, MRI was the original modality used to confirm injury to the area, with hyperintensity seen in the area of the supraspinous ligament and tip of the spinous process. CT confirmed the nonunion and presence of an ossicle in all patients. Surgical exposure of that area easily exposed the ununited ossicle, which was removed in all patients.

 

 

To our knowledge, this is the first report in the literature describing surgical excision of an ununited spinous process fracture in adolescent athletes. The original descriptive case series by Hall1 states “in the minds of surgeons who have seen many of these cases that early operative removal of the fragments is the proper routine treatment.” Since that original series, we have not found articles in the literature that support surgical removal; however, persistent symptoms after fracture are described.5 It is not surprising that these patients developed pain at the site of the fracture given the forces acting in that area. The trapezial and paraspinal muscles acting on that area are forceful and repetitive during activities, especially sports. All our patients had pain with attempts at activity and all had had a significant period of rest. In a recent article, this injury was described in adolescents without the patients having clear relief of symptoms despite a period of inactivity.5 While physical therapy is therapeutic in some patients experiencing pain, it can be a source of aggravation due to neck and shoulder motion and muscle contraction. It is not surprising that therapy would not help in most cases, as neck and shoulder motion and muscle contraction are the sources of continuing discomfort.

Clinical practice suggests that most patients with spinous process fractures will become pain-free; however, that is not universal. This series demonstrates that a small subset of patients with this injury will continue to have significant symptoms despite a period of rest. In those patients who desire a pain-free return to sports, we recommend consideration of surgical excision after confirmation of nonunion with radiographic studies. The inherent risks of surgical treatment are minimal with this procedure, and the benefits include return to pain-free sports activity, with the resultant physical and psychosocial benefits for adolescent athletes.

Fractures of the spinous process of the lower cervical spine or upper thoracic spine are frequently referred to as clay-shoveler’s fractures. Originally reported by Hall1 in 1940, these fractures were described in workers in Australia who dug drains in clay soil and threw the clay overhead with long shovels. Occasionally, the mud would not release from the shovel, causing excess force to be transmitted to the supraspinous ligaments and resulting in a forceful avulsion fracture of one or multiple spinous processes. The few reports following the earliest description in the literature frequently describe the mechanism of injury as being athletic in nature.2-4 The forceful contraction of the paraspinal and trapezius muscles on the supraspinous ligaments and the resultant attachment to the spinous processes make this a not uncommon injury during athletics, especially with a flexed position of the neck and shoulders. The resultant fracture or apophyseal avulsion is painful and often necessitates a visit to the physician, with plain films, computed tomography (CT) scans, or magnetic resonance imaging (MRI) confirming the diagnosis.5

Treatment of these fractures has not been well described, but frequently a period of rest followed by physical therapy will allow a return to activity. We present a series of adolescent athletes who developed nonunion of the fracture of the T1 spinous process with continued symptoms, despite rest and conservative therapy, and who underwent surgical excision of the ununited fragment.

Materials and Methods

We obtained institutional review board permission for this study and searched the surgical database between 2006 and 2013 for patients who had undergone resection of a spinous process nonunion. We collected demographic data on the patients, evaluated the radiographic studies, and reviewed operative reports and follow-up patient data.

Results

Dr. Hedequist operated on 3 patients with a spinous process nonunion over the study time period. The average age of the patients was 14 years; the location of the spinous process fracture was the T1 vertebra in all patients. Two patients sustained the injury while playing hockey and 1 during wrestling. The average duration of symptoms prior to operation was 10 months; all patients had seen physicians without a diagnosis prior to evaluation at out institution. All patients had a trial of physical therapy before surgery, and all had been unable to return to sport after injury secondary to pain.

Examination of all patients revealed pain directly over the fracture site and accentuated by forward flexion of the neck and shoulders. Evaluation of injury plain films revealed a fracture fragment in 2 patients (Figure 1). All 3 patients underwent MRI and CT scans confirming the diagnosis. MRI confirmed areas of increased signal at the tip of the T1 spinous process, with inflammation in the supraspinous ligament directly at that region (Figure 2). The CT scans confirmed the presence of a bony fragment correlating with the tip of the T1 spinous process (Figure 3).

   

Surgery was performed under general endotracheal anesthesia via a midline incision over the affected area down to the spinous process. The supraspinous ligament was opened revealing an easily identified and definable ununited ossicle, which was removed without taking down the interspinous ligament. All 3 nonunions were noted to be atrophic with no evidence of surrounding inflammatory tissue or bursa. The residual end of the spinous process was smoothed down with a rongeur. Standard closure was performed. There were no surgical complications.

All patients had complete relief of pain at follow-up; 1 patient returned to full sports activity at 6 weeks and the other 2 returned to full sports activity at 3 months. There was no loss of cervical motion or trapezial strength at follow-up. All patients voiced satisfaction with the decision for surgical intervention.

Discussion

Clay-shoveler’s fracture is an injury well known to orthopedists. This fracture is thought to be caused by a forceful contraction of the thoracic paraspinal and trapezial muscles, causing an avulsion fracture with pain and frequently a “pop” experienced by the patient.1 Usually considered self-limiting injuries, treatment involves a period of rest and activity modification with occasional physical therapy. Return to sports has been reported with occasional pain but with patient satisfaction.3,5,6

Our series of patients represent a group of adolescent athletes who sustained spinous process fractures of the T1 vertebra and, despite a significant period of rest and activity modification, were unable to return to sports given their pain. The examination of these patients revealed focal tenderness at the tip of the spinous process. The diagnosis is made clinically, with radiographic studies confirming the diagnosis. In our series of patients, MRI was the original modality used to confirm injury to the area, with hyperintensity seen in the area of the supraspinous ligament and tip of the spinous process. CT confirmed the nonunion and presence of an ossicle in all patients. Surgical exposure of that area easily exposed the ununited ossicle, which was removed in all patients.

 

 

To our knowledge, this is the first report in the literature describing surgical excision of an ununited spinous process fracture in adolescent athletes. The original descriptive case series by Hall1 states “in the minds of surgeons who have seen many of these cases that early operative removal of the fragments is the proper routine treatment.” Since that original series, we have not found articles in the literature that support surgical removal; however, persistent symptoms after fracture are described.5 It is not surprising that these patients developed pain at the site of the fracture given the forces acting in that area. The trapezial and paraspinal muscles acting on that area are forceful and repetitive during activities, especially sports. All our patients had pain with attempts at activity and all had had a significant period of rest. In a recent article, this injury was described in adolescents without the patients having clear relief of symptoms despite a period of inactivity.5 While physical therapy is therapeutic in some patients experiencing pain, it can be a source of aggravation due to neck and shoulder motion and muscle contraction. It is not surprising that therapy would not help in most cases, as neck and shoulder motion and muscle contraction are the sources of continuing discomfort.

Clinical practice suggests that most patients with spinous process fractures will become pain-free; however, that is not universal. This series demonstrates that a small subset of patients with this injury will continue to have significant symptoms despite a period of rest. In those patients who desire a pain-free return to sports, we recommend consideration of surgical excision after confirmation of nonunion with radiographic studies. The inherent risks of surgical treatment are minimal with this procedure, and the benefits include return to pain-free sports activity, with the resultant physical and psychosocial benefits for adolescent athletes.

References

1.    Hall RDM. Clay-shoveler’s fracture. J Bone Joint Surg Am. 1940;22(1):63-75.

2.    Herrick RT. Clay-shoveler’s fracture in power-lifting. A case report. Am J Sports Med. 1981;9(1):29-30.

3.    Hetsroni I, Mann G, Dolev E, Morgenstern D, Nyska M. Clay shoveler’s fracture in a volleyball player. Phys Sportsmed. 2005;33(7):38-42.

4.    Kaloostian PE, Kim JE, Calabresi PA, Bydon A, Witham T. Clay-shoveler’s fracture during indoor rock climbing. Orthopedics. 2013;36(3):e381-e383.

5.    Yamaguchi KT Jr, Myung KS, Alonso MA, Skaggs DL. Clay-shoveler’s fracture equivalent in children. Spine. 2012;37(26):e1672-e1675.

6.    Kang DH, Lee SH. Multiple spinous process fractures of the thoracic vertebrae (clay-shoveler’s fracture) in a beginning golfer: a case report. Spine. 2009;34(15):e534-e537.

References

1.    Hall RDM. Clay-shoveler’s fracture. J Bone Joint Surg Am. 1940;22(1):63-75.

2.    Herrick RT. Clay-shoveler’s fracture in power-lifting. A case report. Am J Sports Med. 1981;9(1):29-30.

3.    Hetsroni I, Mann G, Dolev E, Morgenstern D, Nyska M. Clay shoveler’s fracture in a volleyball player. Phys Sportsmed. 2005;33(7):38-42.

4.    Kaloostian PE, Kim JE, Calabresi PA, Bydon A, Witham T. Clay-shoveler’s fracture during indoor rock climbing. Orthopedics. 2013;36(3):e381-e383.

5.    Yamaguchi KT Jr, Myung KS, Alonso MA, Skaggs DL. Clay-shoveler’s fracture equivalent in children. Spine. 2012;37(26):e1672-e1675.

6.    Kang DH, Lee SH. Multiple spinous process fractures of the thoracic vertebrae (clay-shoveler’s fracture) in a beginning golfer: a case report. Spine. 2009;34(15):e534-e537.

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Academic Characteristics of Orthopedic Team Physicians Affiliated With High School, Collegiate, and Professional Teams

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The responsibilities of team physicians have increased dramatically since the early 19th century, when these physicians first appeared on the sidelines during football games.1 Although the primary role of the team physician is to care for the athlete, other responsibilities include administrative and legal duties, equipment- and environment-related duties, teaching, and communication with parents, coaches, and other physicians.2-4 These responsibilities differ greatly by the level of the athlete and the team being covered. For example, compared with high school and collegiate sport physicians, physicians caring for professional athletes may have increased interaction with the media.5

Despite the increasing demands and responsibilities of team physicians, it is important that they continue to advance the field of sports medicine through teaching and research.3,6 Team physicians have direct access to athletes at multiple levels of competition, from novice to professional, and therefore have a unique understanding of the injuries that commonly affect these athletes. Efforts to both teach and study the prevention, diagnosis, and treatment of these injuries have dramatically advanced the field of sports medicine. In fact, several advancements in sports medicine have come from team physicians, including advancements in anterior cruciate ligament reconstruction,7,8 shoulder arthroscopy,9 and “Tommy John” surgery,10 to name a few.

Given the important role of team physicians (particularly orthopedic team physicians) in advancing sports medicine, it is important to understand the degree to which team physicians at all levels of sport contribute to teaching and research.

We conducted a study to determine the overall academic involvement of orthopedic team physicians at all levels of sport, including the degree to which these physicians are affiliated with academic medical centers (by level of sport and by professional sport) and the quantity and impact of these physicians’ scientific publications. We hypothesized that orthopedic physician academic involvement would be higher at the professional level of sport than at the collegiate or high school level and that the degree of physician academic involvement would differ between professional sporting leagues.

Materials and Methods

In August 2012, we performed a comprehensive telephone- and Internet-based search to identify a sample of team physicians caring for athletes at the high school, collegiate, and professional levels of sport. Data were collected on all team physicians, regardless of medical specialty. We defined a physician as any person listed as having either a doctor of medicine (MD) or a doctor of osteopathic medicine (DO) degree. A physician listed as a team physician at 2 different levels of competition (high school, college, professional) was included in both cohorts. A physician listed as a team physician in 2 different professional sports leagues was included independently for both leagues. All other medical personnel, including athletic trainers, therapists, and nursing staff, were excluded. Data on our sample population were collected as follows:

1. High school. Performing a comprehensive database search through the US Department of Education, we generated a list of all 20,989 US schools that include grades 9 to 12.11 We then used a random number generator (random.org) to randomly select a sample of 120 high schools. These schools were contacted by telephone and asked to identify the team physician(s) for their sports teams. Twenty of these schools reported not having an athletic team, so we randomly generated a list of 20 additional high schools. High schools that had an athletic team but denied having a team physician were included in the analysis.

2. College. We used the National Collegiate Athletic Association (NCAA) website (ncaa.org) to generate a list of all colleges affiliated with the NCAA. Of these colleges, 347 were Division I, 316 were Division II, and 443 were Division III. The random.org random number generator was used to generate a list of 40 schools for each division, for a total of 120 schools. An Internet-based search was then performed to identify any and all team physicians caring for athletes at that particular school. In select cases, telephone calls were made to determine all the team physicians involved in the care of athletes at that institution.

3. Professional. Team physician data were collected for 4 of the most popular professional sporting leagues12: Major League Baseball (MLB), National Basketball Association (NBA), National Football League (NFL), and National Hockey League (NHL). Each team’s official website was identified through its league website (mlb.com, nba.com, nfl.com, nhl.com), and the roster or directory listing of all team physicians was recorded. In 2 cases, the team’s medical personnel listing could not be retrieved through the Internet, and a telephone call had to be made to identify all team physicians. Team physicians were identified for 122 professional teams: 30 MLB, 30 NBA, 32 NFL, and 30 NHL.

 

 

For this study, all physicians were classified as either orthopedic or nonorthopedic. Orthopedic surgeons—the focus of this study—were defined as those who completed residency training in orthopedic surgery. Median number of orthopedic and nonorthopedic surgeons per team was calculated at the high school, collegiate, and professional levels.

After identifying all orthopedic team physicians, we performed additional Internet searches to determine any affiliation between each physician and an applicable academic medical center. Physicians were placed in 1 of 3 different categories based on “level” of academic affiliation. Orthopedists with no identifiable connection to an academic medical center were listed under none. The first 100 search results were studied before this determination was made. Orthopedists with any academic affiliation below the level of full professorship were placed in the category associate/assistant/adjunct professor, which included any physician who was an associate professor, adjunct professor, clinical instructor, or volunteer instructor at an academic medical center. Last, orthopedists listed as full professors were placed in the professor category.

Number of publications written by each orthopedic team physician was then calculated using SciVerse Scopus (scopus.com), a comprehensive abstract and citation database of research literature that offers complete coverage of the Medline and Embase databases.13 Scopus offers a Scopus Author Identifier, which assigns each author in Scopus a unique identification number.14 This number is based on an “algorithm that matches author names based on their affiliation, address, subject area, source title, dates of publication citations, and co-authors.”14 Authors whose names did not appear in Scopus were assumed to have no publications, and this was reported after cross-referencing with Medline to ensure no documents were missed. This study included all publications: original research articles, reviews, letters, and commentaries. Any level of authorship (first, second, etc) was included. All publications were scanned, and duplicate listings were not included. Median number of publications per orthopedic team physician was calculated at the high school, college, and professional levels.

We also determined the h-index for each orthopedic team physician. The h-index is used to measure the impact of the published work of a scholar: “A scientist has index h if h of his/her papers have at least h citations each, and the other papers have no more than h citations each.”15 For example, an h-index of 12 means that, out of an author’s total number of publications, 12 have been cited at least 12 times, and all of his or her other publications have been cited fewer than 12 times. All authors in Scopus are automatically assigned h-indexes, and we collected these numbers.16 Of note, citations for articles published before 1996 are not included in the h-index calculation. Median h-index score per orthopedic team physician was calculated at the high school, college, and professional levels.

Analysis of variance was used to compare continuous data (eg, number of publications per surgeon) across different groups (eg, physicians from respective sports). Chi-square tests were used to detect whole-number differences between groups (eg, difference in number of physicians per team across the various professional sports leagues). Statistical significance was set at P < .05.

Results

We identified 1054 team physicians among the 362 total high schools, colleges, and professional sports teams included in this study. Of the 1054 physicians, 678 (64%) were orthopedic surgeons (Table 1). Seventy-two (60%) of the 120 high schools did not have a team physician, whereas all the colleges and professional teams did. Number of orthopedic surgeons per team was higher at the collegiate level (2.29; range, 0-11) and professional level (2.21; range, 1-9) than at the high school level (1.11; range, 0-24) (Table 1). Median number of nonorthopedic surgeons was highest in professional sports (1.88; range, 0-9) followed by college sports (1.06; range, 0-9) and high school sports (0.16; range, 0-2) (Table 1).

Of the 678 orthopedic team physicians, 298 (44%) were officially affiliated with an academic medical center, either as clinical instructor, associate/adjunct professor, or full professor. Percentage of orthopedists affiliated with an academic medical center was highest in professional sports (173/270, 64%) followed by collegiate sports (98/275, 36%) and high school sports (27/133, 20%) (P < .001, Table 2). Percentage of orthopedists identified as full professors was highest at the professional level (42/270, 16%) followed by the collegiate level (14/275, 5.1%) and the high school level (3/133, 2.3%) (P < .001, Table 2).

We found 12,036 publications written by the 678 orthopedic team physicians included in this study. Median number of publications per orthopedist was significantly higher in professional sports (30.6; range, 0-460) than in collegiate sports (10.7; range, 0-581) and high school sports (6.0; range, 0-220) (P < .001). Number of authors with more than 25 publications was highest at the professional level (82) followed by the collegiate level (27) and the high school level (7) (Table 3). Median number of publications per orthopedist was also higher at the professional level (12) than at the collegiate level (2) and high school level (1). Median h-index was higher among orthopedists in professional sports (7.1; range, 0-50) than at colleges (2.7; range, 0-63) and high schools (1.8; range, 0-32) (P < .001). Median h-index was also significantly higher at the professional level (5) than at the collegiate level (1) and high school level (0).

 

 

At the professional level of sports, we identified 499 team physicians (270 orthopedic, 54%; 229 nonorthopedic, 46%). Median number of orthopedic team physicians varied by sport, with MLB (2.8; range, 1-8) and the NFL (2.4; range, 1-4) having relatively more of these physicians than the NHL (2.0; range, 1-6) and the NBA (1.7; range, 1-9) (Table 4). Percentage of orthopedic team physicians affiliated with academic medical centers was highest in MLB (58/83, 69.9%) followed by the NFL (47/76, 61.8%), the NHL (37/60, 61.7%), and the NBA (31/51, 60.8%) (Table 5). Median number of publications by orthopedists also varied by sport, with the highest number in MLB (37.9; range, 0-225) followed by the NBA (32.0; range, 0-227) and the NFL (30.4; range, 0-460), with the lowest number in the NHL (20.7; range, 0-144) (Table 6). Median number of publications was the same (17.5) in MLB and the NFL and lower in the NBA (11) and the NHL (7.5). Median h-index was highest in the NFL (8.2; range, 0-50) and MLB (7.9; range, 0-32) followed by the NBA (6.6; range, 0-35) and the NHL (4.9; range, 0-20) (Table 7) Median h-index was the same (6) in MLB and the NFL and lower (3) in the NBA and the NHL.

     

Discussion

To our knowledge, this is the first study of academic involvement and the research activities of orthopedic team physicians at the high school, college, and professional levels of sport. We found that, on average, there were almost twice as many orthopedists at the collegiate and professional levels than at the high school level—likely because 72 of the 120 high schools randomly selected did not have a team physician, despite having sports teams. We can attribute this to the organizational structure of teams in a high school setting, where it is fairly common that no medically educated health care provider is readily available for the student athletes.5 Although the median number of orthopedists was similar at the collegiate and professional levels, the number of nonorthopedic team physicians was higher at the professional level than at the collegiate level. Although most collegiate and professional teams have an internist and an orthopedist on staff, medical staff at the professional level may also include several subspecialists from a variety of medical fields (eg, dental medicine, ophthalmology, neurology).17

We found that a significantly larger proportion of orthopedists at the professional level (64%) were affiliated with academic medical centers as associate/adjunct professors and full professors compared with orthopedists at the collegiate level (36%) and high school level (20%). The academic relationship with collegiate teams was much lower than expected. Regarding professional sports, however, this finding confirmed our hypothesis, and the explanation is likely multifactorial and historical. Moreover, the median number of publications was higher for orthopedists at the professional level (30.8) than at the collegiate level (10.7) and high school level (6). In the late 1940s and early 1950s, many orthopedic team physicians entered into contracts with major universities.4 For many physicians, this contractual relationship increased their prestige, and some orthopedic groups were alleged to have endorsed scholarships at those schools.4 Given the high level of publicity and scrutiny surrounding medical decisions at the professional level of sports, it is possible that professional sports teams specifically seek orthopedists who are well respected within academia. Moreover, contracts between universities/academic medical centers and professional teams may mandate that a faculty member from that organization provide the orthopedic/medical care for the team. This may also increase the likelihood of professional teams being paired with academic orthopedic physicians. However, such contractual agreements are made between professional teams and large private medical groups as well.

In addition to measuring quantity of publications, we used the h-index to measure their quality. Following the same pattern as the publication rate, median h-index per orthopedic team physician was significantly higher at the professional level (7.1) than at the collegiate level (2.7) and high school level (1.8). As with publication volume, this is not entirely surprising, as h-index has been shown to correlate with academic rank in other surgical specialties,18 and there was a higher percentage of academic physicians at the professional level than at the collegiate and high school levels.

At the professional level of sports, 56% of all team physicians were orthopedic surgeons. Orthopedists caring for MLB teams had the highest median number of publications (37.9), followed by the NBA (32.0), the NFL (30.4), and the NHL (20.7). One likely explanation is the higher percentage of MLB physicians affiliated with academic medical centers. Regarding the h-index, MLB and NFL physicians had the highest values (7.9 and 8.2, respectively).

 

 

Our study had several limitations. First, we may not have captured data on all the team physicians at the high school, college, and professional levels. By following a detailed protocol in identifying surgeons, however, we tried to minimize the impact of any such omissions. In addition, teams may have had many unofficial consultants acting as team physicians, whether orthopedic or nonorthopedic, and, if these physicians were not listed in an official capacity, they may have been omitted from this study. We further realize that a true measure of academic productivity should also include book chapters and books published, research grants awarded, and patents registered. By including only peer-reviewed articles, we omitted these other criteria.

To our knowledge, the data presented here represent the first attempt to quantify the academic involvement and research productivity of orthopedic team physicians at the high school, college, and professional levels of sport. These data help us understand how research productivity varies by orthopedic team physicians at different levels of sport and may be useful to those considering a career as a team physician, as they can better evaluate their own productivity in the context of team physicians across different levels of competition.

References

1.    Thorndike A. Athletic Injuries: Prevention, Diagnosis, and Treatment. Philadelphia, PA: Lea & Febiger; 1956.

2.    The team physician. A statement of the Committee on the Medical Aspects of Sports of the American Medical Association, September 1967. J School Health. 1967;37(10):510-514.

3.     Team physician consensus statement. Am J Sports Med. 2000;28(3):440-441.

4.    Whiteside J, Andrews JR. Trends for the future as a team physician: Herodicus to hereafter. Clin Sports Med. 2007;26(2):285-304.

5.    Goforth M, Almquist J, Matney M, et al. Understanding organization structures of the college, university, high school, clinical, and professional settings. Clin Sports Med. 2007;26(2):201-226.

6.    Hughston JC. Want to be in sports medicine? Get involved. Am J Sports Med. 1979;7(2):79-80.

7.    Marshall JL, Warren RF, Wickiewicz TL, Reider B. The anterior cruciate ligament: a technique of repair and reconstruction. Clin Orthop Relat Res. 1979;(143):97-106.

8.    Clancy WG Jr, Nelson DA, Reider B, Narechania RG. Anterior cruciate ligament reconstruction using one-third of the patellar ligament, augmented by extra-articular tendon transfers. J Bone Joint Surg Am. 1982;64(3):352-359.

9.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

10.  Indelicato PA, Jobe FW, Kerlan RK, Carter VS, Shields CL, Lombardo SJ. Correctable elbow lesions in professional baseball players: a review of 25 cases. Am J Sports Med. 1979;7(1):72-75.

11.  Elementary/Secondary Information System (EISi). National Center for Education Statistics, Institute of Education Sciences, US Department of Education website. http://nces.ed.gov/ccd/elsi/. Accessed September 21, 2015.

12.  Corso RA; Harris Interactive. Football is America’s favorite sport as lead over baseball continues to grow; college football and auto racing come next. Harris Interactive website. http://www.harrisinteractive.com/vault/Harris Poll 9 - Favorite sport_1.25.12.pdf. Harris Poll 9, January 25, 2012. Accessed September 21, 2015.

13.  [Scopus content]. Elsevier website. http://www.elsevier.com/solutions/scopus/content. Accessed September 21, 2015.

14.  Scopus Author Identifier. Scopus website. http://help.scopus.com/Content/h_autsrch_intro.htm. Accessed October 5, 2015.

15.  Hirsch JE. An index to quantify an individual’s scientific research output. Proc Natl Acad Sci U S A. 2005;102(46):16569-16572.

16.  Author Evaluator h Index Tab. Scopus website. http://help.scopus.com/Content/h_auteval_hindex.htm. Accessed October 5, 2015.

17.  Boyd JL. Understanding the politics of being a team physician. Clin Sports Med. 2007;26(2):161-172.

18.   Lee J, Kraus KL, Couldwell WT. Use of the h index in neurosurgery. Clinical article. J Neurosurg. 2009;111(2):387-

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Eric C. Makhni, MD, MBA, John A. Buza, MD, Ian Byram, MD, and Christopher S. Ahmad, MD

Authors’ Disclosure Statement: Dr. Ahmad wishes to report that he is a consultant for Acumed and Arthrex, and receives research support from Arthrex, Major League Baseball, and Stryker. The other authors report no actual or potential conflict of interest in relation to this article.

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The American Journal of Orthopedics - 44(11)
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american journal of orthopedics, AJO, original study, study, sports medicine, academic, orthopedic, team, physicians, high school, college, collegiate, professional, athletes, athletics, sports, makhni, buza, byram, ahmad
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Eric C. Makhni, MD, MBA, John A. Buza, MD, Ian Byram, MD, and Christopher S. Ahmad, MD

Authors’ Disclosure Statement: Dr. Ahmad wishes to report that he is a consultant for Acumed and Arthrex, and receives research support from Arthrex, Major League Baseball, and Stryker. The other authors report no actual or potential conflict of interest in relation to this article.

Author and Disclosure Information

Eric C. Makhni, MD, MBA, John A. Buza, MD, Ian Byram, MD, and Christopher S. Ahmad, MD

Authors’ Disclosure Statement: Dr. Ahmad wishes to report that he is a consultant for Acumed and Arthrex, and receives research support from Arthrex, Major League Baseball, and Stryker. The other authors report no actual or potential conflict of interest in relation to this article.

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Article PDF

The responsibilities of team physicians have increased dramatically since the early 19th century, when these physicians first appeared on the sidelines during football games.1 Although the primary role of the team physician is to care for the athlete, other responsibilities include administrative and legal duties, equipment- and environment-related duties, teaching, and communication with parents, coaches, and other physicians.2-4 These responsibilities differ greatly by the level of the athlete and the team being covered. For example, compared with high school and collegiate sport physicians, physicians caring for professional athletes may have increased interaction with the media.5

Despite the increasing demands and responsibilities of team physicians, it is important that they continue to advance the field of sports medicine through teaching and research.3,6 Team physicians have direct access to athletes at multiple levels of competition, from novice to professional, and therefore have a unique understanding of the injuries that commonly affect these athletes. Efforts to both teach and study the prevention, diagnosis, and treatment of these injuries have dramatically advanced the field of sports medicine. In fact, several advancements in sports medicine have come from team physicians, including advancements in anterior cruciate ligament reconstruction,7,8 shoulder arthroscopy,9 and “Tommy John” surgery,10 to name a few.

Given the important role of team physicians (particularly orthopedic team physicians) in advancing sports medicine, it is important to understand the degree to which team physicians at all levels of sport contribute to teaching and research.

We conducted a study to determine the overall academic involvement of orthopedic team physicians at all levels of sport, including the degree to which these physicians are affiliated with academic medical centers (by level of sport and by professional sport) and the quantity and impact of these physicians’ scientific publications. We hypothesized that orthopedic physician academic involvement would be higher at the professional level of sport than at the collegiate or high school level and that the degree of physician academic involvement would differ between professional sporting leagues.

Materials and Methods

In August 2012, we performed a comprehensive telephone- and Internet-based search to identify a sample of team physicians caring for athletes at the high school, collegiate, and professional levels of sport. Data were collected on all team physicians, regardless of medical specialty. We defined a physician as any person listed as having either a doctor of medicine (MD) or a doctor of osteopathic medicine (DO) degree. A physician listed as a team physician at 2 different levels of competition (high school, college, professional) was included in both cohorts. A physician listed as a team physician in 2 different professional sports leagues was included independently for both leagues. All other medical personnel, including athletic trainers, therapists, and nursing staff, were excluded. Data on our sample population were collected as follows:

1. High school. Performing a comprehensive database search through the US Department of Education, we generated a list of all 20,989 US schools that include grades 9 to 12.11 We then used a random number generator (random.org) to randomly select a sample of 120 high schools. These schools were contacted by telephone and asked to identify the team physician(s) for their sports teams. Twenty of these schools reported not having an athletic team, so we randomly generated a list of 20 additional high schools. High schools that had an athletic team but denied having a team physician were included in the analysis.

2. College. We used the National Collegiate Athletic Association (NCAA) website (ncaa.org) to generate a list of all colleges affiliated with the NCAA. Of these colleges, 347 were Division I, 316 were Division II, and 443 were Division III. The random.org random number generator was used to generate a list of 40 schools for each division, for a total of 120 schools. An Internet-based search was then performed to identify any and all team physicians caring for athletes at that particular school. In select cases, telephone calls were made to determine all the team physicians involved in the care of athletes at that institution.

3. Professional. Team physician data were collected for 4 of the most popular professional sporting leagues12: Major League Baseball (MLB), National Basketball Association (NBA), National Football League (NFL), and National Hockey League (NHL). Each team’s official website was identified through its league website (mlb.com, nba.com, nfl.com, nhl.com), and the roster or directory listing of all team physicians was recorded. In 2 cases, the team’s medical personnel listing could not be retrieved through the Internet, and a telephone call had to be made to identify all team physicians. Team physicians were identified for 122 professional teams: 30 MLB, 30 NBA, 32 NFL, and 30 NHL.

 

 

For this study, all physicians were classified as either orthopedic or nonorthopedic. Orthopedic surgeons—the focus of this study—were defined as those who completed residency training in orthopedic surgery. Median number of orthopedic and nonorthopedic surgeons per team was calculated at the high school, collegiate, and professional levels.

After identifying all orthopedic team physicians, we performed additional Internet searches to determine any affiliation between each physician and an applicable academic medical center. Physicians were placed in 1 of 3 different categories based on “level” of academic affiliation. Orthopedists with no identifiable connection to an academic medical center were listed under none. The first 100 search results were studied before this determination was made. Orthopedists with any academic affiliation below the level of full professorship were placed in the category associate/assistant/adjunct professor, which included any physician who was an associate professor, adjunct professor, clinical instructor, or volunteer instructor at an academic medical center. Last, orthopedists listed as full professors were placed in the professor category.

Number of publications written by each orthopedic team physician was then calculated using SciVerse Scopus (scopus.com), a comprehensive abstract and citation database of research literature that offers complete coverage of the Medline and Embase databases.13 Scopus offers a Scopus Author Identifier, which assigns each author in Scopus a unique identification number.14 This number is based on an “algorithm that matches author names based on their affiliation, address, subject area, source title, dates of publication citations, and co-authors.”14 Authors whose names did not appear in Scopus were assumed to have no publications, and this was reported after cross-referencing with Medline to ensure no documents were missed. This study included all publications: original research articles, reviews, letters, and commentaries. Any level of authorship (first, second, etc) was included. All publications were scanned, and duplicate listings were not included. Median number of publications per orthopedic team physician was calculated at the high school, college, and professional levels.

We also determined the h-index for each orthopedic team physician. The h-index is used to measure the impact of the published work of a scholar: “A scientist has index h if h of his/her papers have at least h citations each, and the other papers have no more than h citations each.”15 For example, an h-index of 12 means that, out of an author’s total number of publications, 12 have been cited at least 12 times, and all of his or her other publications have been cited fewer than 12 times. All authors in Scopus are automatically assigned h-indexes, and we collected these numbers.16 Of note, citations for articles published before 1996 are not included in the h-index calculation. Median h-index score per orthopedic team physician was calculated at the high school, college, and professional levels.

Analysis of variance was used to compare continuous data (eg, number of publications per surgeon) across different groups (eg, physicians from respective sports). Chi-square tests were used to detect whole-number differences between groups (eg, difference in number of physicians per team across the various professional sports leagues). Statistical significance was set at P < .05.

Results

We identified 1054 team physicians among the 362 total high schools, colleges, and professional sports teams included in this study. Of the 1054 physicians, 678 (64%) were orthopedic surgeons (Table 1). Seventy-two (60%) of the 120 high schools did not have a team physician, whereas all the colleges and professional teams did. Number of orthopedic surgeons per team was higher at the collegiate level (2.29; range, 0-11) and professional level (2.21; range, 1-9) than at the high school level (1.11; range, 0-24) (Table 1). Median number of nonorthopedic surgeons was highest in professional sports (1.88; range, 0-9) followed by college sports (1.06; range, 0-9) and high school sports (0.16; range, 0-2) (Table 1).

Of the 678 orthopedic team physicians, 298 (44%) were officially affiliated with an academic medical center, either as clinical instructor, associate/adjunct professor, or full professor. Percentage of orthopedists affiliated with an academic medical center was highest in professional sports (173/270, 64%) followed by collegiate sports (98/275, 36%) and high school sports (27/133, 20%) (P < .001, Table 2). Percentage of orthopedists identified as full professors was highest at the professional level (42/270, 16%) followed by the collegiate level (14/275, 5.1%) and the high school level (3/133, 2.3%) (P < .001, Table 2).

We found 12,036 publications written by the 678 orthopedic team physicians included in this study. Median number of publications per orthopedist was significantly higher in professional sports (30.6; range, 0-460) than in collegiate sports (10.7; range, 0-581) and high school sports (6.0; range, 0-220) (P < .001). Number of authors with more than 25 publications was highest at the professional level (82) followed by the collegiate level (27) and the high school level (7) (Table 3). Median number of publications per orthopedist was also higher at the professional level (12) than at the collegiate level (2) and high school level (1). Median h-index was higher among orthopedists in professional sports (7.1; range, 0-50) than at colleges (2.7; range, 0-63) and high schools (1.8; range, 0-32) (P < .001). Median h-index was also significantly higher at the professional level (5) than at the collegiate level (1) and high school level (0).

 

 

At the professional level of sports, we identified 499 team physicians (270 orthopedic, 54%; 229 nonorthopedic, 46%). Median number of orthopedic team physicians varied by sport, with MLB (2.8; range, 1-8) and the NFL (2.4; range, 1-4) having relatively more of these physicians than the NHL (2.0; range, 1-6) and the NBA (1.7; range, 1-9) (Table 4). Percentage of orthopedic team physicians affiliated with academic medical centers was highest in MLB (58/83, 69.9%) followed by the NFL (47/76, 61.8%), the NHL (37/60, 61.7%), and the NBA (31/51, 60.8%) (Table 5). Median number of publications by orthopedists also varied by sport, with the highest number in MLB (37.9; range, 0-225) followed by the NBA (32.0; range, 0-227) and the NFL (30.4; range, 0-460), with the lowest number in the NHL (20.7; range, 0-144) (Table 6). Median number of publications was the same (17.5) in MLB and the NFL and lower in the NBA (11) and the NHL (7.5). Median h-index was highest in the NFL (8.2; range, 0-50) and MLB (7.9; range, 0-32) followed by the NBA (6.6; range, 0-35) and the NHL (4.9; range, 0-20) (Table 7) Median h-index was the same (6) in MLB and the NFL and lower (3) in the NBA and the NHL.

     

Discussion

To our knowledge, this is the first study of academic involvement and the research activities of orthopedic team physicians at the high school, college, and professional levels of sport. We found that, on average, there were almost twice as many orthopedists at the collegiate and professional levels than at the high school level—likely because 72 of the 120 high schools randomly selected did not have a team physician, despite having sports teams. We can attribute this to the organizational structure of teams in a high school setting, where it is fairly common that no medically educated health care provider is readily available for the student athletes.5 Although the median number of orthopedists was similar at the collegiate and professional levels, the number of nonorthopedic team physicians was higher at the professional level than at the collegiate level. Although most collegiate and professional teams have an internist and an orthopedist on staff, medical staff at the professional level may also include several subspecialists from a variety of medical fields (eg, dental medicine, ophthalmology, neurology).17

We found that a significantly larger proportion of orthopedists at the professional level (64%) were affiliated with academic medical centers as associate/adjunct professors and full professors compared with orthopedists at the collegiate level (36%) and high school level (20%). The academic relationship with collegiate teams was much lower than expected. Regarding professional sports, however, this finding confirmed our hypothesis, and the explanation is likely multifactorial and historical. Moreover, the median number of publications was higher for orthopedists at the professional level (30.8) than at the collegiate level (10.7) and high school level (6). In the late 1940s and early 1950s, many orthopedic team physicians entered into contracts with major universities.4 For many physicians, this contractual relationship increased their prestige, and some orthopedic groups were alleged to have endorsed scholarships at those schools.4 Given the high level of publicity and scrutiny surrounding medical decisions at the professional level of sports, it is possible that professional sports teams specifically seek orthopedists who are well respected within academia. Moreover, contracts between universities/academic medical centers and professional teams may mandate that a faculty member from that organization provide the orthopedic/medical care for the team. This may also increase the likelihood of professional teams being paired with academic orthopedic physicians. However, such contractual agreements are made between professional teams and large private medical groups as well.

In addition to measuring quantity of publications, we used the h-index to measure their quality. Following the same pattern as the publication rate, median h-index per orthopedic team physician was significantly higher at the professional level (7.1) than at the collegiate level (2.7) and high school level (1.8). As with publication volume, this is not entirely surprising, as h-index has been shown to correlate with academic rank in other surgical specialties,18 and there was a higher percentage of academic physicians at the professional level than at the collegiate and high school levels.

At the professional level of sports, 56% of all team physicians were orthopedic surgeons. Orthopedists caring for MLB teams had the highest median number of publications (37.9), followed by the NBA (32.0), the NFL (30.4), and the NHL (20.7). One likely explanation is the higher percentage of MLB physicians affiliated with academic medical centers. Regarding the h-index, MLB and NFL physicians had the highest values (7.9 and 8.2, respectively).

 

 

Our study had several limitations. First, we may not have captured data on all the team physicians at the high school, college, and professional levels. By following a detailed protocol in identifying surgeons, however, we tried to minimize the impact of any such omissions. In addition, teams may have had many unofficial consultants acting as team physicians, whether orthopedic or nonorthopedic, and, if these physicians were not listed in an official capacity, they may have been omitted from this study. We further realize that a true measure of academic productivity should also include book chapters and books published, research grants awarded, and patents registered. By including only peer-reviewed articles, we omitted these other criteria.

To our knowledge, the data presented here represent the first attempt to quantify the academic involvement and research productivity of orthopedic team physicians at the high school, college, and professional levels of sport. These data help us understand how research productivity varies by orthopedic team physicians at different levels of sport and may be useful to those considering a career as a team physician, as they can better evaluate their own productivity in the context of team physicians across different levels of competition.

The responsibilities of team physicians have increased dramatically since the early 19th century, when these physicians first appeared on the sidelines during football games.1 Although the primary role of the team physician is to care for the athlete, other responsibilities include administrative and legal duties, equipment- and environment-related duties, teaching, and communication with parents, coaches, and other physicians.2-4 These responsibilities differ greatly by the level of the athlete and the team being covered. For example, compared with high school and collegiate sport physicians, physicians caring for professional athletes may have increased interaction with the media.5

Despite the increasing demands and responsibilities of team physicians, it is important that they continue to advance the field of sports medicine through teaching and research.3,6 Team physicians have direct access to athletes at multiple levels of competition, from novice to professional, and therefore have a unique understanding of the injuries that commonly affect these athletes. Efforts to both teach and study the prevention, diagnosis, and treatment of these injuries have dramatically advanced the field of sports medicine. In fact, several advancements in sports medicine have come from team physicians, including advancements in anterior cruciate ligament reconstruction,7,8 shoulder arthroscopy,9 and “Tommy John” surgery,10 to name a few.

Given the important role of team physicians (particularly orthopedic team physicians) in advancing sports medicine, it is important to understand the degree to which team physicians at all levels of sport contribute to teaching and research.

We conducted a study to determine the overall academic involvement of orthopedic team physicians at all levels of sport, including the degree to which these physicians are affiliated with academic medical centers (by level of sport and by professional sport) and the quantity and impact of these physicians’ scientific publications. We hypothesized that orthopedic physician academic involvement would be higher at the professional level of sport than at the collegiate or high school level and that the degree of physician academic involvement would differ between professional sporting leagues.

Materials and Methods

In August 2012, we performed a comprehensive telephone- and Internet-based search to identify a sample of team physicians caring for athletes at the high school, collegiate, and professional levels of sport. Data were collected on all team physicians, regardless of medical specialty. We defined a physician as any person listed as having either a doctor of medicine (MD) or a doctor of osteopathic medicine (DO) degree. A physician listed as a team physician at 2 different levels of competition (high school, college, professional) was included in both cohorts. A physician listed as a team physician in 2 different professional sports leagues was included independently for both leagues. All other medical personnel, including athletic trainers, therapists, and nursing staff, were excluded. Data on our sample population were collected as follows:

1. High school. Performing a comprehensive database search through the US Department of Education, we generated a list of all 20,989 US schools that include grades 9 to 12.11 We then used a random number generator (random.org) to randomly select a sample of 120 high schools. These schools were contacted by telephone and asked to identify the team physician(s) for their sports teams. Twenty of these schools reported not having an athletic team, so we randomly generated a list of 20 additional high schools. High schools that had an athletic team but denied having a team physician were included in the analysis.

2. College. We used the National Collegiate Athletic Association (NCAA) website (ncaa.org) to generate a list of all colleges affiliated with the NCAA. Of these colleges, 347 were Division I, 316 were Division II, and 443 were Division III. The random.org random number generator was used to generate a list of 40 schools for each division, for a total of 120 schools. An Internet-based search was then performed to identify any and all team physicians caring for athletes at that particular school. In select cases, telephone calls were made to determine all the team physicians involved in the care of athletes at that institution.

3. Professional. Team physician data were collected for 4 of the most popular professional sporting leagues12: Major League Baseball (MLB), National Basketball Association (NBA), National Football League (NFL), and National Hockey League (NHL). Each team’s official website was identified through its league website (mlb.com, nba.com, nfl.com, nhl.com), and the roster or directory listing of all team physicians was recorded. In 2 cases, the team’s medical personnel listing could not be retrieved through the Internet, and a telephone call had to be made to identify all team physicians. Team physicians were identified for 122 professional teams: 30 MLB, 30 NBA, 32 NFL, and 30 NHL.

 

 

For this study, all physicians were classified as either orthopedic or nonorthopedic. Orthopedic surgeons—the focus of this study—were defined as those who completed residency training in orthopedic surgery. Median number of orthopedic and nonorthopedic surgeons per team was calculated at the high school, collegiate, and professional levels.

After identifying all orthopedic team physicians, we performed additional Internet searches to determine any affiliation between each physician and an applicable academic medical center. Physicians were placed in 1 of 3 different categories based on “level” of academic affiliation. Orthopedists with no identifiable connection to an academic medical center were listed under none. The first 100 search results were studied before this determination was made. Orthopedists with any academic affiliation below the level of full professorship were placed in the category associate/assistant/adjunct professor, which included any physician who was an associate professor, adjunct professor, clinical instructor, or volunteer instructor at an academic medical center. Last, orthopedists listed as full professors were placed in the professor category.

Number of publications written by each orthopedic team physician was then calculated using SciVerse Scopus (scopus.com), a comprehensive abstract and citation database of research literature that offers complete coverage of the Medline and Embase databases.13 Scopus offers a Scopus Author Identifier, which assigns each author in Scopus a unique identification number.14 This number is based on an “algorithm that matches author names based on their affiliation, address, subject area, source title, dates of publication citations, and co-authors.”14 Authors whose names did not appear in Scopus were assumed to have no publications, and this was reported after cross-referencing with Medline to ensure no documents were missed. This study included all publications: original research articles, reviews, letters, and commentaries. Any level of authorship (first, second, etc) was included. All publications were scanned, and duplicate listings were not included. Median number of publications per orthopedic team physician was calculated at the high school, college, and professional levels.

We also determined the h-index for each orthopedic team physician. The h-index is used to measure the impact of the published work of a scholar: “A scientist has index h if h of his/her papers have at least h citations each, and the other papers have no more than h citations each.”15 For example, an h-index of 12 means that, out of an author’s total number of publications, 12 have been cited at least 12 times, and all of his or her other publications have been cited fewer than 12 times. All authors in Scopus are automatically assigned h-indexes, and we collected these numbers.16 Of note, citations for articles published before 1996 are not included in the h-index calculation. Median h-index score per orthopedic team physician was calculated at the high school, college, and professional levels.

Analysis of variance was used to compare continuous data (eg, number of publications per surgeon) across different groups (eg, physicians from respective sports). Chi-square tests were used to detect whole-number differences between groups (eg, difference in number of physicians per team across the various professional sports leagues). Statistical significance was set at P < .05.

Results

We identified 1054 team physicians among the 362 total high schools, colleges, and professional sports teams included in this study. Of the 1054 physicians, 678 (64%) were orthopedic surgeons (Table 1). Seventy-two (60%) of the 120 high schools did not have a team physician, whereas all the colleges and professional teams did. Number of orthopedic surgeons per team was higher at the collegiate level (2.29; range, 0-11) and professional level (2.21; range, 1-9) than at the high school level (1.11; range, 0-24) (Table 1). Median number of nonorthopedic surgeons was highest in professional sports (1.88; range, 0-9) followed by college sports (1.06; range, 0-9) and high school sports (0.16; range, 0-2) (Table 1).

Of the 678 orthopedic team physicians, 298 (44%) were officially affiliated with an academic medical center, either as clinical instructor, associate/adjunct professor, or full professor. Percentage of orthopedists affiliated with an academic medical center was highest in professional sports (173/270, 64%) followed by collegiate sports (98/275, 36%) and high school sports (27/133, 20%) (P < .001, Table 2). Percentage of orthopedists identified as full professors was highest at the professional level (42/270, 16%) followed by the collegiate level (14/275, 5.1%) and the high school level (3/133, 2.3%) (P < .001, Table 2).

We found 12,036 publications written by the 678 orthopedic team physicians included in this study. Median number of publications per orthopedist was significantly higher in professional sports (30.6; range, 0-460) than in collegiate sports (10.7; range, 0-581) and high school sports (6.0; range, 0-220) (P < .001). Number of authors with more than 25 publications was highest at the professional level (82) followed by the collegiate level (27) and the high school level (7) (Table 3). Median number of publications per orthopedist was also higher at the professional level (12) than at the collegiate level (2) and high school level (1). Median h-index was higher among orthopedists in professional sports (7.1; range, 0-50) than at colleges (2.7; range, 0-63) and high schools (1.8; range, 0-32) (P < .001). Median h-index was also significantly higher at the professional level (5) than at the collegiate level (1) and high school level (0).

 

 

At the professional level of sports, we identified 499 team physicians (270 orthopedic, 54%; 229 nonorthopedic, 46%). Median number of orthopedic team physicians varied by sport, with MLB (2.8; range, 1-8) and the NFL (2.4; range, 1-4) having relatively more of these physicians than the NHL (2.0; range, 1-6) and the NBA (1.7; range, 1-9) (Table 4). Percentage of orthopedic team physicians affiliated with academic medical centers was highest in MLB (58/83, 69.9%) followed by the NFL (47/76, 61.8%), the NHL (37/60, 61.7%), and the NBA (31/51, 60.8%) (Table 5). Median number of publications by orthopedists also varied by sport, with the highest number in MLB (37.9; range, 0-225) followed by the NBA (32.0; range, 0-227) and the NFL (30.4; range, 0-460), with the lowest number in the NHL (20.7; range, 0-144) (Table 6). Median number of publications was the same (17.5) in MLB and the NFL and lower in the NBA (11) and the NHL (7.5). Median h-index was highest in the NFL (8.2; range, 0-50) and MLB (7.9; range, 0-32) followed by the NBA (6.6; range, 0-35) and the NHL (4.9; range, 0-20) (Table 7) Median h-index was the same (6) in MLB and the NFL and lower (3) in the NBA and the NHL.

     

Discussion

To our knowledge, this is the first study of academic involvement and the research activities of orthopedic team physicians at the high school, college, and professional levels of sport. We found that, on average, there were almost twice as many orthopedists at the collegiate and professional levels than at the high school level—likely because 72 of the 120 high schools randomly selected did not have a team physician, despite having sports teams. We can attribute this to the organizational structure of teams in a high school setting, where it is fairly common that no medically educated health care provider is readily available for the student athletes.5 Although the median number of orthopedists was similar at the collegiate and professional levels, the number of nonorthopedic team physicians was higher at the professional level than at the collegiate level. Although most collegiate and professional teams have an internist and an orthopedist on staff, medical staff at the professional level may also include several subspecialists from a variety of medical fields (eg, dental medicine, ophthalmology, neurology).17

We found that a significantly larger proportion of orthopedists at the professional level (64%) were affiliated with academic medical centers as associate/adjunct professors and full professors compared with orthopedists at the collegiate level (36%) and high school level (20%). The academic relationship with collegiate teams was much lower than expected. Regarding professional sports, however, this finding confirmed our hypothesis, and the explanation is likely multifactorial and historical. Moreover, the median number of publications was higher for orthopedists at the professional level (30.8) than at the collegiate level (10.7) and high school level (6). In the late 1940s and early 1950s, many orthopedic team physicians entered into contracts with major universities.4 For many physicians, this contractual relationship increased their prestige, and some orthopedic groups were alleged to have endorsed scholarships at those schools.4 Given the high level of publicity and scrutiny surrounding medical decisions at the professional level of sports, it is possible that professional sports teams specifically seek orthopedists who are well respected within academia. Moreover, contracts between universities/academic medical centers and professional teams may mandate that a faculty member from that organization provide the orthopedic/medical care for the team. This may also increase the likelihood of professional teams being paired with academic orthopedic physicians. However, such contractual agreements are made between professional teams and large private medical groups as well.

In addition to measuring quantity of publications, we used the h-index to measure their quality. Following the same pattern as the publication rate, median h-index per orthopedic team physician was significantly higher at the professional level (7.1) than at the collegiate level (2.7) and high school level (1.8). As with publication volume, this is not entirely surprising, as h-index has been shown to correlate with academic rank in other surgical specialties,18 and there was a higher percentage of academic physicians at the professional level than at the collegiate and high school levels.

At the professional level of sports, 56% of all team physicians were orthopedic surgeons. Orthopedists caring for MLB teams had the highest median number of publications (37.9), followed by the NBA (32.0), the NFL (30.4), and the NHL (20.7). One likely explanation is the higher percentage of MLB physicians affiliated with academic medical centers. Regarding the h-index, MLB and NFL physicians had the highest values (7.9 and 8.2, respectively).

 

 

Our study had several limitations. First, we may not have captured data on all the team physicians at the high school, college, and professional levels. By following a detailed protocol in identifying surgeons, however, we tried to minimize the impact of any such omissions. In addition, teams may have had many unofficial consultants acting as team physicians, whether orthopedic or nonorthopedic, and, if these physicians were not listed in an official capacity, they may have been omitted from this study. We further realize that a true measure of academic productivity should also include book chapters and books published, research grants awarded, and patents registered. By including only peer-reviewed articles, we omitted these other criteria.

To our knowledge, the data presented here represent the first attempt to quantify the academic involvement and research productivity of orthopedic team physicians at the high school, college, and professional levels of sport. These data help us understand how research productivity varies by orthopedic team physicians at different levels of sport and may be useful to those considering a career as a team physician, as they can better evaluate their own productivity in the context of team physicians across different levels of competition.

References

1.    Thorndike A. Athletic Injuries: Prevention, Diagnosis, and Treatment. Philadelphia, PA: Lea & Febiger; 1956.

2.    The team physician. A statement of the Committee on the Medical Aspects of Sports of the American Medical Association, September 1967. J School Health. 1967;37(10):510-514.

3.     Team physician consensus statement. Am J Sports Med. 2000;28(3):440-441.

4.    Whiteside J, Andrews JR. Trends for the future as a team physician: Herodicus to hereafter. Clin Sports Med. 2007;26(2):285-304.

5.    Goforth M, Almquist J, Matney M, et al. Understanding organization structures of the college, university, high school, clinical, and professional settings. Clin Sports Med. 2007;26(2):201-226.

6.    Hughston JC. Want to be in sports medicine? Get involved. Am J Sports Med. 1979;7(2):79-80.

7.    Marshall JL, Warren RF, Wickiewicz TL, Reider B. The anterior cruciate ligament: a technique of repair and reconstruction. Clin Orthop Relat Res. 1979;(143):97-106.

8.    Clancy WG Jr, Nelson DA, Reider B, Narechania RG. Anterior cruciate ligament reconstruction using one-third of the patellar ligament, augmented by extra-articular tendon transfers. J Bone Joint Surg Am. 1982;64(3):352-359.

9.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

10.  Indelicato PA, Jobe FW, Kerlan RK, Carter VS, Shields CL, Lombardo SJ. Correctable elbow lesions in professional baseball players: a review of 25 cases. Am J Sports Med. 1979;7(1):72-75.

11.  Elementary/Secondary Information System (EISi). National Center for Education Statistics, Institute of Education Sciences, US Department of Education website. http://nces.ed.gov/ccd/elsi/. Accessed September 21, 2015.

12.  Corso RA; Harris Interactive. Football is America’s favorite sport as lead over baseball continues to grow; college football and auto racing come next. Harris Interactive website. http://www.harrisinteractive.com/vault/Harris Poll 9 - Favorite sport_1.25.12.pdf. Harris Poll 9, January 25, 2012. Accessed September 21, 2015.

13.  [Scopus content]. Elsevier website. http://www.elsevier.com/solutions/scopus/content. Accessed September 21, 2015.

14.  Scopus Author Identifier. Scopus website. http://help.scopus.com/Content/h_autsrch_intro.htm. Accessed October 5, 2015.

15.  Hirsch JE. An index to quantify an individual’s scientific research output. Proc Natl Acad Sci U S A. 2005;102(46):16569-16572.

16.  Author Evaluator h Index Tab. Scopus website. http://help.scopus.com/Content/h_auteval_hindex.htm. Accessed October 5, 2015.

17.  Boyd JL. Understanding the politics of being a team physician. Clin Sports Med. 2007;26(2):161-172.

18.   Lee J, Kraus KL, Couldwell WT. Use of the h index in neurosurgery. Clinical article. J Neurosurg. 2009;111(2):387-

References

1.    Thorndike A. Athletic Injuries: Prevention, Diagnosis, and Treatment. Philadelphia, PA: Lea & Febiger; 1956.

2.    The team physician. A statement of the Committee on the Medical Aspects of Sports of the American Medical Association, September 1967. J School Health. 1967;37(10):510-514.

3.     Team physician consensus statement. Am J Sports Med. 2000;28(3):440-441.

4.    Whiteside J, Andrews JR. Trends for the future as a team physician: Herodicus to hereafter. Clin Sports Med. 2007;26(2):285-304.

5.    Goforth M, Almquist J, Matney M, et al. Understanding organization structures of the college, university, high school, clinical, and professional settings. Clin Sports Med. 2007;26(2):201-226.

6.    Hughston JC. Want to be in sports medicine? Get involved. Am J Sports Med. 1979;7(2):79-80.

7.    Marshall JL, Warren RF, Wickiewicz TL, Reider B. The anterior cruciate ligament: a technique of repair and reconstruction. Clin Orthop Relat Res. 1979;(143):97-106.

8.    Clancy WG Jr, Nelson DA, Reider B, Narechania RG. Anterior cruciate ligament reconstruction using one-third of the patellar ligament, augmented by extra-articular tendon transfers. J Bone Joint Surg Am. 1982;64(3):352-359.

9.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

10.  Indelicato PA, Jobe FW, Kerlan RK, Carter VS, Shields CL, Lombardo SJ. Correctable elbow lesions in professional baseball players: a review of 25 cases. Am J Sports Med. 1979;7(1):72-75.

11.  Elementary/Secondary Information System (EISi). National Center for Education Statistics, Institute of Education Sciences, US Department of Education website. http://nces.ed.gov/ccd/elsi/. Accessed September 21, 2015.

12.  Corso RA; Harris Interactive. Football is America’s favorite sport as lead over baseball continues to grow; college football and auto racing come next. Harris Interactive website. http://www.harrisinteractive.com/vault/Harris Poll 9 - Favorite sport_1.25.12.pdf. Harris Poll 9, January 25, 2012. Accessed September 21, 2015.

13.  [Scopus content]. Elsevier website. http://www.elsevier.com/solutions/scopus/content. Accessed September 21, 2015.

14.  Scopus Author Identifier. Scopus website. http://help.scopus.com/Content/h_autsrch_intro.htm. Accessed October 5, 2015.

15.  Hirsch JE. An index to quantify an individual’s scientific research output. Proc Natl Acad Sci U S A. 2005;102(46):16569-16572.

16.  Author Evaluator h Index Tab. Scopus website. http://help.scopus.com/Content/h_auteval_hindex.htm. Accessed October 5, 2015.

17.  Boyd JL. Understanding the politics of being a team physician. Clin Sports Med. 2007;26(2):161-172.

18.   Lee J, Kraus KL, Couldwell WT. Use of the h index in neurosurgery. Clinical article. J Neurosurg. 2009;111(2):387-

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Conflict of Interest in Sports Medicine: Does It Affect Our Judgment?

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Conflict of Interest in Sports Medicine: Does It Affect Our Judgment?

As defined by the American Academy of Orthopaedic Surgeons (AAOS) in 1996, conflict of interest (COI) is the “circumstance that exists when, because of personal financial gain, an individual has the potential to be less than objective when called on to reach a judgment or interpret a result.”1 In medical research, COIs often occur in relationships between physician-researchers and pharmaceutical, medical device, and biotechnology companies. These relationships usually take the form of research grants but can also arise when the researcher has a financial interest in the product being tested or in the company that manufactures the product.

 Although constructive collaboration between academic medicine and industry has worked to improve health care and ultimately benefit patients, potential drawbacks of such relationships include sequestration and suppression of results that may be disadvantageous to the industry sponsor,2 increased likelihood of reporting positive results (pro-industry),3-7 and biased study designs.8 The nature of such relationships may threaten the integrity of scientific studies, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.9

Financial relationships and affiliations are increasing as we seek to answer a growing number of clinical questions—with funding often being a limiting factor. At national scientific meetings, the number of presentations reporting COIs reflects this trend. Paper and poster presentations accepted for annual meetings of the Orthopaedic Trauma Association (OTA) and reporting a COI increased from 7.6% in 1993 to 12.6% in 2002 (P = .0129).2

Medical subspecialties outside of orthopedics are experiencing similar trends. Most notable is the American Psychiatric Association (APA). After the APA published a mandatory financial COI disclosure policy in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the percentage of task force members reporting industry relationships increased by 12%.10 Analysis of the DSM-5 panels demonstrated that the panels with the largest percentage of reported COIs are those for which pharmacological treatment is the first-line intervention, including the panels for mood disorders (67%), psychotic disorders (83%) and sleep/wake disorders (100%).10 Moreover, the industry ties reported are to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.10

The degree to which financial COIs affect the interpretation of the orthopedic literature has never been quantified. Although it is clear that COIs can confound the results and reporting of data, how the medical community uses disclosures when interpreting the literature and when formulating opinions that may or may not affect their practice patterns is largely unknown.

We conducted a study to evaluate how a hypothetical financial COI disclosure would influence the interpretation of data by orthopedic clinicians. We also wanted to determine the reliability of the data as perceived in association with different study designs, levels of evidence, research institutional settings, and reporting of positive or negative results.

Methods

We asked members of the Arthroscopy Association of North America (AANA) and the American Orthopaedic Society for Sports Medicine (AOSSM) to complete a multiple-choice situational questionnaire (Table). The questionnaire assesses the degree to which respondents use COI disclosures when interpreting the literature. It further explores the perceived clinical value of a study with a given reported COI, assuming variations in study design, research institutional setting, and significance of results. The fictional research team disclosed the project was funded by a pharmaceutical company and all team members received consulting compensation. The survey and study were reviewed and approved by our institutional review board. The survey consisted of 14 multiple-choice questions that allowed for only 1 answer selection per person and allowed survey takers to skip questions they did not wish to answer. The survey questions and associated response options appear in edited form in the Table. A link to the questionnaire (https://www.surveymonkey.com/s/MPCCLCX) was sent with a message explaining the study. The responses to the questionnaire constituted the data.

Results

We sent a request to participate in the survey to 750 physicians and received 522 responses (overall response rate, 70%). The response rate for each question equaled or exceeded 98%.

The majority of respondents (95.6%) were male. Ninety-nine percent of respondents were orthopedic surgeons. The Northeast (US) was the most common geographical practice location of respondents (32%), followed by the Midwest (19.1%) and the Southeast (16.6%). Most respondents (40%) had been in practice for more than 20 years; 67% had been in practice a minimum of 10 years. The majority (68.8%) were employed by private practice groups, either single specialty (57.8%) or multispecialty (11%).

 

 

Eighty percent of respondents strongly agreed that COI disclosure is important when interpreting study results, 62% reported always reading the disclosure slide during academy or other meeting presentations, and 41% reported always using this information when deciding how to interpret scientific data.

Seventy-five percent of respondents thought the study—an academic-center case series with significant results in favor of the pharmaceutical company funding the study—was biased (42% indicated biased with merit, 33% biased without merit). Twenty-three percent thought the study was possibly biased, but likely trustworthy given the academic institutional affiliation. When the study setting was changed to community hospital, 95% thought the study was biased (51% biased with merit, 44% biased without merit). With the same study performed at an academic center, and no statistically significant results (not in favor of the pharmaceutical company funding the study), 88% thought the study had merit (46% biased with merit, 42% unbiased with merit).

When the study design was changed to a randomized controlled trial (level I evidence) conducted at an academic center with negative results, an overwhelming 95% of respondents thought the study had merit (33% biased with merit, 62% unbiased with merit). Given the same study design at an academic center, with positive results, 78% still thought the study had merit (39% biased with merit, 39% unbiased with merit). An additional 18% thought the study was biased, but still likely trustworthy given the academic institutional affiliation. Finally, given a randomized controlled trial and positive results, but with the research setting a small community practice, 90% thought the study had merit (51% biased with merit, 39% unbiased with merit). The percentage of respondents who found the study biased and likely without merit increased from 3.7% to 9.5% when the institutional affiliation changed from academic to community.

Discussion

As governmental funding sources become increasingly limited, the role of industry sponsorship of orthopedic research has grown. Potential drawbacks and biases of such research support have been well described—most notably, increased positive result reporting, suppression of results that may be disadvantageous to the industry sponsor, and biased study designs.2-8 However, the extent to which financial COIs affect the orthopedic medical community’s interpretation of the literature has never been quantified. To our knowledge, the present study is the first to quantify the impact of reported COI on study interpretation.

Our goal was to examine how reported financial COIs influence the interpretation of the literature by the orthopedic medical community. Moreover, we wanted to determine the perceived reliability of the data when variables (study design, institutional affiliation, positive vs negative results) were changed. The results of our survey indicate that, when a financial COI is reported, study reliability is perceived as highest when negative results were found.

Our survey noted a discrepancy between the documented importance of the hypothetical research team’s COI disclosure and the use of such disclosures when interpreting study results. Eighty percent of respondents agreed that COI disclosure is important when interpreting study results, but only 62% reported always reading disclosures, and even fewer (41%) reported always using the information when interpreting results. It is unclear exactly why this trend exists, as one would expect the percentages to be more similar. These particular survey questions were formed around using COI disclosures when interpreting study results during academic presentations at national meetings and not during the review of published literature. It is possible that positioning the COI disclosure at the beginning of a presentation has an effect, but only 3.7% of respondents indicated they seldom remembered the disclosure by the end of the presentation. The results of our survey may have varied if the questions had targeted reading and interpreting the literature.

Interestingly, the results of these survey questions tended to be more consistent with rates of reported financial COI by presenters at national orthopedic meetings. A study published in the New England Journal of Medicine found that less than 80% of orthopedic surgeons reported their disclosures at a large annual meeting (AAOS), even when the disclosure involved payments pertinent to the research they were presenting.5 When the payments were indirectly related to the research, the percentage of surgeons reporting disclosures was 50%, almost the same as the disclosure rate for unrelated payments.5

When the study was changed to a level I randomized controlled trial, more survey respondents found it to be less biased and have more merit. Although it would seem intuitive for a study with a higher level of evidence to carry more clinical value during interpretation, this may not hold true in the setting of industry-sponsored clinical trials. Several studies have documented a significant association between the reporting of positive results and industry-sponsored randomized clinical trials. In 2008, Khan and colleagues3 examined 100 orthopedic randomized clinical trials reported in 5 major orthopedic subspecialty journals over a 2-year period. The association between industry funding and favorable outcome in all original randomized clinical trials was strong and significant (P < .001). This is not surprising, given the amount of time and money required for a well-designed clinical study. Commercial products with preclinical promise are pushed to testing in a clinical trial, whereas resources would not be wasted on products lacking preclinical merit.

 

 

The most important variable affecting interpretation of study merit by survey respondents was the reporting of negative results. As more researchers are developing COIs, many studies are discovering a relationship between COIs and outcomes of research studies. Reviewing the adult total joint literature, Ezzet8 found an industry funding rate of 50%. Positive results were reported in 93% of cases in commercially funded studies versus 37% of cases in independently funded studies. Furthermore, no negative results were reported by investigators who were receiving royalties from the respective companies.

Studies across the medical literature have also found this association between industry sponsorship and reporting of positive results. One such study, reported by Valachis and colleagues7 in the Journal of Clinical Oncology, examined more than 80 economic analyses of targeted oncologic therapies and found the studies funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates. In addition, when studies with a COI disclosure were examined, those reporting any financial relationship with a manufacturer (eg, author affiliation, funding) were more likely than those without such a relationship to report favorable results.

Our study had several limitations. First, as most of the survey respondents were orthopedic surgeons, extrapolating their data to the medical community at large may not be appropriate, as each specialty may view industry affiliations differently. In addition, respondents were asked to base their interpretations of a study on conclusions we predetermined—no direct visualization of the data set or statistical testing methods. It is possible that these responses may have been different had the respondents had the opportunity to further evaluate the study in question. In a recent study, Altwairgi and colleagues11 found that 10% of randomized clinical trials involving lung cancer treatment were reported with different conclusions in their full manuscripts relative to their abstracts. We think our survey design perhaps best mimics an annual meeting environment in which participants have very limited ability to interpret studies and may rely more heavily on the factors we investigated—study design, significance of findings, and setting, all similar to information presented in an abstract—when making informed decisions. Although our response rate was only 70%, this is comparable to or better than the rates in similar survey studies that used email-based questionnaires.12,13

Another limitation was that our survey may have forced respondents into answers they did not entirely agree with, given the limited options of the multiple-choice response format and the specific wording of the questions. Our conclusions may have been more dramatic when we were evaluating whether the study was deemed meritorious or not. However, there is no adopted standard for evaluating the extent of bias perceived by a clinician. We thought it was important to include answer options indicating a study had merit despite obvious bias in design and execution. That a study had merit can mean different things. It may change clinical practice, may require further study and reproducibility, or may not be significant enough to matter. Asking follow-up questions to evaluate this perception among the respondents could have provided validity to the term merit. Further studies in this field are needed to determine how studies are interpreted and translated into clinical practice by various clinicians.

Conclusion

Although the present study is not a quantitative analysis of the determination of bias in the orthopedic community, it is the first to evaluate orthopedic surgeons’ perceptions on the basis of key fundamentals of orthopedic research relative to COI. It is clear from our study results that introducing levels of evidence to the orthopedic milieu has had a significant impact both on the quality of research and on the foundational use of deductive reasoning when interpreting the literature. Reporting negative outcomes is perhaps the most important factor in eliminating the perception of bias among orthopedic surgeons. To what extent a perceived COI plays into medical decision-making and the ultimate treatment of patients is still relatively unknown.

References

1.    Lubahn JD, Mankin CJ, Mankin HJ, Kuhn PJ. Orthopaedics, ethics, and industry. Appropriateness of gifts, grants, and awards. Clin Orthop Relat Res. 2000;(371):256-263.

2.    Kubiak EN, Park SS, Egol K, Zuckerman JD, Koval KJ. Increasingly conflicted: an analysis of conflicts of interest reported at the annual meetings of the Orthopaedic Trauma Association. Bull Hosp Jt Dis. 2006;63(3-4):83-87.

3.    Khan SN, Mermer MJ, Myers E, Sandhu HS. The roles of funding source, clinical trial outcome, and quality of reporting in orthopedic surgery literature. Am J Orthop. 2008;37(12):E205-E212.

4.    Okike K, Kocher MS, Mehlman CT, Bhandari M. Conflict of interest in orthopaedic research. An association between findings and funding in scientific presentations. J Bone Joint Surg Am. 2007;89(3):608-613.

5.    Okike K, Kocher MS, Wei EX, Mehlman CT, Bhandari M. Accuracy of conflict-of-interest disclosures reported by physicians. N Engl J Med. 2009;361(15):1466-1474.

6.    Shah RV, Albert TJ, Bruegel-Sanchez V, Vaccaro AR, Hilibrand AS, Grauer JN. Industry support and correlation to study outcome for papers published in Spine. Spine. 2005;30(9):1099-1104.

7.    Valachis A, Polyzos NP, Nearchou A, Lind P, Mauri D. Financial relationships in economic analyses of targeted therapies in oncology. J Clin Oncol. 2012;30(12):1316-1320.

8.    Ezzet KA. The prevalence of corporate funding in adult lower extremity research and its correlation with reported results. J Arthroplasty. 2003;18(7 suppl 1):138-145.

9.    Lo B, Field MJ, eds; Institute of Medicine, Committee on Conflict of Interest in Medical Research, Education, and Practice, Board on Health Sciences Policy. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009. http://www.ncbi.nlm.nih.gov/books/NBK22942. Accessed September 29, 2015.

10.  Cosgrove L, Krimsky S. A comparison of DSM-IV and DSM-5 panel members’ financial associations with industry: a pernicious problem persists. PLoS Med. 2012;9(3):e1001190.

11.  Altwairgi AK, Booth CM, Hopman WM, Baetz TD. Discordance between conclusions stated in the abstract and conclusions in the article: analysis of published randomized controlled trials of systemic therapy in lung cancer. J Clin Oncol. 2012;30(28):3552-3557.

12.  Decoster LC, Vailas JC, Swartz WG. Functional ACL bracing. A survey of current opinion and practice. Am J Orthop. 1995;24(11):838-843.

13.  Mann BJ, Grana WA, Indelicato PA, O’Neill DF, George SZ. A survey of sports medicine physicians regarding psychological issues in patient-athletes. Am J Sports Med. 2007;35(12):2140-2147.

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Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

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As defined by the American Academy of Orthopaedic Surgeons (AAOS) in 1996, conflict of interest (COI) is the “circumstance that exists when, because of personal financial gain, an individual has the potential to be less than objective when called on to reach a judgment or interpret a result.”1 In medical research, COIs often occur in relationships between physician-researchers and pharmaceutical, medical device, and biotechnology companies. These relationships usually take the form of research grants but can also arise when the researcher has a financial interest in the product being tested or in the company that manufactures the product.

 Although constructive collaboration between academic medicine and industry has worked to improve health care and ultimately benefit patients, potential drawbacks of such relationships include sequestration and suppression of results that may be disadvantageous to the industry sponsor,2 increased likelihood of reporting positive results (pro-industry),3-7 and biased study designs.8 The nature of such relationships may threaten the integrity of scientific studies, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.9

Financial relationships and affiliations are increasing as we seek to answer a growing number of clinical questions—with funding often being a limiting factor. At national scientific meetings, the number of presentations reporting COIs reflects this trend. Paper and poster presentations accepted for annual meetings of the Orthopaedic Trauma Association (OTA) and reporting a COI increased from 7.6% in 1993 to 12.6% in 2002 (P = .0129).2

Medical subspecialties outside of orthopedics are experiencing similar trends. Most notable is the American Psychiatric Association (APA). After the APA published a mandatory financial COI disclosure policy in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the percentage of task force members reporting industry relationships increased by 12%.10 Analysis of the DSM-5 panels demonstrated that the panels with the largest percentage of reported COIs are those for which pharmacological treatment is the first-line intervention, including the panels for mood disorders (67%), psychotic disorders (83%) and sleep/wake disorders (100%).10 Moreover, the industry ties reported are to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.10

The degree to which financial COIs affect the interpretation of the orthopedic literature has never been quantified. Although it is clear that COIs can confound the results and reporting of data, how the medical community uses disclosures when interpreting the literature and when formulating opinions that may or may not affect their practice patterns is largely unknown.

We conducted a study to evaluate how a hypothetical financial COI disclosure would influence the interpretation of data by orthopedic clinicians. We also wanted to determine the reliability of the data as perceived in association with different study designs, levels of evidence, research institutional settings, and reporting of positive or negative results.

Methods

We asked members of the Arthroscopy Association of North America (AANA) and the American Orthopaedic Society for Sports Medicine (AOSSM) to complete a multiple-choice situational questionnaire (Table). The questionnaire assesses the degree to which respondents use COI disclosures when interpreting the literature. It further explores the perceived clinical value of a study with a given reported COI, assuming variations in study design, research institutional setting, and significance of results. The fictional research team disclosed the project was funded by a pharmaceutical company and all team members received consulting compensation. The survey and study were reviewed and approved by our institutional review board. The survey consisted of 14 multiple-choice questions that allowed for only 1 answer selection per person and allowed survey takers to skip questions they did not wish to answer. The survey questions and associated response options appear in edited form in the Table. A link to the questionnaire (https://www.surveymonkey.com/s/MPCCLCX) was sent with a message explaining the study. The responses to the questionnaire constituted the data.

Results

We sent a request to participate in the survey to 750 physicians and received 522 responses (overall response rate, 70%). The response rate for each question equaled or exceeded 98%.

The majority of respondents (95.6%) were male. Ninety-nine percent of respondents were orthopedic surgeons. The Northeast (US) was the most common geographical practice location of respondents (32%), followed by the Midwest (19.1%) and the Southeast (16.6%). Most respondents (40%) had been in practice for more than 20 years; 67% had been in practice a minimum of 10 years. The majority (68.8%) were employed by private practice groups, either single specialty (57.8%) or multispecialty (11%).

 

 

Eighty percent of respondents strongly agreed that COI disclosure is important when interpreting study results, 62% reported always reading the disclosure slide during academy or other meeting presentations, and 41% reported always using this information when deciding how to interpret scientific data.

Seventy-five percent of respondents thought the study—an academic-center case series with significant results in favor of the pharmaceutical company funding the study—was biased (42% indicated biased with merit, 33% biased without merit). Twenty-three percent thought the study was possibly biased, but likely trustworthy given the academic institutional affiliation. When the study setting was changed to community hospital, 95% thought the study was biased (51% biased with merit, 44% biased without merit). With the same study performed at an academic center, and no statistically significant results (not in favor of the pharmaceutical company funding the study), 88% thought the study had merit (46% biased with merit, 42% unbiased with merit).

When the study design was changed to a randomized controlled trial (level I evidence) conducted at an academic center with negative results, an overwhelming 95% of respondents thought the study had merit (33% biased with merit, 62% unbiased with merit). Given the same study design at an academic center, with positive results, 78% still thought the study had merit (39% biased with merit, 39% unbiased with merit). An additional 18% thought the study was biased, but still likely trustworthy given the academic institutional affiliation. Finally, given a randomized controlled trial and positive results, but with the research setting a small community practice, 90% thought the study had merit (51% biased with merit, 39% unbiased with merit). The percentage of respondents who found the study biased and likely without merit increased from 3.7% to 9.5% when the institutional affiliation changed from academic to community.

Discussion

As governmental funding sources become increasingly limited, the role of industry sponsorship of orthopedic research has grown. Potential drawbacks and biases of such research support have been well described—most notably, increased positive result reporting, suppression of results that may be disadvantageous to the industry sponsor, and biased study designs.2-8 However, the extent to which financial COIs affect the orthopedic medical community’s interpretation of the literature has never been quantified. To our knowledge, the present study is the first to quantify the impact of reported COI on study interpretation.

Our goal was to examine how reported financial COIs influence the interpretation of the literature by the orthopedic medical community. Moreover, we wanted to determine the perceived reliability of the data when variables (study design, institutional affiliation, positive vs negative results) were changed. The results of our survey indicate that, when a financial COI is reported, study reliability is perceived as highest when negative results were found.

Our survey noted a discrepancy between the documented importance of the hypothetical research team’s COI disclosure and the use of such disclosures when interpreting study results. Eighty percent of respondents agreed that COI disclosure is important when interpreting study results, but only 62% reported always reading disclosures, and even fewer (41%) reported always using the information when interpreting results. It is unclear exactly why this trend exists, as one would expect the percentages to be more similar. These particular survey questions were formed around using COI disclosures when interpreting study results during academic presentations at national meetings and not during the review of published literature. It is possible that positioning the COI disclosure at the beginning of a presentation has an effect, but only 3.7% of respondents indicated they seldom remembered the disclosure by the end of the presentation. The results of our survey may have varied if the questions had targeted reading and interpreting the literature.

Interestingly, the results of these survey questions tended to be more consistent with rates of reported financial COI by presenters at national orthopedic meetings. A study published in the New England Journal of Medicine found that less than 80% of orthopedic surgeons reported their disclosures at a large annual meeting (AAOS), even when the disclosure involved payments pertinent to the research they were presenting.5 When the payments were indirectly related to the research, the percentage of surgeons reporting disclosures was 50%, almost the same as the disclosure rate for unrelated payments.5

When the study was changed to a level I randomized controlled trial, more survey respondents found it to be less biased and have more merit. Although it would seem intuitive for a study with a higher level of evidence to carry more clinical value during interpretation, this may not hold true in the setting of industry-sponsored clinical trials. Several studies have documented a significant association between the reporting of positive results and industry-sponsored randomized clinical trials. In 2008, Khan and colleagues3 examined 100 orthopedic randomized clinical trials reported in 5 major orthopedic subspecialty journals over a 2-year period. The association between industry funding and favorable outcome in all original randomized clinical trials was strong and significant (P < .001). This is not surprising, given the amount of time and money required for a well-designed clinical study. Commercial products with preclinical promise are pushed to testing in a clinical trial, whereas resources would not be wasted on products lacking preclinical merit.

 

 

The most important variable affecting interpretation of study merit by survey respondents was the reporting of negative results. As more researchers are developing COIs, many studies are discovering a relationship between COIs and outcomes of research studies. Reviewing the adult total joint literature, Ezzet8 found an industry funding rate of 50%. Positive results were reported in 93% of cases in commercially funded studies versus 37% of cases in independently funded studies. Furthermore, no negative results were reported by investigators who were receiving royalties from the respective companies.

Studies across the medical literature have also found this association between industry sponsorship and reporting of positive results. One such study, reported by Valachis and colleagues7 in the Journal of Clinical Oncology, examined more than 80 economic analyses of targeted oncologic therapies and found the studies funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates. In addition, when studies with a COI disclosure were examined, those reporting any financial relationship with a manufacturer (eg, author affiliation, funding) were more likely than those without such a relationship to report favorable results.

Our study had several limitations. First, as most of the survey respondents were orthopedic surgeons, extrapolating their data to the medical community at large may not be appropriate, as each specialty may view industry affiliations differently. In addition, respondents were asked to base their interpretations of a study on conclusions we predetermined—no direct visualization of the data set or statistical testing methods. It is possible that these responses may have been different had the respondents had the opportunity to further evaluate the study in question. In a recent study, Altwairgi and colleagues11 found that 10% of randomized clinical trials involving lung cancer treatment were reported with different conclusions in their full manuscripts relative to their abstracts. We think our survey design perhaps best mimics an annual meeting environment in which participants have very limited ability to interpret studies and may rely more heavily on the factors we investigated—study design, significance of findings, and setting, all similar to information presented in an abstract—when making informed decisions. Although our response rate was only 70%, this is comparable to or better than the rates in similar survey studies that used email-based questionnaires.12,13

Another limitation was that our survey may have forced respondents into answers they did not entirely agree with, given the limited options of the multiple-choice response format and the specific wording of the questions. Our conclusions may have been more dramatic when we were evaluating whether the study was deemed meritorious or not. However, there is no adopted standard for evaluating the extent of bias perceived by a clinician. We thought it was important to include answer options indicating a study had merit despite obvious bias in design and execution. That a study had merit can mean different things. It may change clinical practice, may require further study and reproducibility, or may not be significant enough to matter. Asking follow-up questions to evaluate this perception among the respondents could have provided validity to the term merit. Further studies in this field are needed to determine how studies are interpreted and translated into clinical practice by various clinicians.

Conclusion

Although the present study is not a quantitative analysis of the determination of bias in the orthopedic community, it is the first to evaluate orthopedic surgeons’ perceptions on the basis of key fundamentals of orthopedic research relative to COI. It is clear from our study results that introducing levels of evidence to the orthopedic milieu has had a significant impact both on the quality of research and on the foundational use of deductive reasoning when interpreting the literature. Reporting negative outcomes is perhaps the most important factor in eliminating the perception of bias among orthopedic surgeons. To what extent a perceived COI plays into medical decision-making and the ultimate treatment of patients is still relatively unknown.

As defined by the American Academy of Orthopaedic Surgeons (AAOS) in 1996, conflict of interest (COI) is the “circumstance that exists when, because of personal financial gain, an individual has the potential to be less than objective when called on to reach a judgment or interpret a result.”1 In medical research, COIs often occur in relationships between physician-researchers and pharmaceutical, medical device, and biotechnology companies. These relationships usually take the form of research grants but can also arise when the researcher has a financial interest in the product being tested or in the company that manufactures the product.

 Although constructive collaboration between academic medicine and industry has worked to improve health care and ultimately benefit patients, potential drawbacks of such relationships include sequestration and suppression of results that may be disadvantageous to the industry sponsor,2 increased likelihood of reporting positive results (pro-industry),3-7 and biased study designs.8 The nature of such relationships may threaten the integrity of scientific studies, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.9

Financial relationships and affiliations are increasing as we seek to answer a growing number of clinical questions—with funding often being a limiting factor. At national scientific meetings, the number of presentations reporting COIs reflects this trend. Paper and poster presentations accepted for annual meetings of the Orthopaedic Trauma Association (OTA) and reporting a COI increased from 7.6% in 1993 to 12.6% in 2002 (P = .0129).2

Medical subspecialties outside of orthopedics are experiencing similar trends. Most notable is the American Psychiatric Association (APA). After the APA published a mandatory financial COI disclosure policy in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the percentage of task force members reporting industry relationships increased by 12%.10 Analysis of the DSM-5 panels demonstrated that the panels with the largest percentage of reported COIs are those for which pharmacological treatment is the first-line intervention, including the panels for mood disorders (67%), psychotic disorders (83%) and sleep/wake disorders (100%).10 Moreover, the industry ties reported are to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.10

The degree to which financial COIs affect the interpretation of the orthopedic literature has never been quantified. Although it is clear that COIs can confound the results and reporting of data, how the medical community uses disclosures when interpreting the literature and when formulating opinions that may or may not affect their practice patterns is largely unknown.

We conducted a study to evaluate how a hypothetical financial COI disclosure would influence the interpretation of data by orthopedic clinicians. We also wanted to determine the reliability of the data as perceived in association with different study designs, levels of evidence, research institutional settings, and reporting of positive or negative results.

Methods

We asked members of the Arthroscopy Association of North America (AANA) and the American Orthopaedic Society for Sports Medicine (AOSSM) to complete a multiple-choice situational questionnaire (Table). The questionnaire assesses the degree to which respondents use COI disclosures when interpreting the literature. It further explores the perceived clinical value of a study with a given reported COI, assuming variations in study design, research institutional setting, and significance of results. The fictional research team disclosed the project was funded by a pharmaceutical company and all team members received consulting compensation. The survey and study were reviewed and approved by our institutional review board. The survey consisted of 14 multiple-choice questions that allowed for only 1 answer selection per person and allowed survey takers to skip questions they did not wish to answer. The survey questions and associated response options appear in edited form in the Table. A link to the questionnaire (https://www.surveymonkey.com/s/MPCCLCX) was sent with a message explaining the study. The responses to the questionnaire constituted the data.

Results

We sent a request to participate in the survey to 750 physicians and received 522 responses (overall response rate, 70%). The response rate for each question equaled or exceeded 98%.

The majority of respondents (95.6%) were male. Ninety-nine percent of respondents were orthopedic surgeons. The Northeast (US) was the most common geographical practice location of respondents (32%), followed by the Midwest (19.1%) and the Southeast (16.6%). Most respondents (40%) had been in practice for more than 20 years; 67% had been in practice a minimum of 10 years. The majority (68.8%) were employed by private practice groups, either single specialty (57.8%) or multispecialty (11%).

 

 

Eighty percent of respondents strongly agreed that COI disclosure is important when interpreting study results, 62% reported always reading the disclosure slide during academy or other meeting presentations, and 41% reported always using this information when deciding how to interpret scientific data.

Seventy-five percent of respondents thought the study—an academic-center case series with significant results in favor of the pharmaceutical company funding the study—was biased (42% indicated biased with merit, 33% biased without merit). Twenty-three percent thought the study was possibly biased, but likely trustworthy given the academic institutional affiliation. When the study setting was changed to community hospital, 95% thought the study was biased (51% biased with merit, 44% biased without merit). With the same study performed at an academic center, and no statistically significant results (not in favor of the pharmaceutical company funding the study), 88% thought the study had merit (46% biased with merit, 42% unbiased with merit).

When the study design was changed to a randomized controlled trial (level I evidence) conducted at an academic center with negative results, an overwhelming 95% of respondents thought the study had merit (33% biased with merit, 62% unbiased with merit). Given the same study design at an academic center, with positive results, 78% still thought the study had merit (39% biased with merit, 39% unbiased with merit). An additional 18% thought the study was biased, but still likely trustworthy given the academic institutional affiliation. Finally, given a randomized controlled trial and positive results, but with the research setting a small community practice, 90% thought the study had merit (51% biased with merit, 39% unbiased with merit). The percentage of respondents who found the study biased and likely without merit increased from 3.7% to 9.5% when the institutional affiliation changed from academic to community.

Discussion

As governmental funding sources become increasingly limited, the role of industry sponsorship of orthopedic research has grown. Potential drawbacks and biases of such research support have been well described—most notably, increased positive result reporting, suppression of results that may be disadvantageous to the industry sponsor, and biased study designs.2-8 However, the extent to which financial COIs affect the orthopedic medical community’s interpretation of the literature has never been quantified. To our knowledge, the present study is the first to quantify the impact of reported COI on study interpretation.

Our goal was to examine how reported financial COIs influence the interpretation of the literature by the orthopedic medical community. Moreover, we wanted to determine the perceived reliability of the data when variables (study design, institutional affiliation, positive vs negative results) were changed. The results of our survey indicate that, when a financial COI is reported, study reliability is perceived as highest when negative results were found.

Our survey noted a discrepancy between the documented importance of the hypothetical research team’s COI disclosure and the use of such disclosures when interpreting study results. Eighty percent of respondents agreed that COI disclosure is important when interpreting study results, but only 62% reported always reading disclosures, and even fewer (41%) reported always using the information when interpreting results. It is unclear exactly why this trend exists, as one would expect the percentages to be more similar. These particular survey questions were formed around using COI disclosures when interpreting study results during academic presentations at national meetings and not during the review of published literature. It is possible that positioning the COI disclosure at the beginning of a presentation has an effect, but only 3.7% of respondents indicated they seldom remembered the disclosure by the end of the presentation. The results of our survey may have varied if the questions had targeted reading and interpreting the literature.

Interestingly, the results of these survey questions tended to be more consistent with rates of reported financial COI by presenters at national orthopedic meetings. A study published in the New England Journal of Medicine found that less than 80% of orthopedic surgeons reported their disclosures at a large annual meeting (AAOS), even when the disclosure involved payments pertinent to the research they were presenting.5 When the payments were indirectly related to the research, the percentage of surgeons reporting disclosures was 50%, almost the same as the disclosure rate for unrelated payments.5

When the study was changed to a level I randomized controlled trial, more survey respondents found it to be less biased and have more merit. Although it would seem intuitive for a study with a higher level of evidence to carry more clinical value during interpretation, this may not hold true in the setting of industry-sponsored clinical trials. Several studies have documented a significant association between the reporting of positive results and industry-sponsored randomized clinical trials. In 2008, Khan and colleagues3 examined 100 orthopedic randomized clinical trials reported in 5 major orthopedic subspecialty journals over a 2-year period. The association between industry funding and favorable outcome in all original randomized clinical trials was strong and significant (P < .001). This is not surprising, given the amount of time and money required for a well-designed clinical study. Commercial products with preclinical promise are pushed to testing in a clinical trial, whereas resources would not be wasted on products lacking preclinical merit.

 

 

The most important variable affecting interpretation of study merit by survey respondents was the reporting of negative results. As more researchers are developing COIs, many studies are discovering a relationship between COIs and outcomes of research studies. Reviewing the adult total joint literature, Ezzet8 found an industry funding rate of 50%. Positive results were reported in 93% of cases in commercially funded studies versus 37% of cases in independently funded studies. Furthermore, no negative results were reported by investigators who were receiving royalties from the respective companies.

Studies across the medical literature have also found this association between industry sponsorship and reporting of positive results. One such study, reported by Valachis and colleagues7 in the Journal of Clinical Oncology, examined more than 80 economic analyses of targeted oncologic therapies and found the studies funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates. In addition, when studies with a COI disclosure were examined, those reporting any financial relationship with a manufacturer (eg, author affiliation, funding) were more likely than those without such a relationship to report favorable results.

Our study had several limitations. First, as most of the survey respondents were orthopedic surgeons, extrapolating their data to the medical community at large may not be appropriate, as each specialty may view industry affiliations differently. In addition, respondents were asked to base their interpretations of a study on conclusions we predetermined—no direct visualization of the data set or statistical testing methods. It is possible that these responses may have been different had the respondents had the opportunity to further evaluate the study in question. In a recent study, Altwairgi and colleagues11 found that 10% of randomized clinical trials involving lung cancer treatment were reported with different conclusions in their full manuscripts relative to their abstracts. We think our survey design perhaps best mimics an annual meeting environment in which participants have very limited ability to interpret studies and may rely more heavily on the factors we investigated—study design, significance of findings, and setting, all similar to information presented in an abstract—when making informed decisions. Although our response rate was only 70%, this is comparable to or better than the rates in similar survey studies that used email-based questionnaires.12,13

Another limitation was that our survey may have forced respondents into answers they did not entirely agree with, given the limited options of the multiple-choice response format and the specific wording of the questions. Our conclusions may have been more dramatic when we were evaluating whether the study was deemed meritorious or not. However, there is no adopted standard for evaluating the extent of bias perceived by a clinician. We thought it was important to include answer options indicating a study had merit despite obvious bias in design and execution. That a study had merit can mean different things. It may change clinical practice, may require further study and reproducibility, or may not be significant enough to matter. Asking follow-up questions to evaluate this perception among the respondents could have provided validity to the term merit. Further studies in this field are needed to determine how studies are interpreted and translated into clinical practice by various clinicians.

Conclusion

Although the present study is not a quantitative analysis of the determination of bias in the orthopedic community, it is the first to evaluate orthopedic surgeons’ perceptions on the basis of key fundamentals of orthopedic research relative to COI. It is clear from our study results that introducing levels of evidence to the orthopedic milieu has had a significant impact both on the quality of research and on the foundational use of deductive reasoning when interpreting the literature. Reporting negative outcomes is perhaps the most important factor in eliminating the perception of bias among orthopedic surgeons. To what extent a perceived COI plays into medical decision-making and the ultimate treatment of patients is still relatively unknown.

References

1.    Lubahn JD, Mankin CJ, Mankin HJ, Kuhn PJ. Orthopaedics, ethics, and industry. Appropriateness of gifts, grants, and awards. Clin Orthop Relat Res. 2000;(371):256-263.

2.    Kubiak EN, Park SS, Egol K, Zuckerman JD, Koval KJ. Increasingly conflicted: an analysis of conflicts of interest reported at the annual meetings of the Orthopaedic Trauma Association. Bull Hosp Jt Dis. 2006;63(3-4):83-87.

3.    Khan SN, Mermer MJ, Myers E, Sandhu HS. The roles of funding source, clinical trial outcome, and quality of reporting in orthopedic surgery literature. Am J Orthop. 2008;37(12):E205-E212.

4.    Okike K, Kocher MS, Mehlman CT, Bhandari M. Conflict of interest in orthopaedic research. An association between findings and funding in scientific presentations. J Bone Joint Surg Am. 2007;89(3):608-613.

5.    Okike K, Kocher MS, Wei EX, Mehlman CT, Bhandari M. Accuracy of conflict-of-interest disclosures reported by physicians. N Engl J Med. 2009;361(15):1466-1474.

6.    Shah RV, Albert TJ, Bruegel-Sanchez V, Vaccaro AR, Hilibrand AS, Grauer JN. Industry support and correlation to study outcome for papers published in Spine. Spine. 2005;30(9):1099-1104.

7.    Valachis A, Polyzos NP, Nearchou A, Lind P, Mauri D. Financial relationships in economic analyses of targeted therapies in oncology. J Clin Oncol. 2012;30(12):1316-1320.

8.    Ezzet KA. The prevalence of corporate funding in adult lower extremity research and its correlation with reported results. J Arthroplasty. 2003;18(7 suppl 1):138-145.

9.    Lo B, Field MJ, eds; Institute of Medicine, Committee on Conflict of Interest in Medical Research, Education, and Practice, Board on Health Sciences Policy. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009. http://www.ncbi.nlm.nih.gov/books/NBK22942. Accessed September 29, 2015.

10.  Cosgrove L, Krimsky S. A comparison of DSM-IV and DSM-5 panel members’ financial associations with industry: a pernicious problem persists. PLoS Med. 2012;9(3):e1001190.

11.  Altwairgi AK, Booth CM, Hopman WM, Baetz TD. Discordance between conclusions stated in the abstract and conclusions in the article: analysis of published randomized controlled trials of systemic therapy in lung cancer. J Clin Oncol. 2012;30(28):3552-3557.

12.  Decoster LC, Vailas JC, Swartz WG. Functional ACL bracing. A survey of current opinion and practice. Am J Orthop. 1995;24(11):838-843.

13.  Mann BJ, Grana WA, Indelicato PA, O’Neill DF, George SZ. A survey of sports medicine physicians regarding psychological issues in patient-athletes. Am J Sports Med. 2007;35(12):2140-2147.

References

1.    Lubahn JD, Mankin CJ, Mankin HJ, Kuhn PJ. Orthopaedics, ethics, and industry. Appropriateness of gifts, grants, and awards. Clin Orthop Relat Res. 2000;(371):256-263.

2.    Kubiak EN, Park SS, Egol K, Zuckerman JD, Koval KJ. Increasingly conflicted: an analysis of conflicts of interest reported at the annual meetings of the Orthopaedic Trauma Association. Bull Hosp Jt Dis. 2006;63(3-4):83-87.

3.    Khan SN, Mermer MJ, Myers E, Sandhu HS. The roles of funding source, clinical trial outcome, and quality of reporting in orthopedic surgery literature. Am J Orthop. 2008;37(12):E205-E212.

4.    Okike K, Kocher MS, Mehlman CT, Bhandari M. Conflict of interest in orthopaedic research. An association between findings and funding in scientific presentations. J Bone Joint Surg Am. 2007;89(3):608-613.

5.    Okike K, Kocher MS, Wei EX, Mehlman CT, Bhandari M. Accuracy of conflict-of-interest disclosures reported by physicians. N Engl J Med. 2009;361(15):1466-1474.

6.    Shah RV, Albert TJ, Bruegel-Sanchez V, Vaccaro AR, Hilibrand AS, Grauer JN. Industry support and correlation to study outcome for papers published in Spine. Spine. 2005;30(9):1099-1104.

7.    Valachis A, Polyzos NP, Nearchou A, Lind P, Mauri D. Financial relationships in economic analyses of targeted therapies in oncology. J Clin Oncol. 2012;30(12):1316-1320.

8.    Ezzet KA. The prevalence of corporate funding in adult lower extremity research and its correlation with reported results. J Arthroplasty. 2003;18(7 suppl 1):138-145.

9.    Lo B, Field MJ, eds; Institute of Medicine, Committee on Conflict of Interest in Medical Research, Education, and Practice, Board on Health Sciences Policy. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009. http://www.ncbi.nlm.nih.gov/books/NBK22942. Accessed September 29, 2015.

10.  Cosgrove L, Krimsky S. A comparison of DSM-IV and DSM-5 panel members’ financial associations with industry: a pernicious problem persists. PLoS Med. 2012;9(3):e1001190.

11.  Altwairgi AK, Booth CM, Hopman WM, Baetz TD. Discordance between conclusions stated in the abstract and conclusions in the article: analysis of published randomized controlled trials of systemic therapy in lung cancer. J Clin Oncol. 2012;30(28):3552-3557.

12.  Decoster LC, Vailas JC, Swartz WG. Functional ACL bracing. A survey of current opinion and practice. Am J Orthop. 1995;24(11):838-843.

13.  Mann BJ, Grana WA, Indelicato PA, O’Neill DF, George SZ. A survey of sports medicine physicians regarding psychological issues in patient-athletes. Am J Sports Med. 2007;35(12):2140-2147.

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The American Journal of Orthopedics - 44(11)
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Biceps Tenodesis and Superior Labrum Anterior to Posterior (SLAP) Tears

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Biceps Tenodesis and Superior Labrum Anterior to Posterior (SLAP) Tears

Injuries of the superior labrum–biceps complex (SLBC) have been recognized as a cause of shoulder pain since they were first described by Andrews and colleagues1 in 1985. Superior labrum anterior to posterior (SLAP) tears are relatively uncommon injuries of the shoulder, and their true incidence is difficult to establish. However, recently there has been a significant increase in the reported incidence and operative treatment of SLAP tears.2 SLAP tears can occur in isolation, but they are commonly seen in association with other shoulder lesions, including rotator cuff tear, Bankart lesion, glenohumeral arthritis, acromioclavicular joint pathology, and subacromial impingement.

Although SLAP tears are well described and classified,3-6 our understanding of symptomatic SLAP tears and of their contribution to glenohumeral instability is limited. Diagnosing a SLAP tear on the basis of history and physical examination is a clinical challenge. Pain is the most common presentation of SLAP tears, though localization and characterization of pain are variable and nonspecific.7 The mechanism of injury is helpful in acute presentation (traction injury; fall on outstretched, abducted arm), but an overhead athlete may present with no distinct mechanism other than chronic, repetitive use of the shoulder.8-11 Numerous provocative physical examination tests have been used to assist in the diagnosis of SLAP tear, yet there is no consensus regarding the ideal physical examination test, with high sensitivity, specificity, and accuracy.12-14 Magnetic resonance arthrography, the gold standard imaging modality, is highly sensitive and specific (>95%) for diagnosing SLAP tears.

SLAP tear management is based on lesion type and severity, age, functional demands, and presence of coexisting intra-articular lesions. Management options include nonoperative treatment, débridement or repair of SLBC, biceps tenotomy, and biceps tenodesis.15-19

In this 5-point review, we present an evidence-based analysis of the role of the SLBC in glenohumeral stability and the role of biceps tenodesis in the management of SLAP tears.

1. Role of SLBC in stability of glenohumeral joint

The anatomy of the SLBC has been well described,20,21 and there is consensus that SLBC pathology can be a source of shoulder pain. The superior labrum is relatively more mobile than the rest of the glenoid labrum, and it provides attachment to the long head of the biceps tendon (LHBT) and the superior glenohumeral and middle glenohumeral ligaments.

The functional role of the SLBC in glenohumeral stability and its contribution to the pathogenesis of shoulder instability are not clearly defined. Our understanding of SLBC function is largely derived from simulated cadaveric experiments of SLAP tears. Controlled laboratory studies with simulated type II SLAP tears in cadavers have shown significantly increased glenohumeral translation in the anterior-posterior and superior-inferior directions, suggesting a role of the superior labrum in maintaining glenohumeral stability.22-26 Interestingly, there is conflicting evidence regarding restoration of normal glenohumeral translation in cadaveric shoulders after repair of simulated SLAP lesions in the presence or absence of simulated anterior capsular laxity.22,25-27 However, it is important to understand the limitations of cadaveric experiments in order to appreciate and truly comprehend the results of these experiments. There are inconsistencies in the size of simulated type II SLAP lesions in different studies, which can affect the degree of glenohumeral translation and the results of repair.23-25,28 The amount of glenohumeral translation noticed after simulated SLAP tears in cadavers, though statistically significant, is small in amplitude, and its relevance may not translate to a clinically significant level. The impact of dynamic components of stability (eg, rotator cuff muscles), capsular stretch, and other in vivo variables that affect glenohumeral stability are unaccounted for during cadaveric experiments.

LHBT is a recognized cause of shoulder pain, but its contribution to shoulder stability is a point of continued debate. According to one school of thought, LHBT is a vestigial structure that can be sacrificed without any loss of stability. Another school of thought holds that LHBT is an important active stabilizer of the glenohumeral joint. Cadaveric studies have demonstrated that loading the LHBT decreases glenohumeral translation and rotational range of motion, especially in lower and mid ranges of abduction.23,29,30 Furthermore, LHBT contributes to anterior glenohumeral stability by resisting torsional forces in the abducted and externally rotated shoulder and reducing stress on the inferior glenohumeral ligaments.31-33 Strauss and colleagues22 recently found that simulated anterior and posterior type II SLAP lesions in cadaveric shoulders increased glenohumeral translation in all planes, and biceps tenodesis did not further worsen this abnormal glenohumeral translation. Furthermore, repair of posterior SLAP lesions along with biceps tenodesis restored abnormal glenohumeral translation with no significant difference from the baseline in any plane of motion. Again, the limitations of cadaveric studies should be considered when interpreting these results and applying them clinically.

 

 

2. Biceps tenodesis as primary treatment for SLAP tears

A growing body of evidence suggests that primary tenodesis of LHBT may be an effective alternative treatment to SLAP repairs in select patients.34-36 However, the evidence is weak, and high-quality studies comparing SLAP repair and primary biceps tenodesis are required in order to make a strong recommendation for one technique over another. Gupta and colleagues35 retrospectively analyzed 28 cases of concomitant SLAP tear and biceps tendonitis treated with primary open subpectoral biceps tenodesis. There was significant improvement in patients’ functional outcome scores postoperatively [SANE (Single Assessment Numeric Evaluation), ASES (American Shoulder and Elbow Surgeons shoulder index), SST (Simple Shoulder Test), VAS (visual analog scale), and SF-12 (Short Form-12)]. In addition, 80% of patients were satisfied with their outcome. Mean age was 43.7 years. Forty-two percent of patients had a worker’s compensation claim. Interestingly, 15 patients in this cohort had a type I SLAP tear. Boileau and colleagues34 prospectively followed 25 cases of type II SLAP tear treated with either SLAP repair (10 patients; mean age, 37 years) or primary arthroscopic biceps tenodesis (15 patients; mean age, 52 years). Compared with the SLAP repair group, the biceps tenodesis group had significantly higher rates of satisfaction and return to previous level of sports participation. However, group assignments were nonrandomized, and the decision to treat a patient with SLAP repair versus biceps tenodesis was made by the senior surgeon purely on the basis of age (SLAP repair for patients under 30 years). Ek and colleagues36 retrospectively compared the cases of 10 patients who underwent SLAP repair (mean age, 32 years) and 15 who underwent biceps tenodesis (mean age, 47 years) for type II SLAP tear. There was no significant difference between the groups with respect to outcome scores, return to play or preinjury activity level, or complications.

There continues to be significant debate as to which patient will benefit from primary SLAP repair versus biceps tenodesis. Multiple factors are involved: age, presence of associated shoulder pathology, occupation, preinjury activity level, and worker’s compensation status. Age has convincingly been shown to affect the outcomes of treatment of type II SLAP tears.34,35,37-40 There is consensus that patients over age 40 years will benefit from primary biceps tenodesis for SLAP tears. However, the evidence for this recommendation is weak.

3. Biceps tenodesis and failed SLAP repair

The definition of a failed SLAP repair is not well documented in the literature, but dissatisfaction after SLAP repair can result from continued shoulder pain, poor shoulder function, or inability to return to preinjury functional level.15,41 The etiologic determination and treatment of a failed SLAP repair are challenging, and outcomes of revision SLAP repair are not very promising.42,43 Biceps tenodesis has been proposed as an alternative treatment to revision SLAP repair for failed SLAP repair. McCormick and colleagues41 prospectively evaluated 42 patients (mean age, 39.2 years; minimum follow-up, 2 years) with failed type II SLAP repairs that were treated with open subpectoral biceps tenodesis. There was significant improvement in ASES, SANE, and Western Ontario Shoulder Instability Index (WOSI) outcome scores and in postoperative shoulder range of motion at a mean follow-up of 3.6 years. One patient had transient musculocutaneous neurapraxia after surgery. In a retrospective cohort study, Gupta and colleagues44 found significant improvement in ASES, SANE, SST, SF-12, and VAS outcome scores in 11 patients who underwent open subpectoral biceps tenodesis for failed arthroscopic SLAP repair (mean age at surgery, 40 years; mean follow-up, 26 months). Three of the 11 patients had worker’s compensation claims, and there were no complications and no revision surgeries required after biceps tenodesis. Werner and colleagues16 retrospectively evaluated 17 patients who underwent biceps tenodesis for failed SLAP repair (mean age, 39 years; minimum follow-up, 2 years). Twenty-nine percent of patients had worker’s compensation claims. Compared with the contralateral shoulder, the treated shoulder had better postoperative ASES, SANE, SST, and Veteran RAND 36-item health survey outcome scores; range of motion was near normal.

There are no high-quality studies comparing revision SLAP repair and biceps tenodesis in the management of failed SLAP repair.16,41-44 Case series studies have found improved outcomes and pain relief after biceps tenodesis for failed SLAP repair, but the quality of evidence has been poor (level IV evidence).16,41-44 The senior author recommends treating failed SLAP repairs with biceps tenodesis.

4. Biceps tenodesis as treatment option for SLAP tear in overhead throwing athletes

Biceps tenodesis is a potential alternative treatment to SLAP repair in overhead throwing athletes. Although outcome scores and satisfaction rates after SLAP repair are high in overhead athletes, the rates of return to sport are relatively low, especially in baseball players.38,45-47 In a level III cohort study, Boileau and colleagues34 found that 13 (87%) of 15 patients with type II SLAP tears, including 8 overhead athletes, had returned to their previous level of activity by a mean of 30 months after biceps tenodesis. In contrast, only 2 of 10 patients returned to their previous level of activity after SLAP repair. Interestingly, 3 patients who underwent biceps tenodesis for failed SLAP repair returned to overhead sports. Schöffl and colleagues48 reported on the outcomes of biceps tenodesis for SLAP lesions in 6 high-level rock climbers. By a mean follow-up of 6 months, all 6 patients had returned to their previous level of climbing. Their satisfaction rate was 96.8%. Gupta and colleagues35 reported on a cohort of 28 patients who underwent biceps tenodesis for SLAP tears and concomitant biceps tendonitis. Of the 8 athletes in the group, 5 were able to return to their previous level of play, and 1 was able to return to a lower level of sporting activity. There was significant improvement from preoperative to postoperative scores on ASES, SST, SANE, VAS, SF-12 overall, and SF-12 components.

 

 

Chalmers and colleagues49 recently described motion analyses with simultaneous surface electromyographic measurements in 18 baseball pitchers. Of these 18 players, 7 were uninjured (controls), 6 were pitching after SLAP repair, and 5 were pitching after subpectoral biceps tenodesis. There were no significant differences between controls and postoperative patients with respect to pitching kinematics. Interestingly, compared with the controls and the patients who underwent open biceps tenodesis, the patients who underwent SLAP repair had altered patterns of thoracic rotation during pitching. However, the clinical significance of this finding and the impact of this finding on pitching efficacy are not currently known.

Biceps tenodesis as a primary procedure for type II SLAP lesion in an overhead athlete is a concept in evolution. Increasing evidence suggests a role for primary biceps tenodesis in an overhead athlete with type II SLAP lesion and concomitant biceps pathology. However, this evidence is of poor quality, and the strength of the recommendation is weak. Still to be determined is whether return to preinjury performance level is better with primary biceps tenodesis or with SLAP repair in overhead athletes with type II SLAP lesion. As per the senior author’s treatment algorithm, we prefer SLAP repair for overhead athletes with type II SLAP tears and reserve biceps tenodesis for cases involving significant biceps pathology and/or clinical symptoms involving the bicipital groove consistent with extra-articular biceps pain.

5. Biceps tenodesis for type II SLAP tear in contact athletes and occupations demanding heavy labor (blue-collar jobs)

SLAP tears are less common in contact athletes, and there is general agreement that SLAP repair outcomes are better in contact athletes than in overhead athletes. In a retrospective review of 18 rugby players with SLAP tears, Funk and Snow50 reported excellent results and quicker return to sport after SLAP repair. Patients with isolated SLAP tears had the earliest return to play. Enad and colleagues51 reported SLAP repair outcomes in an active military population. SLAP tears are more common in the military versus the general population because of the unique physical demands placed on military personnel. The authors retrospectively reviewed 27 cases of type II SLAP tears treated with SLAP repair and suture anchors. Outcomes were measured at a mean of 30.5 months after surgery. Twenty-four (89%) of the 27 patients had good to excellent results, and 94% had returned to active duty by a mean of 4.4 months after SLAP repair.

Given the poor-quality evidence in the literature, we believe that biceps tenodesis should be reserved for revision surgery in contact athletes. There is insufficient evidence to recommend biceps tenodesis as primary treatment for type II SLAP tears in contact athletes. SLAP repair should be performed for primary SLAP lesions in contact athletes and for patients in physically demanding professions (eg, military, laborer, weightlifter).

Conclusion

SLAP tears can result in persistent shoulder pain and dysfunction. SLAP tear management depends on lesion type and severity, age, and functional demands. SLAP repair is the treatment of choice for type II SLAP lesions in young, active patients. Biceps tenodesis is a preferred alternative to SLAP repair in failed SLAP repair and in type II SLAP patients who are older than 40 years and who are less active and have a worker’s compensation claim. These recommendations are based on poor-quality evidence. There is an unmet need for randomized clinical studies comparing SLAP repair with biceps tenodesis for type II SLAP tears in different patient populations so as to optimize the current decision-making algorithm for SLAP tears.

References

1.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

2.    Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopaedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.

3.    Snyder SJ, Karzel RP, Del Pizzo W, Ferkel RD, Friedman MJ. SLAP lesions of the shoulder. Arthroscopy. 1990;6(4):274-279.

4.    Morgan CD, Burkhart SS, Palmeri M, Gillespie M. Type II SLAP lesions: three subtypes and their relationships to superior instability and rotator cuff tears. Arthroscopy. 1998;14(6):553-565.

5.    Powell SE, Nord KD, Ryu RKN. The diagnosis, classification, and treatment of SLAP lesions. Oper Tech Sports Med. 2012;20(1):46-56.

6.    Maffet MW, Gartsman GM, Moseley B. Superior labrum-biceps tendon complex lesions of the shoulder. Am J Sports Med. 1995;23(1):93-98.

7.    Kim TK, Queale WS, Cosgarea AJ, McFarland EG. Clinical features of the different types of SLAP lesions: an analysis of one hundred and thirty-nine cases. J Bone Joint Surg Am. 2003;85(1):66-71.

8.    Abrams GD, Safran MR. Diagnosis and management of superior labrum anterior posterior lesions in overhead athletes. Br J Sports Med. 2010;44(5):311-318.

9.    Keener JD, Brophy RH. Superior labral tears of the shoulder: pathogenesis, evaluation, and treatment. J Am Acad Orthop Surg. 2009;17(10):627-637.

10. Abrams GD, Hussey KE, Harris JD, Cole BJ. Clinical results of combined meniscus and femoral osteochondral allograft transplantation: minimum 2-year follow-up. Arthroscopy. 2014;30(8):964-970.e1.

11. Burkhart SS, Morgan CD, Kibler WB. The disabled throwing shoulder: spectrum of pathology part I: pathoanatomy and biomechanics. Arthroscopy. 2003;19(4):404-420.

12. Virk MS, Arciero RA. Superior labrum anterior to posterior tears and glenohumeral instability. Instr Course Lect. 2013;62:501-514.

13. Calvert E, Chambers GK, Regan W, Hawkins RH, Leith JM. Special physical examination tests for superior labrum anterior posterior shoulder tears are clinically limited and invalid: a diagnostic systematic review. J Clin Epidemiol. 2009;62(5):558-563.

14. Jones GL, Galluch DB. Clinical assessment of superior glenoid labral lesions: a systematic review. Clin Orthop Relat Res. 2007;455:45-51.

15. Werner BC, Brockmeier SF, Miller MD. Etiology, diagnosis, and management of failed SLAP repair. J Am Acad Orthop Surg. 2014;22(9):554-565.

16. Werner BC, Pehlivan HC, Hart JM, et al. Biceps tenodesis is a viable option for salvage of failed SLAP repair. J Shoulder Elbow Surg. 2014;23(8):e179-e184.

17. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.

18. Huri G, Hyun YS, Garbis NG, McFarland EG. Treatment of superior labrum anterior posterior lesions: a literature review. Acta Orthop Traumatol Turc. 2014;48(3):290-297.

19. Li X, Lin TJ, Jager M, et al. Management of type II superior labrum anterior posterior lesions: a review of the literature. Orthop Rev. 2010;2(1):e6.

20. Cooper DE, Arnoczky SP, O’Brien SJ, Warren RF, DiCarlo E, Allen AA. Anatomy, histology, and vascularity of the glenoid labrum. An anatomical study. J Bone Joint Surg Am. 1992;74(1):46-52.

21. Vangsness CT, Jorgenson SS, Watson T, Johnson DL. The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. J Bone Joint Surg Br. 1994;76(6):951-954.

22. Strauss EJ, Salata MJ, Sershon RA, et al. Role of the superior labrum after biceps tenodesis in glenohumeral stability. J Shoulder Elbow Surg. 2014;23(4):485-491.

23. Pagnani MJ, Deng XH, Warren RF, Torzilli PA, Altchek DW. Effect of lesions of the superior portion of the glenoid labrum on glenohumeral translation. J Bone Joint Surg Am. 1995;77(7):1003-1010.

24. McMahon PJ, Burkart A, Musahl V, Debski RE. Glenohumeral translations are increased after a type II superior labrum anterior-posterior lesion: a cadaveric study of severity of passive stabilizer injury. J Shoulder Elbow Surg. 2004;13(1):39-44.

25. Burkart A, Debski R, Musahl V, McMahon P, Woo SL. Biomechanical tests for type II SLAP lesions of the shoulder joint before and after arthroscopic repair [in German]. Orthopade. 2003;32(7):600-607.

26. Panossian VR, Mihata T, Tibone JE, Fitzpatrick MJ, McGarry MH, Lee TQ. Biomechanical analysis of isolated type II SLAP lesions and repair. J Shoulder Elbow Surg. 2005;14(5):529-534.

27. Mihata T, McGarry MH, Tibone JE, Fitzpatrick MJ, Kinoshita M, Lee TQ. Biomechanical assessment of type II superior labral anterior-posterior (SLAP) lesions associated with anterior shoulder capsular laxity as seen in throwers: a cadaveric study. Am J Sports Med. 2008;36(8):1604-1610.

28. Youm T, Tibone JE, ElAttrache NS, McGarry MH, Lee TQ. Simulated type II superior labral anterior posterior lesions do not alter the path of glenohumeral articulation: a cadaveric biomechanical study. Am J Sports Med. 2008;36(4):767-774.

29. Youm T, ElAttrache NS, Tibone JE, McGarry MH, Lee TQ. The effect of the long head of the biceps on glenohumeral kinematics. J Shoulder Elbow Surg. 2009;18(1):122-129.

30. McGarry MH, Nguyen ML, Quigley RJ, Hanypsiak B, Gupta R, Lee TQ. The effect of long and short head biceps loading on glenohumeral joint rotational range of motion and humeral head position [published online ahead of print September 26, 2014]. Knee Surg Sports Traumatol Arthrosc.

31. Glousman R, Jobe F, Tibone J, Moynes D, Antonelli D, Perry J. Dynamic electromyographic analysis of the throwing shoulder with glenohumeral instability. J Bone Joint Surg Am. 1988;70(2):220-226.

32. Gowan ID, Jobe FW, Tibone JE, Perry J, Moynes DR. A comparative electromyographic analysis of the shoulder during pitching. Professional versus amateur pitchers. Am J Sports Med. 1987;15(6):586-590.

33. Rodosky MW, Harner CD, Fu FH. The role of the long head of the biceps muscle and superior glenoid labrum in anterior stability of the shoulder. Am J Sports Med. 1994;22(1):121-130.

34. Boileau P, Parratte S, Chuinard C, Roussanne Y, Shia D, Bicknell R. Arthroscopic treatment of isolated type II SLAP lesions: biceps tenodesis as an alternative to reinsertion. Am J Sports Med. 2009;37(5):929-936.

35. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.

36. Ek ET, Shi LL, Tompson JD, Freehill MT, Warner JJ. Surgical treatment of isolated type II superior labrum anterior-posterior (SLAP) lesions: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2014;23(7):1059-1065.

37. Alpert JM, Wuerz TH, O’Donnell TF, Carroll KM, Brucker NN, Gill TJ. The effect of age on the outcomes of arthroscopic repair of type II superior labral anterior and posterior lesions. Am J Sports Med. 2010;38(11):2299-2303.

38. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.

39. Denard PJ, Lädermann A, Burkhart SS. Long-term outcome after arthroscopic repair of type II SLAP lesions: results according to age and workers’ compensation status. Arthroscopy. 2012;28(4):451-457.

40. Burns JP, Bahk M, Snyder SJ. Superior labral tears: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2011;20(2 suppl):S2-S8.

41. McCormick F, Nwachukwu BU, Solomon D, et al. The efficacy of biceps tenodesis in the treatment of failed superior labral anterior posterior repairs. Am J Sports Med. 2014;42(4):820-825.

42. Katz LM, Hsu S, Miller SL, et al. Poor outcomes after SLAP repair: descriptive analysis and prognosis. Arthroscopy. 2009;25(8):849-855.

43. Park S, Glousman RE. Outcomes of revision arthroscopic type II superior labral anterior posterior repairs. Am J Sports Med. 2011;39(6):1290-1294.

44. Gupta AK, Bruce B, Klosterman EL, McCormick F, Harris J, Romeo AA. Subpectoral biceps tenodesis for failed type II SLAP repair. Orthopedics. 2013;36(6):e723-e728.

45. Neuman BJ, Boisvert CB, Reiter B, Lawson K, Ciccotti MG, Cohen SB. Results of arthroscopic repair of type II superior labral anterior posterior lesions in overhead athletes: assessment of return to preinjury playing level and satisfaction. Am J Sports Med. 2011;39(9):1883-1888.

46. Fedoriw WW, Ramkumar P, McCulloch PC, Lintner DM. Return to play after treatment of superior labral tears in professional baseball players. Am J Sports Med. 2014;42(5):1155-1160.

47. Park JY, Chung SW, Jeon SH, Lee JG, Oh KS. Clinical and radiological outcomes of type 2 superior labral anterior posterior repairs in elite overhead athletes. Am J Sports Med. 2013;41(6):1372-1379.

48. Schöffl V, Popp D, Dickschass J, Küpper T. Superior labral anterior-posterior lesions in rock climbers—primary double tenodesis? Clin J Sport Med. 2011;21(3):261-263.

49. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.

50. Funk L, Snow M. SLAP tears of the glenoid labrum in contact athletes. Clin J Sport Med. 2007;17(1):1-4.

51.  Enad JG, Gaines RJ, White SM, Kurtz CA. Arthroscopic superior labrum anterior-posterior repair in military patients. J Shoulder Elbow Surg. 2007;16(3):300-305.

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Mandeep S. Virk, MD, Annemarie K. Tilton, BS, and Brian J. Cole, MD, MBA

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Mandeep S. Virk, MD, Annemarie K. Tilton, BS, and Brian J. Cole, MD, MBA

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Injuries of the superior labrum–biceps complex (SLBC) have been recognized as a cause of shoulder pain since they were first described by Andrews and colleagues1 in 1985. Superior labrum anterior to posterior (SLAP) tears are relatively uncommon injuries of the shoulder, and their true incidence is difficult to establish. However, recently there has been a significant increase in the reported incidence and operative treatment of SLAP tears.2 SLAP tears can occur in isolation, but they are commonly seen in association with other shoulder lesions, including rotator cuff tear, Bankart lesion, glenohumeral arthritis, acromioclavicular joint pathology, and subacromial impingement.

Although SLAP tears are well described and classified,3-6 our understanding of symptomatic SLAP tears and of their contribution to glenohumeral instability is limited. Diagnosing a SLAP tear on the basis of history and physical examination is a clinical challenge. Pain is the most common presentation of SLAP tears, though localization and characterization of pain are variable and nonspecific.7 The mechanism of injury is helpful in acute presentation (traction injury; fall on outstretched, abducted arm), but an overhead athlete may present with no distinct mechanism other than chronic, repetitive use of the shoulder.8-11 Numerous provocative physical examination tests have been used to assist in the diagnosis of SLAP tear, yet there is no consensus regarding the ideal physical examination test, with high sensitivity, specificity, and accuracy.12-14 Magnetic resonance arthrography, the gold standard imaging modality, is highly sensitive and specific (>95%) for diagnosing SLAP tears.

SLAP tear management is based on lesion type and severity, age, functional demands, and presence of coexisting intra-articular lesions. Management options include nonoperative treatment, débridement or repair of SLBC, biceps tenotomy, and biceps tenodesis.15-19

In this 5-point review, we present an evidence-based analysis of the role of the SLBC in glenohumeral stability and the role of biceps tenodesis in the management of SLAP tears.

1. Role of SLBC in stability of glenohumeral joint

The anatomy of the SLBC has been well described,20,21 and there is consensus that SLBC pathology can be a source of shoulder pain. The superior labrum is relatively more mobile than the rest of the glenoid labrum, and it provides attachment to the long head of the biceps tendon (LHBT) and the superior glenohumeral and middle glenohumeral ligaments.

The functional role of the SLBC in glenohumeral stability and its contribution to the pathogenesis of shoulder instability are not clearly defined. Our understanding of SLBC function is largely derived from simulated cadaveric experiments of SLAP tears. Controlled laboratory studies with simulated type II SLAP tears in cadavers have shown significantly increased glenohumeral translation in the anterior-posterior and superior-inferior directions, suggesting a role of the superior labrum in maintaining glenohumeral stability.22-26 Interestingly, there is conflicting evidence regarding restoration of normal glenohumeral translation in cadaveric shoulders after repair of simulated SLAP lesions in the presence or absence of simulated anterior capsular laxity.22,25-27 However, it is important to understand the limitations of cadaveric experiments in order to appreciate and truly comprehend the results of these experiments. There are inconsistencies in the size of simulated type II SLAP lesions in different studies, which can affect the degree of glenohumeral translation and the results of repair.23-25,28 The amount of glenohumeral translation noticed after simulated SLAP tears in cadavers, though statistically significant, is small in amplitude, and its relevance may not translate to a clinically significant level. The impact of dynamic components of stability (eg, rotator cuff muscles), capsular stretch, and other in vivo variables that affect glenohumeral stability are unaccounted for during cadaveric experiments.

LHBT is a recognized cause of shoulder pain, but its contribution to shoulder stability is a point of continued debate. According to one school of thought, LHBT is a vestigial structure that can be sacrificed without any loss of stability. Another school of thought holds that LHBT is an important active stabilizer of the glenohumeral joint. Cadaveric studies have demonstrated that loading the LHBT decreases glenohumeral translation and rotational range of motion, especially in lower and mid ranges of abduction.23,29,30 Furthermore, LHBT contributes to anterior glenohumeral stability by resisting torsional forces in the abducted and externally rotated shoulder and reducing stress on the inferior glenohumeral ligaments.31-33 Strauss and colleagues22 recently found that simulated anterior and posterior type II SLAP lesions in cadaveric shoulders increased glenohumeral translation in all planes, and biceps tenodesis did not further worsen this abnormal glenohumeral translation. Furthermore, repair of posterior SLAP lesions along with biceps tenodesis restored abnormal glenohumeral translation with no significant difference from the baseline in any plane of motion. Again, the limitations of cadaveric studies should be considered when interpreting these results and applying them clinically.

 

 

2. Biceps tenodesis as primary treatment for SLAP tears

A growing body of evidence suggests that primary tenodesis of LHBT may be an effective alternative treatment to SLAP repairs in select patients.34-36 However, the evidence is weak, and high-quality studies comparing SLAP repair and primary biceps tenodesis are required in order to make a strong recommendation for one technique over another. Gupta and colleagues35 retrospectively analyzed 28 cases of concomitant SLAP tear and biceps tendonitis treated with primary open subpectoral biceps tenodesis. There was significant improvement in patients’ functional outcome scores postoperatively [SANE (Single Assessment Numeric Evaluation), ASES (American Shoulder and Elbow Surgeons shoulder index), SST (Simple Shoulder Test), VAS (visual analog scale), and SF-12 (Short Form-12)]. In addition, 80% of patients were satisfied with their outcome. Mean age was 43.7 years. Forty-two percent of patients had a worker’s compensation claim. Interestingly, 15 patients in this cohort had a type I SLAP tear. Boileau and colleagues34 prospectively followed 25 cases of type II SLAP tear treated with either SLAP repair (10 patients; mean age, 37 years) or primary arthroscopic biceps tenodesis (15 patients; mean age, 52 years). Compared with the SLAP repair group, the biceps tenodesis group had significantly higher rates of satisfaction and return to previous level of sports participation. However, group assignments were nonrandomized, and the decision to treat a patient with SLAP repair versus biceps tenodesis was made by the senior surgeon purely on the basis of age (SLAP repair for patients under 30 years). Ek and colleagues36 retrospectively compared the cases of 10 patients who underwent SLAP repair (mean age, 32 years) and 15 who underwent biceps tenodesis (mean age, 47 years) for type II SLAP tear. There was no significant difference between the groups with respect to outcome scores, return to play or preinjury activity level, or complications.

There continues to be significant debate as to which patient will benefit from primary SLAP repair versus biceps tenodesis. Multiple factors are involved: age, presence of associated shoulder pathology, occupation, preinjury activity level, and worker’s compensation status. Age has convincingly been shown to affect the outcomes of treatment of type II SLAP tears.34,35,37-40 There is consensus that patients over age 40 years will benefit from primary biceps tenodesis for SLAP tears. However, the evidence for this recommendation is weak.

3. Biceps tenodesis and failed SLAP repair

The definition of a failed SLAP repair is not well documented in the literature, but dissatisfaction after SLAP repair can result from continued shoulder pain, poor shoulder function, or inability to return to preinjury functional level.15,41 The etiologic determination and treatment of a failed SLAP repair are challenging, and outcomes of revision SLAP repair are not very promising.42,43 Biceps tenodesis has been proposed as an alternative treatment to revision SLAP repair for failed SLAP repair. McCormick and colleagues41 prospectively evaluated 42 patients (mean age, 39.2 years; minimum follow-up, 2 years) with failed type II SLAP repairs that were treated with open subpectoral biceps tenodesis. There was significant improvement in ASES, SANE, and Western Ontario Shoulder Instability Index (WOSI) outcome scores and in postoperative shoulder range of motion at a mean follow-up of 3.6 years. One patient had transient musculocutaneous neurapraxia after surgery. In a retrospective cohort study, Gupta and colleagues44 found significant improvement in ASES, SANE, SST, SF-12, and VAS outcome scores in 11 patients who underwent open subpectoral biceps tenodesis for failed arthroscopic SLAP repair (mean age at surgery, 40 years; mean follow-up, 26 months). Three of the 11 patients had worker’s compensation claims, and there were no complications and no revision surgeries required after biceps tenodesis. Werner and colleagues16 retrospectively evaluated 17 patients who underwent biceps tenodesis for failed SLAP repair (mean age, 39 years; minimum follow-up, 2 years). Twenty-nine percent of patients had worker’s compensation claims. Compared with the contralateral shoulder, the treated shoulder had better postoperative ASES, SANE, SST, and Veteran RAND 36-item health survey outcome scores; range of motion was near normal.

There are no high-quality studies comparing revision SLAP repair and biceps tenodesis in the management of failed SLAP repair.16,41-44 Case series studies have found improved outcomes and pain relief after biceps tenodesis for failed SLAP repair, but the quality of evidence has been poor (level IV evidence).16,41-44 The senior author recommends treating failed SLAP repairs with biceps tenodesis.

4. Biceps tenodesis as treatment option for SLAP tear in overhead throwing athletes

Biceps tenodesis is a potential alternative treatment to SLAP repair in overhead throwing athletes. Although outcome scores and satisfaction rates after SLAP repair are high in overhead athletes, the rates of return to sport are relatively low, especially in baseball players.38,45-47 In a level III cohort study, Boileau and colleagues34 found that 13 (87%) of 15 patients with type II SLAP tears, including 8 overhead athletes, had returned to their previous level of activity by a mean of 30 months after biceps tenodesis. In contrast, only 2 of 10 patients returned to their previous level of activity after SLAP repair. Interestingly, 3 patients who underwent biceps tenodesis for failed SLAP repair returned to overhead sports. Schöffl and colleagues48 reported on the outcomes of biceps tenodesis for SLAP lesions in 6 high-level rock climbers. By a mean follow-up of 6 months, all 6 patients had returned to their previous level of climbing. Their satisfaction rate was 96.8%. Gupta and colleagues35 reported on a cohort of 28 patients who underwent biceps tenodesis for SLAP tears and concomitant biceps tendonitis. Of the 8 athletes in the group, 5 were able to return to their previous level of play, and 1 was able to return to a lower level of sporting activity. There was significant improvement from preoperative to postoperative scores on ASES, SST, SANE, VAS, SF-12 overall, and SF-12 components.

 

 

Chalmers and colleagues49 recently described motion analyses with simultaneous surface electromyographic measurements in 18 baseball pitchers. Of these 18 players, 7 were uninjured (controls), 6 were pitching after SLAP repair, and 5 were pitching after subpectoral biceps tenodesis. There were no significant differences between controls and postoperative patients with respect to pitching kinematics. Interestingly, compared with the controls and the patients who underwent open biceps tenodesis, the patients who underwent SLAP repair had altered patterns of thoracic rotation during pitching. However, the clinical significance of this finding and the impact of this finding on pitching efficacy are not currently known.

Biceps tenodesis as a primary procedure for type II SLAP lesion in an overhead athlete is a concept in evolution. Increasing evidence suggests a role for primary biceps tenodesis in an overhead athlete with type II SLAP lesion and concomitant biceps pathology. However, this evidence is of poor quality, and the strength of the recommendation is weak. Still to be determined is whether return to preinjury performance level is better with primary biceps tenodesis or with SLAP repair in overhead athletes with type II SLAP lesion. As per the senior author’s treatment algorithm, we prefer SLAP repair for overhead athletes with type II SLAP tears and reserve biceps tenodesis for cases involving significant biceps pathology and/or clinical symptoms involving the bicipital groove consistent with extra-articular biceps pain.

5. Biceps tenodesis for type II SLAP tear in contact athletes and occupations demanding heavy labor (blue-collar jobs)

SLAP tears are less common in contact athletes, and there is general agreement that SLAP repair outcomes are better in contact athletes than in overhead athletes. In a retrospective review of 18 rugby players with SLAP tears, Funk and Snow50 reported excellent results and quicker return to sport after SLAP repair. Patients with isolated SLAP tears had the earliest return to play. Enad and colleagues51 reported SLAP repair outcomes in an active military population. SLAP tears are more common in the military versus the general population because of the unique physical demands placed on military personnel. The authors retrospectively reviewed 27 cases of type II SLAP tears treated with SLAP repair and suture anchors. Outcomes were measured at a mean of 30.5 months after surgery. Twenty-four (89%) of the 27 patients had good to excellent results, and 94% had returned to active duty by a mean of 4.4 months after SLAP repair.

Given the poor-quality evidence in the literature, we believe that biceps tenodesis should be reserved for revision surgery in contact athletes. There is insufficient evidence to recommend biceps tenodesis as primary treatment for type II SLAP tears in contact athletes. SLAP repair should be performed for primary SLAP lesions in contact athletes and for patients in physically demanding professions (eg, military, laborer, weightlifter).

Conclusion

SLAP tears can result in persistent shoulder pain and dysfunction. SLAP tear management depends on lesion type and severity, age, and functional demands. SLAP repair is the treatment of choice for type II SLAP lesions in young, active patients. Biceps tenodesis is a preferred alternative to SLAP repair in failed SLAP repair and in type II SLAP patients who are older than 40 years and who are less active and have a worker’s compensation claim. These recommendations are based on poor-quality evidence. There is an unmet need for randomized clinical studies comparing SLAP repair with biceps tenodesis for type II SLAP tears in different patient populations so as to optimize the current decision-making algorithm for SLAP tears.

Injuries of the superior labrum–biceps complex (SLBC) have been recognized as a cause of shoulder pain since they were first described by Andrews and colleagues1 in 1985. Superior labrum anterior to posterior (SLAP) tears are relatively uncommon injuries of the shoulder, and their true incidence is difficult to establish. However, recently there has been a significant increase in the reported incidence and operative treatment of SLAP tears.2 SLAP tears can occur in isolation, but they are commonly seen in association with other shoulder lesions, including rotator cuff tear, Bankart lesion, glenohumeral arthritis, acromioclavicular joint pathology, and subacromial impingement.

Although SLAP tears are well described and classified,3-6 our understanding of symptomatic SLAP tears and of their contribution to glenohumeral instability is limited. Diagnosing a SLAP tear on the basis of history and physical examination is a clinical challenge. Pain is the most common presentation of SLAP tears, though localization and characterization of pain are variable and nonspecific.7 The mechanism of injury is helpful in acute presentation (traction injury; fall on outstretched, abducted arm), but an overhead athlete may present with no distinct mechanism other than chronic, repetitive use of the shoulder.8-11 Numerous provocative physical examination tests have been used to assist in the diagnosis of SLAP tear, yet there is no consensus regarding the ideal physical examination test, with high sensitivity, specificity, and accuracy.12-14 Magnetic resonance arthrography, the gold standard imaging modality, is highly sensitive and specific (>95%) for diagnosing SLAP tears.

SLAP tear management is based on lesion type and severity, age, functional demands, and presence of coexisting intra-articular lesions. Management options include nonoperative treatment, débridement or repair of SLBC, biceps tenotomy, and biceps tenodesis.15-19

In this 5-point review, we present an evidence-based analysis of the role of the SLBC in glenohumeral stability and the role of biceps tenodesis in the management of SLAP tears.

1. Role of SLBC in stability of glenohumeral joint

The anatomy of the SLBC has been well described,20,21 and there is consensus that SLBC pathology can be a source of shoulder pain. The superior labrum is relatively more mobile than the rest of the glenoid labrum, and it provides attachment to the long head of the biceps tendon (LHBT) and the superior glenohumeral and middle glenohumeral ligaments.

The functional role of the SLBC in glenohumeral stability and its contribution to the pathogenesis of shoulder instability are not clearly defined. Our understanding of SLBC function is largely derived from simulated cadaveric experiments of SLAP tears. Controlled laboratory studies with simulated type II SLAP tears in cadavers have shown significantly increased glenohumeral translation in the anterior-posterior and superior-inferior directions, suggesting a role of the superior labrum in maintaining glenohumeral stability.22-26 Interestingly, there is conflicting evidence regarding restoration of normal glenohumeral translation in cadaveric shoulders after repair of simulated SLAP lesions in the presence or absence of simulated anterior capsular laxity.22,25-27 However, it is important to understand the limitations of cadaveric experiments in order to appreciate and truly comprehend the results of these experiments. There are inconsistencies in the size of simulated type II SLAP lesions in different studies, which can affect the degree of glenohumeral translation and the results of repair.23-25,28 The amount of glenohumeral translation noticed after simulated SLAP tears in cadavers, though statistically significant, is small in amplitude, and its relevance may not translate to a clinically significant level. The impact of dynamic components of stability (eg, rotator cuff muscles), capsular stretch, and other in vivo variables that affect glenohumeral stability are unaccounted for during cadaveric experiments.

LHBT is a recognized cause of shoulder pain, but its contribution to shoulder stability is a point of continued debate. According to one school of thought, LHBT is a vestigial structure that can be sacrificed without any loss of stability. Another school of thought holds that LHBT is an important active stabilizer of the glenohumeral joint. Cadaveric studies have demonstrated that loading the LHBT decreases glenohumeral translation and rotational range of motion, especially in lower and mid ranges of abduction.23,29,30 Furthermore, LHBT contributes to anterior glenohumeral stability by resisting torsional forces in the abducted and externally rotated shoulder and reducing stress on the inferior glenohumeral ligaments.31-33 Strauss and colleagues22 recently found that simulated anterior and posterior type II SLAP lesions in cadaveric shoulders increased glenohumeral translation in all planes, and biceps tenodesis did not further worsen this abnormal glenohumeral translation. Furthermore, repair of posterior SLAP lesions along with biceps tenodesis restored abnormal glenohumeral translation with no significant difference from the baseline in any plane of motion. Again, the limitations of cadaveric studies should be considered when interpreting these results and applying them clinically.

 

 

2. Biceps tenodesis as primary treatment for SLAP tears

A growing body of evidence suggests that primary tenodesis of LHBT may be an effective alternative treatment to SLAP repairs in select patients.34-36 However, the evidence is weak, and high-quality studies comparing SLAP repair and primary biceps tenodesis are required in order to make a strong recommendation for one technique over another. Gupta and colleagues35 retrospectively analyzed 28 cases of concomitant SLAP tear and biceps tendonitis treated with primary open subpectoral biceps tenodesis. There was significant improvement in patients’ functional outcome scores postoperatively [SANE (Single Assessment Numeric Evaluation), ASES (American Shoulder and Elbow Surgeons shoulder index), SST (Simple Shoulder Test), VAS (visual analog scale), and SF-12 (Short Form-12)]. In addition, 80% of patients were satisfied with their outcome. Mean age was 43.7 years. Forty-two percent of patients had a worker’s compensation claim. Interestingly, 15 patients in this cohort had a type I SLAP tear. Boileau and colleagues34 prospectively followed 25 cases of type II SLAP tear treated with either SLAP repair (10 patients; mean age, 37 years) or primary arthroscopic biceps tenodesis (15 patients; mean age, 52 years). Compared with the SLAP repair group, the biceps tenodesis group had significantly higher rates of satisfaction and return to previous level of sports participation. However, group assignments were nonrandomized, and the decision to treat a patient with SLAP repair versus biceps tenodesis was made by the senior surgeon purely on the basis of age (SLAP repair for patients under 30 years). Ek and colleagues36 retrospectively compared the cases of 10 patients who underwent SLAP repair (mean age, 32 years) and 15 who underwent biceps tenodesis (mean age, 47 years) for type II SLAP tear. There was no significant difference between the groups with respect to outcome scores, return to play or preinjury activity level, or complications.

There continues to be significant debate as to which patient will benefit from primary SLAP repair versus biceps tenodesis. Multiple factors are involved: age, presence of associated shoulder pathology, occupation, preinjury activity level, and worker’s compensation status. Age has convincingly been shown to affect the outcomes of treatment of type II SLAP tears.34,35,37-40 There is consensus that patients over age 40 years will benefit from primary biceps tenodesis for SLAP tears. However, the evidence for this recommendation is weak.

3. Biceps tenodesis and failed SLAP repair

The definition of a failed SLAP repair is not well documented in the literature, but dissatisfaction after SLAP repair can result from continued shoulder pain, poor shoulder function, or inability to return to preinjury functional level.15,41 The etiologic determination and treatment of a failed SLAP repair are challenging, and outcomes of revision SLAP repair are not very promising.42,43 Biceps tenodesis has been proposed as an alternative treatment to revision SLAP repair for failed SLAP repair. McCormick and colleagues41 prospectively evaluated 42 patients (mean age, 39.2 years; minimum follow-up, 2 years) with failed type II SLAP repairs that were treated with open subpectoral biceps tenodesis. There was significant improvement in ASES, SANE, and Western Ontario Shoulder Instability Index (WOSI) outcome scores and in postoperative shoulder range of motion at a mean follow-up of 3.6 years. One patient had transient musculocutaneous neurapraxia after surgery. In a retrospective cohort study, Gupta and colleagues44 found significant improvement in ASES, SANE, SST, SF-12, and VAS outcome scores in 11 patients who underwent open subpectoral biceps tenodesis for failed arthroscopic SLAP repair (mean age at surgery, 40 years; mean follow-up, 26 months). Three of the 11 patients had worker’s compensation claims, and there were no complications and no revision surgeries required after biceps tenodesis. Werner and colleagues16 retrospectively evaluated 17 patients who underwent biceps tenodesis for failed SLAP repair (mean age, 39 years; minimum follow-up, 2 years). Twenty-nine percent of patients had worker’s compensation claims. Compared with the contralateral shoulder, the treated shoulder had better postoperative ASES, SANE, SST, and Veteran RAND 36-item health survey outcome scores; range of motion was near normal.

There are no high-quality studies comparing revision SLAP repair and biceps tenodesis in the management of failed SLAP repair.16,41-44 Case series studies have found improved outcomes and pain relief after biceps tenodesis for failed SLAP repair, but the quality of evidence has been poor (level IV evidence).16,41-44 The senior author recommends treating failed SLAP repairs with biceps tenodesis.

4. Biceps tenodesis as treatment option for SLAP tear in overhead throwing athletes

Biceps tenodesis is a potential alternative treatment to SLAP repair in overhead throwing athletes. Although outcome scores and satisfaction rates after SLAP repair are high in overhead athletes, the rates of return to sport are relatively low, especially in baseball players.38,45-47 In a level III cohort study, Boileau and colleagues34 found that 13 (87%) of 15 patients with type II SLAP tears, including 8 overhead athletes, had returned to their previous level of activity by a mean of 30 months after biceps tenodesis. In contrast, only 2 of 10 patients returned to their previous level of activity after SLAP repair. Interestingly, 3 patients who underwent biceps tenodesis for failed SLAP repair returned to overhead sports. Schöffl and colleagues48 reported on the outcomes of biceps tenodesis for SLAP lesions in 6 high-level rock climbers. By a mean follow-up of 6 months, all 6 patients had returned to their previous level of climbing. Their satisfaction rate was 96.8%. Gupta and colleagues35 reported on a cohort of 28 patients who underwent biceps tenodesis for SLAP tears and concomitant biceps tendonitis. Of the 8 athletes in the group, 5 were able to return to their previous level of play, and 1 was able to return to a lower level of sporting activity. There was significant improvement from preoperative to postoperative scores on ASES, SST, SANE, VAS, SF-12 overall, and SF-12 components.

 

 

Chalmers and colleagues49 recently described motion analyses with simultaneous surface electromyographic measurements in 18 baseball pitchers. Of these 18 players, 7 were uninjured (controls), 6 were pitching after SLAP repair, and 5 were pitching after subpectoral biceps tenodesis. There were no significant differences between controls and postoperative patients with respect to pitching kinematics. Interestingly, compared with the controls and the patients who underwent open biceps tenodesis, the patients who underwent SLAP repair had altered patterns of thoracic rotation during pitching. However, the clinical significance of this finding and the impact of this finding on pitching efficacy are not currently known.

Biceps tenodesis as a primary procedure for type II SLAP lesion in an overhead athlete is a concept in evolution. Increasing evidence suggests a role for primary biceps tenodesis in an overhead athlete with type II SLAP lesion and concomitant biceps pathology. However, this evidence is of poor quality, and the strength of the recommendation is weak. Still to be determined is whether return to preinjury performance level is better with primary biceps tenodesis or with SLAP repair in overhead athletes with type II SLAP lesion. As per the senior author’s treatment algorithm, we prefer SLAP repair for overhead athletes with type II SLAP tears and reserve biceps tenodesis for cases involving significant biceps pathology and/or clinical symptoms involving the bicipital groove consistent with extra-articular biceps pain.

5. Biceps tenodesis for type II SLAP tear in contact athletes and occupations demanding heavy labor (blue-collar jobs)

SLAP tears are less common in contact athletes, and there is general agreement that SLAP repair outcomes are better in contact athletes than in overhead athletes. In a retrospective review of 18 rugby players with SLAP tears, Funk and Snow50 reported excellent results and quicker return to sport after SLAP repair. Patients with isolated SLAP tears had the earliest return to play. Enad and colleagues51 reported SLAP repair outcomes in an active military population. SLAP tears are more common in the military versus the general population because of the unique physical demands placed on military personnel. The authors retrospectively reviewed 27 cases of type II SLAP tears treated with SLAP repair and suture anchors. Outcomes were measured at a mean of 30.5 months after surgery. Twenty-four (89%) of the 27 patients had good to excellent results, and 94% had returned to active duty by a mean of 4.4 months after SLAP repair.

Given the poor-quality evidence in the literature, we believe that biceps tenodesis should be reserved for revision surgery in contact athletes. There is insufficient evidence to recommend biceps tenodesis as primary treatment for type II SLAP tears in contact athletes. SLAP repair should be performed for primary SLAP lesions in contact athletes and for patients in physically demanding professions (eg, military, laborer, weightlifter).

Conclusion

SLAP tears can result in persistent shoulder pain and dysfunction. SLAP tear management depends on lesion type and severity, age, and functional demands. SLAP repair is the treatment of choice for type II SLAP lesions in young, active patients. Biceps tenodesis is a preferred alternative to SLAP repair in failed SLAP repair and in type II SLAP patients who are older than 40 years and who are less active and have a worker’s compensation claim. These recommendations are based on poor-quality evidence. There is an unmet need for randomized clinical studies comparing SLAP repair with biceps tenodesis for type II SLAP tears in different patient populations so as to optimize the current decision-making algorithm for SLAP tears.

References

1.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

2.    Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopaedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.

3.    Snyder SJ, Karzel RP, Del Pizzo W, Ferkel RD, Friedman MJ. SLAP lesions of the shoulder. Arthroscopy. 1990;6(4):274-279.

4.    Morgan CD, Burkhart SS, Palmeri M, Gillespie M. Type II SLAP lesions: three subtypes and their relationships to superior instability and rotator cuff tears. Arthroscopy. 1998;14(6):553-565.

5.    Powell SE, Nord KD, Ryu RKN. The diagnosis, classification, and treatment of SLAP lesions. Oper Tech Sports Med. 2012;20(1):46-56.

6.    Maffet MW, Gartsman GM, Moseley B. Superior labrum-biceps tendon complex lesions of the shoulder. Am J Sports Med. 1995;23(1):93-98.

7.    Kim TK, Queale WS, Cosgarea AJ, McFarland EG. Clinical features of the different types of SLAP lesions: an analysis of one hundred and thirty-nine cases. J Bone Joint Surg Am. 2003;85(1):66-71.

8.    Abrams GD, Safran MR. Diagnosis and management of superior labrum anterior posterior lesions in overhead athletes. Br J Sports Med. 2010;44(5):311-318.

9.    Keener JD, Brophy RH. Superior labral tears of the shoulder: pathogenesis, evaluation, and treatment. J Am Acad Orthop Surg. 2009;17(10):627-637.

10. Abrams GD, Hussey KE, Harris JD, Cole BJ. Clinical results of combined meniscus and femoral osteochondral allograft transplantation: minimum 2-year follow-up. Arthroscopy. 2014;30(8):964-970.e1.

11. Burkhart SS, Morgan CD, Kibler WB. The disabled throwing shoulder: spectrum of pathology part I: pathoanatomy and biomechanics. Arthroscopy. 2003;19(4):404-420.

12. Virk MS, Arciero RA. Superior labrum anterior to posterior tears and glenohumeral instability. Instr Course Lect. 2013;62:501-514.

13. Calvert E, Chambers GK, Regan W, Hawkins RH, Leith JM. Special physical examination tests for superior labrum anterior posterior shoulder tears are clinically limited and invalid: a diagnostic systematic review. J Clin Epidemiol. 2009;62(5):558-563.

14. Jones GL, Galluch DB. Clinical assessment of superior glenoid labral lesions: a systematic review. Clin Orthop Relat Res. 2007;455:45-51.

15. Werner BC, Brockmeier SF, Miller MD. Etiology, diagnosis, and management of failed SLAP repair. J Am Acad Orthop Surg. 2014;22(9):554-565.

16. Werner BC, Pehlivan HC, Hart JM, et al. Biceps tenodesis is a viable option for salvage of failed SLAP repair. J Shoulder Elbow Surg. 2014;23(8):e179-e184.

17. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.

18. Huri G, Hyun YS, Garbis NG, McFarland EG. Treatment of superior labrum anterior posterior lesions: a literature review. Acta Orthop Traumatol Turc. 2014;48(3):290-297.

19. Li X, Lin TJ, Jager M, et al. Management of type II superior labrum anterior posterior lesions: a review of the literature. Orthop Rev. 2010;2(1):e6.

20. Cooper DE, Arnoczky SP, O’Brien SJ, Warren RF, DiCarlo E, Allen AA. Anatomy, histology, and vascularity of the glenoid labrum. An anatomical study. J Bone Joint Surg Am. 1992;74(1):46-52.

21. Vangsness CT, Jorgenson SS, Watson T, Johnson DL. The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. J Bone Joint Surg Br. 1994;76(6):951-954.

22. Strauss EJ, Salata MJ, Sershon RA, et al. Role of the superior labrum after biceps tenodesis in glenohumeral stability. J Shoulder Elbow Surg. 2014;23(4):485-491.

23. Pagnani MJ, Deng XH, Warren RF, Torzilli PA, Altchek DW. Effect of lesions of the superior portion of the glenoid labrum on glenohumeral translation. J Bone Joint Surg Am. 1995;77(7):1003-1010.

24. McMahon PJ, Burkart A, Musahl V, Debski RE. Glenohumeral translations are increased after a type II superior labrum anterior-posterior lesion: a cadaveric study of severity of passive stabilizer injury. J Shoulder Elbow Surg. 2004;13(1):39-44.

25. Burkart A, Debski R, Musahl V, McMahon P, Woo SL. Biomechanical tests for type II SLAP lesions of the shoulder joint before and after arthroscopic repair [in German]. Orthopade. 2003;32(7):600-607.

26. Panossian VR, Mihata T, Tibone JE, Fitzpatrick MJ, McGarry MH, Lee TQ. Biomechanical analysis of isolated type II SLAP lesions and repair. J Shoulder Elbow Surg. 2005;14(5):529-534.

27. Mihata T, McGarry MH, Tibone JE, Fitzpatrick MJ, Kinoshita M, Lee TQ. Biomechanical assessment of type II superior labral anterior-posterior (SLAP) lesions associated with anterior shoulder capsular laxity as seen in throwers: a cadaveric study. Am J Sports Med. 2008;36(8):1604-1610.

28. Youm T, Tibone JE, ElAttrache NS, McGarry MH, Lee TQ. Simulated type II superior labral anterior posterior lesions do not alter the path of glenohumeral articulation: a cadaveric biomechanical study. Am J Sports Med. 2008;36(4):767-774.

29. Youm T, ElAttrache NS, Tibone JE, McGarry MH, Lee TQ. The effect of the long head of the biceps on glenohumeral kinematics. J Shoulder Elbow Surg. 2009;18(1):122-129.

30. McGarry MH, Nguyen ML, Quigley RJ, Hanypsiak B, Gupta R, Lee TQ. The effect of long and short head biceps loading on glenohumeral joint rotational range of motion and humeral head position [published online ahead of print September 26, 2014]. Knee Surg Sports Traumatol Arthrosc.

31. Glousman R, Jobe F, Tibone J, Moynes D, Antonelli D, Perry J. Dynamic electromyographic analysis of the throwing shoulder with glenohumeral instability. J Bone Joint Surg Am. 1988;70(2):220-226.

32. Gowan ID, Jobe FW, Tibone JE, Perry J, Moynes DR. A comparative electromyographic analysis of the shoulder during pitching. Professional versus amateur pitchers. Am J Sports Med. 1987;15(6):586-590.

33. Rodosky MW, Harner CD, Fu FH. The role of the long head of the biceps muscle and superior glenoid labrum in anterior stability of the shoulder. Am J Sports Med. 1994;22(1):121-130.

34. Boileau P, Parratte S, Chuinard C, Roussanne Y, Shia D, Bicknell R. Arthroscopic treatment of isolated type II SLAP lesions: biceps tenodesis as an alternative to reinsertion. Am J Sports Med. 2009;37(5):929-936.

35. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.

36. Ek ET, Shi LL, Tompson JD, Freehill MT, Warner JJ. Surgical treatment of isolated type II superior labrum anterior-posterior (SLAP) lesions: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2014;23(7):1059-1065.

37. Alpert JM, Wuerz TH, O’Donnell TF, Carroll KM, Brucker NN, Gill TJ. The effect of age on the outcomes of arthroscopic repair of type II superior labral anterior and posterior lesions. Am J Sports Med. 2010;38(11):2299-2303.

38. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.

39. Denard PJ, Lädermann A, Burkhart SS. Long-term outcome after arthroscopic repair of type II SLAP lesions: results according to age and workers’ compensation status. Arthroscopy. 2012;28(4):451-457.

40. Burns JP, Bahk M, Snyder SJ. Superior labral tears: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2011;20(2 suppl):S2-S8.

41. McCormick F, Nwachukwu BU, Solomon D, et al. The efficacy of biceps tenodesis in the treatment of failed superior labral anterior posterior repairs. Am J Sports Med. 2014;42(4):820-825.

42. Katz LM, Hsu S, Miller SL, et al. Poor outcomes after SLAP repair: descriptive analysis and prognosis. Arthroscopy. 2009;25(8):849-855.

43. Park S, Glousman RE. Outcomes of revision arthroscopic type II superior labral anterior posterior repairs. Am J Sports Med. 2011;39(6):1290-1294.

44. Gupta AK, Bruce B, Klosterman EL, McCormick F, Harris J, Romeo AA. Subpectoral biceps tenodesis for failed type II SLAP repair. Orthopedics. 2013;36(6):e723-e728.

45. Neuman BJ, Boisvert CB, Reiter B, Lawson K, Ciccotti MG, Cohen SB. Results of arthroscopic repair of type II superior labral anterior posterior lesions in overhead athletes: assessment of return to preinjury playing level and satisfaction. Am J Sports Med. 2011;39(9):1883-1888.

46. Fedoriw WW, Ramkumar P, McCulloch PC, Lintner DM. Return to play after treatment of superior labral tears in professional baseball players. Am J Sports Med. 2014;42(5):1155-1160.

47. Park JY, Chung SW, Jeon SH, Lee JG, Oh KS. Clinical and radiological outcomes of type 2 superior labral anterior posterior repairs in elite overhead athletes. Am J Sports Med. 2013;41(6):1372-1379.

48. Schöffl V, Popp D, Dickschass J, Küpper T. Superior labral anterior-posterior lesions in rock climbers—primary double tenodesis? Clin J Sport Med. 2011;21(3):261-263.

49. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.

50. Funk L, Snow M. SLAP tears of the glenoid labrum in contact athletes. Clin J Sport Med. 2007;17(1):1-4.

51.  Enad JG, Gaines RJ, White SM, Kurtz CA. Arthroscopic superior labrum anterior-posterior repair in military patients. J Shoulder Elbow Surg. 2007;16(3):300-305.

References

1.    Andrews JR, Carson WG Jr, McLeod WD. Glenoid labrum tears related to the long head of the biceps. Am J Sports Med. 1985;13(5):337-341.

2.    Weber SC, Martin DF, Seiler JG 3rd, Harrast JJ. Superior labrum anterior and posterior lesions of the shoulder: incidence rates, complications, and outcomes as reported by American Board of Orthopaedic Surgery. Part II candidates. Am J Sports Med. 2012;40(7):1538-1543.

3.    Snyder SJ, Karzel RP, Del Pizzo W, Ferkel RD, Friedman MJ. SLAP lesions of the shoulder. Arthroscopy. 1990;6(4):274-279.

4.    Morgan CD, Burkhart SS, Palmeri M, Gillespie M. Type II SLAP lesions: three subtypes and their relationships to superior instability and rotator cuff tears. Arthroscopy. 1998;14(6):553-565.

5.    Powell SE, Nord KD, Ryu RKN. The diagnosis, classification, and treatment of SLAP lesions. Oper Tech Sports Med. 2012;20(1):46-56.

6.    Maffet MW, Gartsman GM, Moseley B. Superior labrum-biceps tendon complex lesions of the shoulder. Am J Sports Med. 1995;23(1):93-98.

7.    Kim TK, Queale WS, Cosgarea AJ, McFarland EG. Clinical features of the different types of SLAP lesions: an analysis of one hundred and thirty-nine cases. J Bone Joint Surg Am. 2003;85(1):66-71.

8.    Abrams GD, Safran MR. Diagnosis and management of superior labrum anterior posterior lesions in overhead athletes. Br J Sports Med. 2010;44(5):311-318.

9.    Keener JD, Brophy RH. Superior labral tears of the shoulder: pathogenesis, evaluation, and treatment. J Am Acad Orthop Surg. 2009;17(10):627-637.

10. Abrams GD, Hussey KE, Harris JD, Cole BJ. Clinical results of combined meniscus and femoral osteochondral allograft transplantation: minimum 2-year follow-up. Arthroscopy. 2014;30(8):964-970.e1.

11. Burkhart SS, Morgan CD, Kibler WB. The disabled throwing shoulder: spectrum of pathology part I: pathoanatomy and biomechanics. Arthroscopy. 2003;19(4):404-420.

12. Virk MS, Arciero RA. Superior labrum anterior to posterior tears and glenohumeral instability. Instr Course Lect. 2013;62:501-514.

13. Calvert E, Chambers GK, Regan W, Hawkins RH, Leith JM. Special physical examination tests for superior labrum anterior posterior shoulder tears are clinically limited and invalid: a diagnostic systematic review. J Clin Epidemiol. 2009;62(5):558-563.

14. Jones GL, Galluch DB. Clinical assessment of superior glenoid labral lesions: a systematic review. Clin Orthop Relat Res. 2007;455:45-51.

15. Werner BC, Brockmeier SF, Miller MD. Etiology, diagnosis, and management of failed SLAP repair. J Am Acad Orthop Surg. 2014;22(9):554-565.

16. Werner BC, Pehlivan HC, Hart JM, et al. Biceps tenodesis is a viable option for salvage of failed SLAP repair. J Shoulder Elbow Surg. 2014;23(8):e179-e184.

17. Erickson J, Lavery K, Monica J, Gatt C, Dhawan A. Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. Am J Sports Med. 2015;43(5):1274-1282.

18. Huri G, Hyun YS, Garbis NG, McFarland EG. Treatment of superior labrum anterior posterior lesions: a literature review. Acta Orthop Traumatol Turc. 2014;48(3):290-297.

19. Li X, Lin TJ, Jager M, et al. Management of type II superior labrum anterior posterior lesions: a review of the literature. Orthop Rev. 2010;2(1):e6.

20. Cooper DE, Arnoczky SP, O’Brien SJ, Warren RF, DiCarlo E, Allen AA. Anatomy, histology, and vascularity of the glenoid labrum. An anatomical study. J Bone Joint Surg Am. 1992;74(1):46-52.

21. Vangsness CT, Jorgenson SS, Watson T, Johnson DL. The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. J Bone Joint Surg Br. 1994;76(6):951-954.

22. Strauss EJ, Salata MJ, Sershon RA, et al. Role of the superior labrum after biceps tenodesis in glenohumeral stability. J Shoulder Elbow Surg. 2014;23(4):485-491.

23. Pagnani MJ, Deng XH, Warren RF, Torzilli PA, Altchek DW. Effect of lesions of the superior portion of the glenoid labrum on glenohumeral translation. J Bone Joint Surg Am. 1995;77(7):1003-1010.

24. McMahon PJ, Burkart A, Musahl V, Debski RE. Glenohumeral translations are increased after a type II superior labrum anterior-posterior lesion: a cadaveric study of severity of passive stabilizer injury. J Shoulder Elbow Surg. 2004;13(1):39-44.

25. Burkart A, Debski R, Musahl V, McMahon P, Woo SL. Biomechanical tests for type II SLAP lesions of the shoulder joint before and after arthroscopic repair [in German]. Orthopade. 2003;32(7):600-607.

26. Panossian VR, Mihata T, Tibone JE, Fitzpatrick MJ, McGarry MH, Lee TQ. Biomechanical analysis of isolated type II SLAP lesions and repair. J Shoulder Elbow Surg. 2005;14(5):529-534.

27. Mihata T, McGarry MH, Tibone JE, Fitzpatrick MJ, Kinoshita M, Lee TQ. Biomechanical assessment of type II superior labral anterior-posterior (SLAP) lesions associated with anterior shoulder capsular laxity as seen in throwers: a cadaveric study. Am J Sports Med. 2008;36(8):1604-1610.

28. Youm T, Tibone JE, ElAttrache NS, McGarry MH, Lee TQ. Simulated type II superior labral anterior posterior lesions do not alter the path of glenohumeral articulation: a cadaveric biomechanical study. Am J Sports Med. 2008;36(4):767-774.

29. Youm T, ElAttrache NS, Tibone JE, McGarry MH, Lee TQ. The effect of the long head of the biceps on glenohumeral kinematics. J Shoulder Elbow Surg. 2009;18(1):122-129.

30. McGarry MH, Nguyen ML, Quigley RJ, Hanypsiak B, Gupta R, Lee TQ. The effect of long and short head biceps loading on glenohumeral joint rotational range of motion and humeral head position [published online ahead of print September 26, 2014]. Knee Surg Sports Traumatol Arthrosc.

31. Glousman R, Jobe F, Tibone J, Moynes D, Antonelli D, Perry J. Dynamic electromyographic analysis of the throwing shoulder with glenohumeral instability. J Bone Joint Surg Am. 1988;70(2):220-226.

32. Gowan ID, Jobe FW, Tibone JE, Perry J, Moynes DR. A comparative electromyographic analysis of the shoulder during pitching. Professional versus amateur pitchers. Am J Sports Med. 1987;15(6):586-590.

33. Rodosky MW, Harner CD, Fu FH. The role of the long head of the biceps muscle and superior glenoid labrum in anterior stability of the shoulder. Am J Sports Med. 1994;22(1):121-130.

34. Boileau P, Parratte S, Chuinard C, Roussanne Y, Shia D, Bicknell R. Arthroscopic treatment of isolated type II SLAP lesions: biceps tenodesis as an alternative to reinsertion. Am J Sports Med. 2009;37(5):929-936.

35. Gupta AK, Chalmers PN, Klosterman EL, et al. Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear. Orthopedics. 2015;38(1):e48-e53.

36. Ek ET, Shi LL, Tompson JD, Freehill MT, Warner JJ. Surgical treatment of isolated type II superior labrum anterior-posterior (SLAP) lesions: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2014;23(7):1059-1065.

37. Alpert JM, Wuerz TH, O’Donnell TF, Carroll KM, Brucker NN, Gill TJ. The effect of age on the outcomes of arthroscopic repair of type II superior labral anterior and posterior lesions. Am J Sports Med. 2010;38(11):2299-2303.

38. Provencher MT, McCormick F, Dewing C, McIntire S, Solomon D. A prospective analysis of 179 type 2 superior labrum anterior and posterior repairs: outcomes and factors associated with success and failure. Am J Sports Med. 2013;41(4):880-886.

39. Denard PJ, Lädermann A, Burkhart SS. Long-term outcome after arthroscopic repair of type II SLAP lesions: results according to age and workers’ compensation status. Arthroscopy. 2012;28(4):451-457.

40. Burns JP, Bahk M, Snyder SJ. Superior labral tears: repair versus biceps tenodesis. J Shoulder Elbow Surg. 2011;20(2 suppl):S2-S8.

41. McCormick F, Nwachukwu BU, Solomon D, et al. The efficacy of biceps tenodesis in the treatment of failed superior labral anterior posterior repairs. Am J Sports Med. 2014;42(4):820-825.

42. Katz LM, Hsu S, Miller SL, et al. Poor outcomes after SLAP repair: descriptive analysis and prognosis. Arthroscopy. 2009;25(8):849-855.

43. Park S, Glousman RE. Outcomes of revision arthroscopic type II superior labral anterior posterior repairs. Am J Sports Med. 2011;39(6):1290-1294.

44. Gupta AK, Bruce B, Klosterman EL, McCormick F, Harris J, Romeo AA. Subpectoral biceps tenodesis for failed type II SLAP repair. Orthopedics. 2013;36(6):e723-e728.

45. Neuman BJ, Boisvert CB, Reiter B, Lawson K, Ciccotti MG, Cohen SB. Results of arthroscopic repair of type II superior labral anterior posterior lesions in overhead athletes: assessment of return to preinjury playing level and satisfaction. Am J Sports Med. 2011;39(9):1883-1888.

46. Fedoriw WW, Ramkumar P, McCulloch PC, Lintner DM. Return to play after treatment of superior labral tears in professional baseball players. Am J Sports Med. 2014;42(5):1155-1160.

47. Park JY, Chung SW, Jeon SH, Lee JG, Oh KS. Clinical and radiological outcomes of type 2 superior labral anterior posterior repairs in elite overhead athletes. Am J Sports Med. 2013;41(6):1372-1379.

48. Schöffl V, Popp D, Dickschass J, Küpper T. Superior labral anterior-posterior lesions in rock climbers—primary double tenodesis? Clin J Sport Med. 2011;21(3):261-263.

49. Chalmers PN, Trombley R, Cip J, et al. Postoperative restoration of upper extremity motion and neuromuscular control during the overhand pitch: evaluation of tenodesis and repair for superior labral anterior-posterior tears. Am J Sports Med. 2014;42(12):2825-2836.

50. Funk L, Snow M. SLAP tears of the glenoid labrum in contact athletes. Clin J Sport Med. 2007;17(1):1-4.

51.  Enad JG, Gaines RJ, White SM, Kurtz CA. Arthroscopic superior labrum anterior-posterior repair in military patients. J Shoulder Elbow Surg. 2007;16(3):300-305.

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CPR Prior to Defibrillation for VF/VT CPA

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A focused investigation of expedited, stack of three shocks versus chest compressions first followed by single shocks for monitored ventricular fibrillation/ventricular tachycardia cardiopulmonary arrest in an in‐hospital setting

Cardiopulmonary arrest (CPA) is a major contributor to overall mortality in both the in‐ and out‐of‐hospital setting.[1, 2, 3] Despite advances in the field of resuscitation science, mortality from CPA remains high.[1, 4] Unlike the out‐of‐hospital environment, inpatient CPA is unique, as trained healthcare providers are the primary responders with a range of expertise available throughout the duration of arrest.

There are inherent opportunities of in‐hospital cardiac arrest that exist, such as the opportunity for near immediate arrest detection, rapid initiation of high‐quality chest compressions, and early defibrillation if indicated. Given the association between improved rates of successful defibrillation and high‐quality chest compressions, the 2005 American Heart Association (AHA) updates changed the recommended guideline ventricular fibrillation/ventricular tachycardia (VF/VT) defibrillation sequence from 3 stacked shocks to a single shock followed by 2 minutes of chest compressions between defibrillation attempts.[5, 6] However, the recommendations were directed primarily at cases of out‐of‐hospital VF/VT CPA, and it currently remains unclear as to whether this strategy offers any advantage to patients who suffer an in‐hospital VF/VT arrest.[7]

Despite the aforementioned findings regarding the benefit of high‐quality chest compressions, there is a paucity of evidence in the medical literature to support whether delivering a period of chest compressions before defibrillation attempt, including initial shock and shock sequence, translate to improved outcomes. With the exception of the statement recommending early defibrillation in case of in‐hospital arrest, there are no formal AHA consensus recommendations.[5, 8, 9] Here we document our experience using the approach of expedited stacked defibrillation shocks in persons experiencing monitored in‐hospital VF/VT arrest.

METHODS

Design

This was a retrospective study of observational data from our in‐hospital resuscitation database. Waiver of informed consent was granted by our institutional investigational review board.

Setting

This study was performed in the University of California San Diego Healthcare System, which includes 2 urban academic hospitals, with a combined total of approximately 500 beds. A designated team is activated in response to code blue requests and includes: code registered nurse (RN), code doctor of medicine (MD), airway MD, respiratory therapist, pharmacist, house nursing supervisor, primary RN, and unit charge RN. Crash carts with defibrillators (ZOLL R and E series; ZOLL Medical Corp., Chelmsford, MA) are located on each inpatient unit. Defibrillator features include real‐time cardiopulmonary resuscitation (CPR) feedback, filtered electrocardiography (ECG), and continuous waveform capnography.

Resuscitation training is provided for all hospital providers as part of the novel Advanced Resuscitation Training (ART) program, which was initiated in 2007.[10] Critical care nurses and physicians receive annual training, whereas noncritical care personnel undergo biennial training. The curriculum is adaptable to institutional treatment algorithms, equipment, and code response. Content is adaptive based on provider type, unit, and opportunities for improvement as revealed by performance improvement data. Resuscitation treatment algorithms are reviewed annually by the Critical Care Committee and Code Blue Subcommittee as part of the ART program, with modifications incorporated into the institutional policies and procedures.

Subjects

All admitted patients with continuous cardiac monitoring who suffered VF/VT arrest between July 2005 and June 2013 were included in this analysis. Patients with active do not attempt resuscitation orders were excluded. Patients were identified from our institutional resuscitation database, into which all in‐hospital cardiopulmonary arrest data are entered. We did not have data on individual patient comorbidity or severity of illness. Overall patient acuity over the course of the study was monitored hospital wide through case‐mix index (CMI). The index is based upon the allocation of hospital resources used to treat a diagnosis‐related group of patients and has previously been used as a surrogate for patient acuity.[11, 12, 13] The code RN who performed the resuscitation is responsible for entering data into a protected performance improvement database. Telecommunications records and the unit log are cross‐referenced to assure complete capture.

Protocols

Specific protocol similarities and differences among the 3 study periods are presented in Table 1.

Institutional In‐hospital Cardiopulmonary Arrest Protocol Variables During the Study Period
Protocol VariableStack Shock Period (20052008)Initial Chest Compression Period (20082011)Modified Stack Shock Period (20112013)
  • NOTE: Abbreviations: IO, intraosseous; IV, intravenous; VF, ventricular fibrillation; VT, ventricular tachycardia. *Only if monitored or witnessed at time of arrest.

Defibrillator typeMedtronic/Physio Control LifePak 12Zoll E SeriesZoll E Series
Joule increment with defibrillation200J‐300J‐360J, manual escalation120J‐150J‐200J, manual escalation120J‐150J‐200J, automatic escalation
Distinction between monitored and unmonitored in‐hospital cardiopulmonary arrestNoYesYes
Chest compressions prior to initial defibrillationNoYesNo*
Initial defibrillation strategy3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT2 minutes of chest compressions prior to initial and in between attempts3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT*
Chest compression to ventilation ratio15:1Continuous chest compressions with ventilation at ratio 10:1Continuous chest compressions with ventilation at ratio 10:1
VasopressorsEpinephrine 1 mg IV/IO every 35 minutes.Epinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutesEpinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutes.

Stacked Shock Period (20052008)

Historically, our institutional cardiopulmonary arrest protocols advocated early defibrillation with administration of 3 stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT before initiating/resuming chest compressions.

Initial Chest Compression Period (20082011)

In 2008 the protocol was modified to reflect recommendations to perform a 2‐minute period of chest compressions prior to each defibrillation, including the initial attempt.

Modified Stacked Shack Period (20112013)

Finally, in 2011 the protocol was modified again, and defibrillators were configured to allow automatic advancement of defibrillation energy (120J‐150J‐200J). The defibrillation protocol included the following elements.

For an unmonitored arrest, chest compressions and ventilations should be initiated upon recognition of cardiopulmonary arrest. If VF/VT was identified upon placement of defibrillator pads, immediate counter shock was performed and chest compressions resumed immediately for a period of 2 minutes before considering a repeat defibrillation attempt. A dose of epinephrine (1 mg intravenous [IV]/emntraosseous [IO]) or vasopressin (40 units IV/IO) was administered as close to the reinitiation of chest compressions as possible. Defibrillation attempts proceeded with a single shock at a time, each preceded by 2 minutes of chest compressions.

For a monitored arrest, defibrillation attempts were expedited. Chest compressions without ventilations were initiated only until defibrillator pads were placed. Defibrillation attempts were initiated as soon as possible, with at least 3 or more successive shocks administered for persistent VF/VT (stacked shocks). Compressions were performed between shocks if they did not interfere with rhythm analysis. Compressions resumed following the initial series of stacked shocks with persistent CPA, regardless of rhythm, and pressors administered (epinephrine 1 mg IV or vasopressin 40 units IV). Persistent VF/VT received defibrillation attempts every 2 minutes following the initial series of stacked shocks, with compressions performed continuously between attempts. Persistent VF/VT should trigger emergent cardiology consultation for possible emergent percutaneous intervention.

Analysis

The primary outcome measure was defined as survival to hospital discharge at baseline and following each protocol change. 2 was used to compare the 3 time periods, with P < 0.05 defined as statistically significant. Specific group comparisons were made with Bonferroni correction, with P < 0.017 defined as statistically significant. Secondary outcome measures included return of spontaneous circulation (ROSC) and number of shocks required. Demographic and clinical data were also presented for each of the 3 study periods.

RESULTS

A total of 661 cardiopulmonary arrests of all rhythms were identified during the entire study period. Primary VF/VT arrests was identified in 106 patients (16%). Of these, 102 (96%) were being monitored with continuous ECG at the time of arrest. Demographic and clinical information for the entire study cohort are displayed in Table 2. There were no differences in age, gender, time of arrest, and location of arrest between study periods (all P > 0.05). The incidence of VF/VT arrest did not vary significantly between the study periods (P = 0.16). There were no differences in mean number of defibrillation attempts per arrest; however, there was a significant improvement in the rate of perfusing rhythm after initial set of defibrillation attempts and overall ROSC favoring stacked shocks (all P < 0.05, Table 2). Survival‐to‐hospital discharge for all VF/VT arrest victims decreased, then increased significantly from the stacked shock period to initial chest compression period to modified stacked shock period (58%, 18%, 71%, respectively, P < 0.01, Figure 1). After Bonferroni correction, specific group differences were significant between the stacked shock and initial chest compression groups (P < 0.01) and modified stacked shocks and initial chest compression groups (P < 0.01, Table 2). Finally, the incidence of bystander CPR appeared to be significantly greater in the modified stacked shock period following implementation of our resuscitation program (Table 2). Overall hospital CMI for fiscal years 2005/2006 through 2012/2013 were significantly different (1.47 vs 1.71, P < 0.0001).

Demographic and Clinical Data for Study Population
ParameterStacked Shocks (n = 31)Initial Chest Compressions (n = 33)Modified Stack Shocks (n = 42)
  • NOTE: Abbreviations: CPR, cardiopulmonary resuscitation; ICC, initial chest compressions; ICU, intensive care unit; MSS, modified stack shocks; PVT, pulseless ventricular tachycardia; ROSC, return of spontaneous circulation; SS, stacked shocks; VF, ventricular fibrillation. *P < 0.001 versus periods SS and MSS. P < 0.05 versus periods SS and ICC. P < 0.05 versus period MSS. P < 0.01 versus periods SS and MSS. P < 0.001 versus periods SS and ICC.

Age (y)54.364.359.8
Male gender (%)16 (52)21 (64)21 (50)
VF/PVT arrest incidence (per 1,000 admissions)0.49 0.70
Arrest 7 am5 pm (%)15 (48)17 (52)21 (50)
Non‐ICU location (%)13 (42)15 (45)17 (40)
CPR prior to code team arrival (%)22 (71)*31 (94)42 (100)
Perfusing rhythm after initial set of defibrillation attempts (%)373370
Mean defibrillation attempts (no.)1.31.81.5
ROSC (%)765690
Survival‐to‐hospital discharge (%)18 (58)6 (18)30 (71)
Case‐mix index (average coefficient by period)1.511.601.69
Figure 1
Survival to discharge for patients with ventricular fibrillation/ventricular tachycardia arrest from 2005 to 2013. Survival was significantly lower during the initial chest compression (ICC) period as compared to stacked shocks (SS) and modified stacked shock (MSS) periods (P < 0.01).

DISCUSSION

The specific focus of this observation was to report on defibrillation strategies that have previously only been reported in an out‐of‐hospital setting. There is no current consensus regarding chest compressions for a predetermined amount of time prior to defibrillation in an inpatient setting. Here we present data suggesting improved outcomes using an approach that expedited defibrillation and included a defibrillation strategy of stacked shocks (stacked shock and modified stack shock, respectively) in monitored inpatient VF/VT arrest.

Early out‐of‐hospital studies initially demonstrated a significant survival benefit for patients who received 1.5 to 3 minutes of chest compressions preceding defibrillation with reported arrest downtimes of 4 to 5 minutes prior to emergency medical services arrival.[14, 15] However, in more recent randomized controlled trials, outcome was not improved when chest compressions were performed prior to defibrillation attempt.[16, 17] Our findings suggest that there is no one size fits all approach to chest compression and defibrillation strategy. Instead, we suggest that factors including whether the arrest occurred while monitored or not aid with decision making and timing of defibrillation.

Our findings favoring expedited defibrillation and stacked shocks in witnessed arrest are consistent with the 3‐phase model of cardiac arrest proposed by Weisfeldt and Becker suggesting that defibrillation success is related to the energy status of the heart.[18] In this model, the first 4 minutes of VF arrest (electrical phase) are characterized by a high‐energy state with higher adenosine triphosphate (ATP)/adenosine monophosphate (AMP) ratios that are associated with increased likelihood for ROSC after defibrillation attempt.[19] Further, VF appears to deplete ATP/AMP ratios after about 4 minutes, at which point the likelihood of defibrillation success is substantially diminished.[18] Between 4 and 10 minutes (circulatory phase), energy stores in the myocardium are severely depleted. However, there is evidence to suggest that high‐quality chest compressions and high chest compression fractionparticularly in conjunction with epinephrinecan replenish ATP stores and increase the likelihood of defibrillation success.[6, 20] Beyond 10 minutes (metabolic phase), survival rates are abysmal, with no therapy yet identified producing clinical utility.

The secondary analyses reveal several interesting trends. We anticipated a higher number of defibrillation attempts during phase II due to a lower likelihood of conversion with a CPR‐first approach. Instead, the number of shocks was similar across all 3 periods. Our findings are consistent with previous reports of a low single or first shock probability of successful defibrillation. However, recent reports document that approximately 80% of patients who ultimately survive to discharge are successfully defibrillated within the first 3 shocks.[21, 22, 23]

It appears that the likelihood of conversion to a perfusing rhythm is higher with expedited, stacked shocks. This underscores the importance of identifying an optimal approach to the treatment of VF/VT, as the initial series of defibrillation attempts may determine outcomes. There also appeared to be an increase in the incidence of VF/VT during the modified stack shock period, although this was not statistically significant. The modified stack shock period correlated temporally with the expansion of our institution's cardiovascular service and the opening of a dedicated inpatient facility, which likely influenced our mixture of inpatients.

These data should be interpreted with consideration of study limitations. Primarily, we did not attempt to determine arrest times prior to initial defibrillation attempts, which is likely an important variable. However, we limited our population studied only to individuals experiencing VF/VT arrest that was witnessed by hospital care staff or occurred while on cardiac monitor. We are confident that these selective criteria resulted in expedited identification and response times well within the electrical phase. We did not evaluate differences or changes in individual patient‐level severity of illness that may have potentially confounded outcome analysis. The effect of individual level in severity of illness and comorbidity are not known. Instead, we used CMI coefficients to explore hospital wide changes in patient acuity during the study period. We noticed an increasing case‐mix coefficient value suggesting higher patient acuity, which would predict increased mortality rather than the decrease noted between the initial chest compression and modified stacked shock periods (Table 2). In addition, we did not integrate CPR process variables, such as depth, rate, recoil, chest compression fraction, and per‐shock pauses, into this analysis. Our previous studies indicated that high‐quality CPR may account for a significant amount of improvement in outcomes following our novel resuscitation program implementation in 2007.[10, 24] Since the program's inception, we have reported continuous improvement in overall in‐hospital mortality that was sustained throughout the duration of the study period despite the significant changes reported in the 3 periods with monitored VF/VT arrest.[10] The use of medications prior to initial defibrillation attempts was not recorded. We have recently reported that during the same period of data collection, there were no significant changes in the use of epinephrine; however, there was a significant increase in the use of vasopressin.[10] It is unclear whether the increased use of vasopressin contributed to the current outcomes. However, given our cohort of witnessed in‐hospital cardiac arrests with an initial shockable rhythm, we anticipate the use of vasopressors as unlikely prior to defibrillation attempt.

Additional important limitations and potential confounding factors in this study were the use of 2 different types of defibrillators, differing escalating energy strategies, and differing defibrillator waveforms. Recent evidence supports biphasic waveforms as more effective than monophasic waveforms.[25, 26, 27] Comparison of defibrillator brand and waveform superiority is out the scope of this study; however, it is interesting to note similar high rates of survival in the stacked shock and modified stack shock phases despite use of different defibrillator brands and waveforms during those respective phases. Regarding escalating energy of defibrillation countershocks, the most recent 2010 AHA guidelines have no position on the superiority of either manual or automatic escalation.[7] However, we noted similar high rates of survival in the stacked shock and modified stack shock periods despite use of differing escalating strategies. Finally, we used survival‐to‐hospital discharge as our main outcome measure rather than neurological status. However, prior studies from our institution suggest that most VF/VT survivors have good neurological outcomes, which are influenced heavily by preadmission functional status.[24]

CONCLUSIONS

Our data suggest that in cases of monitored VF/VT arrest, expeditious defibrillation with use of stacked shocks is associated with a higher rate of ROSC and survival to hospital discharge

Disclosure: Nothing to report.

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References
  1. Morrison LJ, Neumar RW, Zimmerman JL, et al. Strategies for improving survival after in‐hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation. 2013;127:15381563.
  2. Peberdy MA, Ornato JP, Larkin GL, et al. Survival from in‐hospital cardiac arrest during nights and weekends. JAMA. 2008;299:785792.
  3. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25e146.
  4. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out‐of‐hospital cardiac arrest: a systematic review and meta‐analysis. Circ Cardiovasc Qual Outcomes. 2010;3:6381.
  5. Abella BS, Alvarado JP, Myklebust H, et al. Quality of cardiopulmonary resuscitation during in‐hospital cardiac arrest. JAMA. 2005;293:305310.
  6. Christenson J, Andrusiek D, Everson‐Stewart S, et al. Chest compression fraction determines survival in patients with out‐of‐hospital ventricular fibrillation. Circulation. 2009;120:12411247.
  7. Jacobs I, Sunde K, Deakin CD, et al. Part 6: Defibrillation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122:S325S337.
  8. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S640S656.
  9. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S729S767.
  10. Davis DP, Graham PG, Husa RD, et al. A performance improvement‐based resuscitation programme reduces arrest incidence and increases survival from in‐hospital cardiac arrest. Resuscitation. 2015;92:6369.
  11. Averill RF. The evolution of case‐mix measurement using DRGs: past, present and future. Stud Health Technol Inform. 1994;14:7583.
  12. Merchant RM, Yang L, Becker LB, et al. Variability in case‐mix adjusted in‐hospital cardiac arrest rates. Med Care. 2012;50:124130.
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  14. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out‐of‐hospital ventricular fibrillation. JAMA. 1999;281:11821188.
  15. Wik L, Hansen TB, Fylling F, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out‐of‐hospital ventricular fibrillation: a randomized trial. JAMA. 2003;289:13891395.
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  18. Weisfeldt ML, Becker LB. Resuscitation after cardiac arrest: a 3‐phase time‐sensitive model. JAMA. 2002;288:30353038.
  19. Salcido DD, Menegazzi JJ, Suffoletto BP, Logue ES, Sherman LD. Association of intramyocardial high energy phosphate concentrations with quantitative measures of the ventricular fibrillation electrocardiogram waveform. Resuscitation. 2009;80:946950.
  20. Holzer M, Behringer W, Sterz F, et al. Ventricular fibrillation median frequency may not be useful for monitoring during cardiac arrest treated with endothelin‐1 or epinephrine. Anesth Analg. 2004;99:17871793, table of contents.
  21. Eftestøl T, Sunde K, Aase SO, Husøy JH, Steen PA. “Probability of successful defibrillation” as a monitor during CPR in out‐of‐hospital cardiac arrested patients. Resuscitation. 2015;48:245254.
  22. Rodriguez‐Nunez A, Lopez‐Herce J, Castillo J, Bellon JM. Shockable rhythms and defibrillation during in‐hospital pediatric cardiac arrest. Resuscitation. 2014;85:387391.
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Cardiopulmonary arrest (CPA) is a major contributor to overall mortality in both the in‐ and out‐of‐hospital setting.[1, 2, 3] Despite advances in the field of resuscitation science, mortality from CPA remains high.[1, 4] Unlike the out‐of‐hospital environment, inpatient CPA is unique, as trained healthcare providers are the primary responders with a range of expertise available throughout the duration of arrest.

There are inherent opportunities of in‐hospital cardiac arrest that exist, such as the opportunity for near immediate arrest detection, rapid initiation of high‐quality chest compressions, and early defibrillation if indicated. Given the association between improved rates of successful defibrillation and high‐quality chest compressions, the 2005 American Heart Association (AHA) updates changed the recommended guideline ventricular fibrillation/ventricular tachycardia (VF/VT) defibrillation sequence from 3 stacked shocks to a single shock followed by 2 minutes of chest compressions between defibrillation attempts.[5, 6] However, the recommendations were directed primarily at cases of out‐of‐hospital VF/VT CPA, and it currently remains unclear as to whether this strategy offers any advantage to patients who suffer an in‐hospital VF/VT arrest.[7]

Despite the aforementioned findings regarding the benefit of high‐quality chest compressions, there is a paucity of evidence in the medical literature to support whether delivering a period of chest compressions before defibrillation attempt, including initial shock and shock sequence, translate to improved outcomes. With the exception of the statement recommending early defibrillation in case of in‐hospital arrest, there are no formal AHA consensus recommendations.[5, 8, 9] Here we document our experience using the approach of expedited stacked defibrillation shocks in persons experiencing monitored in‐hospital VF/VT arrest.

METHODS

Design

This was a retrospective study of observational data from our in‐hospital resuscitation database. Waiver of informed consent was granted by our institutional investigational review board.

Setting

This study was performed in the University of California San Diego Healthcare System, which includes 2 urban academic hospitals, with a combined total of approximately 500 beds. A designated team is activated in response to code blue requests and includes: code registered nurse (RN), code doctor of medicine (MD), airway MD, respiratory therapist, pharmacist, house nursing supervisor, primary RN, and unit charge RN. Crash carts with defibrillators (ZOLL R and E series; ZOLL Medical Corp., Chelmsford, MA) are located on each inpatient unit. Defibrillator features include real‐time cardiopulmonary resuscitation (CPR) feedback, filtered electrocardiography (ECG), and continuous waveform capnography.

Resuscitation training is provided for all hospital providers as part of the novel Advanced Resuscitation Training (ART) program, which was initiated in 2007.[10] Critical care nurses and physicians receive annual training, whereas noncritical care personnel undergo biennial training. The curriculum is adaptable to institutional treatment algorithms, equipment, and code response. Content is adaptive based on provider type, unit, and opportunities for improvement as revealed by performance improvement data. Resuscitation treatment algorithms are reviewed annually by the Critical Care Committee and Code Blue Subcommittee as part of the ART program, with modifications incorporated into the institutional policies and procedures.

Subjects

All admitted patients with continuous cardiac monitoring who suffered VF/VT arrest between July 2005 and June 2013 were included in this analysis. Patients with active do not attempt resuscitation orders were excluded. Patients were identified from our institutional resuscitation database, into which all in‐hospital cardiopulmonary arrest data are entered. We did not have data on individual patient comorbidity or severity of illness. Overall patient acuity over the course of the study was monitored hospital wide through case‐mix index (CMI). The index is based upon the allocation of hospital resources used to treat a diagnosis‐related group of patients and has previously been used as a surrogate for patient acuity.[11, 12, 13] The code RN who performed the resuscitation is responsible for entering data into a protected performance improvement database. Telecommunications records and the unit log are cross‐referenced to assure complete capture.

Protocols

Specific protocol similarities and differences among the 3 study periods are presented in Table 1.

Institutional In‐hospital Cardiopulmonary Arrest Protocol Variables During the Study Period
Protocol VariableStack Shock Period (20052008)Initial Chest Compression Period (20082011)Modified Stack Shock Period (20112013)
  • NOTE: Abbreviations: IO, intraosseous; IV, intravenous; VF, ventricular fibrillation; VT, ventricular tachycardia. *Only if monitored or witnessed at time of arrest.

Defibrillator typeMedtronic/Physio Control LifePak 12Zoll E SeriesZoll E Series
Joule increment with defibrillation200J‐300J‐360J, manual escalation120J‐150J‐200J, manual escalation120J‐150J‐200J, automatic escalation
Distinction between monitored and unmonitored in‐hospital cardiopulmonary arrestNoYesYes
Chest compressions prior to initial defibrillationNoYesNo*
Initial defibrillation strategy3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT2 minutes of chest compressions prior to initial and in between attempts3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT*
Chest compression to ventilation ratio15:1Continuous chest compressions with ventilation at ratio 10:1Continuous chest compressions with ventilation at ratio 10:1
VasopressorsEpinephrine 1 mg IV/IO every 35 minutes.Epinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutesEpinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutes.

Stacked Shock Period (20052008)

Historically, our institutional cardiopulmonary arrest protocols advocated early defibrillation with administration of 3 stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT before initiating/resuming chest compressions.

Initial Chest Compression Period (20082011)

In 2008 the protocol was modified to reflect recommendations to perform a 2‐minute period of chest compressions prior to each defibrillation, including the initial attempt.

Modified Stacked Shack Period (20112013)

Finally, in 2011 the protocol was modified again, and defibrillators were configured to allow automatic advancement of defibrillation energy (120J‐150J‐200J). The defibrillation protocol included the following elements.

For an unmonitored arrest, chest compressions and ventilations should be initiated upon recognition of cardiopulmonary arrest. If VF/VT was identified upon placement of defibrillator pads, immediate counter shock was performed and chest compressions resumed immediately for a period of 2 minutes before considering a repeat defibrillation attempt. A dose of epinephrine (1 mg intravenous [IV]/emntraosseous [IO]) or vasopressin (40 units IV/IO) was administered as close to the reinitiation of chest compressions as possible. Defibrillation attempts proceeded with a single shock at a time, each preceded by 2 minutes of chest compressions.

For a monitored arrest, defibrillation attempts were expedited. Chest compressions without ventilations were initiated only until defibrillator pads were placed. Defibrillation attempts were initiated as soon as possible, with at least 3 or more successive shocks administered for persistent VF/VT (stacked shocks). Compressions were performed between shocks if they did not interfere with rhythm analysis. Compressions resumed following the initial series of stacked shocks with persistent CPA, regardless of rhythm, and pressors administered (epinephrine 1 mg IV or vasopressin 40 units IV). Persistent VF/VT received defibrillation attempts every 2 minutes following the initial series of stacked shocks, with compressions performed continuously between attempts. Persistent VF/VT should trigger emergent cardiology consultation for possible emergent percutaneous intervention.

Analysis

The primary outcome measure was defined as survival to hospital discharge at baseline and following each protocol change. 2 was used to compare the 3 time periods, with P < 0.05 defined as statistically significant. Specific group comparisons were made with Bonferroni correction, with P < 0.017 defined as statistically significant. Secondary outcome measures included return of spontaneous circulation (ROSC) and number of shocks required. Demographic and clinical data were also presented for each of the 3 study periods.

RESULTS

A total of 661 cardiopulmonary arrests of all rhythms were identified during the entire study period. Primary VF/VT arrests was identified in 106 patients (16%). Of these, 102 (96%) were being monitored with continuous ECG at the time of arrest. Demographic and clinical information for the entire study cohort are displayed in Table 2. There were no differences in age, gender, time of arrest, and location of arrest between study periods (all P > 0.05). The incidence of VF/VT arrest did not vary significantly between the study periods (P = 0.16). There were no differences in mean number of defibrillation attempts per arrest; however, there was a significant improvement in the rate of perfusing rhythm after initial set of defibrillation attempts and overall ROSC favoring stacked shocks (all P < 0.05, Table 2). Survival‐to‐hospital discharge for all VF/VT arrest victims decreased, then increased significantly from the stacked shock period to initial chest compression period to modified stacked shock period (58%, 18%, 71%, respectively, P < 0.01, Figure 1). After Bonferroni correction, specific group differences were significant between the stacked shock and initial chest compression groups (P < 0.01) and modified stacked shocks and initial chest compression groups (P < 0.01, Table 2). Finally, the incidence of bystander CPR appeared to be significantly greater in the modified stacked shock period following implementation of our resuscitation program (Table 2). Overall hospital CMI for fiscal years 2005/2006 through 2012/2013 were significantly different (1.47 vs 1.71, P < 0.0001).

Demographic and Clinical Data for Study Population
ParameterStacked Shocks (n = 31)Initial Chest Compressions (n = 33)Modified Stack Shocks (n = 42)
  • NOTE: Abbreviations: CPR, cardiopulmonary resuscitation; ICC, initial chest compressions; ICU, intensive care unit; MSS, modified stack shocks; PVT, pulseless ventricular tachycardia; ROSC, return of spontaneous circulation; SS, stacked shocks; VF, ventricular fibrillation. *P < 0.001 versus periods SS and MSS. P < 0.05 versus periods SS and ICC. P < 0.05 versus period MSS. P < 0.01 versus periods SS and MSS. P < 0.001 versus periods SS and ICC.

Age (y)54.364.359.8
Male gender (%)16 (52)21 (64)21 (50)
VF/PVT arrest incidence (per 1,000 admissions)0.49 0.70
Arrest 7 am5 pm (%)15 (48)17 (52)21 (50)
Non‐ICU location (%)13 (42)15 (45)17 (40)
CPR prior to code team arrival (%)22 (71)*31 (94)42 (100)
Perfusing rhythm after initial set of defibrillation attempts (%)373370
Mean defibrillation attempts (no.)1.31.81.5
ROSC (%)765690
Survival‐to‐hospital discharge (%)18 (58)6 (18)30 (71)
Case‐mix index (average coefficient by period)1.511.601.69
Figure 1
Survival to discharge for patients with ventricular fibrillation/ventricular tachycardia arrest from 2005 to 2013. Survival was significantly lower during the initial chest compression (ICC) period as compared to stacked shocks (SS) and modified stacked shock (MSS) periods (P < 0.01).

DISCUSSION

The specific focus of this observation was to report on defibrillation strategies that have previously only been reported in an out‐of‐hospital setting. There is no current consensus regarding chest compressions for a predetermined amount of time prior to defibrillation in an inpatient setting. Here we present data suggesting improved outcomes using an approach that expedited defibrillation and included a defibrillation strategy of stacked shocks (stacked shock and modified stack shock, respectively) in monitored inpatient VF/VT arrest.

Early out‐of‐hospital studies initially demonstrated a significant survival benefit for patients who received 1.5 to 3 minutes of chest compressions preceding defibrillation with reported arrest downtimes of 4 to 5 minutes prior to emergency medical services arrival.[14, 15] However, in more recent randomized controlled trials, outcome was not improved when chest compressions were performed prior to defibrillation attempt.[16, 17] Our findings suggest that there is no one size fits all approach to chest compression and defibrillation strategy. Instead, we suggest that factors including whether the arrest occurred while monitored or not aid with decision making and timing of defibrillation.

Our findings favoring expedited defibrillation and stacked shocks in witnessed arrest are consistent with the 3‐phase model of cardiac arrest proposed by Weisfeldt and Becker suggesting that defibrillation success is related to the energy status of the heart.[18] In this model, the first 4 minutes of VF arrest (electrical phase) are characterized by a high‐energy state with higher adenosine triphosphate (ATP)/adenosine monophosphate (AMP) ratios that are associated with increased likelihood for ROSC after defibrillation attempt.[19] Further, VF appears to deplete ATP/AMP ratios after about 4 minutes, at which point the likelihood of defibrillation success is substantially diminished.[18] Between 4 and 10 minutes (circulatory phase), energy stores in the myocardium are severely depleted. However, there is evidence to suggest that high‐quality chest compressions and high chest compression fractionparticularly in conjunction with epinephrinecan replenish ATP stores and increase the likelihood of defibrillation success.[6, 20] Beyond 10 minutes (metabolic phase), survival rates are abysmal, with no therapy yet identified producing clinical utility.

The secondary analyses reveal several interesting trends. We anticipated a higher number of defibrillation attempts during phase II due to a lower likelihood of conversion with a CPR‐first approach. Instead, the number of shocks was similar across all 3 periods. Our findings are consistent with previous reports of a low single or first shock probability of successful defibrillation. However, recent reports document that approximately 80% of patients who ultimately survive to discharge are successfully defibrillated within the first 3 shocks.[21, 22, 23]

It appears that the likelihood of conversion to a perfusing rhythm is higher with expedited, stacked shocks. This underscores the importance of identifying an optimal approach to the treatment of VF/VT, as the initial series of defibrillation attempts may determine outcomes. There also appeared to be an increase in the incidence of VF/VT during the modified stack shock period, although this was not statistically significant. The modified stack shock period correlated temporally with the expansion of our institution's cardiovascular service and the opening of a dedicated inpatient facility, which likely influenced our mixture of inpatients.

These data should be interpreted with consideration of study limitations. Primarily, we did not attempt to determine arrest times prior to initial defibrillation attempts, which is likely an important variable. However, we limited our population studied only to individuals experiencing VF/VT arrest that was witnessed by hospital care staff or occurred while on cardiac monitor. We are confident that these selective criteria resulted in expedited identification and response times well within the electrical phase. We did not evaluate differences or changes in individual patient‐level severity of illness that may have potentially confounded outcome analysis. The effect of individual level in severity of illness and comorbidity are not known. Instead, we used CMI coefficients to explore hospital wide changes in patient acuity during the study period. We noticed an increasing case‐mix coefficient value suggesting higher patient acuity, which would predict increased mortality rather than the decrease noted between the initial chest compression and modified stacked shock periods (Table 2). In addition, we did not integrate CPR process variables, such as depth, rate, recoil, chest compression fraction, and per‐shock pauses, into this analysis. Our previous studies indicated that high‐quality CPR may account for a significant amount of improvement in outcomes following our novel resuscitation program implementation in 2007.[10, 24] Since the program's inception, we have reported continuous improvement in overall in‐hospital mortality that was sustained throughout the duration of the study period despite the significant changes reported in the 3 periods with monitored VF/VT arrest.[10] The use of medications prior to initial defibrillation attempts was not recorded. We have recently reported that during the same period of data collection, there were no significant changes in the use of epinephrine; however, there was a significant increase in the use of vasopressin.[10] It is unclear whether the increased use of vasopressin contributed to the current outcomes. However, given our cohort of witnessed in‐hospital cardiac arrests with an initial shockable rhythm, we anticipate the use of vasopressors as unlikely prior to defibrillation attempt.

Additional important limitations and potential confounding factors in this study were the use of 2 different types of defibrillators, differing escalating energy strategies, and differing defibrillator waveforms. Recent evidence supports biphasic waveforms as more effective than monophasic waveforms.[25, 26, 27] Comparison of defibrillator brand and waveform superiority is out the scope of this study; however, it is interesting to note similar high rates of survival in the stacked shock and modified stack shock phases despite use of different defibrillator brands and waveforms during those respective phases. Regarding escalating energy of defibrillation countershocks, the most recent 2010 AHA guidelines have no position on the superiority of either manual or automatic escalation.[7] However, we noted similar high rates of survival in the stacked shock and modified stack shock periods despite use of differing escalating strategies. Finally, we used survival‐to‐hospital discharge as our main outcome measure rather than neurological status. However, prior studies from our institution suggest that most VF/VT survivors have good neurological outcomes, which are influenced heavily by preadmission functional status.[24]

CONCLUSIONS

Our data suggest that in cases of monitored VF/VT arrest, expeditious defibrillation with use of stacked shocks is associated with a higher rate of ROSC and survival to hospital discharge

Disclosure: Nothing to report.

Cardiopulmonary arrest (CPA) is a major contributor to overall mortality in both the in‐ and out‐of‐hospital setting.[1, 2, 3] Despite advances in the field of resuscitation science, mortality from CPA remains high.[1, 4] Unlike the out‐of‐hospital environment, inpatient CPA is unique, as trained healthcare providers are the primary responders with a range of expertise available throughout the duration of arrest.

There are inherent opportunities of in‐hospital cardiac arrest that exist, such as the opportunity for near immediate arrest detection, rapid initiation of high‐quality chest compressions, and early defibrillation if indicated. Given the association between improved rates of successful defibrillation and high‐quality chest compressions, the 2005 American Heart Association (AHA) updates changed the recommended guideline ventricular fibrillation/ventricular tachycardia (VF/VT) defibrillation sequence from 3 stacked shocks to a single shock followed by 2 minutes of chest compressions between defibrillation attempts.[5, 6] However, the recommendations were directed primarily at cases of out‐of‐hospital VF/VT CPA, and it currently remains unclear as to whether this strategy offers any advantage to patients who suffer an in‐hospital VF/VT arrest.[7]

Despite the aforementioned findings regarding the benefit of high‐quality chest compressions, there is a paucity of evidence in the medical literature to support whether delivering a period of chest compressions before defibrillation attempt, including initial shock and shock sequence, translate to improved outcomes. With the exception of the statement recommending early defibrillation in case of in‐hospital arrest, there are no formal AHA consensus recommendations.[5, 8, 9] Here we document our experience using the approach of expedited stacked defibrillation shocks in persons experiencing monitored in‐hospital VF/VT arrest.

METHODS

Design

This was a retrospective study of observational data from our in‐hospital resuscitation database. Waiver of informed consent was granted by our institutional investigational review board.

Setting

This study was performed in the University of California San Diego Healthcare System, which includes 2 urban academic hospitals, with a combined total of approximately 500 beds. A designated team is activated in response to code blue requests and includes: code registered nurse (RN), code doctor of medicine (MD), airway MD, respiratory therapist, pharmacist, house nursing supervisor, primary RN, and unit charge RN. Crash carts with defibrillators (ZOLL R and E series; ZOLL Medical Corp., Chelmsford, MA) are located on each inpatient unit. Defibrillator features include real‐time cardiopulmonary resuscitation (CPR) feedback, filtered electrocardiography (ECG), and continuous waveform capnography.

Resuscitation training is provided for all hospital providers as part of the novel Advanced Resuscitation Training (ART) program, which was initiated in 2007.[10] Critical care nurses and physicians receive annual training, whereas noncritical care personnel undergo biennial training. The curriculum is adaptable to institutional treatment algorithms, equipment, and code response. Content is adaptive based on provider type, unit, and opportunities for improvement as revealed by performance improvement data. Resuscitation treatment algorithms are reviewed annually by the Critical Care Committee and Code Blue Subcommittee as part of the ART program, with modifications incorporated into the institutional policies and procedures.

Subjects

All admitted patients with continuous cardiac monitoring who suffered VF/VT arrest between July 2005 and June 2013 were included in this analysis. Patients with active do not attempt resuscitation orders were excluded. Patients were identified from our institutional resuscitation database, into which all in‐hospital cardiopulmonary arrest data are entered. We did not have data on individual patient comorbidity or severity of illness. Overall patient acuity over the course of the study was monitored hospital wide through case‐mix index (CMI). The index is based upon the allocation of hospital resources used to treat a diagnosis‐related group of patients and has previously been used as a surrogate for patient acuity.[11, 12, 13] The code RN who performed the resuscitation is responsible for entering data into a protected performance improvement database. Telecommunications records and the unit log are cross‐referenced to assure complete capture.

Protocols

Specific protocol similarities and differences among the 3 study periods are presented in Table 1.

Institutional In‐hospital Cardiopulmonary Arrest Protocol Variables During the Study Period
Protocol VariableStack Shock Period (20052008)Initial Chest Compression Period (20082011)Modified Stack Shock Period (20112013)
  • NOTE: Abbreviations: IO, intraosseous; IV, intravenous; VF, ventricular fibrillation; VT, ventricular tachycardia. *Only if monitored or witnessed at time of arrest.

Defibrillator typeMedtronic/Physio Control LifePak 12Zoll E SeriesZoll E Series
Joule increment with defibrillation200J‐300J‐360J, manual escalation120J‐150J‐200J, manual escalation120J‐150J‐200J, automatic escalation
Distinction between monitored and unmonitored in‐hospital cardiopulmonary arrestNoYesYes
Chest compressions prior to initial defibrillationNoYesNo*
Initial defibrillation strategy3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT2 minutes of chest compressions prior to initial and in between attempts3 expedited stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT*
Chest compression to ventilation ratio15:1Continuous chest compressions with ventilation at ratio 10:1Continuous chest compressions with ventilation at ratio 10:1
VasopressorsEpinephrine 1 mg IV/IO every 35 minutes.Epinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutesEpinephrine 1 mg IV/IO or vasopressin 40 units IV/IO every 35 minutes.

Stacked Shock Period (20052008)

Historically, our institutional cardiopulmonary arrest protocols advocated early defibrillation with administration of 3 stacked shocks with a brief pause between each single defibrillation attempt to confirm sustained VF/VT before initiating/resuming chest compressions.

Initial Chest Compression Period (20082011)

In 2008 the protocol was modified to reflect recommendations to perform a 2‐minute period of chest compressions prior to each defibrillation, including the initial attempt.

Modified Stacked Shack Period (20112013)

Finally, in 2011 the protocol was modified again, and defibrillators were configured to allow automatic advancement of defibrillation energy (120J‐150J‐200J). The defibrillation protocol included the following elements.

For an unmonitored arrest, chest compressions and ventilations should be initiated upon recognition of cardiopulmonary arrest. If VF/VT was identified upon placement of defibrillator pads, immediate counter shock was performed and chest compressions resumed immediately for a period of 2 minutes before considering a repeat defibrillation attempt. A dose of epinephrine (1 mg intravenous [IV]/emntraosseous [IO]) or vasopressin (40 units IV/IO) was administered as close to the reinitiation of chest compressions as possible. Defibrillation attempts proceeded with a single shock at a time, each preceded by 2 minutes of chest compressions.

For a monitored arrest, defibrillation attempts were expedited. Chest compressions without ventilations were initiated only until defibrillator pads were placed. Defibrillation attempts were initiated as soon as possible, with at least 3 or more successive shocks administered for persistent VF/VT (stacked shocks). Compressions were performed between shocks if they did not interfere with rhythm analysis. Compressions resumed following the initial series of stacked shocks with persistent CPA, regardless of rhythm, and pressors administered (epinephrine 1 mg IV or vasopressin 40 units IV). Persistent VF/VT received defibrillation attempts every 2 minutes following the initial series of stacked shocks, with compressions performed continuously between attempts. Persistent VF/VT should trigger emergent cardiology consultation for possible emergent percutaneous intervention.

Analysis

The primary outcome measure was defined as survival to hospital discharge at baseline and following each protocol change. 2 was used to compare the 3 time periods, with P < 0.05 defined as statistically significant. Specific group comparisons were made with Bonferroni correction, with P < 0.017 defined as statistically significant. Secondary outcome measures included return of spontaneous circulation (ROSC) and number of shocks required. Demographic and clinical data were also presented for each of the 3 study periods.

RESULTS

A total of 661 cardiopulmonary arrests of all rhythms were identified during the entire study period. Primary VF/VT arrests was identified in 106 patients (16%). Of these, 102 (96%) were being monitored with continuous ECG at the time of arrest. Demographic and clinical information for the entire study cohort are displayed in Table 2. There were no differences in age, gender, time of arrest, and location of arrest between study periods (all P > 0.05). The incidence of VF/VT arrest did not vary significantly between the study periods (P = 0.16). There were no differences in mean number of defibrillation attempts per arrest; however, there was a significant improvement in the rate of perfusing rhythm after initial set of defibrillation attempts and overall ROSC favoring stacked shocks (all P < 0.05, Table 2). Survival‐to‐hospital discharge for all VF/VT arrest victims decreased, then increased significantly from the stacked shock period to initial chest compression period to modified stacked shock period (58%, 18%, 71%, respectively, P < 0.01, Figure 1). After Bonferroni correction, specific group differences were significant between the stacked shock and initial chest compression groups (P < 0.01) and modified stacked shocks and initial chest compression groups (P < 0.01, Table 2). Finally, the incidence of bystander CPR appeared to be significantly greater in the modified stacked shock period following implementation of our resuscitation program (Table 2). Overall hospital CMI for fiscal years 2005/2006 through 2012/2013 were significantly different (1.47 vs 1.71, P < 0.0001).

Demographic and Clinical Data for Study Population
ParameterStacked Shocks (n = 31)Initial Chest Compressions (n = 33)Modified Stack Shocks (n = 42)
  • NOTE: Abbreviations: CPR, cardiopulmonary resuscitation; ICC, initial chest compressions; ICU, intensive care unit; MSS, modified stack shocks; PVT, pulseless ventricular tachycardia; ROSC, return of spontaneous circulation; SS, stacked shocks; VF, ventricular fibrillation. *P < 0.001 versus periods SS and MSS. P < 0.05 versus periods SS and ICC. P < 0.05 versus period MSS. P < 0.01 versus periods SS and MSS. P < 0.001 versus periods SS and ICC.

Age (y)54.364.359.8
Male gender (%)16 (52)21 (64)21 (50)
VF/PVT arrest incidence (per 1,000 admissions)0.49 0.70
Arrest 7 am5 pm (%)15 (48)17 (52)21 (50)
Non‐ICU location (%)13 (42)15 (45)17 (40)
CPR prior to code team arrival (%)22 (71)*31 (94)42 (100)
Perfusing rhythm after initial set of defibrillation attempts (%)373370
Mean defibrillation attempts (no.)1.31.81.5
ROSC (%)765690
Survival‐to‐hospital discharge (%)18 (58)6 (18)30 (71)
Case‐mix index (average coefficient by period)1.511.601.69
Figure 1
Survival to discharge for patients with ventricular fibrillation/ventricular tachycardia arrest from 2005 to 2013. Survival was significantly lower during the initial chest compression (ICC) period as compared to stacked shocks (SS) and modified stacked shock (MSS) periods (P < 0.01).

DISCUSSION

The specific focus of this observation was to report on defibrillation strategies that have previously only been reported in an out‐of‐hospital setting. There is no current consensus regarding chest compressions for a predetermined amount of time prior to defibrillation in an inpatient setting. Here we present data suggesting improved outcomes using an approach that expedited defibrillation and included a defibrillation strategy of stacked shocks (stacked shock and modified stack shock, respectively) in monitored inpatient VF/VT arrest.

Early out‐of‐hospital studies initially demonstrated a significant survival benefit for patients who received 1.5 to 3 minutes of chest compressions preceding defibrillation with reported arrest downtimes of 4 to 5 minutes prior to emergency medical services arrival.[14, 15] However, in more recent randomized controlled trials, outcome was not improved when chest compressions were performed prior to defibrillation attempt.[16, 17] Our findings suggest that there is no one size fits all approach to chest compression and defibrillation strategy. Instead, we suggest that factors including whether the arrest occurred while monitored or not aid with decision making and timing of defibrillation.

Our findings favoring expedited defibrillation and stacked shocks in witnessed arrest are consistent with the 3‐phase model of cardiac arrest proposed by Weisfeldt and Becker suggesting that defibrillation success is related to the energy status of the heart.[18] In this model, the first 4 minutes of VF arrest (electrical phase) are characterized by a high‐energy state with higher adenosine triphosphate (ATP)/adenosine monophosphate (AMP) ratios that are associated with increased likelihood for ROSC after defibrillation attempt.[19] Further, VF appears to deplete ATP/AMP ratios after about 4 minutes, at which point the likelihood of defibrillation success is substantially diminished.[18] Between 4 and 10 minutes (circulatory phase), energy stores in the myocardium are severely depleted. However, there is evidence to suggest that high‐quality chest compressions and high chest compression fractionparticularly in conjunction with epinephrinecan replenish ATP stores and increase the likelihood of defibrillation success.[6, 20] Beyond 10 minutes (metabolic phase), survival rates are abysmal, with no therapy yet identified producing clinical utility.

The secondary analyses reveal several interesting trends. We anticipated a higher number of defibrillation attempts during phase II due to a lower likelihood of conversion with a CPR‐first approach. Instead, the number of shocks was similar across all 3 periods. Our findings are consistent with previous reports of a low single or first shock probability of successful defibrillation. However, recent reports document that approximately 80% of patients who ultimately survive to discharge are successfully defibrillated within the first 3 shocks.[21, 22, 23]

It appears that the likelihood of conversion to a perfusing rhythm is higher with expedited, stacked shocks. This underscores the importance of identifying an optimal approach to the treatment of VF/VT, as the initial series of defibrillation attempts may determine outcomes. There also appeared to be an increase in the incidence of VF/VT during the modified stack shock period, although this was not statistically significant. The modified stack shock period correlated temporally with the expansion of our institution's cardiovascular service and the opening of a dedicated inpatient facility, which likely influenced our mixture of inpatients.

These data should be interpreted with consideration of study limitations. Primarily, we did not attempt to determine arrest times prior to initial defibrillation attempts, which is likely an important variable. However, we limited our population studied only to individuals experiencing VF/VT arrest that was witnessed by hospital care staff or occurred while on cardiac monitor. We are confident that these selective criteria resulted in expedited identification and response times well within the electrical phase. We did not evaluate differences or changes in individual patient‐level severity of illness that may have potentially confounded outcome analysis. The effect of individual level in severity of illness and comorbidity are not known. Instead, we used CMI coefficients to explore hospital wide changes in patient acuity during the study period. We noticed an increasing case‐mix coefficient value suggesting higher patient acuity, which would predict increased mortality rather than the decrease noted between the initial chest compression and modified stacked shock periods (Table 2). In addition, we did not integrate CPR process variables, such as depth, rate, recoil, chest compression fraction, and per‐shock pauses, into this analysis. Our previous studies indicated that high‐quality CPR may account for a significant amount of improvement in outcomes following our novel resuscitation program implementation in 2007.[10, 24] Since the program's inception, we have reported continuous improvement in overall in‐hospital mortality that was sustained throughout the duration of the study period despite the significant changes reported in the 3 periods with monitored VF/VT arrest.[10] The use of medications prior to initial defibrillation attempts was not recorded. We have recently reported that during the same period of data collection, there were no significant changes in the use of epinephrine; however, there was a significant increase in the use of vasopressin.[10] It is unclear whether the increased use of vasopressin contributed to the current outcomes. However, given our cohort of witnessed in‐hospital cardiac arrests with an initial shockable rhythm, we anticipate the use of vasopressors as unlikely prior to defibrillation attempt.

Additional important limitations and potential confounding factors in this study were the use of 2 different types of defibrillators, differing escalating energy strategies, and differing defibrillator waveforms. Recent evidence supports biphasic waveforms as more effective than monophasic waveforms.[25, 26, 27] Comparison of defibrillator brand and waveform superiority is out the scope of this study; however, it is interesting to note similar high rates of survival in the stacked shock and modified stack shock phases despite use of different defibrillator brands and waveforms during those respective phases. Regarding escalating energy of defibrillation countershocks, the most recent 2010 AHA guidelines have no position on the superiority of either manual or automatic escalation.[7] However, we noted similar high rates of survival in the stacked shock and modified stack shock periods despite use of differing escalating strategies. Finally, we used survival‐to‐hospital discharge as our main outcome measure rather than neurological status. However, prior studies from our institution suggest that most VF/VT survivors have good neurological outcomes, which are influenced heavily by preadmission functional status.[24]

CONCLUSIONS

Our data suggest that in cases of monitored VF/VT arrest, expeditious defibrillation with use of stacked shocks is associated with a higher rate of ROSC and survival to hospital discharge

Disclosure: Nothing to report.

References
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  19. Salcido DD, Menegazzi JJ, Suffoletto BP, Logue ES, Sherman LD. Association of intramyocardial high energy phosphate concentrations with quantitative measures of the ventricular fibrillation electrocardiogram waveform. Resuscitation. 2009;80:946950.
  20. Holzer M, Behringer W, Sterz F, et al. Ventricular fibrillation median frequency may not be useful for monitoring during cardiac arrest treated with endothelin‐1 or epinephrine. Anesth Analg. 2004;99:17871793, table of contents.
  21. Eftestøl T, Sunde K, Aase SO, Husøy JH, Steen PA. “Probability of successful defibrillation” as a monitor during CPR in out‐of‐hospital cardiac arrested patients. Resuscitation. 2015;48:245254.
  22. Rodriguez‐Nunez A, Lopez‐Herce J, Castillo J, Bellon JM. Shockable rhythms and defibrillation during in‐hospital pediatric cardiac arrest. Resuscitation. 2014;85:387391.
  23. Tomkins WG, Swain AH, Bailey M, Larsen PD. Beyond the pre‐shock pause: the effect of prehospital defibrillation mode on CPR interruptions and return of spontaneous circulation. Resuscitation. 2013;84:575579.
  24. Sell RE, Lawrence B, Davis DP. Implementing a “resuscitation bundle” decreases incidence and improves outcomes in inpatient cardiopulmonary arrest. Circulation 2009;120(18 Suppl):S1441.
  25. Schneider T, Martens PR, Paschen H, et al. Multicenter, randomized, controlled trial of 150‐J biphasic shocks compared with 200‐ to 360‐J monophasic shocks in the resuscitation of out‐of‐hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators. Circulation. 2000;102:17801787.
  26. Alem AP, Chapman FW, Lank P, Hart AA, Koster RW. A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out‐of‐hospital cardiac arrest. Resuscitation. 2003;58:1724.
  27. Morrison LJ, Dorian P, Long J, et al. Out‐of‐hospital cardiac arrest rectilinear biphasic to monophasic damped sine defibrillation waveforms with advanced life support intervention trial (ORBIT). Resuscitation. 2005;66:149157.
References
  1. Morrison LJ, Neumar RW, Zimmerman JL, et al. Strategies for improving survival after in‐hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation. 2013;127:15381563.
  2. Peberdy MA, Ornato JP, Larkin GL, et al. Survival from in‐hospital cardiac arrest during nights and weekends. JAMA. 2008;299:785792.
  3. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25e146.
  4. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out‐of‐hospital cardiac arrest: a systematic review and meta‐analysis. Circ Cardiovasc Qual Outcomes. 2010;3:6381.
  5. Abella BS, Alvarado JP, Myklebust H, et al. Quality of cardiopulmonary resuscitation during in‐hospital cardiac arrest. JAMA. 2005;293:305310.
  6. Christenson J, Andrusiek D, Everson‐Stewart S, et al. Chest compression fraction determines survival in patients with out‐of‐hospital ventricular fibrillation. Circulation. 2009;120:12411247.
  7. Jacobs I, Sunde K, Deakin CD, et al. Part 6: Defibrillation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122:S325S337.
  8. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S640S656.
  9. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S729S767.
  10. Davis DP, Graham PG, Husa RD, et al. A performance improvement‐based resuscitation programme reduces arrest incidence and increases survival from in‐hospital cardiac arrest. Resuscitation. 2015;92:6369.
  11. Averill RF. The evolution of case‐mix measurement using DRGs: past, present and future. Stud Health Technol Inform. 1994;14:7583.
  12. Merchant RM, Yang L, Becker LB, et al. Variability in case‐mix adjusted in‐hospital cardiac arrest rates. Med Care. 2012;50:124130.
  13. Timbie JW, Hussey PS, Adams JL, Ruder TW, Mehrotra A. Impact of socioeconomic adjustment on physicians' relative cost of care. Med Care. 2013;51:454460.
  14. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out‐of‐hospital ventricular fibrillation. JAMA. 1999;281:11821188.
  15. Wik L, Hansen TB, Fylling F, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out‐of‐hospital ventricular fibrillation: a randomized trial. JAMA. 2003;289:13891395.
  16. Baker PW, Conway J, Cotton C, et al. Defibrillation or cardiopulmonary resuscitation first for patients with out‐of‐hospital cardiac arrests found by paramedics to be in ventricular fibrillation? A randomised control trial. Resuscitation. 2008;79:424431.
  17. Jacobs IG, Finn JC, Oxer HF, Jelinek GA. CPR before defibrillation in out‐of‐hospital cardiac arrest: a randomized trial. Emerg Med Australas. 2005;17:3945.
  18. Weisfeldt ML, Becker LB. Resuscitation after cardiac arrest: a 3‐phase time‐sensitive model. JAMA. 2002;288:30353038.
  19. Salcido DD, Menegazzi JJ, Suffoletto BP, Logue ES, Sherman LD. Association of intramyocardial high energy phosphate concentrations with quantitative measures of the ventricular fibrillation electrocardiogram waveform. Resuscitation. 2009;80:946950.
  20. Holzer M, Behringer W, Sterz F, et al. Ventricular fibrillation median frequency may not be useful for monitoring during cardiac arrest treated with endothelin‐1 or epinephrine. Anesth Analg. 2004;99:17871793, table of contents.
  21. Eftestøl T, Sunde K, Aase SO, Husøy JH, Steen PA. “Probability of successful defibrillation” as a monitor during CPR in out‐of‐hospital cardiac arrested patients. Resuscitation. 2015;48:245254.
  22. Rodriguez‐Nunez A, Lopez‐Herce J, Castillo J, Bellon JM. Shockable rhythms and defibrillation during in‐hospital pediatric cardiac arrest. Resuscitation. 2014;85:387391.
  23. Tomkins WG, Swain AH, Bailey M, Larsen PD. Beyond the pre‐shock pause: the effect of prehospital defibrillation mode on CPR interruptions and return of spontaneous circulation. Resuscitation. 2013;84:575579.
  24. Sell RE, Lawrence B, Davis DP. Implementing a “resuscitation bundle” decreases incidence and improves outcomes in inpatient cardiopulmonary arrest. Circulation 2009;120(18 Suppl):S1441.
  25. Schneider T, Martens PR, Paschen H, et al. Multicenter, randomized, controlled trial of 150‐J biphasic shocks compared with 200‐ to 360‐J monophasic shocks in the resuscitation of out‐of‐hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators. Circulation. 2000;102:17801787.
  26. Alem AP, Chapman FW, Lank P, Hart AA, Koster RW. A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out‐of‐hospital cardiac arrest. Resuscitation. 2003;58:1724.
  27. Morrison LJ, Dorian P, Long J, et al. Out‐of‐hospital cardiac arrest rectilinear biphasic to monophasic damped sine defibrillation waveforms with advanced life support intervention trial (ORBIT). Resuscitation. 2005;66:149157.
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Journal of Hospital Medicine - 11(4)
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Journal of Hospital Medicine - 11(4)
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A focused investigation of expedited, stack of three shocks versus chest compressions first followed by single shocks for monitored ventricular fibrillation/ventricular tachycardia cardiopulmonary arrest in an in‐hospital setting
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A focused investigation of expedited, stack of three shocks versus chest compressions first followed by single shocks for monitored ventricular fibrillation/ventricular tachycardia cardiopulmonary arrest in an in‐hospital setting
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Address for correspondence and reprint requests: Steve A. Aguilar, MD, UCSD Center for Resuscitation Science, Department of Emergency Medicine, 200 W. Arbor Dr. #8676, San Diego, CA 92103; Telephone: 619‐528‐5164; Fax: 619‐528‐6024; E‐mail: [email protected]
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Evidence synthesis activities of a hospital evidence‐based practice center and impact on hospital decision making

Hospital evidence‐based practice centers (EPCs) are structures with the potential to facilitate the integration of evidence into institutional decision making to close knowing‐doing gaps[1, 2, 3, 4, 5, 6]; in the process, they can support the evolution of their parent institutions into learning healthcare systems.[7] The potential of hospital EPCs stems from their ability to identify and adapt national evidence‐based guidelines and systematic reviews for the local setting,[8] create local evidence‐based guidelines in the absence of national guidelines, use local data to help define problems and assess the impact of solutions,[9] and implement evidence into practice through computerized clinical decision support (CDS) interventions and other quality‐improvement (QI) initiatives.[9, 10] As such, hospital EPCs have the potential to strengthen relationships and understanding between clinicians and administrators[11]; foster a culture of evidence‐based practice; and improve the quality, safety, and value of care provided.[10]

Formal hospital EPCs remain uncommon in the United States,[10, 11, 12] though their numbers have expanded worldwide.[13, 14] This growth is due not to any reduced role for national EPCs, such as the National Institute for Health and Clinical Excellence[15] in the United Kingdom, or the 13 EPCs funded by the Agency for Healthcare Research and Quality (AHRQ)[16, 17] in the United States. Rather, this growth is fueled by the heightened awareness that the value of healthcare interventions often needs to be assessed locally, and that clinical guidelines that consider local context have a greater potential to improve quality and efficiency.[9, 18, 19]

Despite the increasing number of hospital EPCs globally, their impact on administrative and clinical decision making has rarely been examined,[13, 20] especially for hospital EPCs in the United States. The few studies that have assessed the impact of hospital EPCs on institutional decision making have done so in the context of technology acquisition, neglecting the role hospital EPCs may play in the integration of evidence into clinical practice. For example, the Technology Assessment Unit at McGill University Health Center found that of the 27 reviews commissioned in their first 5 years, 25 were implemented, with 6 (24%) recommending investments in new technologies and 19 (76%) recommending rejection, for a reported net hospital savings of $10 million.[21] Understanding the activities and impact of hospital EPCs is particularly critical for hospitalist leaders, who could leverage hospital EPCs to inform efforts to support the quality, safety, and value of care provided, or who may choose to establish or lead such infrastructure. The availability of such opportunities could also support hospitalist recruitment and retention.

In 2006, the University of Pennsylvania Health System (UPHS) created the Center for Evidence‐based Practice (CEP) to support the integration of evidence into practice to strengthen quality, safety, and value.[10] Cofounded by hospitalists with formal training in clinical epidemiology, the CEP performs rapid systematic reviews of the scientific literature to inform local practice and policy. In this article, we describe the first 8 years of the CEP's evidence synthesis activities and examine its impact on decision making across the health system.

METHODS

Setting

The UPHS includes 3 acute care hospitals, and inpatient facilities specializing in acute rehabilitation, skilled nursing, long‐term acute care, and hospice, with a capacity of more than 1800 beds and 75,000 annual admissions, as well as primary care and specialty clinics with more than 2 million annual outpatient visits. The CEP is funded by and organized within the Office of the UPHS Chief Medical Officer, serves all UPHS facilities, has an annual budget of approximately $1 million, and is currently staffed by a hospitalist director, 3 research analysts, 6 physician and nurse liaisons, a health economist, biostatistician, administrator, and librarians, totaling 5.5 full time equivalents.

The mission of the CEP is to support the quality, safety, and value of care at Penn through evidence‐based practice. To accomplish this mission, the CEP performs rapid systematic reviews, translates evidence into practice through the use of CDS interventions and clinical pathways, and offers education in evidence‐based decision making to trainees, staff, and faculty. This study is focused on the CEP's evidence synthesis activities.

Typically, clinical and administrative leaders submit a request to the CEP for an evidence review, the request is discussed and approved at the weekly staff meeting, and a research analyst and clinical liaison are assigned to the request and communicate with the requestor to clearly define the question of interest. Subsequently, the research analyst completes a protocol, a draft search, and a draft report, each reviewed and approved by the clinical liaison and requestor. The final report is posted to the website, disseminated to all key stakeholders across the UPHS as identified by the clinical liaisons, and integrated into decision making through various routes, including in‐person presentations to decision makers, and CDS and QI initiatives.

Study Design

The study included an analysis of an internal database of evidence reviews and a survey of report requestors, and was exempted from institutional review board review. Survey respondents were informed that their responses would be confidential and did not receive incentives.

Internal Database of Reports

Data from the CEP's internal management database were analyzed for its first 8 fiscal years (July 2006June 2014). Variables included requestor characteristics, report characteristics (eg, technology reviewed, clinical specialty examined, completion time, and performance of meta‐analyses and GRADE [Grading of Recommendations Assessment, Development and Evaluation] analyses[22]), report use (eg, integration of report into CDS interventions) and dissemination beyond the UPHS (eg, submission to Center for Reviews and Dissemination [CRD] Health Technology Assessment [HTA] database[23] and to peer‐reviewed journals). Report completion time was defined as the time between the date work began on the report and the date the final report was sent to the requestor. The technology categorization scheme was adapted from that provided by Goodman (2004)[24] and the UK National Institute for Health Research HTA Programme.[25] We systematically assigned the technology reviewed in each report to 1 of 8 mutually exclusive categories. The clinical specialty examined in each report was determined using an algorithm (see Supporting Information, Appendix 1, in the online version of this article).

We compared the report completion times and the proportions of requestor types, technologies reviewed, and clinical specialties examined in the CEP's first 4 fiscal years (July 2006June 2010) to those in the CEP's second 4 fiscal years (July 2010June 2014) using t tests and 2 tests for continuous and categorical variables, respectively.

Survey

We conducted a Web‐based survey (see Supporting Information, Appendix 2, in the online version of this article) of all requestors of the 139 rapid reviews completed in the last 4 fiscal years. Participants who requested multiple reports were surveyed only about the most recent report. Requestors were invited to participate in the survey via e‐mail, and follow‐up e‐mails were sent to nonrespondents at 7, 14, and 16 days. Nonrespondents and respondents were compared with respect to requestor type (physician vs nonphysician) and topic evaluated (traditional HTA topics such as drugs, biologics, and devices vs nontraditional HTA topics such as processes of care). The survey was administered using REDCap[26] electronic data capture tools. The 44‐item questionnaire collected data on the interaction between the requestor and the CEP, report characteristics, report impact, and requestor satisfaction.

Survey results were imported into Microsoft Excel (Microsoft Corp, Redmond, WA) and SPSS (IBM, Armonk, NY) for analysis. Descriptive statistics were generated, and statistical comparisons were conducted using 2 and Fisher exact tests.

RESULTS

Evidence Synthesis Activity

The CEP has produced several different report products since its inception. Evidence reviews (57%, n = 142) consist of a systematic review and analysis of the primary literature. Evidence advisories (32%, n = 79) are summaries of evidence from secondary sources such as guidelines or systematic reviews. Evidence inventories (3%, n = 7) are literature searches that describe the quantity and focus of available evidence, without analysis or synthesis.[27]

The categories of technologies examined, including their definitions and examples, are provided in Table 1. Drugs (24%, n = 60) and devices/equipment/supplies (19%, n = 48) were most commonly examined. The proportion of reports examining technology types traditionally evaluated by HTA organizations significantly decreased when comparing the first 4 years of CEP activity to the second 4 years (62% vs 38%, P < 0.01), whereas reports examining less traditionally reviewed categories increased (38% vs 62%, P < 0.01). The most common clinical specialties represented by the CEP reports were nursing (11%, n = 28), general surgery (11%, n = 28), critical care (10%, n = 24), and general medicine (9%, n = 22) (see Supporting Information, Appendix 3, in the online version of this article). Clinical departments were the most common requestors (29%, n = 72) (Table 2). The proportion of requests from clinical departments significantly increased when comparing the first 4 years to the second 4 years (20% vs 36%, P < 0.01), with requests from purchasing committees significantly decreasing (25% vs 6%, P < 0.01). The overall report completion time was 70 days, and significantly decreased when comparing the first 4 years to the second 4 years (89 days vs 50 days, P < 0.01).

Technology Categories, Definitions, Examples, and Frequencies by Fiscal Years
CategoryDefinitionExamplesTotal2007201020112014P Value
Total  249 (100%)109 (100%)140 (100%) 
DrugA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a pharmacologic agentCelecoxib for pain in joint arthroplasty; colchicine for prevention of pericarditis and atrial fibrillation60 (24%)35 (32%)25 (18%)0.009
Device, equipment, and suppliesA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory that is intended for use in the prevention, diagnosis, or treatment of disease and does not achieve its primary intended purposes though chemical action or metabolism[50]Thermometers for pediatric use; femoral closure devices for cardiac catheterization48 (19%)25 (23%)23 (16%)0.19
Process of careA report primarily examining a clinical pathway or a clinical practice guideline that significantly involves elements of prevention, diagnosis, and/or treatment or significantly incorporates 2 or more of the other technology categoriesPreventing patient falls; prevention and management of delirium31 (12%)18 (17%)13 (9%)0.09
Test, scale, or risk factorA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a test intended to screen for, diagnose, classify, or monitor the progression of a diseaseComputed tomography for acute chest pain; urine drug screening in chronic pain patients on opioid therapy31 (12%)8 (7%)23 (16%)0.03
Medical/surgical procedureA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a medical intervention that is not a drug, device, or test or of the application or removal of a deviceBiliary drainage for chemotherapy patients; cognitive behavioral therapy for insomnia26 (10%)8 (7%)18 (13%)0.16
Policy or organizational/managerial systemA report primarily examining laws or regulations; the organization, financing, or delivery of care, including settings of care; or healthcare providersMedical care costs and productivity changes associated with smoking; physician training and credentialing for robotic surgery in obstetrics and gynecology26 (10%)4 (4%)22 (16%)0.002
Support systemA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an intervention designed to provide a new or improved service to patients or healthcare providers that does not fall into 1 of the other categoriesReconciliation of data from differing electronic medical records; social media, text messaging, and postdischarge communication14 (6%)3 (3%)11 (8%)0.09
BiologicA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a product manufactured in a living systemRecombinant factor VIIa for cardiovascular surgery; osteobiologics for orthopedic fusions13 (5%)8 (7%)5 (4%)0.19
Requestor Categories and Frequencies by Fiscal Years
CategoryTotal2007201020112014P Value
  • NOTE: *Other includes ad hoc committees, CEP, Children's Hospital of Philadelphia, IT committees, payers, and the primary care network.. Abbreviations: CEP, Center for Evidence‐based Practice; CMO, chief medical officer; IT, information technology.

Total249 (100%)109 (100%)140 (100%) 
Clinical department72 (29%)22 (20%)50 (36%)0.007
CMO47 (19%)21 (19%)26 (19%)0.92
Purchasing committee35 (14%)27 (25%)8 (6%)<0.001
Formulary committee22 (9%)12 (11%)10 (7%)0.54
Quality committee21 (8%)11 (10%)10 (7%)0.42
Administrative department19 (8%)5 (5%)14 (10%)0.11
Nursing14 (6%)4 (4%)10 (7%)0.23
Other*19 (8%)7 (6%)12 (9%)0.55

Thirty‐seven (15%) reports included meta‐analyses conducted by CEP staff. Seventy‐five reports (30%) contained an evaluation of the quality of the evidence base using GRADE analyses.[22] Of these reports, the highest GRADE of evidence available for any comparison of interest was moderate (35%, n = 26) or high (33%, n = 25) in most cases, followed by very low (19%, n = 14) and low (13%, n = 10).

Reports were disseminated in a variety of ways beyond direct dissemination and presentation to requestors and posting on the center website. Thirty reports (12%) informed CDS interventions, 24 (10%) resulted in peer‐reviewed publications, and 204 (82%) were posted to the CRD HTA database.

Evidence Synthesis Impact

A total of 139 reports were completed between July 2010 and June 2014 for 65 individual requestors. Email invitations to participate in the survey were sent to the 64 requestors employed by the UPHS. The response rate was 72% (46/64). The proportions of physician requestors and traditional HTA topics evaluated were similar across respondents and nonrespondents (43% [20/46] vs 39% [7/18], P = 0.74; and 37% [17/46] vs 44% [8/18], P = 0.58, respectively). Aggregated survey responses are presented for items using a Likert scale in Figure 1, and for items using a yes/no or ordinal scale in Table 3.

Responses to Yes/No and Ranking Survey Questions
Items% of Respondents Responding Affirmatively
 Percentage of Respondents Ranking as First Choice*
  • NOTE: Abbreviations: CEP, Center for Evidence‐based Practice. *The sum of these percentages is greater than 100 percent because respondents could rank multiple options first.

Requestor activity 
What factors prompted you to request a report from CEP? (Please select all that apply.) 
My own time constraints28% (13/46)
CEP's ability to identify and synthesize evidence89% (41/46)
CEP's objectivity52% (24/46)
Recommendation from colleague30% (14/46)
Did you conduct any of your own literature searches before contacting CEP?67% (31/46)
Did you obtain and read any of the articles cited in CEP's report?63% (29/46)
Did you read the following sections of CEP's report? 
Evidence summary (at beginning of report)100% (45/45)
Introduction/background93% (42/45)
Methods84% (38/45)
Results98% (43/43)
Conclusion100% (43/43)
Report dissemination 
Did you share CEP's report with anyone NOT involved in requesting the report or in making the final decision?67% (30/45)
Did you share CEP's report with anyone outside of Penn?7% (3/45)
Requestor preferences 
Would it be helpful for CEP staff to call you after you receive any future CEP reports to answer any questions you might have?55% (24/44)
Following any future reports you request from CEP, would you be willing to complete a brief questionnaire?100% (44/44)
Please rank how you would prefer to receive reports from CEP in the future. 
E‐mail containing the report as a PDF attachment77% (34/44)
E‐mail containing a link to the report on CEP's website16% (7/44)
In‐person presentation by the CEP analyst writing the report18% (8/44)
In‐person presentation by the CEP director involved in the report16% (7/44)
Figure 1
Requestor responses to Likert survey questions. Abbreviations: CEP, Center for Evidence‐based Practice.

In general, respondents found reports easy to request, easy to use, timely, and relevant, resulting in high requestor satisfaction. In addition, 98% described the scope of content and level of detail as about right. Report impact was rated highly as well, with the evidence summary and conclusions rated as the most critical to decision making. A majority of respondents indicated that reports confirmed their tentative decision (77%, n = 34), whereas some changed their tentative decision (7%, n = 3), and others suggested the report had no effect on their tentative decision (16%, n = 7). Respondents indicated the amount of time that elapsed between receiving reports and making final decisions was 1 to 7 days (5%, n = 2), 8 to 30 days (40%, n = 17), 1 to 3 months (37%, n = 16), 4 to 6 months (9%, n = 4), or greater than 6 months (9%, n = 4). The most common reasons cited for requesting a report were the CEP's evidence synthesis skills and objectivity.

DISCUSSION

To our knowledge, this is the first comprehensive description and assessment of evidence synthesis activity by a hospital EPC in the United States. Our findings suggest that clinical and administrative leaders will request reports from a hospital EPC, and that hospital EPCs can promptly produce reports when requested. Moreover, these syntheses can address a wide range of clinical and policy topics, and can be disseminated through a variety of routes. Lastly, requestors are satisfied by these syntheses, and report that they inform decision making. These results suggest that EPCs may be an effective infrastructure paradigm for promoting evidence‐based decision making within healthcare provider organizations, and are consistent with previous analyses of hospital‐based EPCs.[21, 28, 29]

Over half of report requestors cited CEP's objectivity as a factor in their decision to request a report, underscoring the value of a neutral entity in an environment where clinical departments and hospital committees may have competing interests.[10] This asset was 1 of the primary drivers for establishing our hospital EPC. Concerns by clinical executives about the influence of industry and local politics on institutional decision making, and a desire to have clinical evidence more systematically and objectively integrated into decision making, fueled our center's funding.

The survey results also demonstrate that respondents were satisfied with the reports for many reasons, including readability, concision, timeliness, scope, and content, consistent with the evaluation of the French hospital‐based EPC CEDIT (French Committee for the Assessment and Dissemination of Technological Innovations).[29] Given the importance of readability, concision, and relevance that has been previously described,[16, 28, 30] nearly all CEP reports contain an evidence summary on the first page that highlights key findings in a concise, user‐friendly format.[31] The evidence summaries include bullet points that: (1) reference the most pertinent guideline recommendations along with their strength of recommendation and underlying quality of evidence; (2) organize and summarize study findings using the most critical clinical outcomes, including an assessment of the quality of the underlying evidence for each outcome; and (3) note important limitations of the findings.

Evidence syntheses must be timely to allow decision makers to act on the findings.[28, 32] The primary criticism of CEDIT was the lag between requests and report publication.[29] Rapid reviews, designed to inform urgent decisions, can overcome this challenge.[31, 33, 34] CEP reviews required approximately 2 months to complete on average, consistent with the most rapid timelines reported,[31, 33, 34] and much shorter than standard systematic review timelines, which can take up to 12 to 24 months.[33] Working with requestors to limit the scope of reviews to those issues most critical to a decision, using secondary resources when available, and hiring experienced research analysts help achieve these efficiencies.

The study by Bodeau‐Livinec also argues for the importance of report accessibility to ensure dissemination.[29] This is consistent with the CEP's approach, where all reports are posted on the UPHS internal website. Many also inform QI initiatives, as well as CDS interventions that address topics of general interest to acute care hospitals, such as venous thromboembolism (VTE) prophylaxis,[35] blood product transfusions,[36] sepsis care,[37, 38] and prevention of catheter‐associated urinary tract infections (CAUTI)[39] and hospital readmissions.[40] Most reports are also listed in an international database of rapid reviews,[23] and reports that address topics of general interest, have sufficient evidence to synthesize, and have no prior published systematic reviews are published in the peer‐reviewed literature.[41, 42]

The majority of reports completed by the CEP were evidence reviews, or systematic reviews of primary literature, suggesting that CEP reports often address questions previously unanswered by existing published systematic reviews; however, about a third of reports were evidence advisories, or summaries of evidence from preexisting secondary sources. The relative scarcity of high‐quality evidence bases in those reports where GRADE analyses were conducted might be expected, as requestors may be more likely to seek guidance when the evidence base on a topic is lacking. This was further supported by the small percentage (15%) of reports where adequate data of sufficient homogeneity existed to allow meta‐analyses. The small number of original meta‐analyses performed also reflects our reliance on secondary resources when available.

Only 7% of respondents reported that tentative decisions were changed based on their report. This is not surprising, as evidence reviews infrequently result in clear go or no go recommendations. More commonly, they address or inform complex clinical questions or pathways. In this context, the change/confirm/no effect framework may not completely reflect respondents' use of or benefit from reports. Thus, we included a diverse set of questions in our survey to best estimate the value of our reports. For example, when asked whether the report answered the question posed, informed their final decision, or was consistent with their final decision, 91%, 79%, and 71% agreed or strongly agreed, respectively. When asked whether they would request a report again if they had to do it all over, recommend CEP to their colleagues, and be likely to request reports in the future, at least 95% of survey respondents agreed or strongly agreed. In addition, no respondent indicated that their report was not timely enough to influence their decision. Moreover, only a minority of respondents expressed disappointment that the CEP's report did not provide actionable recommendations due to a lack of published evidence (9%, n = 4). Importantly, the large proportion of requestors indicating that reports confirmed their tentative decisions may be a reflection of hindsight bias.

The most apparent trend in the production of CEP reviews over time is the relative increase in requests by clinical departments, suggesting that the CEP is being increasingly consulted to help define best clinical practices. This is also supported by the relative increase in reports focused on policy or organizational/managerial systems. These findings suggest that hospital EPCs have value beyond the traditional realm of HTA.

This study has a number of limitations. First, not all of the eligible report requestors responded to our survey. Despite this, our response rate of 72% compares favorably with surveys published in medical journals.[43] In addition, nonresponse bias may be less important in physician surveys than surveys of the general population.[44] The similarity in requestor and report characteristics for respondents and nonrespondents supports this. Second, our survey of impact is self‐reported rather than an evaluation of actual decision making or patient outcomes. Thus, the survey relies on the accuracy of the responses. Third, recall bias must be considered, as some respondents were asked to evaluate reports that were greater than 1 year old. To reduce this bias, we asked respondents to consider the most recent report they requested, included that report as an attachment in the survey request, and only surveyed requestors from the most recent 4 of the CEP's 8 fiscal years. Fourth, social desirability bias could have also affected the survey responses, though it was likely minimized by the promise of confidentiality. Fifth, an examination of the impact of the CEP on costs was outside the scope of this evaluation; however, such information may be important to those assessing the sustainability or return on investment of such centers. Simple approaches we have previously used to approximate the value of our activities include: (1) estimating hospital cost savings resulting from decisions supported by our reports, such as the use of technologies like chlorhexidine for surgical site infections[45] or discontinuation of technologies like aprotinin for cardiac surgery[46]; and (2) estimating penalties avoided or rewards attained as a result of center‐led initiatives, such as those to increase VTE prophylaxis,[35] reduce CAUTI rates,[39] and reduce preventable mortality associated with sepsis.[37, 38] Similarly, given the focus of this study on the local evidence synthesis activities of our center, our examination did not include a detailed description of our CDS activities, or teaching activities, including our multidisciplinary workshops for physicians and nurses in evidence‐based QI[47] and our novel evidence‐based practice curriculum for medical students. Our study also did not include a description of our extramural activities, such as those supported by our contract with AHRQ as 1 of their 13 EPCs.[16, 17, 48, 49] A consideration of all of these activities enables a greater appreciation for the potential of such centers. Lastly, we examined a single EPC, which may not be representative of the diversity of hospitals and hospital staff across the United States. However, our EPC serves a diverse array of patient populations, clinical services, and service models throughout our multientity academic healthcare system, which may improve the generalizability of our experience to other settings.

As next steps, we recommend evaluation of other existing hospital EPCs nationally. Such studies could help hospitals and health systems ascertain which of their internal decisions might benefit from locally sourced rapid systematic reviews and determine whether an in‐house EPC could improve the value of care delivered.

In conclusion, our findings suggest that hospital EPCs within academic healthcare systems can efficiently synthesize and disseminate evidence for a variety of stakeholders. Moreover, these syntheses impact decision making in a variety of hospital contexts and clinical specialties. Hospitals and hospitalist leaders seeking to improve the implementation of evidence‐based practice at a systems level might consider establishing such infrastructure locally.

Acknowledgements

The authors thank Fran Barg, PhD (Department of Family Medicine and Community Health, University of Pennsylvania Perelman School of Medicine) and Joel Betesh, MD (University of Pennsylvania Health System) for their contributions to developing the survey. They did not receive any compensation for their contributions.

Disclosures: An earlier version of this work was presented as a poster at the 2014 AMA Research Symposium, November 7, 2014, Dallas, Texas. Mr. Jayakumar reports having received a University of Pennsylvania fellowship as a summer intern at the Center for Evidence‐based Practice. Dr. Umscheid cocreated and directs a hospital evidence‐based practice center, is the Senior Associate Director of an Agency for Healthcare Research and Quality Evidence‐Based Practice Center, and is a past member of the Medicare Evidence Development and Coverage Advisory Committee, which uses evidence reports developed by the Evidence‐based Practice Centers of the Agency for Healthcare Research and Quality. Dr. Umscheid's contribution was supported in part by the National Center for Research Resources, grant UL1RR024134, which is now at the National Center for Advancing Translational Sciences, grant UL1TR000003. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. None of the funders had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Lavenberg, Dr. Mitchell, and Mr. Leas are employed as research analysts by a hospital evidence‐based practice center. Dr. Doshi is supported in part by a hospital evidence‐based practice center and is an Associate Director of an Agency for Healthcare Research and Quality Evidence‐based Practice Center. Dr. Goldmann is emeritus faculty at Penn, is supported in part by a hospital evidence‐based practice center, and is the Vice President and Chief Quality Assurance Officer in Clinical Solutions, a division of Elsevier, Inc., a global publishing company, and director of the division's Evidence‐based Medicine Center. Dr. Williams cocreated and codirects a hospital evidence‐based practice center. Dr. Brennan has oversight for and helped create a hospital evidence‐based practice center.

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References
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  35. Umscheid CA, Hanish A, Chittams J, Weiner MG, Hecht TEH. Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi‐experimental study. BMC Med Inform Decis Mak. 2012;12:92.
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Hospital evidence‐based practice centers (EPCs) are structures with the potential to facilitate the integration of evidence into institutional decision making to close knowing‐doing gaps[1, 2, 3, 4, 5, 6]; in the process, they can support the evolution of their parent institutions into learning healthcare systems.[7] The potential of hospital EPCs stems from their ability to identify and adapt national evidence‐based guidelines and systematic reviews for the local setting,[8] create local evidence‐based guidelines in the absence of national guidelines, use local data to help define problems and assess the impact of solutions,[9] and implement evidence into practice through computerized clinical decision support (CDS) interventions and other quality‐improvement (QI) initiatives.[9, 10] As such, hospital EPCs have the potential to strengthen relationships and understanding between clinicians and administrators[11]; foster a culture of evidence‐based practice; and improve the quality, safety, and value of care provided.[10]

Formal hospital EPCs remain uncommon in the United States,[10, 11, 12] though their numbers have expanded worldwide.[13, 14] This growth is due not to any reduced role for national EPCs, such as the National Institute for Health and Clinical Excellence[15] in the United Kingdom, or the 13 EPCs funded by the Agency for Healthcare Research and Quality (AHRQ)[16, 17] in the United States. Rather, this growth is fueled by the heightened awareness that the value of healthcare interventions often needs to be assessed locally, and that clinical guidelines that consider local context have a greater potential to improve quality and efficiency.[9, 18, 19]

Despite the increasing number of hospital EPCs globally, their impact on administrative and clinical decision making has rarely been examined,[13, 20] especially for hospital EPCs in the United States. The few studies that have assessed the impact of hospital EPCs on institutional decision making have done so in the context of technology acquisition, neglecting the role hospital EPCs may play in the integration of evidence into clinical practice. For example, the Technology Assessment Unit at McGill University Health Center found that of the 27 reviews commissioned in their first 5 years, 25 were implemented, with 6 (24%) recommending investments in new technologies and 19 (76%) recommending rejection, for a reported net hospital savings of $10 million.[21] Understanding the activities and impact of hospital EPCs is particularly critical for hospitalist leaders, who could leverage hospital EPCs to inform efforts to support the quality, safety, and value of care provided, or who may choose to establish or lead such infrastructure. The availability of such opportunities could also support hospitalist recruitment and retention.

In 2006, the University of Pennsylvania Health System (UPHS) created the Center for Evidence‐based Practice (CEP) to support the integration of evidence into practice to strengthen quality, safety, and value.[10] Cofounded by hospitalists with formal training in clinical epidemiology, the CEP performs rapid systematic reviews of the scientific literature to inform local practice and policy. In this article, we describe the first 8 years of the CEP's evidence synthesis activities and examine its impact on decision making across the health system.

METHODS

Setting

The UPHS includes 3 acute care hospitals, and inpatient facilities specializing in acute rehabilitation, skilled nursing, long‐term acute care, and hospice, with a capacity of more than 1800 beds and 75,000 annual admissions, as well as primary care and specialty clinics with more than 2 million annual outpatient visits. The CEP is funded by and organized within the Office of the UPHS Chief Medical Officer, serves all UPHS facilities, has an annual budget of approximately $1 million, and is currently staffed by a hospitalist director, 3 research analysts, 6 physician and nurse liaisons, a health economist, biostatistician, administrator, and librarians, totaling 5.5 full time equivalents.

The mission of the CEP is to support the quality, safety, and value of care at Penn through evidence‐based practice. To accomplish this mission, the CEP performs rapid systematic reviews, translates evidence into practice through the use of CDS interventions and clinical pathways, and offers education in evidence‐based decision making to trainees, staff, and faculty. This study is focused on the CEP's evidence synthesis activities.

Typically, clinical and administrative leaders submit a request to the CEP for an evidence review, the request is discussed and approved at the weekly staff meeting, and a research analyst and clinical liaison are assigned to the request and communicate with the requestor to clearly define the question of interest. Subsequently, the research analyst completes a protocol, a draft search, and a draft report, each reviewed and approved by the clinical liaison and requestor. The final report is posted to the website, disseminated to all key stakeholders across the UPHS as identified by the clinical liaisons, and integrated into decision making through various routes, including in‐person presentations to decision makers, and CDS and QI initiatives.

Study Design

The study included an analysis of an internal database of evidence reviews and a survey of report requestors, and was exempted from institutional review board review. Survey respondents were informed that their responses would be confidential and did not receive incentives.

Internal Database of Reports

Data from the CEP's internal management database were analyzed for its first 8 fiscal years (July 2006June 2014). Variables included requestor characteristics, report characteristics (eg, technology reviewed, clinical specialty examined, completion time, and performance of meta‐analyses and GRADE [Grading of Recommendations Assessment, Development and Evaluation] analyses[22]), report use (eg, integration of report into CDS interventions) and dissemination beyond the UPHS (eg, submission to Center for Reviews and Dissemination [CRD] Health Technology Assessment [HTA] database[23] and to peer‐reviewed journals). Report completion time was defined as the time between the date work began on the report and the date the final report was sent to the requestor. The technology categorization scheme was adapted from that provided by Goodman (2004)[24] and the UK National Institute for Health Research HTA Programme.[25] We systematically assigned the technology reviewed in each report to 1 of 8 mutually exclusive categories. The clinical specialty examined in each report was determined using an algorithm (see Supporting Information, Appendix 1, in the online version of this article).

We compared the report completion times and the proportions of requestor types, technologies reviewed, and clinical specialties examined in the CEP's first 4 fiscal years (July 2006June 2010) to those in the CEP's second 4 fiscal years (July 2010June 2014) using t tests and 2 tests for continuous and categorical variables, respectively.

Survey

We conducted a Web‐based survey (see Supporting Information, Appendix 2, in the online version of this article) of all requestors of the 139 rapid reviews completed in the last 4 fiscal years. Participants who requested multiple reports were surveyed only about the most recent report. Requestors were invited to participate in the survey via e‐mail, and follow‐up e‐mails were sent to nonrespondents at 7, 14, and 16 days. Nonrespondents and respondents were compared with respect to requestor type (physician vs nonphysician) and topic evaluated (traditional HTA topics such as drugs, biologics, and devices vs nontraditional HTA topics such as processes of care). The survey was administered using REDCap[26] electronic data capture tools. The 44‐item questionnaire collected data on the interaction between the requestor and the CEP, report characteristics, report impact, and requestor satisfaction.

Survey results were imported into Microsoft Excel (Microsoft Corp, Redmond, WA) and SPSS (IBM, Armonk, NY) for analysis. Descriptive statistics were generated, and statistical comparisons were conducted using 2 and Fisher exact tests.

RESULTS

Evidence Synthesis Activity

The CEP has produced several different report products since its inception. Evidence reviews (57%, n = 142) consist of a systematic review and analysis of the primary literature. Evidence advisories (32%, n = 79) are summaries of evidence from secondary sources such as guidelines or systematic reviews. Evidence inventories (3%, n = 7) are literature searches that describe the quantity and focus of available evidence, without analysis or synthesis.[27]

The categories of technologies examined, including their definitions and examples, are provided in Table 1. Drugs (24%, n = 60) and devices/equipment/supplies (19%, n = 48) were most commonly examined. The proportion of reports examining technology types traditionally evaluated by HTA organizations significantly decreased when comparing the first 4 years of CEP activity to the second 4 years (62% vs 38%, P < 0.01), whereas reports examining less traditionally reviewed categories increased (38% vs 62%, P < 0.01). The most common clinical specialties represented by the CEP reports were nursing (11%, n = 28), general surgery (11%, n = 28), critical care (10%, n = 24), and general medicine (9%, n = 22) (see Supporting Information, Appendix 3, in the online version of this article). Clinical departments were the most common requestors (29%, n = 72) (Table 2). The proportion of requests from clinical departments significantly increased when comparing the first 4 years to the second 4 years (20% vs 36%, P < 0.01), with requests from purchasing committees significantly decreasing (25% vs 6%, P < 0.01). The overall report completion time was 70 days, and significantly decreased when comparing the first 4 years to the second 4 years (89 days vs 50 days, P < 0.01).

Technology Categories, Definitions, Examples, and Frequencies by Fiscal Years
CategoryDefinitionExamplesTotal2007201020112014P Value
Total  249 (100%)109 (100%)140 (100%) 
DrugA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a pharmacologic agentCelecoxib for pain in joint arthroplasty; colchicine for prevention of pericarditis and atrial fibrillation60 (24%)35 (32%)25 (18%)0.009
Device, equipment, and suppliesA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory that is intended for use in the prevention, diagnosis, or treatment of disease and does not achieve its primary intended purposes though chemical action or metabolism[50]Thermometers for pediatric use; femoral closure devices for cardiac catheterization48 (19%)25 (23%)23 (16%)0.19
Process of careA report primarily examining a clinical pathway or a clinical practice guideline that significantly involves elements of prevention, diagnosis, and/or treatment or significantly incorporates 2 or more of the other technology categoriesPreventing patient falls; prevention and management of delirium31 (12%)18 (17%)13 (9%)0.09
Test, scale, or risk factorA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a test intended to screen for, diagnose, classify, or monitor the progression of a diseaseComputed tomography for acute chest pain; urine drug screening in chronic pain patients on opioid therapy31 (12%)8 (7%)23 (16%)0.03
Medical/surgical procedureA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a medical intervention that is not a drug, device, or test or of the application or removal of a deviceBiliary drainage for chemotherapy patients; cognitive behavioral therapy for insomnia26 (10%)8 (7%)18 (13%)0.16
Policy or organizational/managerial systemA report primarily examining laws or regulations; the organization, financing, or delivery of care, including settings of care; or healthcare providersMedical care costs and productivity changes associated with smoking; physician training and credentialing for robotic surgery in obstetrics and gynecology26 (10%)4 (4%)22 (16%)0.002
Support systemA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an intervention designed to provide a new or improved service to patients or healthcare providers that does not fall into 1 of the other categoriesReconciliation of data from differing electronic medical records; social media, text messaging, and postdischarge communication14 (6%)3 (3%)11 (8%)0.09
BiologicA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a product manufactured in a living systemRecombinant factor VIIa for cardiovascular surgery; osteobiologics for orthopedic fusions13 (5%)8 (7%)5 (4%)0.19
Requestor Categories and Frequencies by Fiscal Years
CategoryTotal2007201020112014P Value
  • NOTE: *Other includes ad hoc committees, CEP, Children's Hospital of Philadelphia, IT committees, payers, and the primary care network.. Abbreviations: CEP, Center for Evidence‐based Practice; CMO, chief medical officer; IT, information technology.

Total249 (100%)109 (100%)140 (100%) 
Clinical department72 (29%)22 (20%)50 (36%)0.007
CMO47 (19%)21 (19%)26 (19%)0.92
Purchasing committee35 (14%)27 (25%)8 (6%)<0.001
Formulary committee22 (9%)12 (11%)10 (7%)0.54
Quality committee21 (8%)11 (10%)10 (7%)0.42
Administrative department19 (8%)5 (5%)14 (10%)0.11
Nursing14 (6%)4 (4%)10 (7%)0.23
Other*19 (8%)7 (6%)12 (9%)0.55

Thirty‐seven (15%) reports included meta‐analyses conducted by CEP staff. Seventy‐five reports (30%) contained an evaluation of the quality of the evidence base using GRADE analyses.[22] Of these reports, the highest GRADE of evidence available for any comparison of interest was moderate (35%, n = 26) or high (33%, n = 25) in most cases, followed by very low (19%, n = 14) and low (13%, n = 10).

Reports were disseminated in a variety of ways beyond direct dissemination and presentation to requestors and posting on the center website. Thirty reports (12%) informed CDS interventions, 24 (10%) resulted in peer‐reviewed publications, and 204 (82%) were posted to the CRD HTA database.

Evidence Synthesis Impact

A total of 139 reports were completed between July 2010 and June 2014 for 65 individual requestors. Email invitations to participate in the survey were sent to the 64 requestors employed by the UPHS. The response rate was 72% (46/64). The proportions of physician requestors and traditional HTA topics evaluated were similar across respondents and nonrespondents (43% [20/46] vs 39% [7/18], P = 0.74; and 37% [17/46] vs 44% [8/18], P = 0.58, respectively). Aggregated survey responses are presented for items using a Likert scale in Figure 1, and for items using a yes/no or ordinal scale in Table 3.

Responses to Yes/No and Ranking Survey Questions
Items% of Respondents Responding Affirmatively
 Percentage of Respondents Ranking as First Choice*
  • NOTE: Abbreviations: CEP, Center for Evidence‐based Practice. *The sum of these percentages is greater than 100 percent because respondents could rank multiple options first.

Requestor activity 
What factors prompted you to request a report from CEP? (Please select all that apply.) 
My own time constraints28% (13/46)
CEP's ability to identify and synthesize evidence89% (41/46)
CEP's objectivity52% (24/46)
Recommendation from colleague30% (14/46)
Did you conduct any of your own literature searches before contacting CEP?67% (31/46)
Did you obtain and read any of the articles cited in CEP's report?63% (29/46)
Did you read the following sections of CEP's report? 
Evidence summary (at beginning of report)100% (45/45)
Introduction/background93% (42/45)
Methods84% (38/45)
Results98% (43/43)
Conclusion100% (43/43)
Report dissemination 
Did you share CEP's report with anyone NOT involved in requesting the report or in making the final decision?67% (30/45)
Did you share CEP's report with anyone outside of Penn?7% (3/45)
Requestor preferences 
Would it be helpful for CEP staff to call you after you receive any future CEP reports to answer any questions you might have?55% (24/44)
Following any future reports you request from CEP, would you be willing to complete a brief questionnaire?100% (44/44)
Please rank how you would prefer to receive reports from CEP in the future. 
E‐mail containing the report as a PDF attachment77% (34/44)
E‐mail containing a link to the report on CEP's website16% (7/44)
In‐person presentation by the CEP analyst writing the report18% (8/44)
In‐person presentation by the CEP director involved in the report16% (7/44)
Figure 1
Requestor responses to Likert survey questions. Abbreviations: CEP, Center for Evidence‐based Practice.

In general, respondents found reports easy to request, easy to use, timely, and relevant, resulting in high requestor satisfaction. In addition, 98% described the scope of content and level of detail as about right. Report impact was rated highly as well, with the evidence summary and conclusions rated as the most critical to decision making. A majority of respondents indicated that reports confirmed their tentative decision (77%, n = 34), whereas some changed their tentative decision (7%, n = 3), and others suggested the report had no effect on their tentative decision (16%, n = 7). Respondents indicated the amount of time that elapsed between receiving reports and making final decisions was 1 to 7 days (5%, n = 2), 8 to 30 days (40%, n = 17), 1 to 3 months (37%, n = 16), 4 to 6 months (9%, n = 4), or greater than 6 months (9%, n = 4). The most common reasons cited for requesting a report were the CEP's evidence synthesis skills and objectivity.

DISCUSSION

To our knowledge, this is the first comprehensive description and assessment of evidence synthesis activity by a hospital EPC in the United States. Our findings suggest that clinical and administrative leaders will request reports from a hospital EPC, and that hospital EPCs can promptly produce reports when requested. Moreover, these syntheses can address a wide range of clinical and policy topics, and can be disseminated through a variety of routes. Lastly, requestors are satisfied by these syntheses, and report that they inform decision making. These results suggest that EPCs may be an effective infrastructure paradigm for promoting evidence‐based decision making within healthcare provider organizations, and are consistent with previous analyses of hospital‐based EPCs.[21, 28, 29]

Over half of report requestors cited CEP's objectivity as a factor in their decision to request a report, underscoring the value of a neutral entity in an environment where clinical departments and hospital committees may have competing interests.[10] This asset was 1 of the primary drivers for establishing our hospital EPC. Concerns by clinical executives about the influence of industry and local politics on institutional decision making, and a desire to have clinical evidence more systematically and objectively integrated into decision making, fueled our center's funding.

The survey results also demonstrate that respondents were satisfied with the reports for many reasons, including readability, concision, timeliness, scope, and content, consistent with the evaluation of the French hospital‐based EPC CEDIT (French Committee for the Assessment and Dissemination of Technological Innovations).[29] Given the importance of readability, concision, and relevance that has been previously described,[16, 28, 30] nearly all CEP reports contain an evidence summary on the first page that highlights key findings in a concise, user‐friendly format.[31] The evidence summaries include bullet points that: (1) reference the most pertinent guideline recommendations along with their strength of recommendation and underlying quality of evidence; (2) organize and summarize study findings using the most critical clinical outcomes, including an assessment of the quality of the underlying evidence for each outcome; and (3) note important limitations of the findings.

Evidence syntheses must be timely to allow decision makers to act on the findings.[28, 32] The primary criticism of CEDIT was the lag between requests and report publication.[29] Rapid reviews, designed to inform urgent decisions, can overcome this challenge.[31, 33, 34] CEP reviews required approximately 2 months to complete on average, consistent with the most rapid timelines reported,[31, 33, 34] and much shorter than standard systematic review timelines, which can take up to 12 to 24 months.[33] Working with requestors to limit the scope of reviews to those issues most critical to a decision, using secondary resources when available, and hiring experienced research analysts help achieve these efficiencies.

The study by Bodeau‐Livinec also argues for the importance of report accessibility to ensure dissemination.[29] This is consistent with the CEP's approach, where all reports are posted on the UPHS internal website. Many also inform QI initiatives, as well as CDS interventions that address topics of general interest to acute care hospitals, such as venous thromboembolism (VTE) prophylaxis,[35] blood product transfusions,[36] sepsis care,[37, 38] and prevention of catheter‐associated urinary tract infections (CAUTI)[39] and hospital readmissions.[40] Most reports are also listed in an international database of rapid reviews,[23] and reports that address topics of general interest, have sufficient evidence to synthesize, and have no prior published systematic reviews are published in the peer‐reviewed literature.[41, 42]

The majority of reports completed by the CEP were evidence reviews, or systematic reviews of primary literature, suggesting that CEP reports often address questions previously unanswered by existing published systematic reviews; however, about a third of reports were evidence advisories, or summaries of evidence from preexisting secondary sources. The relative scarcity of high‐quality evidence bases in those reports where GRADE analyses were conducted might be expected, as requestors may be more likely to seek guidance when the evidence base on a topic is lacking. This was further supported by the small percentage (15%) of reports where adequate data of sufficient homogeneity existed to allow meta‐analyses. The small number of original meta‐analyses performed also reflects our reliance on secondary resources when available.

Only 7% of respondents reported that tentative decisions were changed based on their report. This is not surprising, as evidence reviews infrequently result in clear go or no go recommendations. More commonly, they address or inform complex clinical questions or pathways. In this context, the change/confirm/no effect framework may not completely reflect respondents' use of or benefit from reports. Thus, we included a diverse set of questions in our survey to best estimate the value of our reports. For example, when asked whether the report answered the question posed, informed their final decision, or was consistent with their final decision, 91%, 79%, and 71% agreed or strongly agreed, respectively. When asked whether they would request a report again if they had to do it all over, recommend CEP to their colleagues, and be likely to request reports in the future, at least 95% of survey respondents agreed or strongly agreed. In addition, no respondent indicated that their report was not timely enough to influence their decision. Moreover, only a minority of respondents expressed disappointment that the CEP's report did not provide actionable recommendations due to a lack of published evidence (9%, n = 4). Importantly, the large proportion of requestors indicating that reports confirmed their tentative decisions may be a reflection of hindsight bias.

The most apparent trend in the production of CEP reviews over time is the relative increase in requests by clinical departments, suggesting that the CEP is being increasingly consulted to help define best clinical practices. This is also supported by the relative increase in reports focused on policy or organizational/managerial systems. These findings suggest that hospital EPCs have value beyond the traditional realm of HTA.

This study has a number of limitations. First, not all of the eligible report requestors responded to our survey. Despite this, our response rate of 72% compares favorably with surveys published in medical journals.[43] In addition, nonresponse bias may be less important in physician surveys than surveys of the general population.[44] The similarity in requestor and report characteristics for respondents and nonrespondents supports this. Second, our survey of impact is self‐reported rather than an evaluation of actual decision making or patient outcomes. Thus, the survey relies on the accuracy of the responses. Third, recall bias must be considered, as some respondents were asked to evaluate reports that were greater than 1 year old. To reduce this bias, we asked respondents to consider the most recent report they requested, included that report as an attachment in the survey request, and only surveyed requestors from the most recent 4 of the CEP's 8 fiscal years. Fourth, social desirability bias could have also affected the survey responses, though it was likely minimized by the promise of confidentiality. Fifth, an examination of the impact of the CEP on costs was outside the scope of this evaluation; however, such information may be important to those assessing the sustainability or return on investment of such centers. Simple approaches we have previously used to approximate the value of our activities include: (1) estimating hospital cost savings resulting from decisions supported by our reports, such as the use of technologies like chlorhexidine for surgical site infections[45] or discontinuation of technologies like aprotinin for cardiac surgery[46]; and (2) estimating penalties avoided or rewards attained as a result of center‐led initiatives, such as those to increase VTE prophylaxis,[35] reduce CAUTI rates,[39] and reduce preventable mortality associated with sepsis.[37, 38] Similarly, given the focus of this study on the local evidence synthesis activities of our center, our examination did not include a detailed description of our CDS activities, or teaching activities, including our multidisciplinary workshops for physicians and nurses in evidence‐based QI[47] and our novel evidence‐based practice curriculum for medical students. Our study also did not include a description of our extramural activities, such as those supported by our contract with AHRQ as 1 of their 13 EPCs.[16, 17, 48, 49] A consideration of all of these activities enables a greater appreciation for the potential of such centers. Lastly, we examined a single EPC, which may not be representative of the diversity of hospitals and hospital staff across the United States. However, our EPC serves a diverse array of patient populations, clinical services, and service models throughout our multientity academic healthcare system, which may improve the generalizability of our experience to other settings.

As next steps, we recommend evaluation of other existing hospital EPCs nationally. Such studies could help hospitals and health systems ascertain which of their internal decisions might benefit from locally sourced rapid systematic reviews and determine whether an in‐house EPC could improve the value of care delivered.

In conclusion, our findings suggest that hospital EPCs within academic healthcare systems can efficiently synthesize and disseminate evidence for a variety of stakeholders. Moreover, these syntheses impact decision making in a variety of hospital contexts and clinical specialties. Hospitals and hospitalist leaders seeking to improve the implementation of evidence‐based practice at a systems level might consider establishing such infrastructure locally.

Acknowledgements

The authors thank Fran Barg, PhD (Department of Family Medicine and Community Health, University of Pennsylvania Perelman School of Medicine) and Joel Betesh, MD (University of Pennsylvania Health System) for their contributions to developing the survey. They did not receive any compensation for their contributions.

Disclosures: An earlier version of this work was presented as a poster at the 2014 AMA Research Symposium, November 7, 2014, Dallas, Texas. Mr. Jayakumar reports having received a University of Pennsylvania fellowship as a summer intern at the Center for Evidence‐based Practice. Dr. Umscheid cocreated and directs a hospital evidence‐based practice center, is the Senior Associate Director of an Agency for Healthcare Research and Quality Evidence‐Based Practice Center, and is a past member of the Medicare Evidence Development and Coverage Advisory Committee, which uses evidence reports developed by the Evidence‐based Practice Centers of the Agency for Healthcare Research and Quality. Dr. Umscheid's contribution was supported in part by the National Center for Research Resources, grant UL1RR024134, which is now at the National Center for Advancing Translational Sciences, grant UL1TR000003. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. None of the funders had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Lavenberg, Dr. Mitchell, and Mr. Leas are employed as research analysts by a hospital evidence‐based practice center. Dr. Doshi is supported in part by a hospital evidence‐based practice center and is an Associate Director of an Agency for Healthcare Research and Quality Evidence‐based Practice Center. Dr. Goldmann is emeritus faculty at Penn, is supported in part by a hospital evidence‐based practice center, and is the Vice President and Chief Quality Assurance Officer in Clinical Solutions, a division of Elsevier, Inc., a global publishing company, and director of the division's Evidence‐based Medicine Center. Dr. Williams cocreated and codirects a hospital evidence‐based practice center. Dr. Brennan has oversight for and helped create a hospital evidence‐based practice center.

Hospital evidence‐based practice centers (EPCs) are structures with the potential to facilitate the integration of evidence into institutional decision making to close knowing‐doing gaps[1, 2, 3, 4, 5, 6]; in the process, they can support the evolution of their parent institutions into learning healthcare systems.[7] The potential of hospital EPCs stems from their ability to identify and adapt national evidence‐based guidelines and systematic reviews for the local setting,[8] create local evidence‐based guidelines in the absence of national guidelines, use local data to help define problems and assess the impact of solutions,[9] and implement evidence into practice through computerized clinical decision support (CDS) interventions and other quality‐improvement (QI) initiatives.[9, 10] As such, hospital EPCs have the potential to strengthen relationships and understanding between clinicians and administrators[11]; foster a culture of evidence‐based practice; and improve the quality, safety, and value of care provided.[10]

Formal hospital EPCs remain uncommon in the United States,[10, 11, 12] though their numbers have expanded worldwide.[13, 14] This growth is due not to any reduced role for national EPCs, such as the National Institute for Health and Clinical Excellence[15] in the United Kingdom, or the 13 EPCs funded by the Agency for Healthcare Research and Quality (AHRQ)[16, 17] in the United States. Rather, this growth is fueled by the heightened awareness that the value of healthcare interventions often needs to be assessed locally, and that clinical guidelines that consider local context have a greater potential to improve quality and efficiency.[9, 18, 19]

Despite the increasing number of hospital EPCs globally, their impact on administrative and clinical decision making has rarely been examined,[13, 20] especially for hospital EPCs in the United States. The few studies that have assessed the impact of hospital EPCs on institutional decision making have done so in the context of technology acquisition, neglecting the role hospital EPCs may play in the integration of evidence into clinical practice. For example, the Technology Assessment Unit at McGill University Health Center found that of the 27 reviews commissioned in their first 5 years, 25 were implemented, with 6 (24%) recommending investments in new technologies and 19 (76%) recommending rejection, for a reported net hospital savings of $10 million.[21] Understanding the activities and impact of hospital EPCs is particularly critical for hospitalist leaders, who could leverage hospital EPCs to inform efforts to support the quality, safety, and value of care provided, or who may choose to establish or lead such infrastructure. The availability of such opportunities could also support hospitalist recruitment and retention.

In 2006, the University of Pennsylvania Health System (UPHS) created the Center for Evidence‐based Practice (CEP) to support the integration of evidence into practice to strengthen quality, safety, and value.[10] Cofounded by hospitalists with formal training in clinical epidemiology, the CEP performs rapid systematic reviews of the scientific literature to inform local practice and policy. In this article, we describe the first 8 years of the CEP's evidence synthesis activities and examine its impact on decision making across the health system.

METHODS

Setting

The UPHS includes 3 acute care hospitals, and inpatient facilities specializing in acute rehabilitation, skilled nursing, long‐term acute care, and hospice, with a capacity of more than 1800 beds and 75,000 annual admissions, as well as primary care and specialty clinics with more than 2 million annual outpatient visits. The CEP is funded by and organized within the Office of the UPHS Chief Medical Officer, serves all UPHS facilities, has an annual budget of approximately $1 million, and is currently staffed by a hospitalist director, 3 research analysts, 6 physician and nurse liaisons, a health economist, biostatistician, administrator, and librarians, totaling 5.5 full time equivalents.

The mission of the CEP is to support the quality, safety, and value of care at Penn through evidence‐based practice. To accomplish this mission, the CEP performs rapid systematic reviews, translates evidence into practice through the use of CDS interventions and clinical pathways, and offers education in evidence‐based decision making to trainees, staff, and faculty. This study is focused on the CEP's evidence synthesis activities.

Typically, clinical and administrative leaders submit a request to the CEP for an evidence review, the request is discussed and approved at the weekly staff meeting, and a research analyst and clinical liaison are assigned to the request and communicate with the requestor to clearly define the question of interest. Subsequently, the research analyst completes a protocol, a draft search, and a draft report, each reviewed and approved by the clinical liaison and requestor. The final report is posted to the website, disseminated to all key stakeholders across the UPHS as identified by the clinical liaisons, and integrated into decision making through various routes, including in‐person presentations to decision makers, and CDS and QI initiatives.

Study Design

The study included an analysis of an internal database of evidence reviews and a survey of report requestors, and was exempted from institutional review board review. Survey respondents were informed that their responses would be confidential and did not receive incentives.

Internal Database of Reports

Data from the CEP's internal management database were analyzed for its first 8 fiscal years (July 2006June 2014). Variables included requestor characteristics, report characteristics (eg, technology reviewed, clinical specialty examined, completion time, and performance of meta‐analyses and GRADE [Grading of Recommendations Assessment, Development and Evaluation] analyses[22]), report use (eg, integration of report into CDS interventions) and dissemination beyond the UPHS (eg, submission to Center for Reviews and Dissemination [CRD] Health Technology Assessment [HTA] database[23] and to peer‐reviewed journals). Report completion time was defined as the time between the date work began on the report and the date the final report was sent to the requestor. The technology categorization scheme was adapted from that provided by Goodman (2004)[24] and the UK National Institute for Health Research HTA Programme.[25] We systematically assigned the technology reviewed in each report to 1 of 8 mutually exclusive categories. The clinical specialty examined in each report was determined using an algorithm (see Supporting Information, Appendix 1, in the online version of this article).

We compared the report completion times and the proportions of requestor types, technologies reviewed, and clinical specialties examined in the CEP's first 4 fiscal years (July 2006June 2010) to those in the CEP's second 4 fiscal years (July 2010June 2014) using t tests and 2 tests for continuous and categorical variables, respectively.

Survey

We conducted a Web‐based survey (see Supporting Information, Appendix 2, in the online version of this article) of all requestors of the 139 rapid reviews completed in the last 4 fiscal years. Participants who requested multiple reports were surveyed only about the most recent report. Requestors were invited to participate in the survey via e‐mail, and follow‐up e‐mails were sent to nonrespondents at 7, 14, and 16 days. Nonrespondents and respondents were compared with respect to requestor type (physician vs nonphysician) and topic evaluated (traditional HTA topics such as drugs, biologics, and devices vs nontraditional HTA topics such as processes of care). The survey was administered using REDCap[26] electronic data capture tools. The 44‐item questionnaire collected data on the interaction between the requestor and the CEP, report characteristics, report impact, and requestor satisfaction.

Survey results were imported into Microsoft Excel (Microsoft Corp, Redmond, WA) and SPSS (IBM, Armonk, NY) for analysis. Descriptive statistics were generated, and statistical comparisons were conducted using 2 and Fisher exact tests.

RESULTS

Evidence Synthesis Activity

The CEP has produced several different report products since its inception. Evidence reviews (57%, n = 142) consist of a systematic review and analysis of the primary literature. Evidence advisories (32%, n = 79) are summaries of evidence from secondary sources such as guidelines or systematic reviews. Evidence inventories (3%, n = 7) are literature searches that describe the quantity and focus of available evidence, without analysis or synthesis.[27]

The categories of technologies examined, including their definitions and examples, are provided in Table 1. Drugs (24%, n = 60) and devices/equipment/supplies (19%, n = 48) were most commonly examined. The proportion of reports examining technology types traditionally evaluated by HTA organizations significantly decreased when comparing the first 4 years of CEP activity to the second 4 years (62% vs 38%, P < 0.01), whereas reports examining less traditionally reviewed categories increased (38% vs 62%, P < 0.01). The most common clinical specialties represented by the CEP reports were nursing (11%, n = 28), general surgery (11%, n = 28), critical care (10%, n = 24), and general medicine (9%, n = 22) (see Supporting Information, Appendix 3, in the online version of this article). Clinical departments were the most common requestors (29%, n = 72) (Table 2). The proportion of requests from clinical departments significantly increased when comparing the first 4 years to the second 4 years (20% vs 36%, P < 0.01), with requests from purchasing committees significantly decreasing (25% vs 6%, P < 0.01). The overall report completion time was 70 days, and significantly decreased when comparing the first 4 years to the second 4 years (89 days vs 50 days, P < 0.01).

Technology Categories, Definitions, Examples, and Frequencies by Fiscal Years
CategoryDefinitionExamplesTotal2007201020112014P Value
Total  249 (100%)109 (100%)140 (100%) 
DrugA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a pharmacologic agentCelecoxib for pain in joint arthroplasty; colchicine for prevention of pericarditis and atrial fibrillation60 (24%)35 (32%)25 (18%)0.009
Device, equipment, and suppliesA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory that is intended for use in the prevention, diagnosis, or treatment of disease and does not achieve its primary intended purposes though chemical action or metabolism[50]Thermometers for pediatric use; femoral closure devices for cardiac catheterization48 (19%)25 (23%)23 (16%)0.19
Process of careA report primarily examining a clinical pathway or a clinical practice guideline that significantly involves elements of prevention, diagnosis, and/or treatment or significantly incorporates 2 or more of the other technology categoriesPreventing patient falls; prevention and management of delirium31 (12%)18 (17%)13 (9%)0.09
Test, scale, or risk factorA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a test intended to screen for, diagnose, classify, or monitor the progression of a diseaseComputed tomography for acute chest pain; urine drug screening in chronic pain patients on opioid therapy31 (12%)8 (7%)23 (16%)0.03
Medical/surgical procedureA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a medical intervention that is not a drug, device, or test or of the application or removal of a deviceBiliary drainage for chemotherapy patients; cognitive behavioral therapy for insomnia26 (10%)8 (7%)18 (13%)0.16
Policy or organizational/managerial systemA report primarily examining laws or regulations; the organization, financing, or delivery of care, including settings of care; or healthcare providersMedical care costs and productivity changes associated with smoking; physician training and credentialing for robotic surgery in obstetrics and gynecology26 (10%)4 (4%)22 (16%)0.002
Support systemA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of an intervention designed to provide a new or improved service to patients or healthcare providers that does not fall into 1 of the other categoriesReconciliation of data from differing electronic medical records; social media, text messaging, and postdischarge communication14 (6%)3 (3%)11 (8%)0.09
BiologicA report primarily examining the efficacy/effectiveness, safety, appropriate use, or cost of a product manufactured in a living systemRecombinant factor VIIa for cardiovascular surgery; osteobiologics for orthopedic fusions13 (5%)8 (7%)5 (4%)0.19
Requestor Categories and Frequencies by Fiscal Years
CategoryTotal2007201020112014P Value
  • NOTE: *Other includes ad hoc committees, CEP, Children's Hospital of Philadelphia, IT committees, payers, and the primary care network.. Abbreviations: CEP, Center for Evidence‐based Practice; CMO, chief medical officer; IT, information technology.

Total249 (100%)109 (100%)140 (100%) 
Clinical department72 (29%)22 (20%)50 (36%)0.007
CMO47 (19%)21 (19%)26 (19%)0.92
Purchasing committee35 (14%)27 (25%)8 (6%)<0.001
Formulary committee22 (9%)12 (11%)10 (7%)0.54
Quality committee21 (8%)11 (10%)10 (7%)0.42
Administrative department19 (8%)5 (5%)14 (10%)0.11
Nursing14 (6%)4 (4%)10 (7%)0.23
Other*19 (8%)7 (6%)12 (9%)0.55

Thirty‐seven (15%) reports included meta‐analyses conducted by CEP staff. Seventy‐five reports (30%) contained an evaluation of the quality of the evidence base using GRADE analyses.[22] Of these reports, the highest GRADE of evidence available for any comparison of interest was moderate (35%, n = 26) or high (33%, n = 25) in most cases, followed by very low (19%, n = 14) and low (13%, n = 10).

Reports were disseminated in a variety of ways beyond direct dissemination and presentation to requestors and posting on the center website. Thirty reports (12%) informed CDS interventions, 24 (10%) resulted in peer‐reviewed publications, and 204 (82%) were posted to the CRD HTA database.

Evidence Synthesis Impact

A total of 139 reports were completed between July 2010 and June 2014 for 65 individual requestors. Email invitations to participate in the survey were sent to the 64 requestors employed by the UPHS. The response rate was 72% (46/64). The proportions of physician requestors and traditional HTA topics evaluated were similar across respondents and nonrespondents (43% [20/46] vs 39% [7/18], P = 0.74; and 37% [17/46] vs 44% [8/18], P = 0.58, respectively). Aggregated survey responses are presented for items using a Likert scale in Figure 1, and for items using a yes/no or ordinal scale in Table 3.

Responses to Yes/No and Ranking Survey Questions
Items% of Respondents Responding Affirmatively
 Percentage of Respondents Ranking as First Choice*
  • NOTE: Abbreviations: CEP, Center for Evidence‐based Practice. *The sum of these percentages is greater than 100 percent because respondents could rank multiple options first.

Requestor activity 
What factors prompted you to request a report from CEP? (Please select all that apply.) 
My own time constraints28% (13/46)
CEP's ability to identify and synthesize evidence89% (41/46)
CEP's objectivity52% (24/46)
Recommendation from colleague30% (14/46)
Did you conduct any of your own literature searches before contacting CEP?67% (31/46)
Did you obtain and read any of the articles cited in CEP's report?63% (29/46)
Did you read the following sections of CEP's report? 
Evidence summary (at beginning of report)100% (45/45)
Introduction/background93% (42/45)
Methods84% (38/45)
Results98% (43/43)
Conclusion100% (43/43)
Report dissemination 
Did you share CEP's report with anyone NOT involved in requesting the report or in making the final decision?67% (30/45)
Did you share CEP's report with anyone outside of Penn?7% (3/45)
Requestor preferences 
Would it be helpful for CEP staff to call you after you receive any future CEP reports to answer any questions you might have?55% (24/44)
Following any future reports you request from CEP, would you be willing to complete a brief questionnaire?100% (44/44)
Please rank how you would prefer to receive reports from CEP in the future. 
E‐mail containing the report as a PDF attachment77% (34/44)
E‐mail containing a link to the report on CEP's website16% (7/44)
In‐person presentation by the CEP analyst writing the report18% (8/44)
In‐person presentation by the CEP director involved in the report16% (7/44)
Figure 1
Requestor responses to Likert survey questions. Abbreviations: CEP, Center for Evidence‐based Practice.

In general, respondents found reports easy to request, easy to use, timely, and relevant, resulting in high requestor satisfaction. In addition, 98% described the scope of content and level of detail as about right. Report impact was rated highly as well, with the evidence summary and conclusions rated as the most critical to decision making. A majority of respondents indicated that reports confirmed their tentative decision (77%, n = 34), whereas some changed their tentative decision (7%, n = 3), and others suggested the report had no effect on their tentative decision (16%, n = 7). Respondents indicated the amount of time that elapsed between receiving reports and making final decisions was 1 to 7 days (5%, n = 2), 8 to 30 days (40%, n = 17), 1 to 3 months (37%, n = 16), 4 to 6 months (9%, n = 4), or greater than 6 months (9%, n = 4). The most common reasons cited for requesting a report were the CEP's evidence synthesis skills and objectivity.

DISCUSSION

To our knowledge, this is the first comprehensive description and assessment of evidence synthesis activity by a hospital EPC in the United States. Our findings suggest that clinical and administrative leaders will request reports from a hospital EPC, and that hospital EPCs can promptly produce reports when requested. Moreover, these syntheses can address a wide range of clinical and policy topics, and can be disseminated through a variety of routes. Lastly, requestors are satisfied by these syntheses, and report that they inform decision making. These results suggest that EPCs may be an effective infrastructure paradigm for promoting evidence‐based decision making within healthcare provider organizations, and are consistent with previous analyses of hospital‐based EPCs.[21, 28, 29]

Over half of report requestors cited CEP's objectivity as a factor in their decision to request a report, underscoring the value of a neutral entity in an environment where clinical departments and hospital committees may have competing interests.[10] This asset was 1 of the primary drivers for establishing our hospital EPC. Concerns by clinical executives about the influence of industry and local politics on institutional decision making, and a desire to have clinical evidence more systematically and objectively integrated into decision making, fueled our center's funding.

The survey results also demonstrate that respondents were satisfied with the reports for many reasons, including readability, concision, timeliness, scope, and content, consistent with the evaluation of the French hospital‐based EPC CEDIT (French Committee for the Assessment and Dissemination of Technological Innovations).[29] Given the importance of readability, concision, and relevance that has been previously described,[16, 28, 30] nearly all CEP reports contain an evidence summary on the first page that highlights key findings in a concise, user‐friendly format.[31] The evidence summaries include bullet points that: (1) reference the most pertinent guideline recommendations along with their strength of recommendation and underlying quality of evidence; (2) organize and summarize study findings using the most critical clinical outcomes, including an assessment of the quality of the underlying evidence for each outcome; and (3) note important limitations of the findings.

Evidence syntheses must be timely to allow decision makers to act on the findings.[28, 32] The primary criticism of CEDIT was the lag between requests and report publication.[29] Rapid reviews, designed to inform urgent decisions, can overcome this challenge.[31, 33, 34] CEP reviews required approximately 2 months to complete on average, consistent with the most rapid timelines reported,[31, 33, 34] and much shorter than standard systematic review timelines, which can take up to 12 to 24 months.[33] Working with requestors to limit the scope of reviews to those issues most critical to a decision, using secondary resources when available, and hiring experienced research analysts help achieve these efficiencies.

The study by Bodeau‐Livinec also argues for the importance of report accessibility to ensure dissemination.[29] This is consistent with the CEP's approach, where all reports are posted on the UPHS internal website. Many also inform QI initiatives, as well as CDS interventions that address topics of general interest to acute care hospitals, such as venous thromboembolism (VTE) prophylaxis,[35] blood product transfusions,[36] sepsis care,[37, 38] and prevention of catheter‐associated urinary tract infections (CAUTI)[39] and hospital readmissions.[40] Most reports are also listed in an international database of rapid reviews,[23] and reports that address topics of general interest, have sufficient evidence to synthesize, and have no prior published systematic reviews are published in the peer‐reviewed literature.[41, 42]

The majority of reports completed by the CEP were evidence reviews, or systematic reviews of primary literature, suggesting that CEP reports often address questions previously unanswered by existing published systematic reviews; however, about a third of reports were evidence advisories, or summaries of evidence from preexisting secondary sources. The relative scarcity of high‐quality evidence bases in those reports where GRADE analyses were conducted might be expected, as requestors may be more likely to seek guidance when the evidence base on a topic is lacking. This was further supported by the small percentage (15%) of reports where adequate data of sufficient homogeneity existed to allow meta‐analyses. The small number of original meta‐analyses performed also reflects our reliance on secondary resources when available.

Only 7% of respondents reported that tentative decisions were changed based on their report. This is not surprising, as evidence reviews infrequently result in clear go or no go recommendations. More commonly, they address or inform complex clinical questions or pathways. In this context, the change/confirm/no effect framework may not completely reflect respondents' use of or benefit from reports. Thus, we included a diverse set of questions in our survey to best estimate the value of our reports. For example, when asked whether the report answered the question posed, informed their final decision, or was consistent with their final decision, 91%, 79%, and 71% agreed or strongly agreed, respectively. When asked whether they would request a report again if they had to do it all over, recommend CEP to their colleagues, and be likely to request reports in the future, at least 95% of survey respondents agreed or strongly agreed. In addition, no respondent indicated that their report was not timely enough to influence their decision. Moreover, only a minority of respondents expressed disappointment that the CEP's report did not provide actionable recommendations due to a lack of published evidence (9%, n = 4). Importantly, the large proportion of requestors indicating that reports confirmed their tentative decisions may be a reflection of hindsight bias.

The most apparent trend in the production of CEP reviews over time is the relative increase in requests by clinical departments, suggesting that the CEP is being increasingly consulted to help define best clinical practices. This is also supported by the relative increase in reports focused on policy or organizational/managerial systems. These findings suggest that hospital EPCs have value beyond the traditional realm of HTA.

This study has a number of limitations. First, not all of the eligible report requestors responded to our survey. Despite this, our response rate of 72% compares favorably with surveys published in medical journals.[43] In addition, nonresponse bias may be less important in physician surveys than surveys of the general population.[44] The similarity in requestor and report characteristics for respondents and nonrespondents supports this. Second, our survey of impact is self‐reported rather than an evaluation of actual decision making or patient outcomes. Thus, the survey relies on the accuracy of the responses. Third, recall bias must be considered, as some respondents were asked to evaluate reports that were greater than 1 year old. To reduce this bias, we asked respondents to consider the most recent report they requested, included that report as an attachment in the survey request, and only surveyed requestors from the most recent 4 of the CEP's 8 fiscal years. Fourth, social desirability bias could have also affected the survey responses, though it was likely minimized by the promise of confidentiality. Fifth, an examination of the impact of the CEP on costs was outside the scope of this evaluation; however, such information may be important to those assessing the sustainability or return on investment of such centers. Simple approaches we have previously used to approximate the value of our activities include: (1) estimating hospital cost savings resulting from decisions supported by our reports, such as the use of technologies like chlorhexidine for surgical site infections[45] or discontinuation of technologies like aprotinin for cardiac surgery[46]; and (2) estimating penalties avoided or rewards attained as a result of center‐led initiatives, such as those to increase VTE prophylaxis,[35] reduce CAUTI rates,[39] and reduce preventable mortality associated with sepsis.[37, 38] Similarly, given the focus of this study on the local evidence synthesis activities of our center, our examination did not include a detailed description of our CDS activities, or teaching activities, including our multidisciplinary workshops for physicians and nurses in evidence‐based QI[47] and our novel evidence‐based practice curriculum for medical students. Our study also did not include a description of our extramural activities, such as those supported by our contract with AHRQ as 1 of their 13 EPCs.[16, 17, 48, 49] A consideration of all of these activities enables a greater appreciation for the potential of such centers. Lastly, we examined a single EPC, which may not be representative of the diversity of hospitals and hospital staff across the United States. However, our EPC serves a diverse array of patient populations, clinical services, and service models throughout our multientity academic healthcare system, which may improve the generalizability of our experience to other settings.

As next steps, we recommend evaluation of other existing hospital EPCs nationally. Such studies could help hospitals and health systems ascertain which of their internal decisions might benefit from locally sourced rapid systematic reviews and determine whether an in‐house EPC could improve the value of care delivered.

In conclusion, our findings suggest that hospital EPCs within academic healthcare systems can efficiently synthesize and disseminate evidence for a variety of stakeholders. Moreover, these syntheses impact decision making in a variety of hospital contexts and clinical specialties. Hospitals and hospitalist leaders seeking to improve the implementation of evidence‐based practice at a systems level might consider establishing such infrastructure locally.

Acknowledgements

The authors thank Fran Barg, PhD (Department of Family Medicine and Community Health, University of Pennsylvania Perelman School of Medicine) and Joel Betesh, MD (University of Pennsylvania Health System) for their contributions to developing the survey. They did not receive any compensation for their contributions.

Disclosures: An earlier version of this work was presented as a poster at the 2014 AMA Research Symposium, November 7, 2014, Dallas, Texas. Mr. Jayakumar reports having received a University of Pennsylvania fellowship as a summer intern at the Center for Evidence‐based Practice. Dr. Umscheid cocreated and directs a hospital evidence‐based practice center, is the Senior Associate Director of an Agency for Healthcare Research and Quality Evidence‐Based Practice Center, and is a past member of the Medicare Evidence Development and Coverage Advisory Committee, which uses evidence reports developed by the Evidence‐based Practice Centers of the Agency for Healthcare Research and Quality. Dr. Umscheid's contribution was supported in part by the National Center for Research Resources, grant UL1RR024134, which is now at the National Center for Advancing Translational Sciences, grant UL1TR000003. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. None of the funders had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Lavenberg, Dr. Mitchell, and Mr. Leas are employed as research analysts by a hospital evidence‐based practice center. Dr. Doshi is supported in part by a hospital evidence‐based practice center and is an Associate Director of an Agency for Healthcare Research and Quality Evidence‐based Practice Center. Dr. Goldmann is emeritus faculty at Penn, is supported in part by a hospital evidence‐based practice center, and is the Vice President and Chief Quality Assurance Officer in Clinical Solutions, a division of Elsevier, Inc., a global publishing company, and director of the division's Evidence‐based Medicine Center. Dr. Williams cocreated and codirects a hospital evidence‐based practice center. Dr. Brennan has oversight for and helped create a hospital evidence‐based practice center.

References
  1. Avorn J, Fischer M. “Bench to behavior”: translating comparative effectiveness research into improved clinical practice. Health Aff (Millwood). 2010;29(10):18911900.
  2. Rajab MH, Villamaria FJ, Rohack JJ. Evaluating the status of “translating research into practice” at a major academic healthcare system. Int J Technol Assess Health Care. 2009;25(1):8489.
  3. Timbie JW, Fox DS, Busum K, Schneider EC. Five reasons that many comparative effectiveness studies fail to change patient care and clinical practice. Health Aff (Millwood). 2012;31(10):21682175.
  4. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4(1):50.
  5. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients' care. Lancet. 2003;362(9391):12251230.
  6. Umscheid CA, Brennan PJ. Incentivizing “structures” over “outcomes” to bridge the knowing‐doing gap. JAMA Intern Med. 2015;175(3):354.
  7. Olsen L, Aisner D, McGinnis JM, eds. Institute of Medicine (US) Roundtable on Evidence‐Based Medicine. The Learning Healthcare System: Workshop Summary. Washington, DC: National Academies Press; 2007. Available at: http://www.ncbi.nlm.nih.gov/books/NBK53494/. Accessed October 29, 2014.
  8. Harrison MB, Legare F, Graham ID, Fervers B. Adapting clinical practice guidelines to local context and assessing barriers to their use. Can Med Assoc J. 2010;182(2):E78E84.
  9. Mitchell MD, Williams K, Brennan PJ, Umscheid CA. Integrating local data into hospital‐based healthcare technology assessment: two case studies. Int J Technol Assess Health Care. 2010;26(3):294300.
  10. Umscheid CA, Williams K, Brennan PJ. Hospital‐based comparative effectiveness centers: translating research into practice to improve the quality, safety and value of patient care. J Gen Intern Med. 2010;25(12):13521355.
  11. Gutowski C, Maa J, Hoo KS, Bozic KJ, Bozic K. Health technology assessment at the University of California‐San Francisco. J Healthc Manag Am Coll Healthc Exec. 2011;56(1):1529; discussion 29–30.
  12. Schottinger J, Odell RM. Kaiser Permanente Southern California regional technology management process: evidence‐based medicine operationalized. Perm J. 2006;10(1):3841.
  13. Gagnon M‐P. Hospital‐based health technology assessment: developments to date. Pharmacoeconomics. 2014;32(9):819824.
  14. Cicchetti A, Marchetti M, Dibidino R, Corio M. Hospital based health technology assessment world‐wide survey. Available at: http://www.htai.org/fileadmin/HTAi_Files/ISG/HospitalBasedHTA/2008Files/HospitalBasedHTAISGSurveyReport.pdf. Accessed October 11, 2015.
  15. Stevens AJ, Longson C. At the center of health care policy making: the use of health technology assessment at NICE. Med Decis Making. 2013;33(3):320324.
  16. Atkins D, Fink K, Slutsky J. Better information for better health care: the Evidence‐based Practice Center program and the Agency for Healthcare Research and Quality. Ann Intern Med. 2005;142(12 part 2):10351041.
  17. Slutsky JR, Clancy CM. AHRQ's Effective Health Care Program: why comparative effectiveness matters. Am J Med Qual. 2009;24(1):6770.
  18. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet. 1993;342(8883):13171322.
  19. Graham ID, Logan J, Harrison MB, et al. Lost in knowledge translation: time for a map? J Contin Educ Health Prof. 2006;26(1):1324.
  20. Gagnon M‐P, Desmartis M, Poder T, Witteman W. Effects and repercussions of local/hospital‐based health technology assessment (HTA): a systematic. Syst Rev. 2014;3:129.
  21. McGregor M, Arnoldo J, Barkun J, et al. Impact of TAU Reports. McGill University Health Centre. Available at: https://francais.mcgill.ca/files/tau/FINAL_TAU_IMPACT_REPORT_FEB_2008.pdf. Published Feb 1, 2008. Accessed August 19, 2014.
  22. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924926.
  23. Booth AM, Wright KE, Outhwaite H. Centre for Reviews and Dissemination databases: value, content, and developments. Int J Technol Assess Health Care. 2010;26(4):470472.
  24. Goodman C. HTA 101. Introduction to Health Technology Assessment. Available at: https://www.nlm.nih.gov/nichsr/hta101/ta10103.html. Accessed October 11, 2015.
  25. National Institute for Health Research. Remit. NIHR HTA Programme. Available at: http://www.nets.nihr.ac.uk/programmes/hta/remit. Accessed August 20, 2014.
  26. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377381.
  27. Mitchell MD, Williams K, Kuntz G, Umscheid CA. When the decision is what to decide: Using evidence inventory reports to focus health technology assessments. Int J Technol Assess Health Care. 2011;27(2):127132.
  28. McGregor M, Brophy JM. End‐user involvement in health technology assessment (HTA) development: a way to increase impact. Int J Technol Assess Health Care. 2005;21(02):263267.
  29. Bodeau‐Livinec F, Simon E, Montagnier‐Petrissans C, Joël M‐E, Féry‐Lemonnier E. Impact of CEDIT recommendations: an example of health technology assessment in a hospital network. Int J Technol Assess Health Care. 2006;22(2):161168.
  30. Alexander JA, Hearld LR, Jiang HJ, Fraser I. Increasing the relevance of research to health care managers: hospital CEO imperatives for improving quality and lowering costs. Health Care Manage Rev. 2007;32(2):150159.
  31. Khangura S, Konnyu K, Cushman R, Grimshaw J, Moher D. Evidence summaries: the evolution of a rapid review approach. Syst Rev. 2012;1(1):10.
  32. Brown M, Hurwitz J, Brixner D, Malone DC. Health care decision makers' use of comparative effectiveness research: report from a series of focus groups. J Manag Care Pharm. 2013;19(9):745754.
  33. Watt A, Cameron A, Sturm L, et al. Rapid reviews versus full systematic reviews: an inventory of current methods and practice in health technology assessment. Int J Technol Assess Health Care. 2008;24(2):133139.
  34. Hartling L, Guise J‐M, Kato E, et al. EPC Methods: An Exploration of Methods and Context for the Production of Rapid Reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2015. Available at: http://www.ncbi.nlm.nih.gov/books/NBK274092. Accessed March 5, 2015.
  35. Umscheid CA, Hanish A, Chittams J, Weiner MG, Hecht TEH. Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi‐experimental study. BMC Med Inform Decis Mak. 2012;12:92.
  36. McGreevey JD. Order sets in electronic health records: principles of good practice. Chest. 2013;143(1):228235.
  37. Umscheid CA, Betesh J, VanZandbergen C, et al. Development, implementation, and impact of an automated early warning and response system for sepsis. J Hosp Med. 2015;10(1):2631.
  38. Guidi JL, Clark K, Upton MT, et al. Clinician perception of the effectiveness of an automated early warning and response system for sepsis in an academic medical center. Ann Am Thorac Soc. 2015;12(10):15141519.
  39. Baillie CA, Epps M, Hanish A, Fishman NO, French B, Umscheid CA. Usability and impact of a computerized clinical decision support intervention designed to reduce urinary catheter utilization and catheter‐associated urinary tract infections. Infect Control Hosp Epidemiol. 2014;35(9):11471155.
  40. Baillie CA, VanZandbergen C, Tait G, et al. The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30‐day readmission. J Hosp Med. 2013;8(12):689695.
  41. Mitchell MD, Mikkelsen ME, Umscheid CA, Lee I, Fuchs BD, Halpern SD. A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic. Crit Care Med. 2010;38(6):13981404.
  42. Mitchell MD, Anderson BJ, Williams K, Umscheid CA. Heparin flushing and other interventions to maintain patency of central venous catheters: a systematic review. J Adv Nurs. 2009;65(10):20072021.
  43. Asch DA, Jedrziewski MK, Christakis NA. Response rates to mail surveys published in medical journals. J Clin Epidemiol. 1997;50(10):11291136.
  44. Kellerman SE, Herold J. Physician response to surveys: a review of the literature. Am J Prev Med. 2001;20(1):6167.
  45. Lee I, Agarwal RK, Lee BY, Fishman NO, Umscheid CA. Systematic review and cost analysis comparing use of chlorhexidine with use of iodine for preoperative skin antisepsis to prevent surgical site infection. Infect Control Hosp Epidemiol. 2010;31(12):12191229.
  46. Umscheid CA, Kohl BA, Williams K. Antifibrinolytic use in adult cardiac surgery. Curr Opin Hematol. 2007;14(5):455467.
  47. Wyer PC, Umscheid CA, Wright S, Silva SA, Lang E. Teaching evidence assimilation for collaborative health care (TEACH) 2009–2014: building evidence‐based capacity within health care provider organizations. EGEMS (Wash DC). 2015;3(2):1165.
  48. Han JH, Sullivan N, Leas BF, Pegues DA, Kaczmarek JL, Umscheid CA. Cleaning hospital room surfaces to prevent health care‐associated infections: a technical brief [published online August 11, 2015]. Ann Intern Med. doi:10.7326/M15‐1192.
  49. Umscheid CA, Agarwal RK, Brennan PJ, Healthcare Infection Control Practices Advisory Committee. Updating the guideline development methodology of the Healthcare Infection Control Practices Advisory Committee (HICPAC). Am J Infect Control. 2010;38(4):264273.
  50. U.S. Food and Drug Administration. FDA basics—What is a medical device? Available at: http://www.fda.gov/AboutFDA/Transparency/Basics/ucm211822.htm. Accessed November 12, 2014.
References
  1. Avorn J, Fischer M. “Bench to behavior”: translating comparative effectiveness research into improved clinical practice. Health Aff (Millwood). 2010;29(10):18911900.
  2. Rajab MH, Villamaria FJ, Rohack JJ. Evaluating the status of “translating research into practice” at a major academic healthcare system. Int J Technol Assess Health Care. 2009;25(1):8489.
  3. Timbie JW, Fox DS, Busum K, Schneider EC. Five reasons that many comparative effectiveness studies fail to change patient care and clinical practice. Health Aff (Millwood). 2012;31(10):21682175.
  4. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4(1):50.
  5. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients' care. Lancet. 2003;362(9391):12251230.
  6. Umscheid CA, Brennan PJ. Incentivizing “structures” over “outcomes” to bridge the knowing‐doing gap. JAMA Intern Med. 2015;175(3):354.
  7. Olsen L, Aisner D, McGinnis JM, eds. Institute of Medicine (US) Roundtable on Evidence‐Based Medicine. The Learning Healthcare System: Workshop Summary. Washington, DC: National Academies Press; 2007. Available at: http://www.ncbi.nlm.nih.gov/books/NBK53494/. Accessed October 29, 2014.
  8. Harrison MB, Legare F, Graham ID, Fervers B. Adapting clinical practice guidelines to local context and assessing barriers to their use. Can Med Assoc J. 2010;182(2):E78E84.
  9. Mitchell MD, Williams K, Brennan PJ, Umscheid CA. Integrating local data into hospital‐based healthcare technology assessment: two case studies. Int J Technol Assess Health Care. 2010;26(3):294300.
  10. Umscheid CA, Williams K, Brennan PJ. Hospital‐based comparative effectiveness centers: translating research into practice to improve the quality, safety and value of patient care. J Gen Intern Med. 2010;25(12):13521355.
  11. Gutowski C, Maa J, Hoo KS, Bozic KJ, Bozic K. Health technology assessment at the University of California‐San Francisco. J Healthc Manag Am Coll Healthc Exec. 2011;56(1):1529; discussion 29–30.
  12. Schottinger J, Odell RM. Kaiser Permanente Southern California regional technology management process: evidence‐based medicine operationalized. Perm J. 2006;10(1):3841.
  13. Gagnon M‐P. Hospital‐based health technology assessment: developments to date. Pharmacoeconomics. 2014;32(9):819824.
  14. Cicchetti A, Marchetti M, Dibidino R, Corio M. Hospital based health technology assessment world‐wide survey. Available at: http://www.htai.org/fileadmin/HTAi_Files/ISG/HospitalBasedHTA/2008Files/HospitalBasedHTAISGSurveyReport.pdf. Accessed October 11, 2015.
  15. Stevens AJ, Longson C. At the center of health care policy making: the use of health technology assessment at NICE. Med Decis Making. 2013;33(3):320324.
  16. Atkins D, Fink K, Slutsky J. Better information for better health care: the Evidence‐based Practice Center program and the Agency for Healthcare Research and Quality. Ann Intern Med. 2005;142(12 part 2):10351041.
  17. Slutsky JR, Clancy CM. AHRQ's Effective Health Care Program: why comparative effectiveness matters. Am J Med Qual. 2009;24(1):6770.
  18. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet. 1993;342(8883):13171322.
  19. Graham ID, Logan J, Harrison MB, et al. Lost in knowledge translation: time for a map? J Contin Educ Health Prof. 2006;26(1):1324.
  20. Gagnon M‐P, Desmartis M, Poder T, Witteman W. Effects and repercussions of local/hospital‐based health technology assessment (HTA): a systematic. Syst Rev. 2014;3:129.
  21. McGregor M, Arnoldo J, Barkun J, et al. Impact of TAU Reports. McGill University Health Centre. Available at: https://francais.mcgill.ca/files/tau/FINAL_TAU_IMPACT_REPORT_FEB_2008.pdf. Published Feb 1, 2008. Accessed August 19, 2014.
  22. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924926.
  23. Booth AM, Wright KE, Outhwaite H. Centre for Reviews and Dissemination databases: value, content, and developments. Int J Technol Assess Health Care. 2010;26(4):470472.
  24. Goodman C. HTA 101. Introduction to Health Technology Assessment. Available at: https://www.nlm.nih.gov/nichsr/hta101/ta10103.html. Accessed October 11, 2015.
  25. National Institute for Health Research. Remit. NIHR HTA Programme. Available at: http://www.nets.nihr.ac.uk/programmes/hta/remit. Accessed August 20, 2014.
  26. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—a metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377381.
  27. Mitchell MD, Williams K, Kuntz G, Umscheid CA. When the decision is what to decide: Using evidence inventory reports to focus health technology assessments. Int J Technol Assess Health Care. 2011;27(2):127132.
  28. McGregor M, Brophy JM. End‐user involvement in health technology assessment (HTA) development: a way to increase impact. Int J Technol Assess Health Care. 2005;21(02):263267.
  29. Bodeau‐Livinec F, Simon E, Montagnier‐Petrissans C, Joël M‐E, Féry‐Lemonnier E. Impact of CEDIT recommendations: an example of health technology assessment in a hospital network. Int J Technol Assess Health Care. 2006;22(2):161168.
  30. Alexander JA, Hearld LR, Jiang HJ, Fraser I. Increasing the relevance of research to health care managers: hospital CEO imperatives for improving quality and lowering costs. Health Care Manage Rev. 2007;32(2):150159.
  31. Khangura S, Konnyu K, Cushman R, Grimshaw J, Moher D. Evidence summaries: the evolution of a rapid review approach. Syst Rev. 2012;1(1):10.
  32. Brown M, Hurwitz J, Brixner D, Malone DC. Health care decision makers' use of comparative effectiveness research: report from a series of focus groups. J Manag Care Pharm. 2013;19(9):745754.
  33. Watt A, Cameron A, Sturm L, et al. Rapid reviews versus full systematic reviews: an inventory of current methods and practice in health technology assessment. Int J Technol Assess Health Care. 2008;24(2):133139.
  34. Hartling L, Guise J‐M, Kato E, et al. EPC Methods: An Exploration of Methods and Context for the Production of Rapid Reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2015. Available at: http://www.ncbi.nlm.nih.gov/books/NBK274092. Accessed March 5, 2015.
  35. Umscheid CA, Hanish A, Chittams J, Weiner MG, Hecht TEH. Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi‐experimental study. BMC Med Inform Decis Mak. 2012;12:92.
  36. McGreevey JD. Order sets in electronic health records: principles of good practice. Chest. 2013;143(1):228235.
  37. Umscheid CA, Betesh J, VanZandbergen C, et al. Development, implementation, and impact of an automated early warning and response system for sepsis. J Hosp Med. 2015;10(1):2631.
  38. Guidi JL, Clark K, Upton MT, et al. Clinician perception of the effectiveness of an automated early warning and response system for sepsis in an academic medical center. Ann Am Thorac Soc. 2015;12(10):15141519.
  39. Baillie CA, Epps M, Hanish A, Fishman NO, French B, Umscheid CA. Usability and impact of a computerized clinical decision support intervention designed to reduce urinary catheter utilization and catheter‐associated urinary tract infections. Infect Control Hosp Epidemiol. 2014;35(9):11471155.
  40. Baillie CA, VanZandbergen C, Tait G, et al. The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30‐day readmission. J Hosp Med. 2013;8(12):689695.
  41. Mitchell MD, Mikkelsen ME, Umscheid CA, Lee I, Fuchs BD, Halpern SD. A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic. Crit Care Med. 2010;38(6):13981404.
  42. Mitchell MD, Anderson BJ, Williams K, Umscheid CA. Heparin flushing and other interventions to maintain patency of central venous catheters: a systematic review. J Adv Nurs. 2009;65(10):20072021.
  43. Asch DA, Jedrziewski MK, Christakis NA. Response rates to mail surveys published in medical journals. J Clin Epidemiol. 1997;50(10):11291136.
  44. Kellerman SE, Herold J. Physician response to surveys: a review of the literature. Am J Prev Med. 2001;20(1):6167.
  45. Lee I, Agarwal RK, Lee BY, Fishman NO, Umscheid CA. Systematic review and cost analysis comparing use of chlorhexidine with use of iodine for preoperative skin antisepsis to prevent surgical site infection. Infect Control Hosp Epidemiol. 2010;31(12):12191229.
  46. Umscheid CA, Kohl BA, Williams K. Antifibrinolytic use in adult cardiac surgery. Curr Opin Hematol. 2007;14(5):455467.
  47. Wyer PC, Umscheid CA, Wright S, Silva SA, Lang E. Teaching evidence assimilation for collaborative health care (TEACH) 2009–2014: building evidence‐based capacity within health care provider organizations. EGEMS (Wash DC). 2015;3(2):1165.
  48. Han JH, Sullivan N, Leas BF, Pegues DA, Kaczmarek JL, Umscheid CA. Cleaning hospital room surfaces to prevent health care‐associated infections: a technical brief [published online August 11, 2015]. Ann Intern Med. doi:10.7326/M15‐1192.
  49. Umscheid CA, Agarwal RK, Brennan PJ, Healthcare Infection Control Practices Advisory Committee. Updating the guideline development methodology of the Healthcare Infection Control Practices Advisory Committee (HICPAC). Am J Infect Control. 2010;38(4):264273.
  50. U.S. Food and Drug Administration. FDA basics—What is a medical device? Available at: http://www.fda.gov/AboutFDA/Transparency/Basics/ucm211822.htm. Accessed November 12, 2014.
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Evidence synthesis activities of a hospital evidence‐based practice center and impact on hospital decision making
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Address for correspondence and reprint requests: Craig A. Umscheid, MD, University of Pennsylvania Health System, 3535 Market Street Mezzanine, Suite 50, Philadelphia, PA 19104; Telephone: 215‐349‐8098; Fax: 215‐349‐5829; E‐mail: [email protected]
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Opioid-Induced Androgen Deficiency in Veterans With Chronic Nonmalignant Pain

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Opioid-Induced Androgen Deficiency in Veterans With Chronic Nonmalignant Pain
Patients on chronic opioid therapy or considering it should be counseled about the risks 
associated with opioid-induced androgen deficiency.

According to the CDC, the medical use of opioid painkillers has increased at least 10-fold during the past 
20 years, “because of a movement toward more aggressive management of pain.”1 Although opioid therapy is generally considered effective for the treatment of pain, long-term use (both orally and intrathecally) is associated with adverse effects (AEs) such as constipation, fatigue, nausea, sleep disturbances, depression, sexual dysfunction, and hypogonadism.2,3Opioid-induced androgen deficiency (OPIAD), as defined by Smith and Elliot, is a clinical syndrome characterized by inappropriately low concentrations of gonadotropins (specifically, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), which leads to inadequate production of sex hormones, including estradiol and testosterone.4

Related: Testosterone Replacement Therapy: Playing Catch-up With Patients

The mechanism behind this phenomenon is initiated by either endogenous or exogenous opioids acting on opioid receptors in the hypothalamus, which causes a decrease in the release of gonadotropin-
releasing hormone (GnRH). This decrease in GnRH causes a reduction in the release of LH and FSH from the pituitary gland as well as testosterone or estradiol from the gonads.4,5 Various guidelines report different cutoffs for the lower limit of normal total testosterone: The Endocrine Society recommends 300 ng/dL, the American Association of Clinical Endocrinologists suggests 200 ng/dL, and various other organizations suggest 230 ng/dL.6-8 Hypotestosteronism can result in patients presenting with a broad spectrum of clinical symptoms, including reduced libido, erectile dysfunction (ED), fatigue, hot flashes, depression, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis.4 Women with low testosterone levels can experience irregular menstrual periods, oligomenorrhea, or amenorrhea.9 Opioid-induced androgen deficiency often goes unrecognized and untreated. The reported prevalence of opioid-induced hypogonadism ranges from 21% to 86%.4,9 Given the growing number of patients on chronic opioid therapy, OPIAD warrants further investigation to identify the prevalence in the veteran population to appropriately monitor and manage this deficiency.

The objective of this retrospective review was to identify the presence of secondary hypogonadism in chronic opioid users among a cohort of veterans receiving chronic opioids for nonmalignant pain. In addition to identifying the presence of secondary hypogonadism, the relationship between testosterone concentrations and total daily morphine equivalent doses (MEDs) was reviewed. These data along with the new information recently published on testosterone replacement therapy (TRT) and cardiovascular (CV) risk were then used to evaluate current practices at the West Palm Beach VAMC for OPIAD monitoring and management and to modify and update the local Criteria for Use (CFU) for TRT.

Methods

Patient data from the West Palm Beach VAMC in Florida from January 2013 to December 2013 were reviewed to identify patients who had a total testosterone (TT) level measured. All patient appointments for evaluation and treatment by the clinical pharmacy specialist in pain management were reviewed for data collection. This retrospective review was approved by the scientific advisory committee as part of the facility’s ongoing performance improvement efforts as defined by VHA Handbook 1058.05 and did not require written patient consent.10

Several distinct TT level data were collected. The descriptive data included patient age; gender; type of treated pain; testosterone level(s) drawn, including TT level before opioid therapy, TT level before/during/after TRT, and current total testosterone level; total daily MED of opioid therapy; duration of chronic opioid therapy; symptoms of exhibited hypogonadism; TRT formulation, dose, and duration; TRT prescriber; symptom change (if any); and laboratory tests ordered for TRT monitoring (lipid profile, liver profile, complete blood count, LH/FSH, and prostate specific antigen [PSA] panel).5,11,12

Related: Combination Treatment Relieves Opioid-Induced Constipation

Daily MED of opioid therapy was calculated using the VA/DoD opioid conversion table for patients on oxycodone, hydromorphone, or hydrocodone.13 For those on the fentanyl patch or methadone, conversion factors of 1:2 (fentanyl [µg/h]:morphine [mg/d]) and 1:3 (methadone:morphine) were used to convert to the MED.14 For patients on the buprenorphine patch, the package insert was used to convert to the corresponding MED.15 Combination therapies used the applicable conversions to calculate the total daily MED.

Once the data were collected, descriptive statistics were used to analyze the data. In addition, 4 graphs were generated to review potential relationships. The correlation coefficient was calculated using the Alcula Online Statistics Calculator (http://www.alcula.com; Correlation Coefficient Calculator).

Results

A total of 316 unique veteran patients were seen by the clinical pharmacy specialist in pain management from January 1, 2013, through December 31, 2013. Of these, 73 patients (23.1%) had at least 1 TT level drawn in 2013. Three patients with testosterone levels drawn (4.1%) were excluded from the data analysis for the following reasons: 1 patient did not have testosterone levels on file before receiving testosterone replacement from a non-VA source, 
1 patient received opioids from a non-VA source (MED and duration of opioid therapy could not be calculated), and 1 patient inconsistently received opioids and MED used at the time of testosterone level draw. Per the local TRT CFU, a TT level > 350 ng/dL
does not require treatment, whereas levels < 230 ng/dL (with symptoms) may require TRT, and 
< 200 ng/dL should be treated as 
hypogonadal (interpretation based on local laboratory’s reference range for TT).16 Of the 70 patients included in the analysis, 34 (48.6%) had a TT level < 230 ng/dL and would be considered eligible for TRT if they presented with symptoms 
of low testosterone. Of these 34 patients with a low testosterone level, 28 (40%) were being treated or had been treated with TRT (Figure 1).

 

 

The average age of the male patients with a testosterone level drawn was 58.3 years, which was not significantly different from the calculated median age of 60 years. No female patients had a testosterone level drawn. On average, the TT level was normal before starting opioids (reference range per local laboratory: 175-781 ng/dL). Once opioids were initiated, patients were treated for an average duration of 52.5 months (calculated through December 2013) with an average daily dose of 126.8 MED (Table). Fifty of the 70 patients (71.4%) with testosterone levels drawn in 2013 received TRT. The most common symptoms reported by patients related to low testosterone included ED, decreased libido, depression, chronic fatigue, generalized weakness, and hot flashes or night sweats.

The average TT level prior to TRT was 145.3, and the average 
testosterone level after initiation of or 
during treatment with TRT was 292.4, which is within the normal TT level range. Most patients receiving TRT were treated with testosterone cypionate injections, and this was also the formulation used for the longest periods, likely due to the local CFU. In addition to testosterone cypionate injections, patients were also treated with testosterone enanthate injections, testosterone patches, and testosterone gel.

Figure 1 compares current testosterone level and testosterone level before TRT with total daily MEDs. Figure 2 compares current testosterone level and testosterone level before TRT with length of opioid therapy. The 2 figures use data from all patients included in the analysis and indicate a potential inverse relationship between the total daily MED and duration of therapy with the testosterone level, although none of the calculated correlation coefficients indicate that a strong relationship was present.

Figures 3 and 4 include data only for patients who had both a testosterone level collected before opioids (baseline testosterone level) and a current testosterone level. Figure 3 trends the data using total daily MED, and Figure 4 uses the duration of opioid therapy. The correlation for Figure 4 is slightly stronger; the strongest negative correlations were identified between total daily MED and testosterone level before opioid therapy (r = -0.273) and duration of opioid therapy and testosterone level prior to opioid therapy (r = -0.396). The trends indicate that most patients had a normal TT level before opioid treatment and that patients treated with higher MEDs and for longer durations of time were more likely to have lower total testosterone levels.

Discussion

Low testosterone levels can adversely affect patients’ quality of life (QOL) and add to patients’ medication burden with the initiation of TRT. Given new data analyzing the potential effects of TRT on CV event risk, the use of TRT should be carefully considered, as it may carry significant risks and may not be suitable for all patients.

In November 2013, a study was published regarding TRT and 
increased CV risk.17 This was a retrospective cohort study of men with low testosterone levels (< 300 ng/dL) who had undergone coronary angiography in the VA system between 2005 and 2011 (average age in testosterone group was 60.6 years). The results were significant for an absolute rate of events (all-cause mortality, myocardial infarction [MI], and ischemic stroke) of 19.9% in the no testosterone group and 25.7% in the TRT group, an absolute risk difference of 5.8% at 3 years after coronary angiography. Kaplan-Meier survival curves demonstrated that testosterone use was associated with increased risk of death, MI, and stroke. This result was unchanged when adjusted for the presence of coronary artery disease (CAD). In 
addition, no significant difference was found between the groups in terms of systolic blood pressure, low-
density lipoprotein cholesterol level, or in the use of beta-blocker and statin medications. What is important to note is that in this cohort, 20% had a prior history of MI and heart failure, and more than 50% had confirmed obstructive CAD on angiography. In addition, as this was an observational study, confounding or bias may exist, and given the study population, 
generalizability may be limited to a veteran population.

Related: A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Another retrospective cohort study assessed the risk of acute nonfatal MI following an initial TRT prescription in a large health care database (average age based on TRT prescription was 54.4 years).18 In men aged ≥ 65 years, a 2-fold increase in the risk of MI in the immediate 90 days after filling an initial TRT prescription declined to baseline after 91 to 180 days among those who did not refill their prescription. Younger men with a history of heart disease had a 2- to 3-fold increased risk of MI in the 90 days following initial TRT prescription. No excess risk was observed in the younger men without such a history. Again, this study has its limitations related to the retrospective design and use of a health care database as opposed to a randomized controlled trial.

 

 

In February 2014, a VA National Pharmacy Benefits Management (PBM) bulletin addressed 2 recent studies that had identified a possible risk of increased CV events in men receiving TRT. The bulletin noted that these studies had prompted the FDA to reassess the CV safety of TRT.19 The TRT CFU was updated by VISN 8 to ensure that the patients receive appropriate treatment and are monitored accordingly.

One of the major changes to the CFU was defining the reference ranges for TRT (interpretation based on a local laboratory’s reference range for total testosterone): serum TT < 200 ng/dL be “treated as 
hypogonadal, those with TT 
> 400 ng/dL be considered normal and those with TT 200-400 ng/dL be treated based on their clinical presentation if symptomatic; TT levels 
> 350 ng/dL do not require treatment, and levels below 230 ng/dL (with symptoms) may require testosterone replacement therapy.”16 Other important updates included revision of the exclusion criteria as well as 
highlighting special considerations related to TRT, including the use of free testosterone levels rather than TT levels in patients with suspected protein-binding issues, role in fertility treatments, limited use in patients on spironolactone therapy (due to spironolactone’s anti-androgen effects), and potential association with mood and behavior.16

As chronic opioid therapy is associated with OPIAD, the renewed interest in TRT and its potential AEs provides yet another reason to reconsider opioid therapy. This is especially valid when opioids are the potential cause of hypogonadism and the reaction is treating the AEs of opioids (as opposed to considering elimination of the causative agent) with a therapy that can potentially increase the risk for CV events so that opioids can be continued. Outside the potential CV risk with TRT, opioids carry the innate risk for substance abuse and addiction.

The Opioid Safety Initiative Requirements was released as a memorandum in April 2014 and is the VHA’s effort to “reduce harm from unsafe medications and/or excessive doses while adequately controlling pain in Veterans.”20 Although it does not discuss the risk of OPIAD, it does highlight the need to identify and mitigate high-risk patients as well as high-risk opioid regimens. All these factors, including the possibility of hypogonadism, should be considered before starting opioid therapy and at the time of opioid renewal, as it is known that opioid therapy is not without risks.

At the West Palm Beach VAMC, the primary care providers (PCPs) are responsible for the management of TRT, including the workup, renewal, and monitoring. The Chronic Nonmalignant Pain Management Clinic (CNMPMC) orders testosterone levels on patients who report symptoms of low testosterone, such as hot flashes, depression, and low energy level and refers them to their PCP as indicated. The authors believe that this is most appropriate for a number of reasons: (1) the CNMPMC is a consult service, and patients are not followed indefinitely; (2) patients should be fully evaluated for appropriateness of TRT (including assessment of CV risk) before starting therapy; and (3) the necessary monitoring parameters (laboratory testing, digital rectal exam, and osteoporosis screening) are not typically within the VA pain clinic provider’s scope of practice or expertise. A consideration for future practice would be to incorporate the use of a standardized questionnaire for OPIAD monitoring in patients receiving ≥ 100 mg of morphine daily (eg, the Aging Males’ Symptoms scale).21 It should, however, be at the forefront of the pain specialist’s and PCP’s minds that all patients on chronic opioid therapy or considering chronic opioid therapy should be counseled on the risk for OPIAD. If OPIAD is identified, the patient should be carefully considered for an opioid dose reduction as an initial management strategy.

Limitations

A limitation of this review is the lack of consistency or adequacy of serum testosterone sampling, noting that valid testosterone levels need to be drawn in the morning and not obtained during a time of acute illness. In addition, testosterone levels need to be drawn at an appropriate interval while on TRT (eg, at the midpoint between testosterone injections).16 Although the time of the sample collection is documented in the Computerized Patient Record System (CPRS), it is unknown whether the patient was acutely ill on the day of the sampling unless a progress note is entered, and it is difficult to determine whether the level timing was accurate based on the testosterone replacement formulation. Another limitation is that the average decline in serum testosterone levels with aging in men is 1% to 2% per year. A significant fraction of older men have levels below the lower limit of the normal range for healthy young men, so in older men it can be more difficult to determine whether low testosterone is related to chronic opioid use or to older age.5,16

 

 

As this was a retrospective review, additional limitations included the inability to measure subclinical OPIAD, and the data collection related to symptoms of hypogonadism was restricted by documentation in the CPRS progress notes. The lack of data for females does not contribute to the literature on OPIAD in women. Finally, as the total daily MED does not distinguish between short-acting and long-acting opioid therapy, no differences between the impacts of short-acting vs long-
acting opioid therapy on risk for 
hypogonadism can be inferred. There is evidence to suggest that long-acting opioids are associated with a significantly higher risk for OPIAD compared with short-acting opioids, although the mechanism behind this is not well established.22,23

Conclusions

The average age of the patients 
on chronic opioid therapy with a 
testosterone level drawn in this cohort was 58.3 years, which is younger than originally anticipated. The median age of 60 years is not significantly different from the average age, indicating that outliers did not impact this calculation. On average, the TT level was normal before starting opioids. Once opioids were started, patients were treated for an average duration of 52.5 months with an average daily dose of 126.8 mg MED. In this veteran cohort, 48.6% of patients met the criteria for TRT based on TT level alone, which is within the reported prevalence range of opioid-induced hypogonadism already published.4,9 These results are in line with the original hypothesis that chronic opioid use can adversely impact testosterone levels and can have a poor effect on a patient’s QOL due to symptoms of low testosterone. In addition to TRT, possible and suggested (but not proven) treatment options for OPIAD include discontinuation of opioid therapy, opioid rotation, or conversion to buprenorphine.21 The approach used should account for multiple patient-specific factors and should be individualized.

Based on the data, there is a trend toward lower testosterone levels in veterans treated with higher MED and for longer periods with chronic opioids. Given recent data that infer that TRT carries increased CV risk as well as the VHA’s Opioid Safety Initiative, it is imperative that providers closely evaluate the appropriateness of starting TRT and/or continuing chronic opioid therapy. All patients generally should have failed non-
opioid management prior to opioid therapy for chronic nonmalignant pain, and this should be documented accordingly. It is also crucial to have the “opioid talk” with patients from time to time and discuss the risks vs benefits, the potential for addiction, overdose, dependence, tolerance, constipation, and OPIAD so patients can continue to be an active and informed participants in their care.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

References

1. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Unintentional drug poisoning in the United States, 2010. Atlanta, GA: Centers for Disease Control and Prevention Website. http://www.cdc.gov
/HomeandRecreationalSafety/pdf/poison-issue-brief
.pdf. Published July 2010. Accessed August 28, 2015.

2. American Academy of Family Physicians. Using opioids in the management of chronic pain patients: challenges and future options. University of Kentucky Medical Center Website. http://www
.mc.uky.edu/equip-4-pcps/documents/CRx%20Literature/Opioids%20for%20chronic%20pain.pdf. Published 2010. Accessed August 28, 2015.

3. Duarte RV, Raphael JH, Labib M, Southall JL, Ashford RL. Prevalence and influence of diagnostic criteria in the assessment of hypogonadism in intrathecal opioid therapy patients. Pain Physician. 2013;16(1):9-14.

4. Smith HS, Elliott JA. Opioid-induced androgen deficiency (OPIAD). Pain Physician. 2012;15(suppl 3):ES145-ES156.

5. De Maddalena C, Bellini M, Berra M, Meriggiola MC, Aloisi AM. Opioid-induced hypogonadism: why and how to treat it. Pain Physician. 2012;15(suppl 3):ES111-ES118.

6. Bhasin S, Cunningham GR, Hayes FJ, et al; VM Endocrine Society Task Force. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

7. Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients–2002 update. Endocr Pract. 2002;8(6):440-456.

8. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30(1):1-9.

9. Reddy RG, Aung T, Karavitaki N, Wass JA. Opioid induced hypogonadism. BMJ. 2010;341:c4462.

10. U.S. Department of Veterans Affairs, Veterans Health Administration. VHA Handbook 1058.05: VHA operations activities that may constitute research. U.S. Department of Veterans Affairs Website. http://www.va.gov/vhapublications
/ViewPublication.asp?pub_ID=2456. Published October 28, 2011. Accessed August 28, 2015.

11. AndroGel [package insert]. North Chicago, IL:
AbbVie Inc; 2013.

12. Axiron [package insert]. Indianapolis, IL: Lilly USA, LLC; 2011.

13. U.S. Department of Veterans Affairs. Opioid therapy for chronic pain pocket guide. U.S. Department of Veterans Affairs. http://www.healthquality
.va.gov/guidelines/pain/cot/opioidpocketguide23may2013v1.pdf. Published May 2013 Accessed August 28, 2015.

14. McPherson ML. Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. Bethesda, MD: American Society of Health-System Pharmacists; 2009.

15. Butrans [package insert]. Stamford, CT: Purdue Pharma LP; 2014.

16. Testosterone Replacement Therapy Criteria for Use. VISN 8: VISN Pharmacist Executives, Veterans Health Administration, Department of Veterans Affairs; 2014. [Internal document.]

17. Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836.

18. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805.

19. U.S. Department of Veterans Affairs. Testosterone products and cardiovascular safety. U.S. Department of Veterans Affairs Website. http://www.pbm
.va.gov/PBM/vacenterformedicationsafety
/nationalpbmbulletin/Testosterone_Products_and
_Cardiovascular_Safety_NATIONAL_PBM
_BULLETIN_02.pdf. Published February 7, 2014. Accessed August 28, 2015.

20. U.S. Department of Veterans Affairs Veterans Health Administration (VHA) Pharmacy Benefits Management Services (PBM), Medical Advisory Panel (MAP) and Center for Medication Safety (VA MEDSAFE). Memorandum: Opioid Safety Initiative Requirements. U.S. Department of Veterans Affairs Website. http://www.veterans.senate.gov/imo
/media/doc/VA%20Testimony%20-%20April%2030%20SVAC%20Overmedication%20hearing.pdf. Published April 30, 2014. Accessed August 28, 2015.

21. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18.

22. Rubinstein AL, Carpenter DM, Minkoff JR. Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids. Clin J Pain. 2013;29(10):840-845.

23. Rubinstein A, Carpenter DM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med. 2014;127(12):1195-1201.

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Dr. Brooks is a clinical pharmacy specialist in pain management, Dr. DiScala is a clinical pharmacy specialist in community living center/hospice and palliative care, Dr. Cuevas-Trisán is chief of the Physical Medicine and Rehabilitation Service, and Dr. Meléndez-Benabe is the chronic pain management section chief, all at the West Palm Beach VAMC in Florida. Dr. Nazario is manager of the VISN 8 Pharmacy Benefits Management Program for Pain Management in Bay Pines, Florida.
 

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Dr. Brooks is a clinical pharmacy specialist in pain management, Dr. DiScala is a clinical pharmacy specialist in community living center/hospice and palliative care, Dr. Cuevas-Trisán is chief of the Physical Medicine and Rehabilitation Service, and Dr. Meléndez-Benabe is the chronic pain management section chief, all at the West Palm Beach VAMC in Florida. Dr. Nazario is manager of the VISN 8 Pharmacy Benefits Management Program for Pain Management in Bay Pines, Florida.
 

Author and Disclosure Information

Dr. Brooks is a clinical pharmacy specialist in pain management, Dr. DiScala is a clinical pharmacy specialist in community living center/hospice and palliative care, Dr. Cuevas-Trisán is chief of the Physical Medicine and Rehabilitation Service, and Dr. Meléndez-Benabe is the chronic pain management section chief, all at the West Palm Beach VAMC in Florida. Dr. Nazario is manager of the VISN 8 Pharmacy Benefits Management Program for Pain Management in Bay Pines, Florida.
 

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Related Articles
Patients on chronic opioid therapy or considering it should be counseled about the risks 
associated with opioid-induced androgen deficiency.
Patients on chronic opioid therapy or considering it should be counseled about the risks 
associated with opioid-induced androgen deficiency.

According to the CDC, the medical use of opioid painkillers has increased at least 10-fold during the past 
20 years, “because of a movement toward more aggressive management of pain.”1 Although opioid therapy is generally considered effective for the treatment of pain, long-term use (both orally and intrathecally) is associated with adverse effects (AEs) such as constipation, fatigue, nausea, sleep disturbances, depression, sexual dysfunction, and hypogonadism.2,3Opioid-induced androgen deficiency (OPIAD), as defined by Smith and Elliot, is a clinical syndrome characterized by inappropriately low concentrations of gonadotropins (specifically, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), which leads to inadequate production of sex hormones, including estradiol and testosterone.4

Related: Testosterone Replacement Therapy: Playing Catch-up With Patients

The mechanism behind this phenomenon is initiated by either endogenous or exogenous opioids acting on opioid receptors in the hypothalamus, which causes a decrease in the release of gonadotropin-
releasing hormone (GnRH). This decrease in GnRH causes a reduction in the release of LH and FSH from the pituitary gland as well as testosterone or estradiol from the gonads.4,5 Various guidelines report different cutoffs for the lower limit of normal total testosterone: The Endocrine Society recommends 300 ng/dL, the American Association of Clinical Endocrinologists suggests 200 ng/dL, and various other organizations suggest 230 ng/dL.6-8 Hypotestosteronism can result in patients presenting with a broad spectrum of clinical symptoms, including reduced libido, erectile dysfunction (ED), fatigue, hot flashes, depression, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis.4 Women with low testosterone levels can experience irregular menstrual periods, oligomenorrhea, or amenorrhea.9 Opioid-induced androgen deficiency often goes unrecognized and untreated. The reported prevalence of opioid-induced hypogonadism ranges from 21% to 86%.4,9 Given the growing number of patients on chronic opioid therapy, OPIAD warrants further investigation to identify the prevalence in the veteran population to appropriately monitor and manage this deficiency.

The objective of this retrospective review was to identify the presence of secondary hypogonadism in chronic opioid users among a cohort of veterans receiving chronic opioids for nonmalignant pain. In addition to identifying the presence of secondary hypogonadism, the relationship between testosterone concentrations and total daily morphine equivalent doses (MEDs) was reviewed. These data along with the new information recently published on testosterone replacement therapy (TRT) and cardiovascular (CV) risk were then used to evaluate current practices at the West Palm Beach VAMC for OPIAD monitoring and management and to modify and update the local Criteria for Use (CFU) for TRT.

Methods

Patient data from the West Palm Beach VAMC in Florida from January 2013 to December 2013 were reviewed to identify patients who had a total testosterone (TT) level measured. All patient appointments for evaluation and treatment by the clinical pharmacy specialist in pain management were reviewed for data collection. This retrospective review was approved by the scientific advisory committee as part of the facility’s ongoing performance improvement efforts as defined by VHA Handbook 1058.05 and did not require written patient consent.10

Several distinct TT level data were collected. The descriptive data included patient age; gender; type of treated pain; testosterone level(s) drawn, including TT level before opioid therapy, TT level before/during/after TRT, and current total testosterone level; total daily MED of opioid therapy; duration of chronic opioid therapy; symptoms of exhibited hypogonadism; TRT formulation, dose, and duration; TRT prescriber; symptom change (if any); and laboratory tests ordered for TRT monitoring (lipid profile, liver profile, complete blood count, LH/FSH, and prostate specific antigen [PSA] panel).5,11,12

Related: Combination Treatment Relieves Opioid-Induced Constipation

Daily MED of opioid therapy was calculated using the VA/DoD opioid conversion table for patients on oxycodone, hydromorphone, or hydrocodone.13 For those on the fentanyl patch or methadone, conversion factors of 1:2 (fentanyl [µg/h]:morphine [mg/d]) and 1:3 (methadone:morphine) were used to convert to the MED.14 For patients on the buprenorphine patch, the package insert was used to convert to the corresponding MED.15 Combination therapies used the applicable conversions to calculate the total daily MED.

Once the data were collected, descriptive statistics were used to analyze the data. In addition, 4 graphs were generated to review potential relationships. The correlation coefficient was calculated using the Alcula Online Statistics Calculator (http://www.alcula.com; Correlation Coefficient Calculator).

Results

A total of 316 unique veteran patients were seen by the clinical pharmacy specialist in pain management from January 1, 2013, through December 31, 2013. Of these, 73 patients (23.1%) had at least 1 TT level drawn in 2013. Three patients with testosterone levels drawn (4.1%) were excluded from the data analysis for the following reasons: 1 patient did not have testosterone levels on file before receiving testosterone replacement from a non-VA source, 
1 patient received opioids from a non-VA source (MED and duration of opioid therapy could not be calculated), and 1 patient inconsistently received opioids and MED used at the time of testosterone level draw. Per the local TRT CFU, a TT level > 350 ng/dL
does not require treatment, whereas levels < 230 ng/dL (with symptoms) may require TRT, and 
< 200 ng/dL should be treated as 
hypogonadal (interpretation based on local laboratory’s reference range for TT).16 Of the 70 patients included in the analysis, 34 (48.6%) had a TT level < 230 ng/dL and would be considered eligible for TRT if they presented with symptoms 
of low testosterone. Of these 34 patients with a low testosterone level, 28 (40%) were being treated or had been treated with TRT (Figure 1).

 

 

The average age of the male patients with a testosterone level drawn was 58.3 years, which was not significantly different from the calculated median age of 60 years. No female patients had a testosterone level drawn. On average, the TT level was normal before starting opioids (reference range per local laboratory: 175-781 ng/dL). Once opioids were initiated, patients were treated for an average duration of 52.5 months (calculated through December 2013) with an average daily dose of 126.8 MED (Table). Fifty of the 70 patients (71.4%) with testosterone levels drawn in 2013 received TRT. The most common symptoms reported by patients related to low testosterone included ED, decreased libido, depression, chronic fatigue, generalized weakness, and hot flashes or night sweats.

The average TT level prior to TRT was 145.3, and the average 
testosterone level after initiation of or 
during treatment with TRT was 292.4, which is within the normal TT level range. Most patients receiving TRT were treated with testosterone cypionate injections, and this was also the formulation used for the longest periods, likely due to the local CFU. In addition to testosterone cypionate injections, patients were also treated with testosterone enanthate injections, testosterone patches, and testosterone gel.

Figure 1 compares current testosterone level and testosterone level before TRT with total daily MEDs. Figure 2 compares current testosterone level and testosterone level before TRT with length of opioid therapy. The 2 figures use data from all patients included in the analysis and indicate a potential inverse relationship between the total daily MED and duration of therapy with the testosterone level, although none of the calculated correlation coefficients indicate that a strong relationship was present.

Figures 3 and 4 include data only for patients who had both a testosterone level collected before opioids (baseline testosterone level) and a current testosterone level. Figure 3 trends the data using total daily MED, and Figure 4 uses the duration of opioid therapy. The correlation for Figure 4 is slightly stronger; the strongest negative correlations were identified between total daily MED and testosterone level before opioid therapy (r = -0.273) and duration of opioid therapy and testosterone level prior to opioid therapy (r = -0.396). The trends indicate that most patients had a normal TT level before opioid treatment and that patients treated with higher MEDs and for longer durations of time were more likely to have lower total testosterone levels.

Discussion

Low testosterone levels can adversely affect patients’ quality of life (QOL) and add to patients’ medication burden with the initiation of TRT. Given new data analyzing the potential effects of TRT on CV event risk, the use of TRT should be carefully considered, as it may carry significant risks and may not be suitable for all patients.

In November 2013, a study was published regarding TRT and 
increased CV risk.17 This was a retrospective cohort study of men with low testosterone levels (< 300 ng/dL) who had undergone coronary angiography in the VA system between 2005 and 2011 (average age in testosterone group was 60.6 years). The results were significant for an absolute rate of events (all-cause mortality, myocardial infarction [MI], and ischemic stroke) of 19.9% in the no testosterone group and 25.7% in the TRT group, an absolute risk difference of 5.8% at 3 years after coronary angiography. Kaplan-Meier survival curves demonstrated that testosterone use was associated with increased risk of death, MI, and stroke. This result was unchanged when adjusted for the presence of coronary artery disease (CAD). In 
addition, no significant difference was found between the groups in terms of systolic blood pressure, low-
density lipoprotein cholesterol level, or in the use of beta-blocker and statin medications. What is important to note is that in this cohort, 20% had a prior history of MI and heart failure, and more than 50% had confirmed obstructive CAD on angiography. In addition, as this was an observational study, confounding or bias may exist, and given the study population, 
generalizability may be limited to a veteran population.

Related: A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Another retrospective cohort study assessed the risk of acute nonfatal MI following an initial TRT prescription in a large health care database (average age based on TRT prescription was 54.4 years).18 In men aged ≥ 65 years, a 2-fold increase in the risk of MI in the immediate 90 days after filling an initial TRT prescription declined to baseline after 91 to 180 days among those who did not refill their prescription. Younger men with a history of heart disease had a 2- to 3-fold increased risk of MI in the 90 days following initial TRT prescription. No excess risk was observed in the younger men without such a history. Again, this study has its limitations related to the retrospective design and use of a health care database as opposed to a randomized controlled trial.

 

 

In February 2014, a VA National Pharmacy Benefits Management (PBM) bulletin addressed 2 recent studies that had identified a possible risk of increased CV events in men receiving TRT. The bulletin noted that these studies had prompted the FDA to reassess the CV safety of TRT.19 The TRT CFU was updated by VISN 8 to ensure that the patients receive appropriate treatment and are monitored accordingly.

One of the major changes to the CFU was defining the reference ranges for TRT (interpretation based on a local laboratory’s reference range for total testosterone): serum TT < 200 ng/dL be “treated as 
hypogonadal, those with TT 
> 400 ng/dL be considered normal and those with TT 200-400 ng/dL be treated based on their clinical presentation if symptomatic; TT levels 
> 350 ng/dL do not require treatment, and levels below 230 ng/dL (with symptoms) may require testosterone replacement therapy.”16 Other important updates included revision of the exclusion criteria as well as 
highlighting special considerations related to TRT, including the use of free testosterone levels rather than TT levels in patients with suspected protein-binding issues, role in fertility treatments, limited use in patients on spironolactone therapy (due to spironolactone’s anti-androgen effects), and potential association with mood and behavior.16

As chronic opioid therapy is associated with OPIAD, the renewed interest in TRT and its potential AEs provides yet another reason to reconsider opioid therapy. This is especially valid when opioids are the potential cause of hypogonadism and the reaction is treating the AEs of opioids (as opposed to considering elimination of the causative agent) with a therapy that can potentially increase the risk for CV events so that opioids can be continued. Outside the potential CV risk with TRT, opioids carry the innate risk for substance abuse and addiction.

The Opioid Safety Initiative Requirements was released as a memorandum in April 2014 and is the VHA’s effort to “reduce harm from unsafe medications and/or excessive doses while adequately controlling pain in Veterans.”20 Although it does not discuss the risk of OPIAD, it does highlight the need to identify and mitigate high-risk patients as well as high-risk opioid regimens. All these factors, including the possibility of hypogonadism, should be considered before starting opioid therapy and at the time of opioid renewal, as it is known that opioid therapy is not without risks.

At the West Palm Beach VAMC, the primary care providers (PCPs) are responsible for the management of TRT, including the workup, renewal, and monitoring. The Chronic Nonmalignant Pain Management Clinic (CNMPMC) orders testosterone levels on patients who report symptoms of low testosterone, such as hot flashes, depression, and low energy level and refers them to their PCP as indicated. The authors believe that this is most appropriate for a number of reasons: (1) the CNMPMC is a consult service, and patients are not followed indefinitely; (2) patients should be fully evaluated for appropriateness of TRT (including assessment of CV risk) before starting therapy; and (3) the necessary monitoring parameters (laboratory testing, digital rectal exam, and osteoporosis screening) are not typically within the VA pain clinic provider’s scope of practice or expertise. A consideration for future practice would be to incorporate the use of a standardized questionnaire for OPIAD monitoring in patients receiving ≥ 100 mg of morphine daily (eg, the Aging Males’ Symptoms scale).21 It should, however, be at the forefront of the pain specialist’s and PCP’s minds that all patients on chronic opioid therapy or considering chronic opioid therapy should be counseled on the risk for OPIAD. If OPIAD is identified, the patient should be carefully considered for an opioid dose reduction as an initial management strategy.

Limitations

A limitation of this review is the lack of consistency or adequacy of serum testosterone sampling, noting that valid testosterone levels need to be drawn in the morning and not obtained during a time of acute illness. In addition, testosterone levels need to be drawn at an appropriate interval while on TRT (eg, at the midpoint between testosterone injections).16 Although the time of the sample collection is documented in the Computerized Patient Record System (CPRS), it is unknown whether the patient was acutely ill on the day of the sampling unless a progress note is entered, and it is difficult to determine whether the level timing was accurate based on the testosterone replacement formulation. Another limitation is that the average decline in serum testosterone levels with aging in men is 1% to 2% per year. A significant fraction of older men have levels below the lower limit of the normal range for healthy young men, so in older men it can be more difficult to determine whether low testosterone is related to chronic opioid use or to older age.5,16

 

 

As this was a retrospective review, additional limitations included the inability to measure subclinical OPIAD, and the data collection related to symptoms of hypogonadism was restricted by documentation in the CPRS progress notes. The lack of data for females does not contribute to the literature on OPIAD in women. Finally, as the total daily MED does not distinguish between short-acting and long-acting opioid therapy, no differences between the impacts of short-acting vs long-
acting opioid therapy on risk for 
hypogonadism can be inferred. There is evidence to suggest that long-acting opioids are associated with a significantly higher risk for OPIAD compared with short-acting opioids, although the mechanism behind this is not well established.22,23

Conclusions

The average age of the patients 
on chronic opioid therapy with a 
testosterone level drawn in this cohort was 58.3 years, which is younger than originally anticipated. The median age of 60 years is not significantly different from the average age, indicating that outliers did not impact this calculation. On average, the TT level was normal before starting opioids. Once opioids were started, patients were treated for an average duration of 52.5 months with an average daily dose of 126.8 mg MED. In this veteran cohort, 48.6% of patients met the criteria for TRT based on TT level alone, which is within the reported prevalence range of opioid-induced hypogonadism already published.4,9 These results are in line with the original hypothesis that chronic opioid use can adversely impact testosterone levels and can have a poor effect on a patient’s QOL due to symptoms of low testosterone. In addition to TRT, possible and suggested (but not proven) treatment options for OPIAD include discontinuation of opioid therapy, opioid rotation, or conversion to buprenorphine.21 The approach used should account for multiple patient-specific factors and should be individualized.

Based on the data, there is a trend toward lower testosterone levels in veterans treated with higher MED and for longer periods with chronic opioids. Given recent data that infer that TRT carries increased CV risk as well as the VHA’s Opioid Safety Initiative, it is imperative that providers closely evaluate the appropriateness of starting TRT and/or continuing chronic opioid therapy. All patients generally should have failed non-
opioid management prior to opioid therapy for chronic nonmalignant pain, and this should be documented accordingly. It is also crucial to have the “opioid talk” with patients from time to time and discuss the risks vs benefits, the potential for addiction, overdose, dependence, tolerance, constipation, and OPIAD so patients can continue to be an active and informed participants in their care.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

According to the CDC, the medical use of opioid painkillers has increased at least 10-fold during the past 
20 years, “because of a movement toward more aggressive management of pain.”1 Although opioid therapy is generally considered effective for the treatment of pain, long-term use (both orally and intrathecally) is associated with adverse effects (AEs) such as constipation, fatigue, nausea, sleep disturbances, depression, sexual dysfunction, and hypogonadism.2,3Opioid-induced androgen deficiency (OPIAD), as defined by Smith and Elliot, is a clinical syndrome characterized by inappropriately low concentrations of gonadotropins (specifically, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), which leads to inadequate production of sex hormones, including estradiol and testosterone.4

Related: Testosterone Replacement Therapy: Playing Catch-up With Patients

The mechanism behind this phenomenon is initiated by either endogenous or exogenous opioids acting on opioid receptors in the hypothalamus, which causes a decrease in the release of gonadotropin-
releasing hormone (GnRH). This decrease in GnRH causes a reduction in the release of LH and FSH from the pituitary gland as well as testosterone or estradiol from the gonads.4,5 Various guidelines report different cutoffs for the lower limit of normal total testosterone: The Endocrine Society recommends 300 ng/dL, the American Association of Clinical Endocrinologists suggests 200 ng/dL, and various other organizations suggest 230 ng/dL.6-8 Hypotestosteronism can result in patients presenting with a broad spectrum of clinical symptoms, including reduced libido, erectile dysfunction (ED), fatigue, hot flashes, depression, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis.4 Women with low testosterone levels can experience irregular menstrual periods, oligomenorrhea, or amenorrhea.9 Opioid-induced androgen deficiency often goes unrecognized and untreated. The reported prevalence of opioid-induced hypogonadism ranges from 21% to 86%.4,9 Given the growing number of patients on chronic opioid therapy, OPIAD warrants further investigation to identify the prevalence in the veteran population to appropriately monitor and manage this deficiency.

The objective of this retrospective review was to identify the presence of secondary hypogonadism in chronic opioid users among a cohort of veterans receiving chronic opioids for nonmalignant pain. In addition to identifying the presence of secondary hypogonadism, the relationship between testosterone concentrations and total daily morphine equivalent doses (MEDs) was reviewed. These data along with the new information recently published on testosterone replacement therapy (TRT) and cardiovascular (CV) risk were then used to evaluate current practices at the West Palm Beach VAMC for OPIAD monitoring and management and to modify and update the local Criteria for Use (CFU) for TRT.

Methods

Patient data from the West Palm Beach VAMC in Florida from January 2013 to December 2013 were reviewed to identify patients who had a total testosterone (TT) level measured. All patient appointments for evaluation and treatment by the clinical pharmacy specialist in pain management were reviewed for data collection. This retrospective review was approved by the scientific advisory committee as part of the facility’s ongoing performance improvement efforts as defined by VHA Handbook 1058.05 and did not require written patient consent.10

Several distinct TT level data were collected. The descriptive data included patient age; gender; type of treated pain; testosterone level(s) drawn, including TT level before opioid therapy, TT level before/during/after TRT, and current total testosterone level; total daily MED of opioid therapy; duration of chronic opioid therapy; symptoms of exhibited hypogonadism; TRT formulation, dose, and duration; TRT prescriber; symptom change (if any); and laboratory tests ordered for TRT monitoring (lipid profile, liver profile, complete blood count, LH/FSH, and prostate specific antigen [PSA] panel).5,11,12

Related: Combination Treatment Relieves Opioid-Induced Constipation

Daily MED of opioid therapy was calculated using the VA/DoD opioid conversion table for patients on oxycodone, hydromorphone, or hydrocodone.13 For those on the fentanyl patch or methadone, conversion factors of 1:2 (fentanyl [µg/h]:morphine [mg/d]) and 1:3 (methadone:morphine) were used to convert to the MED.14 For patients on the buprenorphine patch, the package insert was used to convert to the corresponding MED.15 Combination therapies used the applicable conversions to calculate the total daily MED.

Once the data were collected, descriptive statistics were used to analyze the data. In addition, 4 graphs were generated to review potential relationships. The correlation coefficient was calculated using the Alcula Online Statistics Calculator (http://www.alcula.com; Correlation Coefficient Calculator).

Results

A total of 316 unique veteran patients were seen by the clinical pharmacy specialist in pain management from January 1, 2013, through December 31, 2013. Of these, 73 patients (23.1%) had at least 1 TT level drawn in 2013. Three patients with testosterone levels drawn (4.1%) were excluded from the data analysis for the following reasons: 1 patient did not have testosterone levels on file before receiving testosterone replacement from a non-VA source, 
1 patient received opioids from a non-VA source (MED and duration of opioid therapy could not be calculated), and 1 patient inconsistently received opioids and MED used at the time of testosterone level draw. Per the local TRT CFU, a TT level > 350 ng/dL
does not require treatment, whereas levels < 230 ng/dL (with symptoms) may require TRT, and 
< 200 ng/dL should be treated as 
hypogonadal (interpretation based on local laboratory’s reference range for TT).16 Of the 70 patients included in the analysis, 34 (48.6%) had a TT level < 230 ng/dL and would be considered eligible for TRT if they presented with symptoms 
of low testosterone. Of these 34 patients with a low testosterone level, 28 (40%) were being treated or had been treated with TRT (Figure 1).

 

 

The average age of the male patients with a testosterone level drawn was 58.3 years, which was not significantly different from the calculated median age of 60 years. No female patients had a testosterone level drawn. On average, the TT level was normal before starting opioids (reference range per local laboratory: 175-781 ng/dL). Once opioids were initiated, patients were treated for an average duration of 52.5 months (calculated through December 2013) with an average daily dose of 126.8 MED (Table). Fifty of the 70 patients (71.4%) with testosterone levels drawn in 2013 received TRT. The most common symptoms reported by patients related to low testosterone included ED, decreased libido, depression, chronic fatigue, generalized weakness, and hot flashes or night sweats.

The average TT level prior to TRT was 145.3, and the average 
testosterone level after initiation of or 
during treatment with TRT was 292.4, which is within the normal TT level range. Most patients receiving TRT were treated with testosterone cypionate injections, and this was also the formulation used for the longest periods, likely due to the local CFU. In addition to testosterone cypionate injections, patients were also treated with testosterone enanthate injections, testosterone patches, and testosterone gel.

Figure 1 compares current testosterone level and testosterone level before TRT with total daily MEDs. Figure 2 compares current testosterone level and testosterone level before TRT with length of opioid therapy. The 2 figures use data from all patients included in the analysis and indicate a potential inverse relationship between the total daily MED and duration of therapy with the testosterone level, although none of the calculated correlation coefficients indicate that a strong relationship was present.

Figures 3 and 4 include data only for patients who had both a testosterone level collected before opioids (baseline testosterone level) and a current testosterone level. Figure 3 trends the data using total daily MED, and Figure 4 uses the duration of opioid therapy. The correlation for Figure 4 is slightly stronger; the strongest negative correlations were identified between total daily MED and testosterone level before opioid therapy (r = -0.273) and duration of opioid therapy and testosterone level prior to opioid therapy (r = -0.396). The trends indicate that most patients had a normal TT level before opioid treatment and that patients treated with higher MEDs and for longer durations of time were more likely to have lower total testosterone levels.

Discussion

Low testosterone levels can adversely affect patients’ quality of life (QOL) and add to patients’ medication burden with the initiation of TRT. Given new data analyzing the potential effects of TRT on CV event risk, the use of TRT should be carefully considered, as it may carry significant risks and may not be suitable for all patients.

In November 2013, a study was published regarding TRT and 
increased CV risk.17 This was a retrospective cohort study of men with low testosterone levels (< 300 ng/dL) who had undergone coronary angiography in the VA system between 2005 and 2011 (average age in testosterone group was 60.6 years). The results were significant for an absolute rate of events (all-cause mortality, myocardial infarction [MI], and ischemic stroke) of 19.9% in the no testosterone group and 25.7% in the TRT group, an absolute risk difference of 5.8% at 3 years after coronary angiography. Kaplan-Meier survival curves demonstrated that testosterone use was associated with increased risk of death, MI, and stroke. This result was unchanged when adjusted for the presence of coronary artery disease (CAD). In 
addition, no significant difference was found between the groups in terms of systolic blood pressure, low-
density lipoprotein cholesterol level, or in the use of beta-blocker and statin medications. What is important to note is that in this cohort, 20% had a prior history of MI and heart failure, and more than 50% had confirmed obstructive CAD on angiography. In addition, as this was an observational study, confounding or bias may exist, and given the study population, 
generalizability may be limited to a veteran population.

Related: A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Another retrospective cohort study assessed the risk of acute nonfatal MI following an initial TRT prescription in a large health care database (average age based on TRT prescription was 54.4 years).18 In men aged ≥ 65 years, a 2-fold increase in the risk of MI in the immediate 90 days after filling an initial TRT prescription declined to baseline after 91 to 180 days among those who did not refill their prescription. Younger men with a history of heart disease had a 2- to 3-fold increased risk of MI in the 90 days following initial TRT prescription. No excess risk was observed in the younger men without such a history. Again, this study has its limitations related to the retrospective design and use of a health care database as opposed to a randomized controlled trial.

 

 

In February 2014, a VA National Pharmacy Benefits Management (PBM) bulletin addressed 2 recent studies that had identified a possible risk of increased CV events in men receiving TRT. The bulletin noted that these studies had prompted the FDA to reassess the CV safety of TRT.19 The TRT CFU was updated by VISN 8 to ensure that the patients receive appropriate treatment and are monitored accordingly.

One of the major changes to the CFU was defining the reference ranges for TRT (interpretation based on a local laboratory’s reference range for total testosterone): serum TT < 200 ng/dL be “treated as 
hypogonadal, those with TT 
> 400 ng/dL be considered normal and those with TT 200-400 ng/dL be treated based on their clinical presentation if symptomatic; TT levels 
> 350 ng/dL do not require treatment, and levels below 230 ng/dL (with symptoms) may require testosterone replacement therapy.”16 Other important updates included revision of the exclusion criteria as well as 
highlighting special considerations related to TRT, including the use of free testosterone levels rather than TT levels in patients with suspected protein-binding issues, role in fertility treatments, limited use in patients on spironolactone therapy (due to spironolactone’s anti-androgen effects), and potential association with mood and behavior.16

As chronic opioid therapy is associated with OPIAD, the renewed interest in TRT and its potential AEs provides yet another reason to reconsider opioid therapy. This is especially valid when opioids are the potential cause of hypogonadism and the reaction is treating the AEs of opioids (as opposed to considering elimination of the causative agent) with a therapy that can potentially increase the risk for CV events so that opioids can be continued. Outside the potential CV risk with TRT, opioids carry the innate risk for substance abuse and addiction.

The Opioid Safety Initiative Requirements was released as a memorandum in April 2014 and is the VHA’s effort to “reduce harm from unsafe medications and/or excessive doses while adequately controlling pain in Veterans.”20 Although it does not discuss the risk of OPIAD, it does highlight the need to identify and mitigate high-risk patients as well as high-risk opioid regimens. All these factors, including the possibility of hypogonadism, should be considered before starting opioid therapy and at the time of opioid renewal, as it is known that opioid therapy is not without risks.

At the West Palm Beach VAMC, the primary care providers (PCPs) are responsible for the management of TRT, including the workup, renewal, and monitoring. The Chronic Nonmalignant Pain Management Clinic (CNMPMC) orders testosterone levels on patients who report symptoms of low testosterone, such as hot flashes, depression, and low energy level and refers them to their PCP as indicated. The authors believe that this is most appropriate for a number of reasons: (1) the CNMPMC is a consult service, and patients are not followed indefinitely; (2) patients should be fully evaluated for appropriateness of TRT (including assessment of CV risk) before starting therapy; and (3) the necessary monitoring parameters (laboratory testing, digital rectal exam, and osteoporosis screening) are not typically within the VA pain clinic provider’s scope of practice or expertise. A consideration for future practice would be to incorporate the use of a standardized questionnaire for OPIAD monitoring in patients receiving ≥ 100 mg of morphine daily (eg, the Aging Males’ Symptoms scale).21 It should, however, be at the forefront of the pain specialist’s and PCP’s minds that all patients on chronic opioid therapy or considering chronic opioid therapy should be counseled on the risk for OPIAD. If OPIAD is identified, the patient should be carefully considered for an opioid dose reduction as an initial management strategy.

Limitations

A limitation of this review is the lack of consistency or adequacy of serum testosterone sampling, noting that valid testosterone levels need to be drawn in the morning and not obtained during a time of acute illness. In addition, testosterone levels need to be drawn at an appropriate interval while on TRT (eg, at the midpoint between testosterone injections).16 Although the time of the sample collection is documented in the Computerized Patient Record System (CPRS), it is unknown whether the patient was acutely ill on the day of the sampling unless a progress note is entered, and it is difficult to determine whether the level timing was accurate based on the testosterone replacement formulation. Another limitation is that the average decline in serum testosterone levels with aging in men is 1% to 2% per year. A significant fraction of older men have levels below the lower limit of the normal range for healthy young men, so in older men it can be more difficult to determine whether low testosterone is related to chronic opioid use or to older age.5,16

 

 

As this was a retrospective review, additional limitations included the inability to measure subclinical OPIAD, and the data collection related to symptoms of hypogonadism was restricted by documentation in the CPRS progress notes. The lack of data for females does not contribute to the literature on OPIAD in women. Finally, as the total daily MED does not distinguish between short-acting and long-acting opioid therapy, no differences between the impacts of short-acting vs long-
acting opioid therapy on risk for 
hypogonadism can be inferred. There is evidence to suggest that long-acting opioids are associated with a significantly higher risk for OPIAD compared with short-acting opioids, although the mechanism behind this is not well established.22,23

Conclusions

The average age of the patients 
on chronic opioid therapy with a 
testosterone level drawn in this cohort was 58.3 years, which is younger than originally anticipated. The median age of 60 years is not significantly different from the average age, indicating that outliers did not impact this calculation. On average, the TT level was normal before starting opioids. Once opioids were started, patients were treated for an average duration of 52.5 months with an average daily dose of 126.8 mg MED. In this veteran cohort, 48.6% of patients met the criteria for TRT based on TT level alone, which is within the reported prevalence range of opioid-induced hypogonadism already published.4,9 These results are in line with the original hypothesis that chronic opioid use can adversely impact testosterone levels and can have a poor effect on a patient’s QOL due to symptoms of low testosterone. In addition to TRT, possible and suggested (but not proven) treatment options for OPIAD include discontinuation of opioid therapy, opioid rotation, or conversion to buprenorphine.21 The approach used should account for multiple patient-specific factors and should be individualized.

Based on the data, there is a trend toward lower testosterone levels in veterans treated with higher MED and for longer periods with chronic opioids. Given recent data that infer that TRT carries increased CV risk as well as the VHA’s Opioid Safety Initiative, it is imperative that providers closely evaluate the appropriateness of starting TRT and/or continuing chronic opioid therapy. All patients generally should have failed non-
opioid management prior to opioid therapy for chronic nonmalignant pain, and this should be documented accordingly. It is also crucial to have the “opioid talk” with patients from time to time and discuss the risks vs benefits, the potential for addiction, overdose, dependence, tolerance, constipation, and OPIAD so patients can continue to be an active and informed participants in their care.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

References

1. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Unintentional drug poisoning in the United States, 2010. Atlanta, GA: Centers for Disease Control and Prevention Website. http://www.cdc.gov
/HomeandRecreationalSafety/pdf/poison-issue-brief
.pdf. Published July 2010. Accessed August 28, 2015.

2. American Academy of Family Physicians. Using opioids in the management of chronic pain patients: challenges and future options. University of Kentucky Medical Center Website. http://www
.mc.uky.edu/equip-4-pcps/documents/CRx%20Literature/Opioids%20for%20chronic%20pain.pdf. Published 2010. Accessed August 28, 2015.

3. Duarte RV, Raphael JH, Labib M, Southall JL, Ashford RL. Prevalence and influence of diagnostic criteria in the assessment of hypogonadism in intrathecal opioid therapy patients. Pain Physician. 2013;16(1):9-14.

4. Smith HS, Elliott JA. Opioid-induced androgen deficiency (OPIAD). Pain Physician. 2012;15(suppl 3):ES145-ES156.

5. De Maddalena C, Bellini M, Berra M, Meriggiola MC, Aloisi AM. Opioid-induced hypogonadism: why and how to treat it. Pain Physician. 2012;15(suppl 3):ES111-ES118.

6. Bhasin S, Cunningham GR, Hayes FJ, et al; VM Endocrine Society Task Force. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

7. Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients–2002 update. Endocr Pract. 2002;8(6):440-456.

8. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30(1):1-9.

9. Reddy RG, Aung T, Karavitaki N, Wass JA. Opioid induced hypogonadism. BMJ. 2010;341:c4462.

10. U.S. Department of Veterans Affairs, Veterans Health Administration. VHA Handbook 1058.05: VHA operations activities that may constitute research. U.S. Department of Veterans Affairs Website. http://www.va.gov/vhapublications
/ViewPublication.asp?pub_ID=2456. Published October 28, 2011. Accessed August 28, 2015.

11. AndroGel [package insert]. North Chicago, IL:
AbbVie Inc; 2013.

12. Axiron [package insert]. Indianapolis, IL: Lilly USA, LLC; 2011.

13. U.S. Department of Veterans Affairs. Opioid therapy for chronic pain pocket guide. U.S. Department of Veterans Affairs. http://www.healthquality
.va.gov/guidelines/pain/cot/opioidpocketguide23may2013v1.pdf. Published May 2013 Accessed August 28, 2015.

14. McPherson ML. Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. Bethesda, MD: American Society of Health-System Pharmacists; 2009.

15. Butrans [package insert]. Stamford, CT: Purdue Pharma LP; 2014.

16. Testosterone Replacement Therapy Criteria for Use. VISN 8: VISN Pharmacist Executives, Veterans Health Administration, Department of Veterans Affairs; 2014. [Internal document.]

17. Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836.

18. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805.

19. U.S. Department of Veterans Affairs. Testosterone products and cardiovascular safety. U.S. Department of Veterans Affairs Website. http://www.pbm
.va.gov/PBM/vacenterformedicationsafety
/nationalpbmbulletin/Testosterone_Products_and
_Cardiovascular_Safety_NATIONAL_PBM
_BULLETIN_02.pdf. Published February 7, 2014. Accessed August 28, 2015.

20. U.S. Department of Veterans Affairs Veterans Health Administration (VHA) Pharmacy Benefits Management Services (PBM), Medical Advisory Panel (MAP) and Center for Medication Safety (VA MEDSAFE). Memorandum: Opioid Safety Initiative Requirements. U.S. Department of Veterans Affairs Website. http://www.veterans.senate.gov/imo
/media/doc/VA%20Testimony%20-%20April%2030%20SVAC%20Overmedication%20hearing.pdf. Published April 30, 2014. Accessed August 28, 2015.

21. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18.

22. Rubinstein AL, Carpenter DM, Minkoff JR. Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids. Clin J Pain. 2013;29(10):840-845.

23. Rubinstein A, Carpenter DM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med. 2014;127(12):1195-1201.

References

1. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Unintentional drug poisoning in the United States, 2010. Atlanta, GA: Centers for Disease Control and Prevention Website. http://www.cdc.gov
/HomeandRecreationalSafety/pdf/poison-issue-brief
.pdf. Published July 2010. Accessed August 28, 2015.

2. American Academy of Family Physicians. Using opioids in the management of chronic pain patients: challenges and future options. University of Kentucky Medical Center Website. http://www
.mc.uky.edu/equip-4-pcps/documents/CRx%20Literature/Opioids%20for%20chronic%20pain.pdf. Published 2010. Accessed August 28, 2015.

3. Duarte RV, Raphael JH, Labib M, Southall JL, Ashford RL. Prevalence and influence of diagnostic criteria in the assessment of hypogonadism in intrathecal opioid therapy patients. Pain Physician. 2013;16(1):9-14.

4. Smith HS, Elliott JA. Opioid-induced androgen deficiency (OPIAD). Pain Physician. 2012;15(suppl 3):ES145-ES156.

5. De Maddalena C, Bellini M, Berra M, Meriggiola MC, Aloisi AM. Opioid-induced hypogonadism: why and how to treat it. Pain Physician. 2012;15(suppl 3):ES111-ES118.

6. Bhasin S, Cunningham GR, Hayes FJ, et al; VM Endocrine Society Task Force. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.

7. Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients–2002 update. Endocr Pract. 2002;8(6):440-456.

8. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30(1):1-9.

9. Reddy RG, Aung T, Karavitaki N, Wass JA. Opioid induced hypogonadism. BMJ. 2010;341:c4462.

10. U.S. Department of Veterans Affairs, Veterans Health Administration. VHA Handbook 1058.05: VHA operations activities that may constitute research. U.S. Department of Veterans Affairs Website. http://www.va.gov/vhapublications
/ViewPublication.asp?pub_ID=2456. Published October 28, 2011. Accessed August 28, 2015.

11. AndroGel [package insert]. North Chicago, IL:
AbbVie Inc; 2013.

12. Axiron [package insert]. Indianapolis, IL: Lilly USA, LLC; 2011.

13. U.S. Department of Veterans Affairs. Opioid therapy for chronic pain pocket guide. U.S. Department of Veterans Affairs. http://www.healthquality
.va.gov/guidelines/pain/cot/opioidpocketguide23may2013v1.pdf. Published May 2013 Accessed August 28, 2015.

14. McPherson ML. Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. Bethesda, MD: American Society of Health-System Pharmacists; 2009.

15. Butrans [package insert]. Stamford, CT: Purdue Pharma LP; 2014.

16. Testosterone Replacement Therapy Criteria for Use. VISN 8: VISN Pharmacist Executives, Veterans Health Administration, Department of Veterans Affairs; 2014. [Internal document.]

17. Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836.

18. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805.

19. U.S. Department of Veterans Affairs. Testosterone products and cardiovascular safety. U.S. Department of Veterans Affairs Website. http://www.pbm
.va.gov/PBM/vacenterformedicationsafety
/nationalpbmbulletin/Testosterone_Products_and
_Cardiovascular_Safety_NATIONAL_PBM
_BULLETIN_02.pdf. Published February 7, 2014. Accessed August 28, 2015.

20. U.S. Department of Veterans Affairs Veterans Health Administration (VHA) Pharmacy Benefits Management Services (PBM), Medical Advisory Panel (MAP) and Center for Medication Safety (VA MEDSAFE). Memorandum: Opioid Safety Initiative Requirements. U.S. Department of Veterans Affairs Website. http://www.veterans.senate.gov/imo
/media/doc/VA%20Testimony%20-%20April%2030%20SVAC%20Overmedication%20hearing.pdf. Published April 30, 2014. Accessed August 28, 2015.

21. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18.

22. Rubinstein AL, Carpenter DM, Minkoff JR. Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids. Clin J Pain. 2013;29(10):840-845.

23. Rubinstein A, Carpenter DM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med. 2014;127(12):1195-1201.

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Craniotomy and stereotactic radiosurgery seem to be similarly effective and appropriate choices for the treatment of patients with favorable prognostic factors and limited brain metastases.

Since the 1980s, patients with a single intracranial metastatic lesion traditionally have been treated with surgery followed by whole brain radiation therapy (WBRT). However, there is growing concern about the debilitating cognitive effects associated with WBRT in long-term survivors.

Limbrick and colleagues studied the outcomes of surgery followed by stereotactic radiosurgery (SRS) instead of WBRT and found that the less invasive surgical resection (SR) followed by SRS was an equally effective therapeutic option for the treatment of patients with limited metastatic disease to the brain.1 Median overall survival (OS) was 20 months and was 
22 and 13 months for Classes 1 and 2 recursive partitioning analysis (RPA) patients, respectively. Recursive partitioning analysis refers to 3 prognostic classes based on a database of 
3 trial studies and 1,200 patients (Table 1).2 According to RPA, the best survival was observed in Class 1 patients, and the worst survival was seen in Class 3 patients. Limbrick and colleagues found that survival outcome was equivalent to or greater than that reported by other studies using surgery plus WBRT or SRS plus WBRT.1 The WBRT was not used and was reserved as salvage therapy in cases of initial failure such as disease progression of brain metastasis.

Radiation Therapies

Stereotactic radiosurgery is not a surgical procedure but a newly developed radiotherapy technique. It is a highly precise, intensive form of radiation therapy, focused on the tumor, with the goal of protecting the surrounding normal brain tissue as much as possible. Radiosurgery was initially introduced with the Gamma Knife by Lars Leksell several decades ago in order to deliver an intense radiation dose to a small, well-defined, single focal point using extreme precision. Stereotactic radiosurgery delivers efficient and focused radiation treatment to the tumor lesion.

There are 2 practical and commercially available radiation delivery systems for SRS: linear accelerator (LINAC)-based radiosurgery and Gamma Knife systems. Use of the Gamma Knife is limited largely to treatment of central nervous system (CNS) malignancies and certain head and neck cancers. Linear 
accelerator-based SRS is applicable to neoplasms in any organ system of the body (Table 2).

Proton therapy is yet another evolving and completely different mode of radiation therapy. There are currently 14 proton therapy centers in operation in the U.S., and 11 more centers are now under construction. Proton therapy uses charged heavy-particle therapy using proton beams, whereas conventional LINAC-based radiotherapy is X-ray radiotherapy, which uses high energy photon beams. Because of their relatively large mass, protons have little scatter of radiation to surrounding normal structures and can remain sharply focused on the tumor lesion. Accordingly, proton therapy delivers negligible radiation doses beyond tumor lesions, and much of the surrounding normal tissues can be saved from excessive and unnecessary radiation doses.

Related: Bone Metastasis: A Concise Overview

A single proton beam produces a narrow Bragg peak dose distribution at depth, and multiple consecutive stepwise series of different energies of proton beams are needed to administer complete coverage of the target tumor volume. The accumulation of these beam energies produces a uniform radiation dose distribution covering the entire tumor volume (Figure 1). In spite of the theoretical beneficial effects of proton beam therapy, more clinical experience is needed for it to be validated. Even then, the significantly higher costs of proton therapy represent another barrier to its wider implementation. Proton beam radiosurgery is still, in large part, an evolving technology, not widely and uniformly available.

Role of Radiosurgery

Photon (X-ray)-based radiosurgery can be an alternative to craniotomy. Patients can return to their activities immediately after treatment. The ideal candidate for radiosurgery should have a small tumor (1-3 cm is best) with a well-defined margin. Retrospective studies reported no significant difference in therapy outcomes between the 2 therapies.3,4 Additional benefits of radiosurgery include low morbidity and mortality. Furthermore, radiosurgery can be applied to tumors near critical structures, such as the thalamus, basal ganglia, and brainstem, that are otherwise surgically inaccessible.

Most brain metastases are well defined and spherical, so they are ideally treated using SRS (Figure 1). Additionally, the brain is encased in the bony skull, which prevents significant intrafraction motion and provides a reproducible fidulial for accurate setup. Radiosurgery can tailor the radiation dose in order to precisely concentrate radiation distribution to the tumor lesion with a rapid dose falloff beyond the margin of the tumor bed, so surrounding normal brain tissues are spared from high-dose radiation. In sharp contrast, WBRT indiscriminately irradiates the entire brain without sparing the adjacent normal brain tissue (Figure 2). However, because of its limited dose distribution, radiosurgery offers no protection elsewhere in the brain from future metastasis, which is a benefit of whole brain radiation.

 

 

Future Use of SBRT

Based on successful experience with intracranial lesions, stereotactic techniques have been expanded to additional anatomical body sites other than the brain. Stereotactic body radiation therapy (SBRT), also called stereotactic body ablative radiotherapy, is progressively gaining acceptance and is being applied to various extracranial tumors, especially lung cancers and hepatic malignancies. Dosimetric studies and early phase clinical trials have clearly established the feasibility, safety, and efficacy of SBRT for certain tumor sites, such as lung, liver, kidney, spine, and paraspinal tumors. Additionally, SBRT may reduce treatment time and therapy costs and thus provide increased convenience to patients.

Effectiveness of SRS

Stafinski and colleagues conducted a meta-analysis of randomized trials to study the effectiveness of SRS in improving the survival as well as the quality of life (QOL) and functional status following SRS of patients with brain metastasis.5 This study found that SRS plus WBRT increased OS for patients with single brain metastasis compared with WBRT alone. Although no significant difference in OS was found in patients with multiple brain metastases, the addition of SRS to WBRT improved the local control and functional independence of this group of patients.

Related: Palliative Radiotherapy for the Management of Metastatic Cancer

Kondziolka and colleagues reported a local failure rate at 1 year of merely 8% following SRS boost therapy after WBRT compared with 100% without SRS.6 There was also a remarkable difference in median time to local failure—36 months vs 6 months, respectively. A randomized study designed to assess the possible benefit of SRS for the treatment of brain metastasis found a survival gain for patients with a single brain metastasis with a median survival time of 6.5 months (SRS) vs 4.9 months (no SRS).7

There are sparse data and reporting related to QOL measurements after SRS for brain metastasis. Andrews and colleagues reported improved functional and independent abilities at 6 months after completion of SRS therapy.7 The criteria used in that study for performance assessments included the Karnofsky Performance Status (KPS) scale, the need for steroid use, and mental status. They found that KPS improvement was statistically significant, and patients were able to decrease the dosage of steroid medication at 6 months after therapy with SRS (Table 3). Despite these reports suggesting superior outcomes with SRS, more rigorous investigations that adequately control for other factors influencing QOL in patients with cancer are needed.

Two major limitations of SRS include large tumor size and multiple numbers of metastatic brain lesions. As the radiation dose to adjacent normal brain tissue quickly increases with larger tumor lesions (> 3-4 cm), the complication risks consequently rise proportionally, necessitating a decrease in the prescribed dose. Patients with poor performance status 
(< 70 KPS) and presence of active/progressive extracranial disease are also not ideal candidates for SRS.

Other unfavorable conditions for SRS include life expectancy of 
< 6 months, metastatic lesions in the posterior fossa, and severe acute CNS symptoms due to increased intracranial pressure, brain edema, or massive tumor effects. These factors do not necessarily contraindicate SRS but can increase the risks of such treatment. The authors recommend an experienced multispecialty approach to patients presenting with these findings.

Managing Brain Metastastis

To prevent symptoms related to brain edema (due to brain tumor itself and/or radiation-induced edema), steroid medication is generally administered to most patients, 1 to 3 days prior to initiation of radiation therapy. Corticosteroid use typically results in rapid improvement of existing CNS symptoms, such as headaches, and helps prevent the development of additional CNS symptoms due to radiation therapy-induced cerebral edema. A dexamethasone dose as low as 4 mg per day may be effective for prophylaxis if no symptoms or signs of increased intracranial pressure or altered consciousness exist. If the patient experiences symptomatic elevations in intracranial pressure, however, a 16-mg dose of dexamethasone per day orally, following a loading dose of 10-mg IV dexamethasone, should be considered. The latter scenario is not common.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The benefits of steroids, however, need to be carefully balanced against the possible adverse effects (AEs) associated with steroid use, including peripheral edema, gastrointestinal bleeding, risk of infections, hyperglycemia, insomnia, as well as mental status changes, such as anxiety, depression, and confusion. In long-term users, the additional AEs of oral candidiasis and osteoporosis should also be taken into account.

Craniotomy vs SRS

A retrospective study by Schöggl and colleagues compared single brain metastasis cases treated using either Gamma Knife or brain surgery followed by WBRT (30 Gy/10 fractions).3 Local control was significantly better after radiosurgery 
(95% vs 83%), and median survival was 12 months and 9 months after radiosurgery and brain surgery, respectively. There was no significant difference in OS.

 

 

Another comparative study of SR and SRS for solitary brain metastasis revealed no statistically significant difference in survival between the 
2 therapeutic modalities (SR or SRS); the 1-year survival rate was 62% (SR) and 56% (SRS).4 A significant prognostic factor for survival was a good performance status of the patients. There was, however, a significant difference in local tumor control: None of the patients in the SRS group experienced local recurrence in contrast to 19 (58%) patients in the SR group.

Whereas selection criteria and treatment choice depend to a large extent on tumor location, tumor size, and availability of SRS, most studies demonstrated that both surgery and SRS result in comparable OS rates for patients with a single brain metastasis.

Multiple Brain Metastases

Jawahar and colleagues studied the role of SRS for multiple brain metastases.8 In their retrospective review of 50 patients with ≥ 3 brain metastases, they found an overall response rate (RR) of 82% and a median survival of 12 months after SRS. As a result of similar studies and their own data, Hasegawa and colleagues recommended radiosurgery alone as initial therapy for patients with a limited number of brain metastases.9

SRS vs SRS Plus WBRT

Studies on the role of SRS plus WBRT are somewhat conflicting. A Radiation Therapy Oncology Group study revealed statistically significant improvement in median survival when SRS boost therapy was added to WBRT in patients with a single brain metastasis compared with SRS alone.5 According to another study, the addition of SRS to WBRT provided better intracranial and local control of metastatic tumors.10

A randomized controlled study by Aoyama and colleagues reported no survival improvement using SRS and WBRT in patients with 1 to 4 brain metastases compared with SRS alone.11 In addition, a retrospective review found no difference in median survival outcomes between SRS alone and SRS plus WBRT (Table 4). In the absence of a clear survival benefit with the use of both modalities and in light of the added toxicity of WBRT, most clinicians have ceased offering both modalities upfront and instead reserve WBRT as a salvage option in cases of subsequent intracranial progression of disease.

SRS vs WBRT

In general, both SR (crainotomy) and SRS for the treatment of brain metastases seem to be effective therapeutic modalities. Comparisons of both treatments did not reveal significant differences and showed similar outcomes after treatment of smaller lesions. For example, Rades and colleagues reported that SRS alone is as effective as surgery and WBRT for limited metastatic lesions (< 2) in the brain.16 Either SRS or surgery can be used, depending on performance status and metastatic burden (size, location, number of lesions, etc).

There are some inconsistencies in the final results of various studies, such as survival, local tumor control, mortality rate, and pattern of failures. For large, symptomatic brain metastasis, initial surgical debulking remains the preferred approach as a way of achieving immediate decompression and relief of swelling/symptoms. Additionally, for patients who have > 10 brain lesions and/or a histology that corroborates diffuse subclinical involvement of the brain parenchyma (eg, small-cell lung cancer), WBRT is also typically preferred to upfront SRS. Alternatively, radiosurgery is the preferred method for fewer and smaller lesions as a way of minimizing the toxicity from whole brain irradiation. The optimal treatment of multiple small brain metastases remains controversial with some investigators recommending SRS for > 4 metastases only in the setting of controlled extracranial disease based on the more favorable expected survival of such patients.

Multidisciplinary Approach for Lung and Breast Cancers

Prognostic outcomes of patients with brain metastases can vary by primary cancer type. Therefore, clinicians should consider cancer-specific management and tailor their recommendation for specific types of radiation depending on the 
individual cancer diagnosis. Various investigators have attempted to develop disease-specific prognostic tools to aid clinicians in their decision making. For example, Sperduto and colleagues analyzed significant indexes and diagnosis-specific prognostic factors and published the 
diagnostic-specific graded prognostic assessment factors.17 They were able to identify several significant prognostic factors, specific to different primary cancer types.

Bimodality Therapies

For certain cancers such as lung and breast primary cancers, bimodality therapy using chemotherapy and radiation treatment should be considered based on promising responses reported in the literature.

Recent studies on the efficacy of chemotherapy for brain metastases from small-cell lung cancer (43%-82%) have also been reported.18-20 Postmus and colleagues reported superior RR of 57% with combination chemotherapy and radiation vs a 22% RR for chemotherapy alone.21 They also found favorable long-term survival trends in patients treated with combined radiochemotherapy.

 

 

The efficacy of chemotherapy in non-small cell carcinoma of the lung has been reported in multiple phase 2 studies using various chemotherapeutic agents. The reported RR ranged from 35% to 50%.22-24 Comparative studies of combined chemoradiotherapy demonstrated a 33% RR in contrast to a 27% RR for combined therapy or chemotherapy alone, respectively. However, no difference was noted in median survival rates.25

Care must be taken when interpreting these studies due to heterogeneity of the patient population studied and a lack of data on potential synergistic toxicities between radiation to the CNS and systemic therapy. The authors generally avoid concurrent chemotherapy during CNS irradiation in patients who may have significant survival times > 1 year.

The prognosis of breast cancer patients with brain metastasis largely depends on the number and size of metastatic brain lesions, performance status, extracranial or systemic involvement, and systemic treatment following brain irradiation. The median survival of patients with brain metastasis and radiation therapy is generally about 18 months. The median survival for patients with breast cancer who develop brain metastasis was 3 years from diagnosis of the primary breast cancer.26

Recent advances in systemic agents/options for patients with breast cancer can significantly affect the decision-making process in regard to the treatment of brain lesions in these patients. For example, a few retrospective studies have clearly demonstrated the beneficial effect of trastuzumab in patients with breast cancer with brain metastasis. The median OS in HER2-positive patients with brain metastasis was significantly extended to 41 months when treated with HER2-targeted trastuzumab vs only 
13 months for patients who received no treatment.27,28 As a result of the expected prolonged survival, SRS for small and isolated brain lesions has recently become a much more attractive option as a way of mitigating the deleterious long-term effect of whole brain irradiation (memory decline, somnolence, etc).

Summary

Stereotactic radiosurgery is a newly developed radiation therapy technique of highly conformal and focused radiation. For the treatment of patients with favorable prognostic factors and limited brain metastases, especially single brain metastasis, crainiotomy and SRS seems similarly effective and appropriate choices of therapy. Some studies question the possible benefits of additional WBRT to local therapy, such as crainiotomy or radiosurgery.

Some authors recommend deferral of WBRT after local brain therapy and reserving it for salvage therapy in cases of recurrence or progression of brain disease because of possible long-term AEs of whole brain irradiation as well as deterioration of QOL in long-term survivors. Thus, the role of additional WBRT to other local therapy has not been fully settled; further randomized studies may be necessary. Due to the controversies and complexities surrounding the treatment choices for patients with brain disease, all treatment decisions should be individualized and should involve close multidisciplinary collaboration between neurosurgeons, medical oncologists, and radiation oncologists.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

References

1. Limbrick DD Jr, Lusis EA, Chicoine MR, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol. 2009;71(3):280-288.

2. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745-751.

3. Schöggl A, Kitz K, Reddy M, et al. Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases. Acta Neurochir (Wien). 2000;142(6):621-626.

4. O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169-1176.

5. Stafinski T, Jhangri GS, Yan E, Manon D. Effectiveness of stereotactic radiosurgery alone or in combination with whole brain radiotherapy compared to conventional surgery and/or whole brain radiotherapy for the treatment of one or more brain metastases: a systematic review and meta-analysis. Cancer Treat Rev. 2006;32(3):203-213.

6. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999;45(2):427-434.

7. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665-1672.

8. Jawahar A, Shaya M, Campbell P, et al. Role of stereotactic radiosurgery as a primary treatment option in the management of newly diagnosed multiple (3-6) intracranial metastases. Surg Neurol. 2005;64(3):207-212.

9. Hasegawa T, Kondziolka D, Flickinger JC, Germanwala A, Lunsford LD. Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Neurosurgery. 2003;52(6):1318-1326.

10. Rades D, Kueter JD, Hornung D, et al. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases. Strahlenther Onkol. 2008;184(12):655-662.

11. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483-2491.

12. Chidel MA, Suh JH, Reddy CA, Chao ST, Lundbeck MF, Barnett GH. Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys. 2000;47(4):993-999.

13. Sneed PK, Lamborn KR, Forstner JM, et al. Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999;43(3):549-558.

14. Noel G, Medioni J, Valery CA, et al. Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer. Lung Cancer. 2003;41(3):333-343.

15. Hoffman R, Sneed PK, McDermott MW, et al. Radiosurgery for brain metastases from primary lung carcinoma. Cancer J. 2001;7(2):121-131.

16. Rades D, Bohlen G, Pluemer A, et al. Stereotactic radiosurgery alone versus resection plus whole brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer. 2007;109(12):2515-2521.

17. Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655-661.

18. Twelves CJ, Souhami RL, Harper PG, et al. The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer. 1990;61(1):147-150.

19. Tanaka H, Takifuj N, Masuda N, et al. [Systemic chemotherapy for brain metastases from small-cell lung cancer]. Nihon Kyobu Shikkan Gakkai Zasshi. 1993;31(4):492-497. Japanese.

20. Lee JS, Murphy WK, Glisson BS, Dhingra HM, Holoye PY, Hong WK. Primary chemotherapy of brain metastasis in small-cell lung cancer. J Clin Oncol. 1989;7(7):216-222.

21. Postmus PE, Haaxma-Reiche H, Smit EF, et al. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy—a phase III study of the European Organisation for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000;18(19):3400-3408.

22. Cortes J, Rodriguez J, Aramendia JM, et al. Frontline paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology. 2003;64(1):28-35.

23. Minotti V, Crinò L, Meacci ML, et al. Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer. Lung Cancer. 1998;20(2):23-28.

24. Fujita A, Fukuoka S, Takabatake H, Tagaki S, Sekine K. Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patient with brain metastases from non-small cell lung cancer. Oncology. 2000;59(4):291-295.

25. Robinet G, Thomas R, Breton JL, et al. Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1. Ann Oncol. 2001;12(1):29-67.

26. Kiricuta IC, Kölbl O, Willner J, Bohndorf W. Central nervous system metastases in breast cancer. J Cancer Res Clin Oncol. 1992;118(7):542-546.

27. Berghoff AS, Bago-Horvath Z, Dubsky P, et al. Impact of HER-2-targeted therapy on overall survival in patients with HER-2 positive metastatic breast cancer. Breast J. 2013;19(2):149-155.

28. Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH. Truastzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol. 2009;20(1):56-62.

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Related Articles
Craniotomy and stereotactic radiosurgery seem to be similarly effective and appropriate choices for the treatment of patients with favorable prognostic factors and limited brain metastases.
Craniotomy and stereotactic radiosurgery seem to be similarly effective and appropriate choices for the treatment of patients with favorable prognostic factors and limited brain metastases.

Since the 1980s, patients with a single intracranial metastatic lesion traditionally have been treated with surgery followed by whole brain radiation therapy (WBRT). However, there is growing concern about the debilitating cognitive effects associated with WBRT in long-term survivors.

Limbrick and colleagues studied the outcomes of surgery followed by stereotactic radiosurgery (SRS) instead of WBRT and found that the less invasive surgical resection (SR) followed by SRS was an equally effective therapeutic option for the treatment of patients with limited metastatic disease to the brain.1 Median overall survival (OS) was 20 months and was 
22 and 13 months for Classes 1 and 2 recursive partitioning analysis (RPA) patients, respectively. Recursive partitioning analysis refers to 3 prognostic classes based on a database of 
3 trial studies and 1,200 patients (Table 1).2 According to RPA, the best survival was observed in Class 1 patients, and the worst survival was seen in Class 3 patients. Limbrick and colleagues found that survival outcome was equivalent to or greater than that reported by other studies using surgery plus WBRT or SRS plus WBRT.1 The WBRT was not used and was reserved as salvage therapy in cases of initial failure such as disease progression of brain metastasis.

Radiation Therapies

Stereotactic radiosurgery is not a surgical procedure but a newly developed radiotherapy technique. It is a highly precise, intensive form of radiation therapy, focused on the tumor, with the goal of protecting the surrounding normal brain tissue as much as possible. Radiosurgery was initially introduced with the Gamma Knife by Lars Leksell several decades ago in order to deliver an intense radiation dose to a small, well-defined, single focal point using extreme precision. Stereotactic radiosurgery delivers efficient and focused radiation treatment to the tumor lesion.

There are 2 practical and commercially available radiation delivery systems for SRS: linear accelerator (LINAC)-based radiosurgery and Gamma Knife systems. Use of the Gamma Knife is limited largely to treatment of central nervous system (CNS) malignancies and certain head and neck cancers. Linear 
accelerator-based SRS is applicable to neoplasms in any organ system of the body (Table 2).

Proton therapy is yet another evolving and completely different mode of radiation therapy. There are currently 14 proton therapy centers in operation in the U.S., and 11 more centers are now under construction. Proton therapy uses charged heavy-particle therapy using proton beams, whereas conventional LINAC-based radiotherapy is X-ray radiotherapy, which uses high energy photon beams. Because of their relatively large mass, protons have little scatter of radiation to surrounding normal structures and can remain sharply focused on the tumor lesion. Accordingly, proton therapy delivers negligible radiation doses beyond tumor lesions, and much of the surrounding normal tissues can be saved from excessive and unnecessary radiation doses.

Related: Bone Metastasis: A Concise Overview

A single proton beam produces a narrow Bragg peak dose distribution at depth, and multiple consecutive stepwise series of different energies of proton beams are needed to administer complete coverage of the target tumor volume. The accumulation of these beam energies produces a uniform radiation dose distribution covering the entire tumor volume (Figure 1). In spite of the theoretical beneficial effects of proton beam therapy, more clinical experience is needed for it to be validated. Even then, the significantly higher costs of proton therapy represent another barrier to its wider implementation. Proton beam radiosurgery is still, in large part, an evolving technology, not widely and uniformly available.

Role of Radiosurgery

Photon (X-ray)-based radiosurgery can be an alternative to craniotomy. Patients can return to their activities immediately after treatment. The ideal candidate for radiosurgery should have a small tumor (1-3 cm is best) with a well-defined margin. Retrospective studies reported no significant difference in therapy outcomes between the 2 therapies.3,4 Additional benefits of radiosurgery include low morbidity and mortality. Furthermore, radiosurgery can be applied to tumors near critical structures, such as the thalamus, basal ganglia, and brainstem, that are otherwise surgically inaccessible.

Most brain metastases are well defined and spherical, so they are ideally treated using SRS (Figure 1). Additionally, the brain is encased in the bony skull, which prevents significant intrafraction motion and provides a reproducible fidulial for accurate setup. Radiosurgery can tailor the radiation dose in order to precisely concentrate radiation distribution to the tumor lesion with a rapid dose falloff beyond the margin of the tumor bed, so surrounding normal brain tissues are spared from high-dose radiation. In sharp contrast, WBRT indiscriminately irradiates the entire brain without sparing the adjacent normal brain tissue (Figure 2). However, because of its limited dose distribution, radiosurgery offers no protection elsewhere in the brain from future metastasis, which is a benefit of whole brain radiation.

 

 

Future Use of SBRT

Based on successful experience with intracranial lesions, stereotactic techniques have been expanded to additional anatomical body sites other than the brain. Stereotactic body radiation therapy (SBRT), also called stereotactic body ablative radiotherapy, is progressively gaining acceptance and is being applied to various extracranial tumors, especially lung cancers and hepatic malignancies. Dosimetric studies and early phase clinical trials have clearly established the feasibility, safety, and efficacy of SBRT for certain tumor sites, such as lung, liver, kidney, spine, and paraspinal tumors. Additionally, SBRT may reduce treatment time and therapy costs and thus provide increased convenience to patients.

Effectiveness of SRS

Stafinski and colleagues conducted a meta-analysis of randomized trials to study the effectiveness of SRS in improving the survival as well as the quality of life (QOL) and functional status following SRS of patients with brain metastasis.5 This study found that SRS plus WBRT increased OS for patients with single brain metastasis compared with WBRT alone. Although no significant difference in OS was found in patients with multiple brain metastases, the addition of SRS to WBRT improved the local control and functional independence of this group of patients.

Related: Palliative Radiotherapy for the Management of Metastatic Cancer

Kondziolka and colleagues reported a local failure rate at 1 year of merely 8% following SRS boost therapy after WBRT compared with 100% without SRS.6 There was also a remarkable difference in median time to local failure—36 months vs 6 months, respectively. A randomized study designed to assess the possible benefit of SRS for the treatment of brain metastasis found a survival gain for patients with a single brain metastasis with a median survival time of 6.5 months (SRS) vs 4.9 months (no SRS).7

There are sparse data and reporting related to QOL measurements after SRS for brain metastasis. Andrews and colleagues reported improved functional and independent abilities at 6 months after completion of SRS therapy.7 The criteria used in that study for performance assessments included the Karnofsky Performance Status (KPS) scale, the need for steroid use, and mental status. They found that KPS improvement was statistically significant, and patients were able to decrease the dosage of steroid medication at 6 months after therapy with SRS (Table 3). Despite these reports suggesting superior outcomes with SRS, more rigorous investigations that adequately control for other factors influencing QOL in patients with cancer are needed.

Two major limitations of SRS include large tumor size and multiple numbers of metastatic brain lesions. As the radiation dose to adjacent normal brain tissue quickly increases with larger tumor lesions (> 3-4 cm), the complication risks consequently rise proportionally, necessitating a decrease in the prescribed dose. Patients with poor performance status 
(< 70 KPS) and presence of active/progressive extracranial disease are also not ideal candidates for SRS.

Other unfavorable conditions for SRS include life expectancy of 
< 6 months, metastatic lesions in the posterior fossa, and severe acute CNS symptoms due to increased intracranial pressure, brain edema, or massive tumor effects. These factors do not necessarily contraindicate SRS but can increase the risks of such treatment. The authors recommend an experienced multispecialty approach to patients presenting with these findings.

Managing Brain Metastastis

To prevent symptoms related to brain edema (due to brain tumor itself and/or radiation-induced edema), steroid medication is generally administered to most patients, 1 to 3 days prior to initiation of radiation therapy. Corticosteroid use typically results in rapid improvement of existing CNS symptoms, such as headaches, and helps prevent the development of additional CNS symptoms due to radiation therapy-induced cerebral edema. A dexamethasone dose as low as 4 mg per day may be effective for prophylaxis if no symptoms or signs of increased intracranial pressure or altered consciousness exist. If the patient experiences symptomatic elevations in intracranial pressure, however, a 16-mg dose of dexamethasone per day orally, following a loading dose of 10-mg IV dexamethasone, should be considered. The latter scenario is not common.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The benefits of steroids, however, need to be carefully balanced against the possible adverse effects (AEs) associated with steroid use, including peripheral edema, gastrointestinal bleeding, risk of infections, hyperglycemia, insomnia, as well as mental status changes, such as anxiety, depression, and confusion. In long-term users, the additional AEs of oral candidiasis and osteoporosis should also be taken into account.

Craniotomy vs SRS

A retrospective study by Schöggl and colleagues compared single brain metastasis cases treated using either Gamma Knife or brain surgery followed by WBRT (30 Gy/10 fractions).3 Local control was significantly better after radiosurgery 
(95% vs 83%), and median survival was 12 months and 9 months after radiosurgery and brain surgery, respectively. There was no significant difference in OS.

 

 

Another comparative study of SR and SRS for solitary brain metastasis revealed no statistically significant difference in survival between the 
2 therapeutic modalities (SR or SRS); the 1-year survival rate was 62% (SR) and 56% (SRS).4 A significant prognostic factor for survival was a good performance status of the patients. There was, however, a significant difference in local tumor control: None of the patients in the SRS group experienced local recurrence in contrast to 19 (58%) patients in the SR group.

Whereas selection criteria and treatment choice depend to a large extent on tumor location, tumor size, and availability of SRS, most studies demonstrated that both surgery and SRS result in comparable OS rates for patients with a single brain metastasis.

Multiple Brain Metastases

Jawahar and colleagues studied the role of SRS for multiple brain metastases.8 In their retrospective review of 50 patients with ≥ 3 brain metastases, they found an overall response rate (RR) of 82% and a median survival of 12 months after SRS. As a result of similar studies and their own data, Hasegawa and colleagues recommended radiosurgery alone as initial therapy for patients with a limited number of brain metastases.9

SRS vs SRS Plus WBRT

Studies on the role of SRS plus WBRT are somewhat conflicting. A Radiation Therapy Oncology Group study revealed statistically significant improvement in median survival when SRS boost therapy was added to WBRT in patients with a single brain metastasis compared with SRS alone.5 According to another study, the addition of SRS to WBRT provided better intracranial and local control of metastatic tumors.10

A randomized controlled study by Aoyama and colleagues reported no survival improvement using SRS and WBRT in patients with 1 to 4 brain metastases compared with SRS alone.11 In addition, a retrospective review found no difference in median survival outcomes between SRS alone and SRS plus WBRT (Table 4). In the absence of a clear survival benefit with the use of both modalities and in light of the added toxicity of WBRT, most clinicians have ceased offering both modalities upfront and instead reserve WBRT as a salvage option in cases of subsequent intracranial progression of disease.

SRS vs WBRT

In general, both SR (crainotomy) and SRS for the treatment of brain metastases seem to be effective therapeutic modalities. Comparisons of both treatments did not reveal significant differences and showed similar outcomes after treatment of smaller lesions. For example, Rades and colleagues reported that SRS alone is as effective as surgery and WBRT for limited metastatic lesions (< 2) in the brain.16 Either SRS or surgery can be used, depending on performance status and metastatic burden (size, location, number of lesions, etc).

There are some inconsistencies in the final results of various studies, such as survival, local tumor control, mortality rate, and pattern of failures. For large, symptomatic brain metastasis, initial surgical debulking remains the preferred approach as a way of achieving immediate decompression and relief of swelling/symptoms. Additionally, for patients who have > 10 brain lesions and/or a histology that corroborates diffuse subclinical involvement of the brain parenchyma (eg, small-cell lung cancer), WBRT is also typically preferred to upfront SRS. Alternatively, radiosurgery is the preferred method for fewer and smaller lesions as a way of minimizing the toxicity from whole brain irradiation. The optimal treatment of multiple small brain metastases remains controversial with some investigators recommending SRS for > 4 metastases only in the setting of controlled extracranial disease based on the more favorable expected survival of such patients.

Multidisciplinary Approach for Lung and Breast Cancers

Prognostic outcomes of patients with brain metastases can vary by primary cancer type. Therefore, clinicians should consider cancer-specific management and tailor their recommendation for specific types of radiation depending on the 
individual cancer diagnosis. Various investigators have attempted to develop disease-specific prognostic tools to aid clinicians in their decision making. For example, Sperduto and colleagues analyzed significant indexes and diagnosis-specific prognostic factors and published the 
diagnostic-specific graded prognostic assessment factors.17 They were able to identify several significant prognostic factors, specific to different primary cancer types.

Bimodality Therapies

For certain cancers such as lung and breast primary cancers, bimodality therapy using chemotherapy and radiation treatment should be considered based on promising responses reported in the literature.

Recent studies on the efficacy of chemotherapy for brain metastases from small-cell lung cancer (43%-82%) have also been reported.18-20 Postmus and colleagues reported superior RR of 57% with combination chemotherapy and radiation vs a 22% RR for chemotherapy alone.21 They also found favorable long-term survival trends in patients treated with combined radiochemotherapy.

 

 

The efficacy of chemotherapy in non-small cell carcinoma of the lung has been reported in multiple phase 2 studies using various chemotherapeutic agents. The reported RR ranged from 35% to 50%.22-24 Comparative studies of combined chemoradiotherapy demonstrated a 33% RR in contrast to a 27% RR for combined therapy or chemotherapy alone, respectively. However, no difference was noted in median survival rates.25

Care must be taken when interpreting these studies due to heterogeneity of the patient population studied and a lack of data on potential synergistic toxicities between radiation to the CNS and systemic therapy. The authors generally avoid concurrent chemotherapy during CNS irradiation in patients who may have significant survival times > 1 year.

The prognosis of breast cancer patients with brain metastasis largely depends on the number and size of metastatic brain lesions, performance status, extracranial or systemic involvement, and systemic treatment following brain irradiation. The median survival of patients with brain metastasis and radiation therapy is generally about 18 months. The median survival for patients with breast cancer who develop brain metastasis was 3 years from diagnosis of the primary breast cancer.26

Recent advances in systemic agents/options for patients with breast cancer can significantly affect the decision-making process in regard to the treatment of brain lesions in these patients. For example, a few retrospective studies have clearly demonstrated the beneficial effect of trastuzumab in patients with breast cancer with brain metastasis. The median OS in HER2-positive patients with brain metastasis was significantly extended to 41 months when treated with HER2-targeted trastuzumab vs only 
13 months for patients who received no treatment.27,28 As a result of the expected prolonged survival, SRS for small and isolated brain lesions has recently become a much more attractive option as a way of mitigating the deleterious long-term effect of whole brain irradiation (memory decline, somnolence, etc).

Summary

Stereotactic radiosurgery is a newly developed radiation therapy technique of highly conformal and focused radiation. For the treatment of patients with favorable prognostic factors and limited brain metastases, especially single brain metastasis, crainiotomy and SRS seems similarly effective and appropriate choices of therapy. Some studies question the possible benefits of additional WBRT to local therapy, such as crainiotomy or radiosurgery.

Some authors recommend deferral of WBRT after local brain therapy and reserving it for salvage therapy in cases of recurrence or progression of brain disease because of possible long-term AEs of whole brain irradiation as well as deterioration of QOL in long-term survivors. Thus, the role of additional WBRT to other local therapy has not been fully settled; further randomized studies may be necessary. Due to the controversies and complexities surrounding the treatment choices for patients with brain disease, all treatment decisions should be individualized and should involve close multidisciplinary collaboration between neurosurgeons, medical oncologists, and radiation oncologists.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Since the 1980s, patients with a single intracranial metastatic lesion traditionally have been treated with surgery followed by whole brain radiation therapy (WBRT). However, there is growing concern about the debilitating cognitive effects associated with WBRT in long-term survivors.

Limbrick and colleagues studied the outcomes of surgery followed by stereotactic radiosurgery (SRS) instead of WBRT and found that the less invasive surgical resection (SR) followed by SRS was an equally effective therapeutic option for the treatment of patients with limited metastatic disease to the brain.1 Median overall survival (OS) was 20 months and was 
22 and 13 months for Classes 1 and 2 recursive partitioning analysis (RPA) patients, respectively. Recursive partitioning analysis refers to 3 prognostic classes based on a database of 
3 trial studies and 1,200 patients (Table 1).2 According to RPA, the best survival was observed in Class 1 patients, and the worst survival was seen in Class 3 patients. Limbrick and colleagues found that survival outcome was equivalent to or greater than that reported by other studies using surgery plus WBRT or SRS plus WBRT.1 The WBRT was not used and was reserved as salvage therapy in cases of initial failure such as disease progression of brain metastasis.

Radiation Therapies

Stereotactic radiosurgery is not a surgical procedure but a newly developed radiotherapy technique. It is a highly precise, intensive form of radiation therapy, focused on the tumor, with the goal of protecting the surrounding normal brain tissue as much as possible. Radiosurgery was initially introduced with the Gamma Knife by Lars Leksell several decades ago in order to deliver an intense radiation dose to a small, well-defined, single focal point using extreme precision. Stereotactic radiosurgery delivers efficient and focused radiation treatment to the tumor lesion.

There are 2 practical and commercially available radiation delivery systems for SRS: linear accelerator (LINAC)-based radiosurgery and Gamma Knife systems. Use of the Gamma Knife is limited largely to treatment of central nervous system (CNS) malignancies and certain head and neck cancers. Linear 
accelerator-based SRS is applicable to neoplasms in any organ system of the body (Table 2).

Proton therapy is yet another evolving and completely different mode of radiation therapy. There are currently 14 proton therapy centers in operation in the U.S., and 11 more centers are now under construction. Proton therapy uses charged heavy-particle therapy using proton beams, whereas conventional LINAC-based radiotherapy is X-ray radiotherapy, which uses high energy photon beams. Because of their relatively large mass, protons have little scatter of radiation to surrounding normal structures and can remain sharply focused on the tumor lesion. Accordingly, proton therapy delivers negligible radiation doses beyond tumor lesions, and much of the surrounding normal tissues can be saved from excessive and unnecessary radiation doses.

Related: Bone Metastasis: A Concise Overview

A single proton beam produces a narrow Bragg peak dose distribution at depth, and multiple consecutive stepwise series of different energies of proton beams are needed to administer complete coverage of the target tumor volume. The accumulation of these beam energies produces a uniform radiation dose distribution covering the entire tumor volume (Figure 1). In spite of the theoretical beneficial effects of proton beam therapy, more clinical experience is needed for it to be validated. Even then, the significantly higher costs of proton therapy represent another barrier to its wider implementation. Proton beam radiosurgery is still, in large part, an evolving technology, not widely and uniformly available.

Role of Radiosurgery

Photon (X-ray)-based radiosurgery can be an alternative to craniotomy. Patients can return to their activities immediately after treatment. The ideal candidate for radiosurgery should have a small tumor (1-3 cm is best) with a well-defined margin. Retrospective studies reported no significant difference in therapy outcomes between the 2 therapies.3,4 Additional benefits of radiosurgery include low morbidity and mortality. Furthermore, radiosurgery can be applied to tumors near critical structures, such as the thalamus, basal ganglia, and brainstem, that are otherwise surgically inaccessible.

Most brain metastases are well defined and spherical, so they are ideally treated using SRS (Figure 1). Additionally, the brain is encased in the bony skull, which prevents significant intrafraction motion and provides a reproducible fidulial for accurate setup. Radiosurgery can tailor the radiation dose in order to precisely concentrate radiation distribution to the tumor lesion with a rapid dose falloff beyond the margin of the tumor bed, so surrounding normal brain tissues are spared from high-dose radiation. In sharp contrast, WBRT indiscriminately irradiates the entire brain without sparing the adjacent normal brain tissue (Figure 2). However, because of its limited dose distribution, radiosurgery offers no protection elsewhere in the brain from future metastasis, which is a benefit of whole brain radiation.

 

 

Future Use of SBRT

Based on successful experience with intracranial lesions, stereotactic techniques have been expanded to additional anatomical body sites other than the brain. Stereotactic body radiation therapy (SBRT), also called stereotactic body ablative radiotherapy, is progressively gaining acceptance and is being applied to various extracranial tumors, especially lung cancers and hepatic malignancies. Dosimetric studies and early phase clinical trials have clearly established the feasibility, safety, and efficacy of SBRT for certain tumor sites, such as lung, liver, kidney, spine, and paraspinal tumors. Additionally, SBRT may reduce treatment time and therapy costs and thus provide increased convenience to patients.

Effectiveness of SRS

Stafinski and colleagues conducted a meta-analysis of randomized trials to study the effectiveness of SRS in improving the survival as well as the quality of life (QOL) and functional status following SRS of patients with brain metastasis.5 This study found that SRS plus WBRT increased OS for patients with single brain metastasis compared with WBRT alone. Although no significant difference in OS was found in patients with multiple brain metastases, the addition of SRS to WBRT improved the local control and functional independence of this group of patients.

Related: Palliative Radiotherapy for the Management of Metastatic Cancer

Kondziolka and colleagues reported a local failure rate at 1 year of merely 8% following SRS boost therapy after WBRT compared with 100% without SRS.6 There was also a remarkable difference in median time to local failure—36 months vs 6 months, respectively. A randomized study designed to assess the possible benefit of SRS for the treatment of brain metastasis found a survival gain for patients with a single brain metastasis with a median survival time of 6.5 months (SRS) vs 4.9 months (no SRS).7

There are sparse data and reporting related to QOL measurements after SRS for brain metastasis. Andrews and colleagues reported improved functional and independent abilities at 6 months after completion of SRS therapy.7 The criteria used in that study for performance assessments included the Karnofsky Performance Status (KPS) scale, the need for steroid use, and mental status. They found that KPS improvement was statistically significant, and patients were able to decrease the dosage of steroid medication at 6 months after therapy with SRS (Table 3). Despite these reports suggesting superior outcomes with SRS, more rigorous investigations that adequately control for other factors influencing QOL in patients with cancer are needed.

Two major limitations of SRS include large tumor size and multiple numbers of metastatic brain lesions. As the radiation dose to adjacent normal brain tissue quickly increases with larger tumor lesions (> 3-4 cm), the complication risks consequently rise proportionally, necessitating a decrease in the prescribed dose. Patients with poor performance status 
(< 70 KPS) and presence of active/progressive extracranial disease are also not ideal candidates for SRS.

Other unfavorable conditions for SRS include life expectancy of 
< 6 months, metastatic lesions in the posterior fossa, and severe acute CNS symptoms due to increased intracranial pressure, brain edema, or massive tumor effects. These factors do not necessarily contraindicate SRS but can increase the risks of such treatment. The authors recommend an experienced multispecialty approach to patients presenting with these findings.

Managing Brain Metastastis

To prevent symptoms related to brain edema (due to brain tumor itself and/or radiation-induced edema), steroid medication is generally administered to most patients, 1 to 3 days prior to initiation of radiation therapy. Corticosteroid use typically results in rapid improvement of existing CNS symptoms, such as headaches, and helps prevent the development of additional CNS symptoms due to radiation therapy-induced cerebral edema. A dexamethasone dose as low as 4 mg per day may be effective for prophylaxis if no symptoms or signs of increased intracranial pressure or altered consciousness exist. If the patient experiences symptomatic elevations in intracranial pressure, however, a 16-mg dose of dexamethasone per day orally, following a loading dose of 10-mg IV dexamethasone, should be considered. The latter scenario is not common.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The benefits of steroids, however, need to be carefully balanced against the possible adverse effects (AEs) associated with steroid use, including peripheral edema, gastrointestinal bleeding, risk of infections, hyperglycemia, insomnia, as well as mental status changes, such as anxiety, depression, and confusion. In long-term users, the additional AEs of oral candidiasis and osteoporosis should also be taken into account.

Craniotomy vs SRS

A retrospective study by Schöggl and colleagues compared single brain metastasis cases treated using either Gamma Knife or brain surgery followed by WBRT (30 Gy/10 fractions).3 Local control was significantly better after radiosurgery 
(95% vs 83%), and median survival was 12 months and 9 months after radiosurgery and brain surgery, respectively. There was no significant difference in OS.

 

 

Another comparative study of SR and SRS for solitary brain metastasis revealed no statistically significant difference in survival between the 
2 therapeutic modalities (SR or SRS); the 1-year survival rate was 62% (SR) and 56% (SRS).4 A significant prognostic factor for survival was a good performance status of the patients. There was, however, a significant difference in local tumor control: None of the patients in the SRS group experienced local recurrence in contrast to 19 (58%) patients in the SR group.

Whereas selection criteria and treatment choice depend to a large extent on tumor location, tumor size, and availability of SRS, most studies demonstrated that both surgery and SRS result in comparable OS rates for patients with a single brain metastasis.

Multiple Brain Metastases

Jawahar and colleagues studied the role of SRS for multiple brain metastases.8 In their retrospective review of 50 patients with ≥ 3 brain metastases, they found an overall response rate (RR) of 82% and a median survival of 12 months after SRS. As a result of similar studies and their own data, Hasegawa and colleagues recommended radiosurgery alone as initial therapy for patients with a limited number of brain metastases.9

SRS vs SRS Plus WBRT

Studies on the role of SRS plus WBRT are somewhat conflicting. A Radiation Therapy Oncology Group study revealed statistically significant improvement in median survival when SRS boost therapy was added to WBRT in patients with a single brain metastasis compared with SRS alone.5 According to another study, the addition of SRS to WBRT provided better intracranial and local control of metastatic tumors.10

A randomized controlled study by Aoyama and colleagues reported no survival improvement using SRS and WBRT in patients with 1 to 4 brain metastases compared with SRS alone.11 In addition, a retrospective review found no difference in median survival outcomes between SRS alone and SRS plus WBRT (Table 4). In the absence of a clear survival benefit with the use of both modalities and in light of the added toxicity of WBRT, most clinicians have ceased offering both modalities upfront and instead reserve WBRT as a salvage option in cases of subsequent intracranial progression of disease.

SRS vs WBRT

In general, both SR (crainotomy) and SRS for the treatment of brain metastases seem to be effective therapeutic modalities. Comparisons of both treatments did not reveal significant differences and showed similar outcomes after treatment of smaller lesions. For example, Rades and colleagues reported that SRS alone is as effective as surgery and WBRT for limited metastatic lesions (< 2) in the brain.16 Either SRS or surgery can be used, depending on performance status and metastatic burden (size, location, number of lesions, etc).

There are some inconsistencies in the final results of various studies, such as survival, local tumor control, mortality rate, and pattern of failures. For large, symptomatic brain metastasis, initial surgical debulking remains the preferred approach as a way of achieving immediate decompression and relief of swelling/symptoms. Additionally, for patients who have > 10 brain lesions and/or a histology that corroborates diffuse subclinical involvement of the brain parenchyma (eg, small-cell lung cancer), WBRT is also typically preferred to upfront SRS. Alternatively, radiosurgery is the preferred method for fewer and smaller lesions as a way of minimizing the toxicity from whole brain irradiation. The optimal treatment of multiple small brain metastases remains controversial with some investigators recommending SRS for > 4 metastases only in the setting of controlled extracranial disease based on the more favorable expected survival of such patients.

Multidisciplinary Approach for Lung and Breast Cancers

Prognostic outcomes of patients with brain metastases can vary by primary cancer type. Therefore, clinicians should consider cancer-specific management and tailor their recommendation for specific types of radiation depending on the 
individual cancer diagnosis. Various investigators have attempted to develop disease-specific prognostic tools to aid clinicians in their decision making. For example, Sperduto and colleagues analyzed significant indexes and diagnosis-specific prognostic factors and published the 
diagnostic-specific graded prognostic assessment factors.17 They were able to identify several significant prognostic factors, specific to different primary cancer types.

Bimodality Therapies

For certain cancers such as lung and breast primary cancers, bimodality therapy using chemotherapy and radiation treatment should be considered based on promising responses reported in the literature.

Recent studies on the efficacy of chemotherapy for brain metastases from small-cell lung cancer (43%-82%) have also been reported.18-20 Postmus and colleagues reported superior RR of 57% with combination chemotherapy and radiation vs a 22% RR for chemotherapy alone.21 They also found favorable long-term survival trends in patients treated with combined radiochemotherapy.

 

 

The efficacy of chemotherapy in non-small cell carcinoma of the lung has been reported in multiple phase 2 studies using various chemotherapeutic agents. The reported RR ranged from 35% to 50%.22-24 Comparative studies of combined chemoradiotherapy demonstrated a 33% RR in contrast to a 27% RR for combined therapy or chemotherapy alone, respectively. However, no difference was noted in median survival rates.25

Care must be taken when interpreting these studies due to heterogeneity of the patient population studied and a lack of data on potential synergistic toxicities between radiation to the CNS and systemic therapy. The authors generally avoid concurrent chemotherapy during CNS irradiation in patients who may have significant survival times > 1 year.

The prognosis of breast cancer patients with brain metastasis largely depends on the number and size of metastatic brain lesions, performance status, extracranial or systemic involvement, and systemic treatment following brain irradiation. The median survival of patients with brain metastasis and radiation therapy is generally about 18 months. The median survival for patients with breast cancer who develop brain metastasis was 3 years from diagnosis of the primary breast cancer.26

Recent advances in systemic agents/options for patients with breast cancer can significantly affect the decision-making process in regard to the treatment of brain lesions in these patients. For example, a few retrospective studies have clearly demonstrated the beneficial effect of trastuzumab in patients with breast cancer with brain metastasis. The median OS in HER2-positive patients with brain metastasis was significantly extended to 41 months when treated with HER2-targeted trastuzumab vs only 
13 months for patients who received no treatment.27,28 As a result of the expected prolonged survival, SRS for small and isolated brain lesions has recently become a much more attractive option as a way of mitigating the deleterious long-term effect of whole brain irradiation (memory decline, somnolence, etc).

Summary

Stereotactic radiosurgery is a newly developed radiation therapy technique of highly conformal and focused radiation. For the treatment of patients with favorable prognostic factors and limited brain metastases, especially single brain metastasis, crainiotomy and SRS seems similarly effective and appropriate choices of therapy. Some studies question the possible benefits of additional WBRT to local therapy, such as crainiotomy or radiosurgery.

Some authors recommend deferral of WBRT after local brain therapy and reserving it for salvage therapy in cases of recurrence or progression of brain disease because of possible long-term AEs of whole brain irradiation as well as deterioration of QOL in long-term survivors. Thus, the role of additional WBRT to other local therapy has not been fully settled; further randomized studies may be necessary. Due to the controversies and complexities surrounding the treatment choices for patients with brain disease, all treatment decisions should be individualized and should involve close multidisciplinary collaboration between neurosurgeons, medical oncologists, and radiation oncologists.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

References

1. Limbrick DD Jr, Lusis EA, Chicoine MR, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol. 2009;71(3):280-288.

2. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745-751.

3. Schöggl A, Kitz K, Reddy M, et al. Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases. Acta Neurochir (Wien). 2000;142(6):621-626.

4. O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169-1176.

5. Stafinski T, Jhangri GS, Yan E, Manon D. Effectiveness of stereotactic radiosurgery alone or in combination with whole brain radiotherapy compared to conventional surgery and/or whole brain radiotherapy for the treatment of one or more brain metastases: a systematic review and meta-analysis. Cancer Treat Rev. 2006;32(3):203-213.

6. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999;45(2):427-434.

7. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665-1672.

8. Jawahar A, Shaya M, Campbell P, et al. Role of stereotactic radiosurgery as a primary treatment option in the management of newly diagnosed multiple (3-6) intracranial metastases. Surg Neurol. 2005;64(3):207-212.

9. Hasegawa T, Kondziolka D, Flickinger JC, Germanwala A, Lunsford LD. Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Neurosurgery. 2003;52(6):1318-1326.

10. Rades D, Kueter JD, Hornung D, et al. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases. Strahlenther Onkol. 2008;184(12):655-662.

11. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483-2491.

12. Chidel MA, Suh JH, Reddy CA, Chao ST, Lundbeck MF, Barnett GH. Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys. 2000;47(4):993-999.

13. Sneed PK, Lamborn KR, Forstner JM, et al. Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999;43(3):549-558.

14. Noel G, Medioni J, Valery CA, et al. Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer. Lung Cancer. 2003;41(3):333-343.

15. Hoffman R, Sneed PK, McDermott MW, et al. Radiosurgery for brain metastases from primary lung carcinoma. Cancer J. 2001;7(2):121-131.

16. Rades D, Bohlen G, Pluemer A, et al. Stereotactic radiosurgery alone versus resection plus whole brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer. 2007;109(12):2515-2521.

17. Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655-661.

18. Twelves CJ, Souhami RL, Harper PG, et al. The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer. 1990;61(1):147-150.

19. Tanaka H, Takifuj N, Masuda N, et al. [Systemic chemotherapy for brain metastases from small-cell lung cancer]. Nihon Kyobu Shikkan Gakkai Zasshi. 1993;31(4):492-497. Japanese.

20. Lee JS, Murphy WK, Glisson BS, Dhingra HM, Holoye PY, Hong WK. Primary chemotherapy of brain metastasis in small-cell lung cancer. J Clin Oncol. 1989;7(7):216-222.

21. Postmus PE, Haaxma-Reiche H, Smit EF, et al. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy—a phase III study of the European Organisation for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000;18(19):3400-3408.

22. Cortes J, Rodriguez J, Aramendia JM, et al. Frontline paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology. 2003;64(1):28-35.

23. Minotti V, Crinò L, Meacci ML, et al. Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer. Lung Cancer. 1998;20(2):23-28.

24. Fujita A, Fukuoka S, Takabatake H, Tagaki S, Sekine K. Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patient with brain metastases from non-small cell lung cancer. Oncology. 2000;59(4):291-295.

25. Robinet G, Thomas R, Breton JL, et al. Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1. Ann Oncol. 2001;12(1):29-67.

26. Kiricuta IC, Kölbl O, Willner J, Bohndorf W. Central nervous system metastases in breast cancer. J Cancer Res Clin Oncol. 1992;118(7):542-546.

27. Berghoff AS, Bago-Horvath Z, Dubsky P, et al. Impact of HER-2-targeted therapy on overall survival in patients with HER-2 positive metastatic breast cancer. Breast J. 2013;19(2):149-155.

28. Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH. Truastzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol. 2009;20(1):56-62.

References

1. Limbrick DD Jr, Lusis EA, Chicoine MR, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol. 2009;71(3):280-288.

2. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745-751.

3. Schöggl A, Kitz K, Reddy M, et al. Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases. Acta Neurochir (Wien). 2000;142(6):621-626.

4. O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169-1176.

5. Stafinski T, Jhangri GS, Yan E, Manon D. Effectiveness of stereotactic radiosurgery alone or in combination with whole brain radiotherapy compared to conventional surgery and/or whole brain radiotherapy for the treatment of one or more brain metastases: a systematic review and meta-analysis. Cancer Treat Rev. 2006;32(3):203-213.

6. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999;45(2):427-434.

7. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665-1672.

8. Jawahar A, Shaya M, Campbell P, et al. Role of stereotactic radiosurgery as a primary treatment option in the management of newly diagnosed multiple (3-6) intracranial metastases. Surg Neurol. 2005;64(3):207-212.

9. Hasegawa T, Kondziolka D, Flickinger JC, Germanwala A, Lunsford LD. Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Neurosurgery. 2003;52(6):1318-1326.

10. Rades D, Kueter JD, Hornung D, et al. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases. Strahlenther Onkol. 2008;184(12):655-662.

11. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483-2491.

12. Chidel MA, Suh JH, Reddy CA, Chao ST, Lundbeck MF, Barnett GH. Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys. 2000;47(4):993-999.

13. Sneed PK, Lamborn KR, Forstner JM, et al. Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999;43(3):549-558.

14. Noel G, Medioni J, Valery CA, et al. Three irradiation treatment options including radiosurgery for brain metastases from primary lung cancer. Lung Cancer. 2003;41(3):333-343.

15. Hoffman R, Sneed PK, McDermott MW, et al. Radiosurgery for brain metastases from primary lung carcinoma. Cancer J. 2001;7(2):121-131.

16. Rades D, Bohlen G, Pluemer A, et al. Stereotactic radiosurgery alone versus resection plus whole brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer. 2007;109(12):2515-2521.

17. Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655-661.

18. Twelves CJ, Souhami RL, Harper PG, et al. The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer. 1990;61(1):147-150.

19. Tanaka H, Takifuj N, Masuda N, et al. [Systemic chemotherapy for brain metastases from small-cell lung cancer]. Nihon Kyobu Shikkan Gakkai Zasshi. 1993;31(4):492-497. Japanese.

20. Lee JS, Murphy WK, Glisson BS, Dhingra HM, Holoye PY, Hong WK. Primary chemotherapy of brain metastasis in small-cell lung cancer. J Clin Oncol. 1989;7(7):216-222.

21. Postmus PE, Haaxma-Reiche H, Smit EF, et al. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy—a phase III study of the European Organisation for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000;18(19):3400-3408.

22. Cortes J, Rodriguez J, Aramendia JM, et al. Frontline paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology. 2003;64(1):28-35.

23. Minotti V, Crinò L, Meacci ML, et al. Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer. Lung Cancer. 1998;20(2):23-28.

24. Fujita A, Fukuoka S, Takabatake H, Tagaki S, Sekine K. Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patient with brain metastases from non-small cell lung cancer. Oncology. 2000;59(4):291-295.

25. Robinet G, Thomas R, Breton JL, et al. Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1. Ann Oncol. 2001;12(1):29-67.

26. Kiricuta IC, Kölbl O, Willner J, Bohndorf W. Central nervous system metastases in breast cancer. J Cancer Res Clin Oncol. 1992;118(7):542-546.

27. Berghoff AS, Bago-Horvath Z, Dubsky P, et al. Impact of HER-2-targeted therapy on overall survival in patients with HER-2 positive metastatic breast cancer. Breast J. 2013;19(2):149-155.

28. Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH. Truastzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol. 2009;20(1):56-62.

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Federal Practitioner - 32(10)
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Federal Practitioner - 32(10)
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Role of Radiosurgery in the Treatment of Brain Metastasis
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Role of Radiosurgery in the Treatment of Brain Metastasis
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stereotactic radiosurgery, brain metastasis, surgical resection, recursive partitioning analysis, Gamma Knife, LINAC-based radiotherapy
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stereotactic radiosurgery, brain metastasis, surgical resection, recursive partitioning analysis, Gamma Knife, LINAC-based radiotherapy
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