Original Research

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

 

 

OUTCOMES

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

 

 

DISCUSSION

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

 

 

STUDY LIMITATIONS

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

 

 

OUTCOMES

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

 

 

DISCUSSION

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

 

 

STUDY LIMITATIONS

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

 

 

OUTCOMES

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

 

 

DISCUSSION

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

 

 

STUDY LIMITATIONS

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

ABSTRACT

We conducted a study to determine the common characteristics of patients who developed radiculopathy symptoms and corresponding heterotopic ossification (HO) from transforaminal lumbar interbody fusions (TLIF) using recombinant human bone morphogenetic protein 2 (rhBMP-2). HO can arise from a disk space with rhBMP-2 use in TLIF. Formation of bone around nerve roots or the thecal sac can cause a radiculopathy with a consistent pattern of symptoms.

We identified 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years who developed radiculopathy symptoms and corresponding HO from TLIF with rhBMP-2 in the disk space between 2002 and 2015. To document this complication and improve its recognition, we recorded common patterns of symptom development and radiologic findings: specifically, time from implantation of rhBMP-2 to symptom development, consistency with side of TLIF placement, and radiologic findings.

Radicular pain generally developed a mean (SD) of 3.8 (1.0) months after TLIF with rhBMP-2. Development of radiculopathy symptoms corresponded to consistent “pseudo-pedicle”-like HO. In all 38 patients, HO arising from the annulotomy site showed a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. In addition, development of radiculopathy symptoms and corresponding HO appear to be independent of amount of rhBMP-2. HO resulting from TLIF with rhBMP-2 in the disk space is a pain generator and a recognizable complication that can be diagnosed by assessment of symptoms and computed tomography characteristics.

Continue to: Bone morphogenetic proteins...

Bone morphogenetic proteins (BMPs), first isolated by Urist in 1964¹, are a family of growth factors that stimulate the cascade of bone formation. Recombinant human BMP (rhBMP), specifically rhBMP-2 and rhBMP-7 (also known as osteogenic protein 1 [OP-1]), was developed in the 1990s after the advent of gene splicing. Then, in 2002, the US Food and Drug Administration (FDA) approved use of rhBMP to stimulate fusion in the human spine. Specifically, rhBMP-2 (Medtronic) was approved for use in combination with a specific brand of interbody cage in 1-level anterior lumbar interbody fusion.² Over the past decade, off-label use of rhBMP-2 to achieve osseous union has increased dramatically, particularly in spinal surgery: transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion, and posterolateral lumbar fusion.^3-9 However, this widespread off-label use for posterior spinal fusion began despite FDA data indicating that specific complications were underreported in the peer-reviewed literature.^10,11 Although rhBMP-2 is very effective in increasing osteoblast formation and improving osteogenesis and subsequent bone healing in spinal surgery,^12,13 its use in TLIF resulted in significant adverse side effects, including radiculopathy with and without neuroforaminal heterotopic ossification (HO); ^14-24 complications in the FDA studies; ^14,22,25-27 and osteolysis causing intervertebral cage subsidence, inflammatory radiculitis, genitourinary complications, infections, possible systemic effects, and significant HO complications.^10,28-30 Of these, HO complications involved rhBMP leakage through the annulotomy to the disk space that led to HO. Specifically, rhBMP leaked directly out of the disk space and formed a pillar of bone that encased the nerve roots and dura, which led to occlusion of the foramen and symptoms of radiculopathy.^10,28-30

Despite this frequent finding of HO in the intervertebral space outside the target fusion area, use of rhBMP-2 with intervertebral cages increased so rapidly that rhBMP-2 was used more often than autologous bone.^5,11,17,31 In this study, we reviewed the common characteristics of patients who developed HO and subsequent radiculopathy from TLIF with rhBMP.

METHODS

After this study received Institutional Review Board approval, we retrospectively reviewed cases of radiculopathy symptoms that developed after TLIF with rhBMP between January 2002 and January 2015. During this period, 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years and radiculopathy symptoms arising from TLIF with rhBMP-2 were identified to determine commonalities and defining characteristics that will help facilitate diagnosis.

Inclusion criteria were computed tomography (CT)–documented HO arising from the TLIF annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell with contouring around the thecal sac or nerve roots, as well as recurrence or initial occurrence of radiculopathy with signs and symptoms corresponding to the CT site of aberrant bone growth in terms of laterality and particular nerve root(s) involved. Exclusion criteria were malplacement of interbody cage or pedicle screws, disk herniation, systemic neuropathic disease, and new or unresolved radiculopathy immediately after index surgery.

To improve recognition of this complication, we also documented the amount of BMP used, common patterns of radiculopathy symptom development, and radiologic findings. Type and timing of radiculopathy symptom onset and consistency with side of TLIF placement were documented as well. Radiculopathy symptoms included shooting pain in the legs, incontinence, sexual dysfunction, and severe paralysis. Radiologic findings were specific to bone formation from the disk space (detected with CT).

Continue to: RESULTS

 

 

RESULTS

All 38 selected patients had radiculopathy symptoms from HO out of the intervertebral space. The Table lists the patients’ overall characteristics. The left side had the most radiculopathy symptoms (31/38 patients), followed by the right side (5/38) and both sides (2/38). Radiculopathy symptoms began a mean (SD) of 3.8 (1.0) months (range, 2-6 months) after index surgery. The 38 patients had 4 characteristics in common:

Table. Transforaminal Lumbar Interbody Fusion With Recombinant Human Bone Morphogenetic Protein 2: Onset Time for Radiculopathy Symptoms, Surgery Level, Side of Pseudo-Pedicle Bone Formation, and Subsequent Complications

1. Bone growing out of the annulotomy site for TLIF cage placement was present and in continuity with the disk space in 33 (87%) of the 38 cases. In the other 5 cases (13%), HO was present around the neural tissue, but not necessarily in continuity with the disk space. This bone appeared ectopic and not osteophytic and facet-related, as it formed a shell around either the nerve root or the thecal sac, contouring to the structure.

2. The common, novel finding on CT was a “pseudo-pedicle” (Figures 1A, 1B), which appeared as ectopic growth from the disk space—a solid piece of bone in the same direction as the anatomical pedicle. Confusing similarity to the anatomical pedicle is present on axial cuts and during surgery. The pseudo-pedicle varied in thickness and extent out of the disk space, but was always presented as a bar of bone arising from the annulotomy site. After arising from the disk space, the HO could disperse in any direction, further calcifying neural structures or the facet joints above or below. There was no apparent distinguishable repeating pattern, given the variable nature of arthritic facet changes, scoliotic deformities, size of annulotomies, amount of rhBMP used, and placement in cage and disk space or only in cage.

3. In 36 (95%) of the 38 cases, the initial interpretation of HO on magnetic resonance imaging (MRI) was of tissue other than bone, such as fibrous tissue, granulation tissue, recurrent disk herniation, or postoperative changes. However, this tissue was later determined to be bone from HO complications, which we confirmed with CT in all 38 cases. It is important to note that HO on MRI (Figures 2A, 2B) was initially interpreted by a radiologist as fibrous tissue, but same-level CT of the same case (Figures 3A, 3B) showed clear HO.

4. The radiculopathy symptoms caused by HO were independent of the amount of rhBMP-2 used in TLIF. Of the 38 patients, 19 had 1 rhBMP-2 sponge placed in the cage, 12 had a small kit sponge (1.05 mg), 5 had 1 sponge placed in the cage and 1 sponge placed directly in the disk space before cage placement (no notation of precise size or amount of rhBMP-2), and 2 had 1 sponge placed in the cage (no notation of rhBMP-2 amount). The data showed that HO can occur with even a small amount of rhBMP-2.

Continue to: Bone formation with rhBMP-2...

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

DISCUSSION

We identified 38 patients with a recognizable and consistent pattern of complications of off-label use of rhBMP-2 in TLIF performed at our institution between 2002 and 2015. This pattern included consistent radiculopathy symptoms with corresponding HO at the annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell around the thecal sac or nerve roots, as well as showing a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. Our finding differs from other findings of similar complication characteristics, but with much larger variations without consistency within the patient population.^19,20,22,24 Specifically, previous studies found an association between off-label rhBMP-2 use in the posterior spine and radiculopathy with and without neuroforaminal HO. However, our study found consistent radiculopathy symptoms with pseudo-pedicle-like HO complications in all its 38 patients a mean (SD) of 3.8 (1.0) months after surgery.

In this study, consistent radiculopathy symptoms with pseudo-pedicle-like HO complications were independent of the amount of rhBMP-2 used, as some complications occurred with use of small pack rhBMP-2 with TLIF. It is well understood that high doses of rhBMP-2 may be required to improve fusion rates, but to our knowledge an optimal dosing strategy for TLIF has not been reported, particularly with respect to potential complications.^8,20,31-33 For anterior lumbar interbody fusion surgery, the FDA-approved use of rhBMP-2 appears to have a significantly decreased risk of neuroforaminal HO complications. This may be attributable to the protective presence of the intact posterior annulus and longitudinal ligament for this procedure.^20,33 For TLIF, it has been suggested that rhBMP-2 should be placed only along the anterior annulus with a posterior strut and morselized bone allograft barricade,³³ and that fibrin glue should be used to limit BMP diffusion through the annulotomy site³¹ to prevent this complication.

Our study results suggest that radiculopathy symptoms with pseudo-pedicle-like HO complications appear to be caused by leakage of rhBMP-2 from the disk space through the annulotomy site. This was often initially interpreted incorrectly on MRI in the first year after surgery as being fibrous or granulation tissue, or even postoperative changes that the heterotopic tissue was bone was obvious only on CT. Even then the tissue may be incorrectly identified, as the encasing nerve roots in bone are similar to the scar tissue having no compressive effect. HO may compress, but it also has an inflammatory component that the scars lack. Additionally, the HO from the disk space, caused by leakage of the BMP placed in or around the fusion cage, can create a pseudo-pedicle of varying size and extent. This was present in all 38 of our cases.

This retrospective case series had its limitations. Its clinical and radiographic findings were not blinded. Confounding variables cannot be isolated for causal relationships, if any, to the complication in a case series such as this.

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

ABSTRACT

We conducted a study to determine the common characteristics of patients who developed radiculopathy symptoms and corresponding heterotopic ossification (HO) from transforaminal lumbar interbody fusions (TLIF) using recombinant human bone morphogenetic protein 2 (rhBMP-2). HO can arise from a disk space with rhBMP-2 use in TLIF. Formation of bone around nerve roots or the thecal sac can cause a radiculopathy with a consistent pattern of symptoms.

We identified 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years who developed radiculopathy symptoms and corresponding HO from TLIF with rhBMP-2 in the disk space between 2002 and 2015. To document this complication and improve its recognition, we recorded common patterns of symptom development and radiologic findings: specifically, time from implantation of rhBMP-2 to symptom development, consistency with side of TLIF placement, and radiologic findings.

Radicular pain generally developed a mean (SD) of 3.8 (1.0) months after TLIF with rhBMP-2. Development of radiculopathy symptoms corresponded to consistent “pseudo-pedicle”-like HO. In all 38 patients, HO arising from the annulotomy site showed a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. In addition, development of radiculopathy symptoms and corresponding HO appear to be independent of amount of rhBMP-2. HO resulting from TLIF with rhBMP-2 in the disk space is a pain generator and a recognizable complication that can be diagnosed by assessment of symptoms and computed tomography characteristics.

Continue to: Bone morphogenetic proteins...

Bone morphogenetic proteins (BMPs), first isolated by Urist in 1964¹, are a family of growth factors that stimulate the cascade of bone formation. Recombinant human BMP (rhBMP), specifically rhBMP-2 and rhBMP-7 (also known as osteogenic protein 1 [OP-1]), was developed in the 1990s after the advent of gene splicing. Then, in 2002, the US Food and Drug Administration (FDA) approved use of rhBMP to stimulate fusion in the human spine. Specifically, rhBMP-2 (Medtronic) was approved for use in combination with a specific brand of interbody cage in 1-level anterior lumbar interbody fusion.² Over the past decade, off-label use of rhBMP-2 to achieve osseous union has increased dramatically, particularly in spinal surgery: transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion, and posterolateral lumbar fusion.^3-9 However, this widespread off-label use for posterior spinal fusion began despite FDA data indicating that specific complications were underreported in the peer-reviewed literature.^10,11 Although rhBMP-2 is very effective in increasing osteoblast formation and improving osteogenesis and subsequent bone healing in spinal surgery,^12,13 its use in TLIF resulted in significant adverse side effects, including radiculopathy with and without neuroforaminal heterotopic ossification (HO); ^14-24 complications in the FDA studies; ^14,22,25-27 and osteolysis causing intervertebral cage subsidence, inflammatory radiculitis, genitourinary complications, infections, possible systemic effects, and significant HO complications.^10,28-30 Of these, HO complications involved rhBMP leakage through the annulotomy to the disk space that led to HO. Specifically, rhBMP leaked directly out of the disk space and formed a pillar of bone that encased the nerve roots and dura, which led to occlusion of the foramen and symptoms of radiculopathy.^10,28-30

Despite this frequent finding of HO in the intervertebral space outside the target fusion area, use of rhBMP-2 with intervertebral cages increased so rapidly that rhBMP-2 was used more often than autologous bone.^5,11,17,31 In this study, we reviewed the common characteristics of patients who developed HO and subsequent radiculopathy from TLIF with rhBMP.

METHODS

After this study received Institutional Review Board approval, we retrospectively reviewed cases of radiculopathy symptoms that developed after TLIF with rhBMP between January 2002 and January 2015. During this period, 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years and radiculopathy symptoms arising from TLIF with rhBMP-2 were identified to determine commonalities and defining characteristics that will help facilitate diagnosis.

Inclusion criteria were computed tomography (CT)–documented HO arising from the TLIF annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell with contouring around the thecal sac or nerve roots, as well as recurrence or initial occurrence of radiculopathy with signs and symptoms corresponding to the CT site of aberrant bone growth in terms of laterality and particular nerve root(s) involved. Exclusion criteria were malplacement of interbody cage or pedicle screws, disk herniation, systemic neuropathic disease, and new or unresolved radiculopathy immediately after index surgery.

To improve recognition of this complication, we also documented the amount of BMP used, common patterns of radiculopathy symptom development, and radiologic findings. Type and timing of radiculopathy symptom onset and consistency with side of TLIF placement were documented as well. Radiculopathy symptoms included shooting pain in the legs, incontinence, sexual dysfunction, and severe paralysis. Radiologic findings were specific to bone formation from the disk space (detected with CT).

Continue to: RESULTS

 

 

RESULTS

All 38 selected patients had radiculopathy symptoms from HO out of the intervertebral space. The Table lists the patients’ overall characteristics. The left side had the most radiculopathy symptoms (31/38 patients), followed by the right side (5/38) and both sides (2/38). Radiculopathy symptoms began a mean (SD) of 3.8 (1.0) months (range, 2-6 months) after index surgery. The 38 patients had 4 characteristics in common:

Table. Transforaminal Lumbar Interbody Fusion With Recombinant Human Bone Morphogenetic Protein 2: Onset Time for Radiculopathy Symptoms, Surgery Level, Side of Pseudo-Pedicle Bone Formation, and Subsequent Complications

1. Bone growing out of the annulotomy site for TLIF cage placement was present and in continuity with the disk space in 33 (87%) of the 38 cases. In the other 5 cases (13%), HO was present around the neural tissue, but not necessarily in continuity with the disk space. This bone appeared ectopic and not osteophytic and facet-related, as it formed a shell around either the nerve root or the thecal sac, contouring to the structure.

2. The common, novel finding on CT was a “pseudo-pedicle” (Figures 1A, 1B), which appeared as ectopic growth from the disk space—a solid piece of bone in the same direction as the anatomical pedicle. Confusing similarity to the anatomical pedicle is present on axial cuts and during surgery. The pseudo-pedicle varied in thickness and extent out of the disk space, but was always presented as a bar of bone arising from the annulotomy site. After arising from the disk space, the HO could disperse in any direction, further calcifying neural structures or the facet joints above or below. There was no apparent distinguishable repeating pattern, given the variable nature of arthritic facet changes, scoliotic deformities, size of annulotomies, amount of rhBMP used, and placement in cage and disk space or only in cage.

3. In 36 (95%) of the 38 cases, the initial interpretation of HO on magnetic resonance imaging (MRI) was of tissue other than bone, such as fibrous tissue, granulation tissue, recurrent disk herniation, or postoperative changes. However, this tissue was later determined to be bone from HO complications, which we confirmed with CT in all 38 cases. It is important to note that HO on MRI (Figures 2A, 2B) was initially interpreted by a radiologist as fibrous tissue, but same-level CT of the same case (Figures 3A, 3B) showed clear HO.

4. The radiculopathy symptoms caused by HO were independent of the amount of rhBMP-2 used in TLIF. Of the 38 patients, 19 had 1 rhBMP-2 sponge placed in the cage, 12 had a small kit sponge (1.05 mg), 5 had 1 sponge placed in the cage and 1 sponge placed directly in the disk space before cage placement (no notation of precise size or amount of rhBMP-2), and 2 had 1 sponge placed in the cage (no notation of rhBMP-2 amount). The data showed that HO can occur with even a small amount of rhBMP-2.

Continue to: Bone formation with rhBMP-2...

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

DISCUSSION

We identified 38 patients with a recognizable and consistent pattern of complications of off-label use of rhBMP-2 in TLIF performed at our institution between 2002 and 2015. This pattern included consistent radiculopathy symptoms with corresponding HO at the annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell around the thecal sac or nerve roots, as well as showing a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. Our finding differs from other findings of similar complication characteristics, but with much larger variations without consistency within the patient population.^19,20,22,24 Specifically, previous studies found an association between off-label rhBMP-2 use in the posterior spine and radiculopathy with and without neuroforaminal HO. However, our study found consistent radiculopathy symptoms with pseudo-pedicle-like HO complications in all its 38 patients a mean (SD) of 3.8 (1.0) months after surgery.

In this study, consistent radiculopathy symptoms with pseudo-pedicle-like HO complications were independent of the amount of rhBMP-2 used, as some complications occurred with use of small pack rhBMP-2 with TLIF. It is well understood that high doses of rhBMP-2 may be required to improve fusion rates, but to our knowledge an optimal dosing strategy for TLIF has not been reported, particularly with respect to potential complications.^8,20,31-33 For anterior lumbar interbody fusion surgery, the FDA-approved use of rhBMP-2 appears to have a significantly decreased risk of neuroforaminal HO complications. This may be attributable to the protective presence of the intact posterior annulus and longitudinal ligament for this procedure.^20,33 For TLIF, it has been suggested that rhBMP-2 should be placed only along the anterior annulus with a posterior strut and morselized bone allograft barricade,³³ and that fibrin glue should be used to limit BMP diffusion through the annulotomy site³¹ to prevent this complication.

Our study results suggest that radiculopathy symptoms with pseudo-pedicle-like HO complications appear to be caused by leakage of rhBMP-2 from the disk space through the annulotomy site. This was often initially interpreted incorrectly on MRI in the first year after surgery as being fibrous or granulation tissue, or even postoperative changes that the heterotopic tissue was bone was obvious only on CT. Even then the tissue may be incorrectly identified, as the encasing nerve roots in bone are similar to the scar tissue having no compressive effect. HO may compress, but it also has an inflammatory component that the scars lack. Additionally, the HO from the disk space, caused by leakage of the BMP placed in or around the fusion cage, can create a pseudo-pedicle of varying size and extent. This was present in all 38 of our cases.

This retrospective case series had its limitations. Its clinical and radiographic findings were not blinded. Confounding variables cannot be isolated for causal relationships, if any, to the complication in a case series such as this.

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

ABSTRACT

We conducted a study to determine the common characteristics of patients who developed radiculopathy symptoms and corresponding heterotopic ossification (HO) from transforaminal lumbar interbody fusions (TLIF) using recombinant human bone morphogenetic protein 2 (rhBMP-2). HO can arise from a disk space with rhBMP-2 use in TLIF. Formation of bone around nerve roots or the thecal sac can cause a radiculopathy with a consistent pattern of symptoms.

We identified 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years who developed radiculopathy symptoms and corresponding HO from TLIF with rhBMP-2 in the disk space between 2002 and 2015. To document this complication and improve its recognition, we recorded common patterns of symptom development and radiologic findings: specifically, time from implantation of rhBMP-2 to symptom development, consistency with side of TLIF placement, and radiologic findings.

Radicular pain generally developed a mean (SD) of 3.8 (1.0) months after TLIF with rhBMP-2. Development of radiculopathy symptoms corresponded to consistent “pseudo-pedicle”-like HO. In all 38 patients, HO arising from the annulotomy site showed a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. In addition, development of radiculopathy symptoms and corresponding HO appear to be independent of amount of rhBMP-2. HO resulting from TLIF with rhBMP-2 in the disk space is a pain generator and a recognizable complication that can be diagnosed by assessment of symptoms and computed tomography characteristics.

Continue to: Bone morphogenetic proteins...

Bone morphogenetic proteins (BMPs), first isolated by Urist in 1964¹, are a family of growth factors that stimulate the cascade of bone formation. Recombinant human BMP (rhBMP), specifically rhBMP-2 and rhBMP-7 (also known as osteogenic protein 1 [OP-1]), was developed in the 1990s after the advent of gene splicing. Then, in 2002, the US Food and Drug Administration (FDA) approved use of rhBMP to stimulate fusion in the human spine. Specifically, rhBMP-2 (Medtronic) was approved for use in combination with a specific brand of interbody cage in 1-level anterior lumbar interbody fusion.² Over the past decade, off-label use of rhBMP-2 to achieve osseous union has increased dramatically, particularly in spinal surgery: transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion, and posterolateral lumbar fusion.^3-9 However, this widespread off-label use for posterior spinal fusion began despite FDA data indicating that specific complications were underreported in the peer-reviewed literature.^10,11 Although rhBMP-2 is very effective in increasing osteoblast formation and improving osteogenesis and subsequent bone healing in spinal surgery,^12,13 its use in TLIF resulted in significant adverse side effects, including radiculopathy with and without neuroforaminal heterotopic ossification (HO); ^14-24 complications in the FDA studies; ^14,22,25-27 and osteolysis causing intervertebral cage subsidence, inflammatory radiculitis, genitourinary complications, infections, possible systemic effects, and significant HO complications.^10,28-30 Of these, HO complications involved rhBMP leakage through the annulotomy to the disk space that led to HO. Specifically, rhBMP leaked directly out of the disk space and formed a pillar of bone that encased the nerve roots and dura, which led to occlusion of the foramen and symptoms of radiculopathy.^10,28-30

Despite this frequent finding of HO in the intervertebral space outside the target fusion area, use of rhBMP-2 with intervertebral cages increased so rapidly that rhBMP-2 was used more often than autologous bone.^5,11,17,31 In this study, we reviewed the common characteristics of patients who developed HO and subsequent radiculopathy from TLIF with rhBMP.

METHODS

After this study received Institutional Review Board approval, we retrospectively reviewed cases of radiculopathy symptoms that developed after TLIF with rhBMP between January 2002 and January 2015. During this period, 38 patients (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years and radiculopathy symptoms arising from TLIF with rhBMP-2 were identified to determine commonalities and defining characteristics that will help facilitate diagnosis.

Inclusion criteria were computed tomography (CT)–documented HO arising from the TLIF annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell with contouring around the thecal sac or nerve roots, as well as recurrence or initial occurrence of radiculopathy with signs and symptoms corresponding to the CT site of aberrant bone growth in terms of laterality and particular nerve root(s) involved. Exclusion criteria were malplacement of interbody cage or pedicle screws, disk herniation, systemic neuropathic disease, and new or unresolved radiculopathy immediately after index surgery.

To improve recognition of this complication, we also documented the amount of BMP used, common patterns of radiculopathy symptom development, and radiologic findings. Type and timing of radiculopathy symptom onset and consistency with side of TLIF placement were documented as well. Radiculopathy symptoms included shooting pain in the legs, incontinence, sexual dysfunction, and severe paralysis. Radiologic findings were specific to bone formation from the disk space (detected with CT).

Continue to: RESULTS

 

 

RESULTS

All 38 selected patients had radiculopathy symptoms from HO out of the intervertebral space. The Table lists the patients’ overall characteristics. The left side had the most radiculopathy symptoms (31/38 patients), followed by the right side (5/38) and both sides (2/38). Radiculopathy symptoms began a mean (SD) of 3.8 (1.0) months (range, 2-6 months) after index surgery. The 38 patients had 4 characteristics in common:

Table. Transforaminal Lumbar Interbody Fusion With Recombinant Human Bone Morphogenetic Protein 2: Onset Time for Radiculopathy Symptoms, Surgery Level, Side of Pseudo-Pedicle Bone Formation, and Subsequent Complications

1. Bone growing out of the annulotomy site for TLIF cage placement was present and in continuity with the disk space in 33 (87%) of the 38 cases. In the other 5 cases (13%), HO was present around the neural tissue, but not necessarily in continuity with the disk space. This bone appeared ectopic and not osteophytic and facet-related, as it formed a shell around either the nerve root or the thecal sac, contouring to the structure.

2. The common, novel finding on CT was a “pseudo-pedicle” (Figures 1A, 1B), which appeared as ectopic growth from the disk space—a solid piece of bone in the same direction as the anatomical pedicle. Confusing similarity to the anatomical pedicle is present on axial cuts and during surgery. The pseudo-pedicle varied in thickness and extent out of the disk space, but was always presented as a bar of bone arising from the annulotomy site. After arising from the disk space, the HO could disperse in any direction, further calcifying neural structures or the facet joints above or below. There was no apparent distinguishable repeating pattern, given the variable nature of arthritic facet changes, scoliotic deformities, size of annulotomies, amount of rhBMP used, and placement in cage and disk space or only in cage.

3. In 36 (95%) of the 38 cases, the initial interpretation of HO on magnetic resonance imaging (MRI) was of tissue other than bone, such as fibrous tissue, granulation tissue, recurrent disk herniation, or postoperative changes. However, this tissue was later determined to be bone from HO complications, which we confirmed with CT in all 38 cases. It is important to note that HO on MRI (Figures 2A, 2B) was initially interpreted by a radiologist as fibrous tissue, but same-level CT of the same case (Figures 3A, 3B) showed clear HO.

4. The radiculopathy symptoms caused by HO were independent of the amount of rhBMP-2 used in TLIF. Of the 38 patients, 19 had 1 rhBMP-2 sponge placed in the cage, 12 had a small kit sponge (1.05 mg), 5 had 1 sponge placed in the cage and 1 sponge placed directly in the disk space before cage placement (no notation of precise size or amount of rhBMP-2), and 2 had 1 sponge placed in the cage (no notation of rhBMP-2 amount). The data showed that HO can occur with even a small amount of rhBMP-2.

Continue to: Bone formation with rhBMP-2...

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

DISCUSSION

We identified 38 patients with a recognizable and consistent pattern of complications of off-label use of rhBMP-2 in TLIF performed at our institution between 2002 and 2015. This pattern included consistent radiculopathy symptoms with corresponding HO at the annulotomy site in continuity with bone in the disk space or ectopic bone forming a distinctive shell around the thecal sac or nerve roots, as well as showing a distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. Our finding differs from other findings of similar complication characteristics, but with much larger variations without consistency within the patient population.^19,20,22,24 Specifically, previous studies found an association between off-label rhBMP-2 use in the posterior spine and radiculopathy with and without neuroforaminal HO. However, our study found consistent radiculopathy symptoms with pseudo-pedicle-like HO complications in all its 38 patients a mean (SD) of 3.8 (1.0) months after surgery.

In this study, consistent radiculopathy symptoms with pseudo-pedicle-like HO complications were independent of the amount of rhBMP-2 used, as some complications occurred with use of small pack rhBMP-2 with TLIF. It is well understood that high doses of rhBMP-2 may be required to improve fusion rates, but to our knowledge an optimal dosing strategy for TLIF has not been reported, particularly with respect to potential complications.^8,20,31-33 For anterior lumbar interbody fusion surgery, the FDA-approved use of rhBMP-2 appears to have a significantly decreased risk of neuroforaminal HO complications. This may be attributable to the protective presence of the intact posterior annulus and longitudinal ligament for this procedure.^20,33 For TLIF, it has been suggested that rhBMP-2 should be placed only along the anterior annulus with a posterior strut and morselized bone allograft barricade,³³ and that fibrin glue should be used to limit BMP diffusion through the annulotomy site³¹ to prevent this complication.

Our study results suggest that radiculopathy symptoms with pseudo-pedicle-like HO complications appear to be caused by leakage of rhBMP-2 from the disk space through the annulotomy site. This was often initially interpreted incorrectly on MRI in the first year after surgery as being fibrous or granulation tissue, or even postoperative changes that the heterotopic tissue was bone was obvious only on CT. Even then the tissue may be incorrectly identified, as the encasing nerve roots in bone are similar to the scar tissue having no compressive effect. HO may compress, but it also has an inflammatory component that the scars lack. Additionally, the HO from the disk space, caused by leakage of the BMP placed in or around the fusion cage, can create a pseudo-pedicle of varying size and extent. This was present in all 38 of our cases.

This retrospective case series had its limitations. Its clinical and radiographic findings were not blinded. Confounding variables cannot be isolated for causal relationships, if any, to the complication in a case series such as this.

Bone formation with rhBMP-2 is robust and beneficial, but HO-related complications are significant, and identifiable on assessment of radiculopathy symptoms and CT characteristics.

ABSTRACT

Anterior ankle impingement is a frequent cause of pain and disability in athletes with impingement of soft-tissue or osseous structures along the anterior margin of the tibiotalar joint during dorsiflexion.

In this study, we hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and range of motion (ROM), and would allow National Football League (NFL) players to return to their preoperative level of play.

We reviewed 29 arthroscopic ankle débridements performed by a single surgeon. Each NFL player underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to return to play (RTP), events missed secondary to surgery, and complications were recorded.

All athletes returned to the same level of NFL play at a mean (SD) of 8.4 (4.1) weeks after surgery and continued playing for a mean (SD) of 3.43 (2.57) years after surgery. Mean (SD) VAS pain scores decreased significantly (P < .001), to 0.38 (0.89) from 4.21 (1.52). Mean (SD) active ankle dorsiflexion increased significantly (P < .001), to 18.86° (2.62°) from 8.28° (4.14°). Mean (SD) AOFAS hindfoot scores increased significantly (P < .001), to 97.45 (4.72) from 70.62 (10.39). Degree of arthritis (r = 0.305) and age (r = 0.106) were poorly correlated to time to RTP.

In all cases, arthroscopic débridement of anterior ankle impingement resulted in RTP at the same level at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM.

Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

Continue to: Anterior ankle impingement...

Anterior ankle impingement is a frequent cause of disability in athletes.¹ This condition results from repetitive trauma over time, which leads to osseous and soft-tissue impingement, pain, and decreased ankle range of motion (ROM).

First termed footballer’s ankle, this condition is linked to repeated, forceful plantarflexion,² though later studies attributed the phenomenon to repeated dorsiflexion resulting in periosteal hemorrhage.³ Both osseous and soft-tissue structures can cause impingement at the tibiotalar joint, often with osteophytes anteromedially at the tibial talar joint. Soft-tissue structures, including hypertrophic synovium, meniscoid lesions, and a thickened anterior talofibular ligament, more often cause anterolateral impingement.^4-6 This process results in pain in extreme dorsiflexion, which comes into play in almost all football maneuvers, including sprinting, back-peddling, and offensive and defensive stances. Therefore, maintenance of pain-free dorsiflexion is required for high-level football. Decreased ROM can lead to decreased ability to perform these high-level athletic functions and can limit performance.

Arthroscopic débridement improves functional outcomes and functional motion in both athletes and nonathletes.^7,8 In addition, findings of a recent systematic review provide support for arthroscopic treatment of ankle impingement.⁹ Although arthroscopic treatment is effective in nonathletes and recreational athletes,¹⁰ there is a paucity of data on the efficacy of this procedure and on time to return to play (RTP) in professional football players.

We conducted a study to evaluate the outcomes (pain, ROM, RTP) of arthroscopic débridement for anterior ankle impingement in National Football League (NFL) players. We hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and ROM, and would allow NFL players to return to their preoperative level of play.

METHODS

After this study was granted Institutional Review Board approval, we retrospectively reviewed a consecutive series of arthroscopically treated anterior ankle impingement athletes by a single surgeon (JPB). Indications for surgery were anterior ankle impingement resulting in ankle pain and decreased ROM that interfered with sport. Active NFL players who underwent ankle arthroscopy for symptomatic anterior ankle impingement were included. Excluded were players who underwent surgery after retirement or who retired before returning to play for reasons unrelated to the ankle. Medical records, operative reports, and rehabilitation reports were reviewed.

Continue to: Preoperative and postoperative...

Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to RTP, events missed secondary to surgery, and complications were recorded. These preoperative and postoperative variables were compared with paired Student 2-way t tests for continuous variables. Pearson correlation coefficients were calculated.

PROCEDURE

Ankle arthroscopy was performed with the patient supine after spinal or general anesthesia was induced. Prophylactic antibiotics were given in each case. Arthroscopy was performed with standard anterolateral and anteromedial portals. First, an incision was made through skin only, followed by blunt subcutaneous dissection down to the ankle capsule. A capsulotomy was then made bluntly. Care was taken to avoid all neurovascular structures. Posterior portals were not used. A 2.7-mm arthroscope was inserted and alternated between the anteromedial and anterolateral portals to maximally visualize the ankle joint. Diagnostic arthroscopy was performed to document synovitis, chondral injury, osseous, and soft-tissue impingement and any other noted pathology (Figures 1A-1C).

A full radius resector was then used to perform a synovectomy and débridement of impinging soft tissue from the anterior talofibular ligament or anterior inferior talofibular ligament. All patients underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. A small burr was used to débride and remove the osteophytes on the talus and/or tibia. Soft-tissue and osseous structures were resected until the contours of the talus and tibia were normal. Any unstable articular defects were débrided and loose bodies were removed. Ankle ROM was checked to confirm complete resolution of impingement (Figures 2A-2D). Patients were not immobilized and were allowed progressive weight-bearing as tolerated. Crutches were used for assisted ambulation the first 3 to 5 postoperative days.

Physical therapy progressed through 3 phases: (1) inflammation control and ROM restoration, (2) initiation of ankle strengthening, including eversion and inversion, and (3) agility, proprioception, and functional rehabilitation.

RESULTS

Twenty-five NFL players (29 surgeries) were included in the study. Two players were excluded because they had retired at the end of the season before the surgery for reasons unrelated to the operative ankle. Mean (SD) age was 28.1 (2.9) years. Six included players had a history of ankle sprains, 1 had a history of ipsilateral ankle fracture, and 1 had a history of ipsilateral ankle dislocation. Table 1 lists the positions of players who underwent ankle arthroscopic decompression.

Table 1. Positions of National Football League Players Who Underwent Ankle Arthroscopic Decompression for Anterior Ankle Impingement

Continue to: During diagnostic arthroscopy...

During diagnostic arthroscopy, changes to the articular cartilage were noted: grade 0 in 38% of patients, grade 1 in 17%, grade 2 in 21%, grade 3 in 21%, and grade 4 in 3%. Four patients had an osteochondral lesion (<1 cm in each case), which was treated with chondroplasty without microfracture.

Each included patient returned to NFL play. Mean (SD) time to RTP without restrictions was 8.4 (4.1) weeks after surgery (range, 2-20 weeks). There was a poor correlation between degree of chondrosis and time to RTP (r = 0.305). In addition, there was a poor correlation between age and time to RTP (r = 0.106).

Dorsiflexion improved significantly (P < .001), patients had significantly less pain after surgery (P < .001), and AOFAS hindfoot scores improved significantly (P < .001) (Table 2).

Table 2. Preoperative and Postoperative Dorsiflexion, Pain, and AOFAS Score Before and After Arthroscopic Débridement of Anterior Ankle Impingement^a

^aAll values were significantly improved after surgery (P < .001).

Abbreviations: AOFAS, American Orthopaedic Foot and Ankle Society; VAS, visual analog scale.

The athletes played in the NFL for a mean (SD) of 3.43 (2.57) years after surgery (range, 1-10 seasons). These players included 6 who were still active at time of publication. No patient required revision surgery or additional surgery on the ipsilateral ankle. The one patient who was treated for superficial thrombophlebitis after surgery reported symptoms before surgery as well.

DISCUSSION

Arthroscopic decompression of anterior ankle impingement is safe and significantly improves pain and ROM in professional American football players. The procedure results in reliable RTP at an elite level, with durable results over the time remaining in their NFL careers.

Continue to: before the 1988 study by Hawkins...

Before the 1988 study by Hawkins,¹¹ ankle spurs were removed with open procedures. Hawkins¹¹ used arthroscopy for better and safer visualization of the ankle joint and used a burr for less painful removal of spurs from the tibia and the talus. In 2002, a series of 105 patients (median age, 35 years) had reduced pain and improved function a minimum of 2 years after arthroscopic débridement.¹² These patients had a mix of pathology, including soft-tissue impingement, bony impingement, chondral lesions, loose bodies, and osteoarthritis.

For many elite athletes, anterior ankle impingement can cause significant limitation. Reduced ankle dorsiflexion can alter all limb mechanics and predispose athletes to injury.¹³ In addition, because NFL players’ ankle ROM often approaches or exceeds normal physiologic limits,¹⁴ an ankle ROM limitation will often hinder their performance.

Miyamoto and colleagues¹⁵ studied a series of 9 professional athletes (6 soccer players, 1 baseball pitcher, 1 mixed martial artist, 1 golfer) who underwent decompression of both anterior and posterior impingement. With regard to anterior impingement, they found anterior osteophytes in all the ankles, as was seen in the present study. Furthermore, they noted that mean dorsiflexion improved from 10° before surgery to 15° after surgery and that their athletes returned to play 12 to 15 weeks after surgery. Their results are similar to ours, though we noted more improvement in dorsiflexion, from 8.28° before surgery to 18.86° after surgery.

One of the most important metrics in evaluating treatment options for professional athletes is time from surgery to RTP without restrictions. Mean time to full RTP was shorter in our study (8.4 weeks) than in the study by Miyamoto and colleagues¹⁵ (up to 20 weeks). However, many of their procedures were performed during the off-season, when there was no need to expeditiously clear patients for full sports participation. In addition, the patients in their study had both anterior and posterior pathology.

Faster return to high-level athletics was supported in a study of 11 elite ballet dancers,¹⁶ whose pain and dance performance improved after arthroscopic débridement. Of the 11 patients, 9 returned to dance at a mean of 7 weeks after surgery; the other 2 required reoperation. Although the pathology differed in their study of elite professional soccer players, Calder and colleagues¹⁷ found that mean time to RTP after ankle arthroscopy for posterior impingement was 5 weeks.

Continue to: For the NFL players in our study...

For the NFL players in our study, RTP at their elite level was 100% after arthroscopic débridement of anterior ankle impingement. In the literature, time to RTP varies. Table 3 lists RTP rates for recreational athletes in published studies.^18-27 In their recent systematic literature review, Zwiers and colleagues¹⁰ noted that 24% to 96.4% of recreational athletes returned to play after arthroscopic treatment for anterior ankle impingement. The percentage was significantly higher for the professional athletes in our study. Historical comparison supports an evolution in the indications and techniques for this procedure, with more recent literature suggesting a RTP rate much higher than earlier rates. In addition, compared with recreational athletes, professional athletes have strong financial incentives to return to their sports. Furthermore, our professional cohort was significantly younger than the recreational cohorts in those studies.

Table 3. Frequency of Recreational Athletes’ Return to Play After Arthroscopic Débridement of Anterior Ankle Impingement, as Reported in the Literature

Current recommendations for recreational athletes include initial conservative treatment with rest, ankle bracing, and avoidance of jumping and other repetitive dorsiflexing activities. Physical therapy should include joint mobilization and work along the entire kinetic chain. Night splints or a removable walking boot can be used temporarily, as can a single intra-articular corticosteroid injection to reduce inflammation and evaluate improvement in more refractory cases.²⁸ Commonly, conservative treatments fail if patients remain active, and soft tissue and/or osteophytes can be resected, though resection typically is reserved for recreational athletes for whom nonoperative treatments have been exhausted.^29,30

This study had several limitations, including its retrospective nature and lack of control group. In addition, follow-up was relatively short, and we did not use more recently described outcome measures, such as the Sports subscale of the Foot and Ankle Ability Measure, which may be more sensitive in describing function in elite athletes. However, many of the cases in our study predated these measures, but the rate of RTP at the NFL level requires a very high degree of postoperative ankle function, making this outcome the most meaningful. In the context of professional athletes, specifically the length of their careers, our study results provide valuable information regarding expectations about RTP and the durability of arthroscopic débridement of anterior ankle impingement in a high-demand setting.

CONCLUSION

For all the NFL players in this study, arthroscopic débridement of anterior ankle impingement resulted in return to preoperative level of play at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM. Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

ABSTRACT

Anterior ankle impingement is a frequent cause of pain and disability in athletes with impingement of soft-tissue or osseous structures along the anterior margin of the tibiotalar joint during dorsiflexion.

In this study, we hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and range of motion (ROM), and would allow National Football League (NFL) players to return to their preoperative level of play.

We reviewed 29 arthroscopic ankle débridements performed by a single surgeon. Each NFL player underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to return to play (RTP), events missed secondary to surgery, and complications were recorded.

All athletes returned to the same level of NFL play at a mean (SD) of 8.4 (4.1) weeks after surgery and continued playing for a mean (SD) of 3.43 (2.57) years after surgery. Mean (SD) VAS pain scores decreased significantly (P < .001), to 0.38 (0.89) from 4.21 (1.52). Mean (SD) active ankle dorsiflexion increased significantly (P < .001), to 18.86° (2.62°) from 8.28° (4.14°). Mean (SD) AOFAS hindfoot scores increased significantly (P < .001), to 97.45 (4.72) from 70.62 (10.39). Degree of arthritis (r = 0.305) and age (r = 0.106) were poorly correlated to time to RTP.

In all cases, arthroscopic débridement of anterior ankle impingement resulted in RTP at the same level at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM.

Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

Continue to: Anterior ankle impingement...

Anterior ankle impingement is a frequent cause of disability in athletes.¹ This condition results from repetitive trauma over time, which leads to osseous and soft-tissue impingement, pain, and decreased ankle range of motion (ROM).

First termed footballer’s ankle, this condition is linked to repeated, forceful plantarflexion,² though later studies attributed the phenomenon to repeated dorsiflexion resulting in periosteal hemorrhage.³ Both osseous and soft-tissue structures can cause impingement at the tibiotalar joint, often with osteophytes anteromedially at the tibial talar joint. Soft-tissue structures, including hypertrophic synovium, meniscoid lesions, and a thickened anterior talofibular ligament, more often cause anterolateral impingement.^4-6 This process results in pain in extreme dorsiflexion, which comes into play in almost all football maneuvers, including sprinting, back-peddling, and offensive and defensive stances. Therefore, maintenance of pain-free dorsiflexion is required for high-level football. Decreased ROM can lead to decreased ability to perform these high-level athletic functions and can limit performance.

Arthroscopic débridement improves functional outcomes and functional motion in both athletes and nonathletes.^7,8 In addition, findings of a recent systematic review provide support for arthroscopic treatment of ankle impingement.⁹ Although arthroscopic treatment is effective in nonathletes and recreational athletes,¹⁰ there is a paucity of data on the efficacy of this procedure and on time to return to play (RTP) in professional football players.

We conducted a study to evaluate the outcomes (pain, ROM, RTP) of arthroscopic débridement for anterior ankle impingement in National Football League (NFL) players. We hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and ROM, and would allow NFL players to return to their preoperative level of play.

METHODS

After this study was granted Institutional Review Board approval, we retrospectively reviewed a consecutive series of arthroscopically treated anterior ankle impingement athletes by a single surgeon (JPB). Indications for surgery were anterior ankle impingement resulting in ankle pain and decreased ROM that interfered with sport. Active NFL players who underwent ankle arthroscopy for symptomatic anterior ankle impingement were included. Excluded were players who underwent surgery after retirement or who retired before returning to play for reasons unrelated to the ankle. Medical records, operative reports, and rehabilitation reports were reviewed.

Continue to: Preoperative and postoperative...

Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to RTP, events missed secondary to surgery, and complications were recorded. These preoperative and postoperative variables were compared with paired Student 2-way t tests for continuous variables. Pearson correlation coefficients were calculated.

PROCEDURE

Ankle arthroscopy was performed with the patient supine after spinal or general anesthesia was induced. Prophylactic antibiotics were given in each case. Arthroscopy was performed with standard anterolateral and anteromedial portals. First, an incision was made through skin only, followed by blunt subcutaneous dissection down to the ankle capsule. A capsulotomy was then made bluntly. Care was taken to avoid all neurovascular structures. Posterior portals were not used. A 2.7-mm arthroscope was inserted and alternated between the anteromedial and anterolateral portals to maximally visualize the ankle joint. Diagnostic arthroscopy was performed to document synovitis, chondral injury, osseous, and soft-tissue impingement and any other noted pathology (Figures 1A-1C).

A full radius resector was then used to perform a synovectomy and débridement of impinging soft tissue from the anterior talofibular ligament or anterior inferior talofibular ligament. All patients underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. A small burr was used to débride and remove the osteophytes on the talus and/or tibia. Soft-tissue and osseous structures were resected until the contours of the talus and tibia were normal. Any unstable articular defects were débrided and loose bodies were removed. Ankle ROM was checked to confirm complete resolution of impingement (Figures 2A-2D). Patients were not immobilized and were allowed progressive weight-bearing as tolerated. Crutches were used for assisted ambulation the first 3 to 5 postoperative days.

Physical therapy progressed through 3 phases: (1) inflammation control and ROM restoration, (2) initiation of ankle strengthening, including eversion and inversion, and (3) agility, proprioception, and functional rehabilitation.

RESULTS

Twenty-five NFL players (29 surgeries) were included in the study. Two players were excluded because they had retired at the end of the season before the surgery for reasons unrelated to the operative ankle. Mean (SD) age was 28.1 (2.9) years. Six included players had a history of ankle sprains, 1 had a history of ipsilateral ankle fracture, and 1 had a history of ipsilateral ankle dislocation. Table 1 lists the positions of players who underwent ankle arthroscopic decompression.

Table 1. Positions of National Football League Players Who Underwent Ankle Arthroscopic Decompression for Anterior Ankle Impingement

Continue to: During diagnostic arthroscopy...

During diagnostic arthroscopy, changes to the articular cartilage were noted: grade 0 in 38% of patients, grade 1 in 17%, grade 2 in 21%, grade 3 in 21%, and grade 4 in 3%. Four patients had an osteochondral lesion (<1 cm in each case), which was treated with chondroplasty without microfracture.

Each included patient returned to NFL play. Mean (SD) time to RTP without restrictions was 8.4 (4.1) weeks after surgery (range, 2-20 weeks). There was a poor correlation between degree of chondrosis and time to RTP (r = 0.305). In addition, there was a poor correlation between age and time to RTP (r = 0.106).

Dorsiflexion improved significantly (P < .001), patients had significantly less pain after surgery (P < .001), and AOFAS hindfoot scores improved significantly (P < .001) (Table 2).

Table 2. Preoperative and Postoperative Dorsiflexion, Pain, and AOFAS Score Before and After Arthroscopic Débridement of Anterior Ankle Impingement^a

^aAll values were significantly improved after surgery (P < .001).

Abbreviations: AOFAS, American Orthopaedic Foot and Ankle Society; VAS, visual analog scale.

The athletes played in the NFL for a mean (SD) of 3.43 (2.57) years after surgery (range, 1-10 seasons). These players included 6 who were still active at time of publication. No patient required revision surgery or additional surgery on the ipsilateral ankle. The one patient who was treated for superficial thrombophlebitis after surgery reported symptoms before surgery as well.

DISCUSSION

Arthroscopic decompression of anterior ankle impingement is safe and significantly improves pain and ROM in professional American football players. The procedure results in reliable RTP at an elite level, with durable results over the time remaining in their NFL careers.

Continue to: before the 1988 study by Hawkins...

Before the 1988 study by Hawkins,¹¹ ankle spurs were removed with open procedures. Hawkins¹¹ used arthroscopy for better and safer visualization of the ankle joint and used a burr for less painful removal of spurs from the tibia and the talus. In 2002, a series of 105 patients (median age, 35 years) had reduced pain and improved function a minimum of 2 years after arthroscopic débridement.¹² These patients had a mix of pathology, including soft-tissue impingement, bony impingement, chondral lesions, loose bodies, and osteoarthritis.

For many elite athletes, anterior ankle impingement can cause significant limitation. Reduced ankle dorsiflexion can alter all limb mechanics and predispose athletes to injury.¹³ In addition, because NFL players’ ankle ROM often approaches or exceeds normal physiologic limits,¹⁴ an ankle ROM limitation will often hinder their performance.

Miyamoto and colleagues¹⁵ studied a series of 9 professional athletes (6 soccer players, 1 baseball pitcher, 1 mixed martial artist, 1 golfer) who underwent decompression of both anterior and posterior impingement. With regard to anterior impingement, they found anterior osteophytes in all the ankles, as was seen in the present study. Furthermore, they noted that mean dorsiflexion improved from 10° before surgery to 15° after surgery and that their athletes returned to play 12 to 15 weeks after surgery. Their results are similar to ours, though we noted more improvement in dorsiflexion, from 8.28° before surgery to 18.86° after surgery.

One of the most important metrics in evaluating treatment options for professional athletes is time from surgery to RTP without restrictions. Mean time to full RTP was shorter in our study (8.4 weeks) than in the study by Miyamoto and colleagues¹⁵ (up to 20 weeks). However, many of their procedures were performed during the off-season, when there was no need to expeditiously clear patients for full sports participation. In addition, the patients in their study had both anterior and posterior pathology.

Faster return to high-level athletics was supported in a study of 11 elite ballet dancers,¹⁶ whose pain and dance performance improved after arthroscopic débridement. Of the 11 patients, 9 returned to dance at a mean of 7 weeks after surgery; the other 2 required reoperation. Although the pathology differed in their study of elite professional soccer players, Calder and colleagues¹⁷ found that mean time to RTP after ankle arthroscopy for posterior impingement was 5 weeks.

Continue to: For the NFL players in our study...

For the NFL players in our study, RTP at their elite level was 100% after arthroscopic débridement of anterior ankle impingement. In the literature, time to RTP varies. Table 3 lists RTP rates for recreational athletes in published studies.^18-27 In their recent systematic literature review, Zwiers and colleagues¹⁰ noted that 24% to 96.4% of recreational athletes returned to play after arthroscopic treatment for anterior ankle impingement. The percentage was significantly higher for the professional athletes in our study. Historical comparison supports an evolution in the indications and techniques for this procedure, with more recent literature suggesting a RTP rate much higher than earlier rates. In addition, compared with recreational athletes, professional athletes have strong financial incentives to return to their sports. Furthermore, our professional cohort was significantly younger than the recreational cohorts in those studies.

Table 3. Frequency of Recreational Athletes’ Return to Play After Arthroscopic Débridement of Anterior Ankle Impingement, as Reported in the Literature

Current recommendations for recreational athletes include initial conservative treatment with rest, ankle bracing, and avoidance of jumping and other repetitive dorsiflexing activities. Physical therapy should include joint mobilization and work along the entire kinetic chain. Night splints or a removable walking boot can be used temporarily, as can a single intra-articular corticosteroid injection to reduce inflammation and evaluate improvement in more refractory cases.²⁸ Commonly, conservative treatments fail if patients remain active, and soft tissue and/or osteophytes can be resected, though resection typically is reserved for recreational athletes for whom nonoperative treatments have been exhausted.^29,30

This study had several limitations, including its retrospective nature and lack of control group. In addition, follow-up was relatively short, and we did not use more recently described outcome measures, such as the Sports subscale of the Foot and Ankle Ability Measure, which may be more sensitive in describing function in elite athletes. However, many of the cases in our study predated these measures, but the rate of RTP at the NFL level requires a very high degree of postoperative ankle function, making this outcome the most meaningful. In the context of professional athletes, specifically the length of their careers, our study results provide valuable information regarding expectations about RTP and the durability of arthroscopic débridement of anterior ankle impingement in a high-demand setting.

CONCLUSION

For all the NFL players in this study, arthroscopic débridement of anterior ankle impingement resulted in return to preoperative level of play at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM. Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

ABSTRACT

Anterior ankle impingement is a frequent cause of pain and disability in athletes with impingement of soft-tissue or osseous structures along the anterior margin of the tibiotalar joint during dorsiflexion.

In this study, we hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and range of motion (ROM), and would allow National Football League (NFL) players to return to their preoperative level of play.

We reviewed 29 arthroscopic ankle débridements performed by a single surgeon. Each NFL player underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to return to play (RTP), events missed secondary to surgery, and complications were recorded.

All athletes returned to the same level of NFL play at a mean (SD) of 8.4 (4.1) weeks after surgery and continued playing for a mean (SD) of 3.43 (2.57) years after surgery. Mean (SD) VAS pain scores decreased significantly (P < .001), to 0.38 (0.89) from 4.21 (1.52). Mean (SD) active ankle dorsiflexion increased significantly (P < .001), to 18.86° (2.62°) from 8.28° (4.14°). Mean (SD) AOFAS hindfoot scores increased significantly (P < .001), to 97.45 (4.72) from 70.62 (10.39). Degree of arthritis (r = 0.305) and age (r = 0.106) were poorly correlated to time to RTP.

In all cases, arthroscopic débridement of anterior ankle impingement resulted in RTP at the same level at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM.

Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

Continue to: Anterior ankle impingement...

Anterior ankle impingement is a frequent cause of disability in athletes.¹ This condition results from repetitive trauma over time, which leads to osseous and soft-tissue impingement, pain, and decreased ankle range of motion (ROM).

First termed footballer’s ankle, this condition is linked to repeated, forceful plantarflexion,² though later studies attributed the phenomenon to repeated dorsiflexion resulting in periosteal hemorrhage.³ Both osseous and soft-tissue structures can cause impingement at the tibiotalar joint, often with osteophytes anteromedially at the tibial talar joint. Soft-tissue structures, including hypertrophic synovium, meniscoid lesions, and a thickened anterior talofibular ligament, more often cause anterolateral impingement.^4-6 This process results in pain in extreme dorsiflexion, which comes into play in almost all football maneuvers, including sprinting, back-peddling, and offensive and defensive stances. Therefore, maintenance of pain-free dorsiflexion is required for high-level football. Decreased ROM can lead to decreased ability to perform these high-level athletic functions and can limit performance.

Arthroscopic débridement improves functional outcomes and functional motion in both athletes and nonathletes.^7,8 In addition, findings of a recent systematic review provide support for arthroscopic treatment of ankle impingement.⁹ Although arthroscopic treatment is effective in nonathletes and recreational athletes,¹⁰ there is a paucity of data on the efficacy of this procedure and on time to return to play (RTP) in professional football players.

We conducted a study to evaluate the outcomes (pain, ROM, RTP) of arthroscopic débridement for anterior ankle impingement in National Football League (NFL) players. We hypothesized that arthroscopic decompression of anterior ankle impingement would result in significant, reliable, and durable improvement in pain and ROM, and would allow NFL players to return to their preoperative level of play.

METHODS

After this study was granted Institutional Review Board approval, we retrospectively reviewed a consecutive series of arthroscopically treated anterior ankle impingement athletes by a single surgeon (JPB). Indications for surgery were anterior ankle impingement resulting in ankle pain and decreased ROM that interfered with sport. Active NFL players who underwent ankle arthroscopy for symptomatic anterior ankle impingement were included. Excluded were players who underwent surgery after retirement or who retired before returning to play for reasons unrelated to the ankle. Medical records, operative reports, and rehabilitation reports were reviewed.

Continue to: Preoperative and postoperative...

Preoperative and postoperative visual analog scale (VAS) pain scores, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle ROM were compared; time to RTP, events missed secondary to surgery, and complications were recorded. These preoperative and postoperative variables were compared with paired Student 2-way t tests for continuous variables. Pearson correlation coefficients were calculated.

PROCEDURE

Ankle arthroscopy was performed with the patient supine after spinal or general anesthesia was induced. Prophylactic antibiotics were given in each case. Arthroscopy was performed with standard anterolateral and anteromedial portals. First, an incision was made through skin only, followed by blunt subcutaneous dissection down to the ankle capsule. A capsulotomy was then made bluntly. Care was taken to avoid all neurovascular structures. Posterior portals were not used. A 2.7-mm arthroscope was inserted and alternated between the anteromedial and anterolateral portals to maximally visualize the ankle joint. Diagnostic arthroscopy was performed to document synovitis, chondral injury, osseous, and soft-tissue impingement and any other noted pathology (Figures 1A-1C).

A full radius resector was then used to perform a synovectomy and débridement of impinging soft tissue from the anterior talofibular ligament or anterior inferior talofibular ligament. All patients underwent arthroscopic débridement of pathologic soft tissue and of tibial and talar osteophytes in the anterior ankle. A small burr was used to débride and remove the osteophytes on the talus and/or tibia. Soft-tissue and osseous structures were resected until the contours of the talus and tibia were normal. Any unstable articular defects were débrided and loose bodies were removed. Ankle ROM was checked to confirm complete resolution of impingement (Figures 2A-2D). Patients were not immobilized and were allowed progressive weight-bearing as tolerated. Crutches were used for assisted ambulation the first 3 to 5 postoperative days.

Physical therapy progressed through 3 phases: (1) inflammation control and ROM restoration, (2) initiation of ankle strengthening, including eversion and inversion, and (3) agility, proprioception, and functional rehabilitation.

RESULTS

Twenty-five NFL players (29 surgeries) were included in the study. Two players were excluded because they had retired at the end of the season before the surgery for reasons unrelated to the operative ankle. Mean (SD) age was 28.1 (2.9) years. Six included players had a history of ankle sprains, 1 had a history of ipsilateral ankle fracture, and 1 had a history of ipsilateral ankle dislocation. Table 1 lists the positions of players who underwent ankle arthroscopic decompression.

Table 1. Positions of National Football League Players Who Underwent Ankle Arthroscopic Decompression for Anterior Ankle Impingement

Continue to: During diagnostic arthroscopy...

During diagnostic arthroscopy, changes to the articular cartilage were noted: grade 0 in 38% of patients, grade 1 in 17%, grade 2 in 21%, grade 3 in 21%, and grade 4 in 3%. Four patients had an osteochondral lesion (<1 cm in each case), which was treated with chondroplasty without microfracture.

Each included patient returned to NFL play. Mean (SD) time to RTP without restrictions was 8.4 (4.1) weeks after surgery (range, 2-20 weeks). There was a poor correlation between degree of chondrosis and time to RTP (r = 0.305). In addition, there was a poor correlation between age and time to RTP (r = 0.106).

Dorsiflexion improved significantly (P < .001), patients had significantly less pain after surgery (P < .001), and AOFAS hindfoot scores improved significantly (P < .001) (Table 2).

Table 2. Preoperative and Postoperative Dorsiflexion, Pain, and AOFAS Score Before and After Arthroscopic Débridement of Anterior Ankle Impingement^a

^aAll values were significantly improved after surgery (P < .001).

Abbreviations: AOFAS, American Orthopaedic Foot and Ankle Society; VAS, visual analog scale.

The athletes played in the NFL for a mean (SD) of 3.43 (2.57) years after surgery (range, 1-10 seasons). These players included 6 who were still active at time of publication. No patient required revision surgery or additional surgery on the ipsilateral ankle. The one patient who was treated for superficial thrombophlebitis after surgery reported symptoms before surgery as well.

DISCUSSION

Arthroscopic decompression of anterior ankle impingement is safe and significantly improves pain and ROM in professional American football players. The procedure results in reliable RTP at an elite level, with durable results over the time remaining in their NFL careers.

Continue to: before the 1988 study by Hawkins...

Before the 1988 study by Hawkins,¹¹ ankle spurs were removed with open procedures. Hawkins¹¹ used arthroscopy for better and safer visualization of the ankle joint and used a burr for less painful removal of spurs from the tibia and the talus. In 2002, a series of 105 patients (median age, 35 years) had reduced pain and improved function a minimum of 2 years after arthroscopic débridement.¹² These patients had a mix of pathology, including soft-tissue impingement, bony impingement, chondral lesions, loose bodies, and osteoarthritis.

For many elite athletes, anterior ankle impingement can cause significant limitation. Reduced ankle dorsiflexion can alter all limb mechanics and predispose athletes to injury.¹³ In addition, because NFL players’ ankle ROM often approaches or exceeds normal physiologic limits,¹⁴ an ankle ROM limitation will often hinder their performance.

Miyamoto and colleagues¹⁵ studied a series of 9 professional athletes (6 soccer players, 1 baseball pitcher, 1 mixed martial artist, 1 golfer) who underwent decompression of both anterior and posterior impingement. With regard to anterior impingement, they found anterior osteophytes in all the ankles, as was seen in the present study. Furthermore, they noted that mean dorsiflexion improved from 10° before surgery to 15° after surgery and that their athletes returned to play 12 to 15 weeks after surgery. Their results are similar to ours, though we noted more improvement in dorsiflexion, from 8.28° before surgery to 18.86° after surgery.

One of the most important metrics in evaluating treatment options for professional athletes is time from surgery to RTP without restrictions. Mean time to full RTP was shorter in our study (8.4 weeks) than in the study by Miyamoto and colleagues¹⁵ (up to 20 weeks). However, many of their procedures were performed during the off-season, when there was no need to expeditiously clear patients for full sports participation. In addition, the patients in their study had both anterior and posterior pathology.

Faster return to high-level athletics was supported in a study of 11 elite ballet dancers,¹⁶ whose pain and dance performance improved after arthroscopic débridement. Of the 11 patients, 9 returned to dance at a mean of 7 weeks after surgery; the other 2 required reoperation. Although the pathology differed in their study of elite professional soccer players, Calder and colleagues¹⁷ found that mean time to RTP after ankle arthroscopy for posterior impingement was 5 weeks.

Continue to: For the NFL players in our study...

For the NFL players in our study, RTP at their elite level was 100% after arthroscopic débridement of anterior ankle impingement. In the literature, time to RTP varies. Table 3 lists RTP rates for recreational athletes in published studies.^18-27 In their recent systematic literature review, Zwiers and colleagues¹⁰ noted that 24% to 96.4% of recreational athletes returned to play after arthroscopic treatment for anterior ankle impingement. The percentage was significantly higher for the professional athletes in our study. Historical comparison supports an evolution in the indications and techniques for this procedure, with more recent literature suggesting a RTP rate much higher than earlier rates. In addition, compared with recreational athletes, professional athletes have strong financial incentives to return to their sports. Furthermore, our professional cohort was significantly younger than the recreational cohorts in those studies.

Table 3. Frequency of Recreational Athletes’ Return to Play After Arthroscopic Débridement of Anterior Ankle Impingement, as Reported in the Literature

Current recommendations for recreational athletes include initial conservative treatment with rest, ankle bracing, and avoidance of jumping and other repetitive dorsiflexing activities. Physical therapy should include joint mobilization and work along the entire kinetic chain. Night splints or a removable walking boot can be used temporarily, as can a single intra-articular corticosteroid injection to reduce inflammation and evaluate improvement in more refractory cases.²⁸ Commonly, conservative treatments fail if patients remain active, and soft tissue and/or osteophytes can be resected, though resection typically is reserved for recreational athletes for whom nonoperative treatments have been exhausted.^29,30

This study had several limitations, including its retrospective nature and lack of control group. In addition, follow-up was relatively short, and we did not use more recently described outcome measures, such as the Sports subscale of the Foot and Ankle Ability Measure, which may be more sensitive in describing function in elite athletes. However, many of the cases in our study predated these measures, but the rate of RTP at the NFL level requires a very high degree of postoperative ankle function, making this outcome the most meaningful. In the context of professional athletes, specifically the length of their careers, our study results provide valuable information regarding expectations about RTP and the durability of arthroscopic débridement of anterior ankle impingement in a high-demand setting.

CONCLUSION

For all the NFL players in this study, arthroscopic débridement of anterior ankle impingement resulted in return to preoperative level of play at a mean of 2 months after surgery. There were significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM. Arthroscopic débridement of anterior ankle impingement relieves pain, restores ROM and function, and results in reliable RTP in professional football players.

Peripherally inserted central catheters (PICCs) are integral to the care of hospitalized patients in the United States.¹ Consequently, utilization of these devices in acutely ill patients has steadily increased in the past decade.² Although originally designed to support the delivery of total parenteral nutrition, PICCs have found broader applications in the hospital setting given the ease and safety of placement, the advances in technology that facilitate insertion, and the growing availability of specially trained vascular nurses that place these devices at the bedside.³ Furthermore, because they are placed in deeper veins of the arm, PICCs are more durable than peripheral catheters and can support venous access for extended durations.^4-6

However, the growing use of PICCs has led to the realization that these devices are not without attendant risks. For example, PICCs are associated with venous thromboembolism (VTE) and central-line associated blood stream infection (CLABSI).^7,8 Additionally, complications such as catheter occlusion and tip migration commonly occur and may interrupt care or necessitate device removal.^9-11 Hence, thoughtful weighing of the risks against the benefits of PICC use prior to placement is necessary. To facilitate such decision-making, we developed the Michigan Appropriateness Guide for Intravenous (IV) Catheters (MAGIC) criteria,¹² which is an evidence-based tool that defines when the use of a PICC is appropriate in hospitalized adults.

The use of PICCs for infusion of peripherally compatible therapies for 5 or fewer days is rated as inappropriate by MAGIC.¹² This strategy is also endorsed by the Centers for Disease Control and Prevention’s (CDC) guidelines for the prevention of catheter-related infections.¹³ Despite these recommendations, short-term PICC use remains common. For example, a study conducted at a tertiary pediatric care center reported a trend toward shorter PICC dwell times and increasing rates of early removal.² However, factors that prompt such short-term PICC use are poorly understood. Without understanding drivers and outcomes of short-term PICC use, interventions to prevent such practice are unlikely to succeed.

Therefore, by using data from a multicenter cohort study, we examined patterns of short-term PICC use and sought to identify which patient, provider, and device factors were associated with such use. We hypothesized that short-term placement would be associated with difficult venous access and would also be associated with the risk of major and minor complications.

Study Setting and Design

We used data from the Michigan Hospital Medicine Safety (HMS) Consortium to examine patterns and predictors of short-term PICC use.¹⁴ As a multi-institutional clinical quality initiative sponsored by Blue Cross Blue Shield of Michigan and Blue Care Network, HMS aims to improve the quality of care by preventing adverse events in hospitalized medical patients.^4,15-17 In January of 2014, dedicated, trained abstractors started collecting data on PICC placements at participating HMS hospitals by using a standard protocol and template for data collection. Patients who received PICCs while admitted to either a general medicine unit or an intensive care unit (ICU) during clinical care were eligible for inclusion. Patients were excluded if they were (a) under the age of 18 years, (b) pregnant, (c) admitted to a nonmedical service (eg, surgery), or (d) admitted under observation status.

Every 14 days, each hospital collected data on the first 17 eligible patients that received a PICC, with at least 7 of these placements occurring in an ICU setting. All patients were prospectively followed until the PICC was removed, death, or until 70 days after insertion, whichever occurred first. For patients who had their PICC removed prior to hospital discharge, follow-up occurred via a review of medical records. For those discharged with a PICC in place, both medical record review and telephone follow-up were performed. To ensure data quality, annual random audits at each participating hospital were performed by the coordinating center at the University of Michigan.

For this analysis, we included all available data as of June 30, 2016. However, HMS hospitals continue to collect data on PICC use and outcomes as part of an ongoing clinical quality initiative to reduce the incidence of PICC-related complications.

Patient, Provider, and Device Data

Patient characteristics, including demographics, detailed medical history, comorbidities, physical findings, laboratory results, and medications were abstracted directly from medical records. To estimate the comorbidity burden, the Charlson-Deyo comorbidity score was calculated for each patient by using data available in the medical record at the time of PICC placement.¹⁸ Data, such as the documented indication for PICC insertion and the reason for removal, were obtained directly from medical records. Provider characteristics, including the specialty of the attending physician at the time of insertion and the type of operator who inserted the PICC, were also collected. Institutional characteristics, such as total number of beds, teaching versus nonteaching, and urban versus rural, were obtained from hospital publicly reported data and semiannual surveys of HMS sites.^19,20 Data on device characteristics, such as catheter gauge, coating, insertion attempts, tip location, and number of lumens, were abstracted from PICC insertion notes.

Outcomes of Interest

The outcome of interest was short-term PICC use, defined as PICCs removed within 5 days of insertion. Patients who expired with a PICC in situ were excluded. Secondary outcomes of interest included PICC-related complications, categorized as major (eg, symptomatic VTE and CLABSI) or minor (eg, catheter occlusion, superficial thrombosis, mechanical complications [kinking, coiling], exit site infection, and tip migration). Symptomatic VTE was defined as clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) not present at the time of PICC placement and confirmed via imaging (ultrasound or venogram for DVT; computed tomography scan, ventilation perfusion scan, or pulmonary angiogram for PE). CLABSI was defined in accordance with the CDC’s National Healthcare Safety Network criteria or according to Infectious Diseases Society of America recommendations.^21,22 All minor PICC complications were defined in accordance with prior published definitions.⁴

Statistical Analysis

Cases of short-term PICC use were identified and compared with patients with a PICC dwell time of 6 or more days by patient, provider, and device characteristics. The initial analyses for the associations of putative factors with short-term PICC use were performed using χ2 or Wilcoxon tests for categorical and continuous variables, respectively. Univariable mixed effect logistic regression models (with a random hospital-specific intercept) were then used to control for hospital-level clustering. Next, a mixed effects multivariable logistic regression model was used to identify factors associated with short-term PICC use. Variables with P ≤ .25 were considered as candidate predictors for the final multivariable model, which was chosen through a stepwise variable selection algorithm performed on 1000 bootstrapped data sets.²³ Variables in the final model were retained based on their frequency of selection in the bootstrapped samples, significance level, and contribution to the overall model likelihood. Results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (CI). SAS for Windows (version 9.3, SAS Institute Inc., Cary, NC) was used for analyses.

Ethical and Regulatory Oversight

The study was classified as “not regulated” by the Institutional Review Board at the University of Michigan (HUM00078730).

Overall Characteristics of the Study Cohort

Characteristics of Short-Term Peripherally Inserted Central Catheter Use

Of the 15,397 PICCs included, we identified 3902 PICCs (25.3%) with a dwell time of ≤5 days (median = 3 days; IQR, 2-4 days). When compared to PICCs that were in place for longer durations, no significant differences in age or comorbidity scores were observed. Importantly, despite recommendations to avoid PICCs in patients with moderate to severe chronic kidney disease (glomerular filtration rate [GFR] ≤ 59 ml/min), 1292 (33.1%) short-term PICCs occurred in patients that met such criteria.

Among short-term PICCs, 3618 (92.7%) were power-capable devices, 2785 (71.4%) were 5-French, and 2813 (72.1%) were multilumen. Indications for the use of short-term PICCs differed from longer term devices in important ways (P <  .001). For example, the most common documented indication for short-term PICC use was difficult venous access (28.2%), while for long-term PICCs, it was antibiotic administration (39.8%). General internists and hospitalists were the most common attending physicians for patients with short-term and long-term PICCs (65.1% and 65.5%, respectively [P = .73]). Also, the proportion of critical care physicians responsible for patients with short versus long-term PICC use was similar (14.0% vs 15.0%, respectively [P = .123]). Of the short-term PICCs, 2583 (66.2%) were inserted by vascular access nurses, 795 (20.4%) by interventional radiologists, and 439 (11.3%) by advance practice professionals. Almost all of the PICCs placed ≤5 days (95.5%) were removed during hospitalization.

Complications Associated with Short-Term Peripherally Inserted Central Catheter Use

This large, multisite prospective cohort study is the first to examine patterns and predictors of short-term PICC use in hospitalized adults. By examining clinically granular data derived from the medical records of patients across 52 hospitals, we found that short-term use was common, representing 25% of all PICCs placed. Almost all such PICCs were removed prior to discharge, suggesting that they were placed primarily to meet acute needs during hospitalization. Multivariable models indicated that patients with difficult venous access, multilumen devices, and teaching hospital settings were associated with short-term use. Given that (a) short term PICC use is not recommended by published evidence-based guidelines,^12,13 (b) both major and minor complications were not uncommon despite brief exposure, and (c) specific factors might be targeted to avoid such use, strategies to improve PICC decision-making in the hospital appear increasingly necessary.

In our study, difficult venous access was the most common documented indication for short-term PICC placement. For patients in whom an anticipated catheter dwell time of 5 days or less is expected, MAGIC recommends the consideration of midline or peripheral IV catheters placed under ultrasound guidance.¹² A midline is a type of peripheral IV catheter that is about 7.5 cm to 25 cm in length and is typically inserted in the larger diameter veins of the upper extremity, such as the cephalic or basilic veins, with the tip terminating distal to the subclavian vein.^7,12 While there is a paucity of information that directly compares PICCs to midlines, some data suggest a lower risk of bloodstream infection and thrombosis associated with the latter.^24-26 For example, at one quaternary teaching hospital, house staff who are trained to insert midline catheters under ultrasound guidance in critically ill patients with difficult venous access reported no CLABSI and DVT events.²⁶

Interestingly, multilumen catheters were used twice as often as single lumen catheters in patients with short-term PICCs. In these instances, the use of additional lumens is questionable, as infusion of multiple incompatible fluids was not commonly listed as an indication prompting PICC use. Because multilumen PICCs are associated with higher risks of both VTE and CLABSI compared to single lumen devices, such use represents an important safety concern.^27-29 Institutional efforts that not only limit the use of multilumen PICCs but also fundamentally define when use of a PICC is appropriate may substantially improve outcomes related to vascular access.^28,30,31We observed that short-term PICCs were more common in teaching compared to nonteaching hospitals. While the design of the present study precludes understanding the reasons for such a difference, some plausible theories include the presence of physician trainees who may not appreciate the risks of PICC use, diminishing peripheral IV access securement skills, and the lack of alternatives to PICC use. Educating trainees who most often order PICCs in teaching settings as to when they should or should not consider this device may represent an important quality improvement opportunity.³² Similarly, auditing and assessing the clinical skills of those entrusted to place peripheral IVs might prove helpful.^33,34 Finally, the introduction of a midline program, or similar programs that expand the scope of vascular access teams to place alternative devices, should be explored as a means to improve PICC use and patient safety.

Our study also found that a third of patients who received PICCs for 5 or fewer days had moderate to severe chronic kidney disease. In these patients who may require renal replacement therapy, prior PICC placement is among the strongest predictors of arteriovenous fistula failure.^35,36 Therefore, even though national guidelines discourage the use of PICCs in these patients and recommend alternative routes of venous access,^12,37,38 such practice is clearly not happening. System-based interventions that begin by identifying patients who require vein preservation (eg, those with a GFR < 45 ml/min) and are therefore not appropriate for a PICC would be a welcomed first step in improving care for such patients.^37,38Our study has limitations. First, the observational nature of the study limits the ability to assess for causality or to account for the effects of unmeasured confounders. Second, while the use of medical records to collect granular data is valuable, differences in documentation patterns within and across hospitals, including patterns of missing data, may produce a misclassification of covariates or outcomes. Third, while we found that higher rates of short-term PICC use were associated with teaching hospitals and patients with difficult venous access, we were unable to determine the precise reasons for this practice trend. Qualitative or mixed-methods approaches to understand provider decision-making in these settings would be welcomed.

Our study also has several strengths. First, to our knowledge, this is the first study to systematically describe and evaluate patterns and predictors of short-term PICC use. The finding that PICCs placed for difficult venous access is a dominant category of short-term placement confirms clinical suspicions regarding inappropriate use and strengthens the need for pathways or protocols to manage such patients. Second, the inclusion of medical patients in diverse institutions offers not only real-world insights related to PICC use, but also offers findings that should be generalizable to other hospitals and health systems. Third, the use of a robust data collection strategy that emphasized standardized data collection, dedicated trained abstractors, and random audits to ensure data quality strengthen the findings of this work. Finally, our findings highlight an urgent need to develop policies related to PICC use, including limiting the use of multiple lumens and avoidance in patients with moderate to severe kidney disease.

In conclusion, short-term use of PICCs is prevalent and associated with key patient, provider, and device factors. Such use is also associated with complications, such as catheter occlusion, tip migration, VTE, and CLABSI. Limiting the use of multiple-lumen PICCs, enhancing education for when a PICC should be used, and defining strategies for patients with difficult access may help reduce inappropriate PICC use and improve patient safety. Future studies to examine implementation of such interventions would be welcomed.

Disclosure: Drs. Paje, Conlon, Swaminathan, and Boldenow disclose no conflicts of interest. Dr. Chopra has received honoraria for talks at hospitals as a visiting professor. Dr. Flanders discloses consultancies for the Institute for Healthcare Improvement and the Society of Hospital Medicine, royalties from Wiley Publishing, honoraria for various talks at hospitals as a visiting professor, grants from the CDC Foundation, Agency for Healthcare Research and Quality, Blue Cross Blue Shield of Michigan (BCBSM), and Michigan Hospital Association, and expert witness testimony. Dr. Bernstein discloses consultancies for Blue Care Network and grants from BCBSM, Department of Veterans Affairs, and National Institutes of Health. Dr. Kaatz discloses no relevant conflicts of interest. BCBSM and Blue Care Network provided support for the Michigan HMS Consortium as part of the BCBSM Value Partnerships program. Although BCBSM and HMS work collaboratively, the opinions, beliefs, and viewpoints expressed by the author do not necessarily reflect the opinions, beliefs, and viewpoints of BCBSM or any of its employees. Dr. Chopra is supported by a career development award from the Agency for Healthcare Research and Quality (1-K08-HS022835-01). BCBSM and Blue Care Network supported data collection at each participating site and funded the data coordinating center but had no role in study concept, interpretation of findings, or in the preparation, final approval, or decision to submit the manuscript.

Peripherally inserted central catheters (PICCs) are integral to the care of hospitalized patients in the United States.¹ Consequently, utilization of these devices in acutely ill patients has steadily increased in the past decade.² Although originally designed to support the delivery of total parenteral nutrition, PICCs have found broader applications in the hospital setting given the ease and safety of placement, the advances in technology that facilitate insertion, and the growing availability of specially trained vascular nurses that place these devices at the bedside.³ Furthermore, because they are placed in deeper veins of the arm, PICCs are more durable than peripheral catheters and can support venous access for extended durations.^4-6

However, the growing use of PICCs has led to the realization that these devices are not without attendant risks. For example, PICCs are associated with venous thromboembolism (VTE) and central-line associated blood stream infection (CLABSI).^7,8 Additionally, complications such as catheter occlusion and tip migration commonly occur and may interrupt care or necessitate device removal.^9-11 Hence, thoughtful weighing of the risks against the benefits of PICC use prior to placement is necessary. To facilitate such decision-making, we developed the Michigan Appropriateness Guide for Intravenous (IV) Catheters (MAGIC) criteria,¹² which is an evidence-based tool that defines when the use of a PICC is appropriate in hospitalized adults.

The use of PICCs for infusion of peripherally compatible therapies for 5 or fewer days is rated as inappropriate by MAGIC.¹² This strategy is also endorsed by the Centers for Disease Control and Prevention’s (CDC) guidelines for the prevention of catheter-related infections.¹³ Despite these recommendations, short-term PICC use remains common. For example, a study conducted at a tertiary pediatric care center reported a trend toward shorter PICC dwell times and increasing rates of early removal.² However, factors that prompt such short-term PICC use are poorly understood. Without understanding drivers and outcomes of short-term PICC use, interventions to prevent such practice are unlikely to succeed.

Therefore, by using data from a multicenter cohort study, we examined patterns of short-term PICC use and sought to identify which patient, provider, and device factors were associated with such use. We hypothesized that short-term placement would be associated with difficult venous access and would also be associated with the risk of major and minor complications.

Study Setting and Design

We used data from the Michigan Hospital Medicine Safety (HMS) Consortium to examine patterns and predictors of short-term PICC use.¹⁴ As a multi-institutional clinical quality initiative sponsored by Blue Cross Blue Shield of Michigan and Blue Care Network, HMS aims to improve the quality of care by preventing adverse events in hospitalized medical patients.^4,15-17 In January of 2014, dedicated, trained abstractors started collecting data on PICC placements at participating HMS hospitals by using a standard protocol and template for data collection. Patients who received PICCs while admitted to either a general medicine unit or an intensive care unit (ICU) during clinical care were eligible for inclusion. Patients were excluded if they were (a) under the age of 18 years, (b) pregnant, (c) admitted to a nonmedical service (eg, surgery), or (d) admitted under observation status.

Every 14 days, each hospital collected data on the first 17 eligible patients that received a PICC, with at least 7 of these placements occurring in an ICU setting. All patients were prospectively followed until the PICC was removed, death, or until 70 days after insertion, whichever occurred first. For patients who had their PICC removed prior to hospital discharge, follow-up occurred via a review of medical records. For those discharged with a PICC in place, both medical record review and telephone follow-up were performed. To ensure data quality, annual random audits at each participating hospital were performed by the coordinating center at the University of Michigan.

For this analysis, we included all available data as of June 30, 2016. However, HMS hospitals continue to collect data on PICC use and outcomes as part of an ongoing clinical quality initiative to reduce the incidence of PICC-related complications.

Patient, Provider, and Device Data

Patient characteristics, including demographics, detailed medical history, comorbidities, physical findings, laboratory results, and medications were abstracted directly from medical records. To estimate the comorbidity burden, the Charlson-Deyo comorbidity score was calculated for each patient by using data available in the medical record at the time of PICC placement.¹⁸ Data, such as the documented indication for PICC insertion and the reason for removal, were obtained directly from medical records. Provider characteristics, including the specialty of the attending physician at the time of insertion and the type of operator who inserted the PICC, were also collected. Institutional characteristics, such as total number of beds, teaching versus nonteaching, and urban versus rural, were obtained from hospital publicly reported data and semiannual surveys of HMS sites.^19,20 Data on device characteristics, such as catheter gauge, coating, insertion attempts, tip location, and number of lumens, were abstracted from PICC insertion notes.

Outcomes of Interest

The outcome of interest was short-term PICC use, defined as PICCs removed within 5 days of insertion. Patients who expired with a PICC in situ were excluded. Secondary outcomes of interest included PICC-related complications, categorized as major (eg, symptomatic VTE and CLABSI) or minor (eg, catheter occlusion, superficial thrombosis, mechanical complications [kinking, coiling], exit site infection, and tip migration). Symptomatic VTE was defined as clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) not present at the time of PICC placement and confirmed via imaging (ultrasound or venogram for DVT; computed tomography scan, ventilation perfusion scan, or pulmonary angiogram for PE). CLABSI was defined in accordance with the CDC’s National Healthcare Safety Network criteria or according to Infectious Diseases Society of America recommendations.^21,22 All minor PICC complications were defined in accordance with prior published definitions.⁴

Statistical Analysis

Cases of short-term PICC use were identified and compared with patients with a PICC dwell time of 6 or more days by patient, provider, and device characteristics. The initial analyses for the associations of putative factors with short-term PICC use were performed using χ2 or Wilcoxon tests for categorical and continuous variables, respectively. Univariable mixed effect logistic regression models (with a random hospital-specific intercept) were then used to control for hospital-level clustering. Next, a mixed effects multivariable logistic regression model was used to identify factors associated with short-term PICC use. Variables with P ≤ .25 were considered as candidate predictors for the final multivariable model, which was chosen through a stepwise variable selection algorithm performed on 1000 bootstrapped data sets.²³ Variables in the final model were retained based on their frequency of selection in the bootstrapped samples, significance level, and contribution to the overall model likelihood. Results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (CI). SAS for Windows (version 9.3, SAS Institute Inc., Cary, NC) was used for analyses.

Ethical and Regulatory Oversight

The study was classified as “not regulated” by the Institutional Review Board at the University of Michigan (HUM00078730).

Overall Characteristics of the Study Cohort

Characteristics of Short-Term Peripherally Inserted Central Catheter Use

Of the 15,397 PICCs included, we identified 3902 PICCs (25.3%) with a dwell time of ≤5 days (median = 3 days; IQR, 2-4 days). When compared to PICCs that were in place for longer durations, no significant differences in age or comorbidity scores were observed. Importantly, despite recommendations to avoid PICCs in patients with moderate to severe chronic kidney disease (glomerular filtration rate [GFR] ≤ 59 ml/min), 1292 (33.1%) short-term PICCs occurred in patients that met such criteria.

Among short-term PICCs, 3618 (92.7%) were power-capable devices, 2785 (71.4%) were 5-French, and 2813 (72.1%) were multilumen. Indications for the use of short-term PICCs differed from longer term devices in important ways (P <  .001). For example, the most common documented indication for short-term PICC use was difficult venous access (28.2%), while for long-term PICCs, it was antibiotic administration (39.8%). General internists and hospitalists were the most common attending physicians for patients with short-term and long-term PICCs (65.1% and 65.5%, respectively [P = .73]). Also, the proportion of critical care physicians responsible for patients with short versus long-term PICC use was similar (14.0% vs 15.0%, respectively [P = .123]). Of the short-term PICCs, 2583 (66.2%) were inserted by vascular access nurses, 795 (20.4%) by interventional radiologists, and 439 (11.3%) by advance practice professionals. Almost all of the PICCs placed ≤5 days (95.5%) were removed during hospitalization.

Complications Associated with Short-Term Peripherally Inserted Central Catheter Use

This large, multisite prospective cohort study is the first to examine patterns and predictors of short-term PICC use in hospitalized adults. By examining clinically granular data derived from the medical records of patients across 52 hospitals, we found that short-term use was common, representing 25% of all PICCs placed. Almost all such PICCs were removed prior to discharge, suggesting that they were placed primarily to meet acute needs during hospitalization. Multivariable models indicated that patients with difficult venous access, multilumen devices, and teaching hospital settings were associated with short-term use. Given that (a) short term PICC use is not recommended by published evidence-based guidelines,^12,13 (b) both major and minor complications were not uncommon despite brief exposure, and (c) specific factors might be targeted to avoid such use, strategies to improve PICC decision-making in the hospital appear increasingly necessary.

In our study, difficult venous access was the most common documented indication for short-term PICC placement. For patients in whom an anticipated catheter dwell time of 5 days or less is expected, MAGIC recommends the consideration of midline or peripheral IV catheters placed under ultrasound guidance.¹² A midline is a type of peripheral IV catheter that is about 7.5 cm to 25 cm in length and is typically inserted in the larger diameter veins of the upper extremity, such as the cephalic or basilic veins, with the tip terminating distal to the subclavian vein.^7,12 While there is a paucity of information that directly compares PICCs to midlines, some data suggest a lower risk of bloodstream infection and thrombosis associated with the latter.^24-26 For example, at one quaternary teaching hospital, house staff who are trained to insert midline catheters under ultrasound guidance in critically ill patients with difficult venous access reported no CLABSI and DVT events.²⁶

Interestingly, multilumen catheters were used twice as often as single lumen catheters in patients with short-term PICCs. In these instances, the use of additional lumens is questionable, as infusion of multiple incompatible fluids was not commonly listed as an indication prompting PICC use. Because multilumen PICCs are associated with higher risks of both VTE and CLABSI compared to single lumen devices, such use represents an important safety concern.^27-29 Institutional efforts that not only limit the use of multilumen PICCs but also fundamentally define when use of a PICC is appropriate may substantially improve outcomes related to vascular access.^28,30,31We observed that short-term PICCs were more common in teaching compared to nonteaching hospitals. While the design of the present study precludes understanding the reasons for such a difference, some plausible theories include the presence of physician trainees who may not appreciate the risks of PICC use, diminishing peripheral IV access securement skills, and the lack of alternatives to PICC use. Educating trainees who most often order PICCs in teaching settings as to when they should or should not consider this device may represent an important quality improvement opportunity.³² Similarly, auditing and assessing the clinical skills of those entrusted to place peripheral IVs might prove helpful.^33,34 Finally, the introduction of a midline program, or similar programs that expand the scope of vascular access teams to place alternative devices, should be explored as a means to improve PICC use and patient safety.

Our study also found that a third of patients who received PICCs for 5 or fewer days had moderate to severe chronic kidney disease. In these patients who may require renal replacement therapy, prior PICC placement is among the strongest predictors of arteriovenous fistula failure.^35,36 Therefore, even though national guidelines discourage the use of PICCs in these patients and recommend alternative routes of venous access,^12,37,38 such practice is clearly not happening. System-based interventions that begin by identifying patients who require vein preservation (eg, those with a GFR < 45 ml/min) and are therefore not appropriate for a PICC would be a welcomed first step in improving care for such patients.^37,38Our study has limitations. First, the observational nature of the study limits the ability to assess for causality or to account for the effects of unmeasured confounders. Second, while the use of medical records to collect granular data is valuable, differences in documentation patterns within and across hospitals, including patterns of missing data, may produce a misclassification of covariates or outcomes. Third, while we found that higher rates of short-term PICC use were associated with teaching hospitals and patients with difficult venous access, we were unable to determine the precise reasons for this practice trend. Qualitative or mixed-methods approaches to understand provider decision-making in these settings would be welcomed.

Our study also has several strengths. First, to our knowledge, this is the first study to systematically describe and evaluate patterns and predictors of short-term PICC use. The finding that PICCs placed for difficult venous access is a dominant category of short-term placement confirms clinical suspicions regarding inappropriate use and strengthens the need for pathways or protocols to manage such patients. Second, the inclusion of medical patients in diverse institutions offers not only real-world insights related to PICC use, but also offers findings that should be generalizable to other hospitals and health systems. Third, the use of a robust data collection strategy that emphasized standardized data collection, dedicated trained abstractors, and random audits to ensure data quality strengthen the findings of this work. Finally, our findings highlight an urgent need to develop policies related to PICC use, including limiting the use of multiple lumens and avoidance in patients with moderate to severe kidney disease.

In conclusion, short-term use of PICCs is prevalent and associated with key patient, provider, and device factors. Such use is also associated with complications, such as catheter occlusion, tip migration, VTE, and CLABSI. Limiting the use of multiple-lumen PICCs, enhancing education for when a PICC should be used, and defining strategies for patients with difficult access may help reduce inappropriate PICC use and improve patient safety. Future studies to examine implementation of such interventions would be welcomed.

Disclosure: Drs. Paje, Conlon, Swaminathan, and Boldenow disclose no conflicts of interest. Dr. Chopra has received honoraria for talks at hospitals as a visiting professor. Dr. Flanders discloses consultancies for the Institute for Healthcare Improvement and the Society of Hospital Medicine, royalties from Wiley Publishing, honoraria for various talks at hospitals as a visiting professor, grants from the CDC Foundation, Agency for Healthcare Research and Quality, Blue Cross Blue Shield of Michigan (BCBSM), and Michigan Hospital Association, and expert witness testimony. Dr. Bernstein discloses consultancies for Blue Care Network and grants from BCBSM, Department of Veterans Affairs, and National Institutes of Health. Dr. Kaatz discloses no relevant conflicts of interest. BCBSM and Blue Care Network provided support for the Michigan HMS Consortium as part of the BCBSM Value Partnerships program. Although BCBSM and HMS work collaboratively, the opinions, beliefs, and viewpoints expressed by the author do not necessarily reflect the opinions, beliefs, and viewpoints of BCBSM or any of its employees. Dr. Chopra is supported by a career development award from the Agency for Healthcare Research and Quality (1-K08-HS022835-01). BCBSM and Blue Care Network supported data collection at each participating site and funded the data coordinating center but had no role in study concept, interpretation of findings, or in the preparation, final approval, or decision to submit the manuscript.

Peripherally inserted central catheters (PICCs) are integral to the care of hospitalized patients in the United States.¹ Consequently, utilization of these devices in acutely ill patients has steadily increased in the past decade.² Although originally designed to support the delivery of total parenteral nutrition, PICCs have found broader applications in the hospital setting given the ease and safety of placement, the advances in technology that facilitate insertion, and the growing availability of specially trained vascular nurses that place these devices at the bedside.³ Furthermore, because they are placed in deeper veins of the arm, PICCs are more durable than peripheral catheters and can support venous access for extended durations.^4-6

However, the growing use of PICCs has led to the realization that these devices are not without attendant risks. For example, PICCs are associated with venous thromboembolism (VTE) and central-line associated blood stream infection (CLABSI).^7,8 Additionally, complications such as catheter occlusion and tip migration commonly occur and may interrupt care or necessitate device removal.^9-11 Hence, thoughtful weighing of the risks against the benefits of PICC use prior to placement is necessary. To facilitate such decision-making, we developed the Michigan Appropriateness Guide for Intravenous (IV) Catheters (MAGIC) criteria,¹² which is an evidence-based tool that defines when the use of a PICC is appropriate in hospitalized adults.

The use of PICCs for infusion of peripherally compatible therapies for 5 or fewer days is rated as inappropriate by MAGIC.¹² This strategy is also endorsed by the Centers for Disease Control and Prevention’s (CDC) guidelines for the prevention of catheter-related infections.¹³ Despite these recommendations, short-term PICC use remains common. For example, a study conducted at a tertiary pediatric care center reported a trend toward shorter PICC dwell times and increasing rates of early removal.² However, factors that prompt such short-term PICC use are poorly understood. Without understanding drivers and outcomes of short-term PICC use, interventions to prevent such practice are unlikely to succeed.

Therefore, by using data from a multicenter cohort study, we examined patterns of short-term PICC use and sought to identify which patient, provider, and device factors were associated with such use. We hypothesized that short-term placement would be associated with difficult venous access and would also be associated with the risk of major and minor complications.

Study Setting and Design

We used data from the Michigan Hospital Medicine Safety (HMS) Consortium to examine patterns and predictors of short-term PICC use.¹⁴ As a multi-institutional clinical quality initiative sponsored by Blue Cross Blue Shield of Michigan and Blue Care Network, HMS aims to improve the quality of care by preventing adverse events in hospitalized medical patients.^4,15-17 In January of 2014, dedicated, trained abstractors started collecting data on PICC placements at participating HMS hospitals by using a standard protocol and template for data collection. Patients who received PICCs while admitted to either a general medicine unit or an intensive care unit (ICU) during clinical care were eligible for inclusion. Patients were excluded if they were (a) under the age of 18 years, (b) pregnant, (c) admitted to a nonmedical service (eg, surgery), or (d) admitted under observation status.

Every 14 days, each hospital collected data on the first 17 eligible patients that received a PICC, with at least 7 of these placements occurring in an ICU setting. All patients were prospectively followed until the PICC was removed, death, or until 70 days after insertion, whichever occurred first. For patients who had their PICC removed prior to hospital discharge, follow-up occurred via a review of medical records. For those discharged with a PICC in place, both medical record review and telephone follow-up were performed. To ensure data quality, annual random audits at each participating hospital were performed by the coordinating center at the University of Michigan.

For this analysis, we included all available data as of June 30, 2016. However, HMS hospitals continue to collect data on PICC use and outcomes as part of an ongoing clinical quality initiative to reduce the incidence of PICC-related complications.

Patient, Provider, and Device Data

Patient characteristics, including demographics, detailed medical history, comorbidities, physical findings, laboratory results, and medications were abstracted directly from medical records. To estimate the comorbidity burden, the Charlson-Deyo comorbidity score was calculated for each patient by using data available in the medical record at the time of PICC placement.¹⁸ Data, such as the documented indication for PICC insertion and the reason for removal, were obtained directly from medical records. Provider characteristics, including the specialty of the attending physician at the time of insertion and the type of operator who inserted the PICC, were also collected. Institutional characteristics, such as total number of beds, teaching versus nonteaching, and urban versus rural, were obtained from hospital publicly reported data and semiannual surveys of HMS sites.^19,20 Data on device characteristics, such as catheter gauge, coating, insertion attempts, tip location, and number of lumens, were abstracted from PICC insertion notes.

Outcomes of Interest

The outcome of interest was short-term PICC use, defined as PICCs removed within 5 days of insertion. Patients who expired with a PICC in situ were excluded. Secondary outcomes of interest included PICC-related complications, categorized as major (eg, symptomatic VTE and CLABSI) or minor (eg, catheter occlusion, superficial thrombosis, mechanical complications [kinking, coiling], exit site infection, and tip migration). Symptomatic VTE was defined as clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) not present at the time of PICC placement and confirmed via imaging (ultrasound or venogram for DVT; computed tomography scan, ventilation perfusion scan, or pulmonary angiogram for PE). CLABSI was defined in accordance with the CDC’s National Healthcare Safety Network criteria or according to Infectious Diseases Society of America recommendations.^21,22 All minor PICC complications were defined in accordance with prior published definitions.⁴

Statistical Analysis

Cases of short-term PICC use were identified and compared with patients with a PICC dwell time of 6 or more days by patient, provider, and device characteristics. The initial analyses for the associations of putative factors with short-term PICC use were performed using χ2 or Wilcoxon tests for categorical and continuous variables, respectively. Univariable mixed effect logistic regression models (with a random hospital-specific intercept) were then used to control for hospital-level clustering. Next, a mixed effects multivariable logistic regression model was used to identify factors associated with short-term PICC use. Variables with P ≤ .25 were considered as candidate predictors for the final multivariable model, which was chosen through a stepwise variable selection algorithm performed on 1000 bootstrapped data sets.²³ Variables in the final model were retained based on their frequency of selection in the bootstrapped samples, significance level, and contribution to the overall model likelihood. Results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (CI). SAS for Windows (version 9.3, SAS Institute Inc., Cary, NC) was used for analyses.

Ethical and Regulatory Oversight

The study was classified as “not regulated” by the Institutional Review Board at the University of Michigan (HUM00078730).

Overall Characteristics of the Study Cohort

Characteristics of Short-Term Peripherally Inserted Central Catheter Use

Of the 15,397 PICCs included, we identified 3902 PICCs (25.3%) with a dwell time of ≤5 days (median = 3 days; IQR, 2-4 days). When compared to PICCs that were in place for longer durations, no significant differences in age or comorbidity scores were observed. Importantly, despite recommendations to avoid PICCs in patients with moderate to severe chronic kidney disease (glomerular filtration rate [GFR] ≤ 59 ml/min), 1292 (33.1%) short-term PICCs occurred in patients that met such criteria.

Among short-term PICCs, 3618 (92.7%) were power-capable devices, 2785 (71.4%) were 5-French, and 2813 (72.1%) were multilumen. Indications for the use of short-term PICCs differed from longer term devices in important ways (P <  .001). For example, the most common documented indication for short-term PICC use was difficult venous access (28.2%), while for long-term PICCs, it was antibiotic administration (39.8%). General internists and hospitalists were the most common attending physicians for patients with short-term and long-term PICCs (65.1% and 65.5%, respectively [P = .73]). Also, the proportion of critical care physicians responsible for patients with short versus long-term PICC use was similar (14.0% vs 15.0%, respectively [P = .123]). Of the short-term PICCs, 2583 (66.2%) were inserted by vascular access nurses, 795 (20.4%) by interventional radiologists, and 439 (11.3%) by advance practice professionals. Almost all of the PICCs placed ≤5 days (95.5%) were removed during hospitalization.

Complications Associated with Short-Term Peripherally Inserted Central Catheter Use

This large, multisite prospective cohort study is the first to examine patterns and predictors of short-term PICC use in hospitalized adults. By examining clinically granular data derived from the medical records of patients across 52 hospitals, we found that short-term use was common, representing 25% of all PICCs placed. Almost all such PICCs were removed prior to discharge, suggesting that they were placed primarily to meet acute needs during hospitalization. Multivariable models indicated that patients with difficult venous access, multilumen devices, and teaching hospital settings were associated with short-term use. Given that (a) short term PICC use is not recommended by published evidence-based guidelines,^12,13 (b) both major and minor complications were not uncommon despite brief exposure, and (c) specific factors might be targeted to avoid such use, strategies to improve PICC decision-making in the hospital appear increasingly necessary.

In our study, difficult venous access was the most common documented indication for short-term PICC placement. For patients in whom an anticipated catheter dwell time of 5 days or less is expected, MAGIC recommends the consideration of midline or peripheral IV catheters placed under ultrasound guidance.¹² A midline is a type of peripheral IV catheter that is about 7.5 cm to 25 cm in length and is typically inserted in the larger diameter veins of the upper extremity, such as the cephalic or basilic veins, with the tip terminating distal to the subclavian vein.^7,12 While there is a paucity of information that directly compares PICCs to midlines, some data suggest a lower risk of bloodstream infection and thrombosis associated with the latter.^24-26 For example, at one quaternary teaching hospital, house staff who are trained to insert midline catheters under ultrasound guidance in critically ill patients with difficult venous access reported no CLABSI and DVT events.²⁶

Interestingly, multilumen catheters were used twice as often as single lumen catheters in patients with short-term PICCs. In these instances, the use of additional lumens is questionable, as infusion of multiple incompatible fluids was not commonly listed as an indication prompting PICC use. Because multilumen PICCs are associated with higher risks of both VTE and CLABSI compared to single lumen devices, such use represents an important safety concern.^27-29 Institutional efforts that not only limit the use of multilumen PICCs but also fundamentally define when use of a PICC is appropriate may substantially improve outcomes related to vascular access.^28,30,31We observed that short-term PICCs were more common in teaching compared to nonteaching hospitals. While the design of the present study precludes understanding the reasons for such a difference, some plausible theories include the presence of physician trainees who may not appreciate the risks of PICC use, diminishing peripheral IV access securement skills, and the lack of alternatives to PICC use. Educating trainees who most often order PICCs in teaching settings as to when they should or should not consider this device may represent an important quality improvement opportunity.³² Similarly, auditing and assessing the clinical skills of those entrusted to place peripheral IVs might prove helpful.^33,34 Finally, the introduction of a midline program, or similar programs that expand the scope of vascular access teams to place alternative devices, should be explored as a means to improve PICC use and patient safety.

Our study also found that a third of patients who received PICCs for 5 or fewer days had moderate to severe chronic kidney disease. In these patients who may require renal replacement therapy, prior PICC placement is among the strongest predictors of arteriovenous fistula failure.^35,36 Therefore, even though national guidelines discourage the use of PICCs in these patients and recommend alternative routes of venous access,^12,37,38 such practice is clearly not happening. System-based interventions that begin by identifying patients who require vein preservation (eg, those with a GFR < 45 ml/min) and are therefore not appropriate for a PICC would be a welcomed first step in improving care for such patients.^37,38Our study has limitations. First, the observational nature of the study limits the ability to assess for causality or to account for the effects of unmeasured confounders. Second, while the use of medical records to collect granular data is valuable, differences in documentation patterns within and across hospitals, including patterns of missing data, may produce a misclassification of covariates or outcomes. Third, while we found that higher rates of short-term PICC use were associated with teaching hospitals and patients with difficult venous access, we were unable to determine the precise reasons for this practice trend. Qualitative or mixed-methods approaches to understand provider decision-making in these settings would be welcomed.

Our study also has several strengths. First, to our knowledge, this is the first study to systematically describe and evaluate patterns and predictors of short-term PICC use. The finding that PICCs placed for difficult venous access is a dominant category of short-term placement confirms clinical suspicions regarding inappropriate use and strengthens the need for pathways or protocols to manage such patients. Second, the inclusion of medical patients in diverse institutions offers not only real-world insights related to PICC use, but also offers findings that should be generalizable to other hospitals and health systems. Third, the use of a robust data collection strategy that emphasized standardized data collection, dedicated trained abstractors, and random audits to ensure data quality strengthen the findings of this work. Finally, our findings highlight an urgent need to develop policies related to PICC use, including limiting the use of multiple lumens and avoidance in patients with moderate to severe kidney disease.

In conclusion, short-term use of PICCs is prevalent and associated with key patient, provider, and device factors. Such use is also associated with complications, such as catheter occlusion, tip migration, VTE, and CLABSI. Limiting the use of multiple-lumen PICCs, enhancing education for when a PICC should be used, and defining strategies for patients with difficult access may help reduce inappropriate PICC use and improve patient safety. Future studies to examine implementation of such interventions would be welcomed.

Disclosure: Drs. Paje, Conlon, Swaminathan, and Boldenow disclose no conflicts of interest. Dr. Chopra has received honoraria for talks at hospitals as a visiting professor. Dr. Flanders discloses consultancies for the Institute for Healthcare Improvement and the Society of Hospital Medicine, royalties from Wiley Publishing, honoraria for various talks at hospitals as a visiting professor, grants from the CDC Foundation, Agency for Healthcare Research and Quality, Blue Cross Blue Shield of Michigan (BCBSM), and Michigan Hospital Association, and expert witness testimony. Dr. Bernstein discloses consultancies for Blue Care Network and grants from BCBSM, Department of Veterans Affairs, and National Institutes of Health. Dr. Kaatz discloses no relevant conflicts of interest. BCBSM and Blue Care Network provided support for the Michigan HMS Consortium as part of the BCBSM Value Partnerships program. Although BCBSM and HMS work collaboratively, the opinions, beliefs, and viewpoints expressed by the author do not necessarily reflect the opinions, beliefs, and viewpoints of BCBSM or any of its employees. Dr. Chopra is supported by a career development award from the Agency for Healthcare Research and Quality (1-K08-HS022835-01). BCBSM and Blue Care Network supported data collection at each participating site and funded the data coordinating center but had no role in study concept, interpretation of findings, or in the preparation, final approval, or decision to submit the manuscript.

The “weekend effect” refers to the association between weekend hospital admissions and poorer outcomes, such as higher mortality rates. Analysis of National Health Service claims data from the United Kingdom suggested a 10% increase in 30-day mortality in patients admitted on Saturdays and 15% in patients admitted on Sundays,¹ leading to the push for a 7-day work week and invoking controversial changes in their junior doctor (residency) working contract. Studies in the United States highlighting differences in outcomes for patients admitted on weekends compared to weekdays have mostly focused on specific diagnoses and results have been variable. Few have gone on to look at the association of weekend hospital admissions on cost^2,3 and length of stay³ but results are overall inconclusive. Some have suggested that such poorer outcomes for patients admitted on weekends are due to reduced staffing and delayed procedures on weekends compared to weekdays, although this has been debated.⁴ The lack of consensus has made it difficult for hospitals to plan if and how to expand weekend manpower or services.

In the United States, increase in mortality rate for patients admitted on weekends has been demonstrated for a range of diagnoses, including pulmonary embolism,⁵ intracerebral hemorrhage,⁶ upper gastrointestinal hemorrhage,^7,8 ruptured aortic aneurysm,⁹ heart failure,¹⁰ and acute kidney injury.¹¹ However, other diagnoses such as atrial flutter or fibrillation,² hip fractures,¹² ischemic stroke,¹³ and esophageal variceal hemorrhage,¹⁴ show no difference in mortality between weekday and weekend admissions. Yet, other conditions such as myocardial infarction^15,16 and subarachnoid hemorrhage^17,18 have multiple studies with conflicting results. None of these studies have comprehensively looked at the effect of weekend admissions across all diagnoses nor compared the effect size between common diagnoses in the United States using the same risk adjustment. Reporting of differences in length of stay and cost is also rare.

We postulated that the weekend admissions are associated with increased mortality and length of stay, but that the effect would be heterogeneous between different diagnosis groups. Using a large nationally representative inpatient database, we investigated the association between weekend versus weekday admissions on in-hospital mortality, length of stay, and cost for acute hospitalizations in the United States. We performed subgroup analyses of the top 20 diagnoses to determine which diagnoses, if any, should be targeted for expanded weekend manpower or services.

Data Sources

We used information from the National Inpatient Sample (NIS) database for this study,¹⁹ which is the largest all-payer inpatient healthcare database in the United States. It contains administrative claims information on a 20% stratified sample of discharges from all hospitals participating in the Healthcare Cost and Utilization Project (HCUP), which includes over 90% of hospitals and 95% of discharges in the country. The NIS contains clinical and nonclinical data elements, including diagnoses, severity and comorbidity measures, demographics, admission characteristics, and charges.

Study Patients

The study included all patients who were 18 years or older and were admitted to hospitals participating in HCUP from 2012 to 2014. Elective or planned admissions were excluded from this study because of the anticipated degree of unmeasured confounding that would be present between patients electively admitted on weekends compared to weekdays.

Study Variables

The primary exposure variable was admission on weekends (defined as Friday midnight to Sunday midnight) compared to the rest of the week. The primary outcome variable was in-hospital mortality. The secondary outcome variables were length of stay (measured in integer days) and cost. Length of stay was compared only using only patients who survived the hospital admission to eliminate the effect of death in shortening the length of stay. Cost was calculated by using charges available in the NIS and multiplied by the accompanying cost-to-charge ratios. Charges reflect total amount that hospitals billed for services but do not reflect how much these services actually cost. The HCUP cost-to-charge ratios are hospital-specific data based on hospital accounting reports collected by the Centers for Medicare & Medicaid Services.¹⁹

Covariates included age, sex, race, income, payer, presence or absence of comorbidities as defined by the Elixhauser comorbidity index,²⁰ risk of mortality, and severity of illness scores as defined by the 3M Health Information Systems.²¹ Mortality risk and severity of illness groups are defined by using a proprietary iterative process developed by 3M Health Information Systems using International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) principal and secondary diagnosis codes and procedure codes, age, sex, and discharge disposition, evaluated with historical data.²¹ Severity of illness refers to the extent of physiologic decompensation or loss of function of an organ system, whereas risk of mortality refers to the likelihood of dying.

Statistical Analysis

We compared patient characteristics and other covariates between patients emergently admitted on weekends and weekdays. Continuous variables that were not normally distributed were either categorized (age, risk of mortality, and severity of illness scores) or log-transformed if right skewed (length of stay and cost). Categorical data were reported as percentages and continuous data as medians (interquartile range). We compared the inpatient mortality rate between weekend and weekday admissions by using χ² tests. Multivariable logistic regression was used to adjust for covariates of age, gender, race, payer, income, risk of mortality and severity of illness scores, number of comorbidities, and the presence or absence of each of the 29 comorbidities available in the database to determine an adjusted odds ratio (OR), P values, and confidence intervals (CIs).

We also compared the length of stay amongst survivors and costs between weekend and weekday admissions. Multivariable linear regression was applied to the natural log of these outcome variables and the coefficients exponentiated to determine the difference in length of stay and cost of weekend admissions as compared to weekday. Covariates in the model were the same as those used for the primary outcome.

To determine if particular diagnoses had a pronounced weekend effect, the above analyses were repeated in subgroups of the top 20 most prevalent diagnoses on weekends by using the Clinical Classifications Software for ICD-9-CM diagnosis groups. For subgroup analyses, a Bonferroni correction was used, so P values of <.0025 were considered significant.

Statistical analyses were performed by using SAS version 9.4 (SAS Institute Inc, Cary, NC). All regression models were run using PROC SURVEYREG for continuous outcomes and PROC SURVEYLOGISTIC for binary outcomes to account for the sampling structure of NIS. Two-sided P values of .05 were considered significant, apart from the Bonferroni correction applied to the subgroup analysis. As this study involved publicly available deidentified data, our study was exempt from institutional board review.

Patient Characteristics

Mortality

The crude in-hospital mortality rate was 2.8% for patients admitted on weekends and 2.5% for patients admitted on weekdays (unadjusted OR, 1.110; 95% CI, 1.105-1.113; P < .0001). This relationship was attenuated after adjustment for demographics, severity, and comorbidities, but remained statistically significant (OR 1.029; 95% CI, 1.020-1.039; P < .0001; Table 2), which corresponds to an adjusted risk difference of 0.07% increase in mortality of weekend admissions. The OR for mortality on weekends compared to weekdays was further calculated for each of the top 20 diagnoses (Table 3). Out of all the diagnosis groups, only 1 (urinary tract infection) had a statistically significant P value after Bonferroni correction. We also looked separately at patients who were electively admitted—there was a highly significant OR of mortality of 1.67 (95% CI, 1.60-1.74). Patients classified as elective admissions were excluded for subsequent analyses.

Length of Stay

Cost

The magnitude of association between weekend admissions and mortality in this large administrative database contradicts existing literature, which some believe conclusively proves the international phenomenon of the weekend effect.^22,23 However, our results support a minimal increase in odds of death of 2.9%, with no consistent effect amongst the top 20 diagnoses. Only 1 diagnosis group (urinary tract infection) showed a statistically significant increase in mortality, which could be due to chance. In contrast, the policy-influencing paper in the United Kingdom reports that patients admitted on Saturdays and Sundays have an increased risk of death of 10% and 15%, respectively, compared to patients admitted on Wednesdays.²⁴ They also repeated their measurements on a United Health Care Systems database, comprising 254 leading managed care hospitals in the US, over a time period of 3 months in 2010, and found a hazard ratio of 1.18 (95% CI, 1.11-1.26). Ruiz et al.²² combined almost 3 million medical records from 28 metropolitan hospitals in 5 different countries in the Global Comparators Project, including 5 in the United States, and showed increased mortality on weekends in all countries, concluding that the weekend effect is a systematic phenomenon.

There are several possible explanations for differences in our findings. Freemantle’s study differed to ours by comparing outcomes of weekends to an index of Wednesday; they also found an increased mortality on Mondays and Fridays, which could suggest the presence of residual confounding and doubt as to whether Wednesday is the ideal control group. A further difference is the definition of mortality—we looked at in-hospital mortality, as compared to 30-day mortality. In addition, Freemantle’s study included elective admissions. When we looked at the effect of weekend admissions on mortality, we found a highly significant OR of 1.67, compared to 1.03 in emergency admissions. We attributed this discrepancy to unmeasured confounding, such as preference of physicians or difference in classification of elective admissions in different hospitals. Because of significant effect modification of elective compared to emergency admissions, we decided to restrict our analysis to emergency admissions only. This also enabled direct associations with potential policy recommendations on whether to expand weekend clinical care, which is most relevant to emergency admissions. Finally, the Global Comparators Project only samples a small proportion of hospitals in each country, leading to limited generalizability; in addition, international comparisons are difficult to interpret due to differing health systems.

The overall and diagnosis-specific difference in length of stay was small and of doubtful clinical significance. With an adjusted decrease in length of stay in patients admitted on weekends of 2.24%, when applied to a median length of stay of 3 days, it translates into a 1.7-hour difference in length of stay. However, there was striking heterogeneity noted between diagnoses, with a difference ranging from 8.91% decrease in length of stay (mood disorders) to 7.14% increase in length of stay (nonspecific chest pain), which is likely to explain the overall small magnitude of effect. We noted that the diagnoses associated with increased length of stay for weekend admissions tended to be those requiring inpatient procedures or investigations, such as acute myocardial infarction (3.90% increase), acute cerebrovascular disease (2.15% increase), cardiac dysrhythmias (1.39% increase), nonspecific chest pain (7.14% increase), and biliary tract disease (4.88% increase). As hospitals often do not provide certain nonemergent procedures or investigations on weekends, delay in procedures or investigations may explain the increase in length of stay. These include percutaneous coronary intervention or stress testing for evaluation of cardiac ischemia and endoscopic procedures for biliary tract disease and gastrointestinal hemorrhage. It must, however, be noted in conjunction that numerous studies have established higher complication rates when nonemergent surgeries are performed out of hours or on weekends.^25-28 Therefore, we suggest further studies to compare the effect of weekends on increased procedural complications as to any morbidity caused by increased length of stay, which the present dataset was unable to capture. Another potential explanation for the heterogeneity in length of stay could be the greater availability of caregivers to assist with discharge on weekends, such as for patients admitted for mood disorders.

Surprisingly, weekend admissions appeared to be less costly than weekday admissions overall. Because of the large sample size, very minor differences in cost are likely to be statistically significant. Indeed, for the absolute difference of 0.45%, given a median cost of $6562 on weekends, this only represents a cost saving of approximately $30 per patient admission. There was also heterogeneity observed amongst the different diagnosis groups, and cerebrovascular disease, biliary tract disease and gastrointestinal hemorrhage, which were also associated with increase length of stay, were associated with an increased cost. However, our study is unable to establish causation, and differences in staffing numbers and reimbursement on weekends may confound cost estimates. We propose that further studies using hospital databases with greater granularity in data are necessary to determine the etiology of cost differences between weekends and weekdays.

Our study’s key strengths are the large sample size and generalizability to the US. As a large administrative database, we recognize the likelihood of inconsistencies in hospital coding for covariates, diagnoses, and charges, which may lead to misclassification bias. The NIS definition of weekend (Friday midnight to Sunday midnight) may differ from other definitions of weekend; ideally Friday 5 pm to Monday 8 am may be more clinically representative. This cohort of hospital admissions also does not account for the day of presentation to the emergency department, but rather only the day that ward admission was documented. The variable delays in emergency department, for example if emergency departments are busier on weekends, leading to delays in ward admission, may confound our results. Our exclusion of elective admissions was dependent on the administrative coding of elective versus emergency admissions, of which the definition may differ between hospitals. Finally, despite adjustment on clinical and sociodemographic covariates, there is a possibility of residual confounding in this retrospective comparison between weekend and weekday admissions.

Our study does not suggest that system-wide policies to increase weekend service coverage will impact mortality, although effects on length of stay and cost are inconclusive. Hospitals wishing to improve coverage may consider focusing on procedural diagnoses as listed above which may shorten length of stay, although the out-of-hours complication rate should be carefully monitored.

Disclosure

The authors declare no conflicts of interest.

The “weekend effect” refers to the association between weekend hospital admissions and poorer outcomes, such as higher mortality rates. Analysis of National Health Service claims data from the United Kingdom suggested a 10% increase in 30-day mortality in patients admitted on Saturdays and 15% in patients admitted on Sundays,¹ leading to the push for a 7-day work week and invoking controversial changes in their junior doctor (residency) working contract. Studies in the United States highlighting differences in outcomes for patients admitted on weekends compared to weekdays have mostly focused on specific diagnoses and results have been variable. Few have gone on to look at the association of weekend hospital admissions on cost^2,3 and length of stay³ but results are overall inconclusive. Some have suggested that such poorer outcomes for patients admitted on weekends are due to reduced staffing and delayed procedures on weekends compared to weekdays, although this has been debated.⁴ The lack of consensus has made it difficult for hospitals to plan if and how to expand weekend manpower or services.

In the United States, increase in mortality rate for patients admitted on weekends has been demonstrated for a range of diagnoses, including pulmonary embolism,⁵ intracerebral hemorrhage,⁶ upper gastrointestinal hemorrhage,^7,8 ruptured aortic aneurysm,⁹ heart failure,¹⁰ and acute kidney injury.¹¹ However, other diagnoses such as atrial flutter or fibrillation,² hip fractures,¹² ischemic stroke,¹³ and esophageal variceal hemorrhage,¹⁴ show no difference in mortality between weekday and weekend admissions. Yet, other conditions such as myocardial infarction^15,16 and subarachnoid hemorrhage^17,18 have multiple studies with conflicting results. None of these studies have comprehensively looked at the effect of weekend admissions across all diagnoses nor compared the effect size between common diagnoses in the United States using the same risk adjustment. Reporting of differences in length of stay and cost is also rare.

We postulated that the weekend admissions are associated with increased mortality and length of stay, but that the effect would be heterogeneous between different diagnosis groups. Using a large nationally representative inpatient database, we investigated the association between weekend versus weekday admissions on in-hospital mortality, length of stay, and cost for acute hospitalizations in the United States. We performed subgroup analyses of the top 20 diagnoses to determine which diagnoses, if any, should be targeted for expanded weekend manpower or services.

Data Sources

We used information from the National Inpatient Sample (NIS) database for this study,¹⁹ which is the largest all-payer inpatient healthcare database in the United States. It contains administrative claims information on a 20% stratified sample of discharges from all hospitals participating in the Healthcare Cost and Utilization Project (HCUP), which includes over 90% of hospitals and 95% of discharges in the country. The NIS contains clinical and nonclinical data elements, including diagnoses, severity and comorbidity measures, demographics, admission characteristics, and charges.

Study Patients

The study included all patients who were 18 years or older and were admitted to hospitals participating in HCUP from 2012 to 2014. Elective or planned admissions were excluded from this study because of the anticipated degree of unmeasured confounding that would be present between patients electively admitted on weekends compared to weekdays.

Study Variables

The primary exposure variable was admission on weekends (defined as Friday midnight to Sunday midnight) compared to the rest of the week. The primary outcome variable was in-hospital mortality. The secondary outcome variables were length of stay (measured in integer days) and cost. Length of stay was compared only using only patients who survived the hospital admission to eliminate the effect of death in shortening the length of stay. Cost was calculated by using charges available in the NIS and multiplied by the accompanying cost-to-charge ratios. Charges reflect total amount that hospitals billed for services but do not reflect how much these services actually cost. The HCUP cost-to-charge ratios are hospital-specific data based on hospital accounting reports collected by the Centers for Medicare & Medicaid Services.¹⁹

Covariates included age, sex, race, income, payer, presence or absence of comorbidities as defined by the Elixhauser comorbidity index,²⁰ risk of mortality, and severity of illness scores as defined by the 3M Health Information Systems.²¹ Mortality risk and severity of illness groups are defined by using a proprietary iterative process developed by 3M Health Information Systems using International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) principal and secondary diagnosis codes and procedure codes, age, sex, and discharge disposition, evaluated with historical data.²¹ Severity of illness refers to the extent of physiologic decompensation or loss of function of an organ system, whereas risk of mortality refers to the likelihood of dying.

Statistical Analysis

We compared patient characteristics and other covariates between patients emergently admitted on weekends and weekdays. Continuous variables that were not normally distributed were either categorized (age, risk of mortality, and severity of illness scores) or log-transformed if right skewed (length of stay and cost). Categorical data were reported as percentages and continuous data as medians (interquartile range). We compared the inpatient mortality rate between weekend and weekday admissions by using χ² tests. Multivariable logistic regression was used to adjust for covariates of age, gender, race, payer, income, risk of mortality and severity of illness scores, number of comorbidities, and the presence or absence of each of the 29 comorbidities available in the database to determine an adjusted odds ratio (OR), P values, and confidence intervals (CIs).

We also compared the length of stay amongst survivors and costs between weekend and weekday admissions. Multivariable linear regression was applied to the natural log of these outcome variables and the coefficients exponentiated to determine the difference in length of stay and cost of weekend admissions as compared to weekday. Covariates in the model were the same as those used for the primary outcome.

To determine if particular diagnoses had a pronounced weekend effect, the above analyses were repeated in subgroups of the top 20 most prevalent diagnoses on weekends by using the Clinical Classifications Software for ICD-9-CM diagnosis groups. For subgroup analyses, a Bonferroni correction was used, so P values of <.0025 were considered significant.

Statistical analyses were performed by using SAS version 9.4 (SAS Institute Inc, Cary, NC). All regression models were run using PROC SURVEYREG for continuous outcomes and PROC SURVEYLOGISTIC for binary outcomes to account for the sampling structure of NIS. Two-sided P values of .05 were considered significant, apart from the Bonferroni correction applied to the subgroup analysis. As this study involved publicly available deidentified data, our study was exempt from institutional board review.

Patient Characteristics

Mortality

The crude in-hospital mortality rate was 2.8% for patients admitted on weekends and 2.5% for patients admitted on weekdays (unadjusted OR, 1.110; 95% CI, 1.105-1.113; P < .0001). This relationship was attenuated after adjustment for demographics, severity, and comorbidities, but remained statistically significant (OR 1.029; 95% CI, 1.020-1.039; P < .0001; Table 2), which corresponds to an adjusted risk difference of 0.07% increase in mortality of weekend admissions. The OR for mortality on weekends compared to weekdays was further calculated for each of the top 20 diagnoses (Table 3). Out of all the diagnosis groups, only 1 (urinary tract infection) had a statistically significant P value after Bonferroni correction. We also looked separately at patients who were electively admitted—there was a highly significant OR of mortality of 1.67 (95% CI, 1.60-1.74). Patients classified as elective admissions were excluded for subsequent analyses.

Length of Stay

Cost

The magnitude of association between weekend admissions and mortality in this large administrative database contradicts existing literature, which some believe conclusively proves the international phenomenon of the weekend effect.^22,23 However, our results support a minimal increase in odds of death of 2.9%, with no consistent effect amongst the top 20 diagnoses. Only 1 diagnosis group (urinary tract infection) showed a statistically significant increase in mortality, which could be due to chance. In contrast, the policy-influencing paper in the United Kingdom reports that patients admitted on Saturdays and Sundays have an increased risk of death of 10% and 15%, respectively, compared to patients admitted on Wednesdays.²⁴ They also repeated their measurements on a United Health Care Systems database, comprising 254 leading managed care hospitals in the US, over a time period of 3 months in 2010, and found a hazard ratio of 1.18 (95% CI, 1.11-1.26). Ruiz et al.²² combined almost 3 million medical records from 28 metropolitan hospitals in 5 different countries in the Global Comparators Project, including 5 in the United States, and showed increased mortality on weekends in all countries, concluding that the weekend effect is a systematic phenomenon.

There are several possible explanations for differences in our findings. Freemantle’s study differed to ours by comparing outcomes of weekends to an index of Wednesday; they also found an increased mortality on Mondays and Fridays, which could suggest the presence of residual confounding and doubt as to whether Wednesday is the ideal control group. A further difference is the definition of mortality—we looked at in-hospital mortality, as compared to 30-day mortality. In addition, Freemantle’s study included elective admissions. When we looked at the effect of weekend admissions on mortality, we found a highly significant OR of 1.67, compared to 1.03 in emergency admissions. We attributed this discrepancy to unmeasured confounding, such as preference of physicians or difference in classification of elective admissions in different hospitals. Because of significant effect modification of elective compared to emergency admissions, we decided to restrict our analysis to emergency admissions only. This also enabled direct associations with potential policy recommendations on whether to expand weekend clinical care, which is most relevant to emergency admissions. Finally, the Global Comparators Project only samples a small proportion of hospitals in each country, leading to limited generalizability; in addition, international comparisons are difficult to interpret due to differing health systems.

The overall and diagnosis-specific difference in length of stay was small and of doubtful clinical significance. With an adjusted decrease in length of stay in patients admitted on weekends of 2.24%, when applied to a median length of stay of 3 days, it translates into a 1.7-hour difference in length of stay. However, there was striking heterogeneity noted between diagnoses, with a difference ranging from 8.91% decrease in length of stay (mood disorders) to 7.14% increase in length of stay (nonspecific chest pain), which is likely to explain the overall small magnitude of effect. We noted that the diagnoses associated with increased length of stay for weekend admissions tended to be those requiring inpatient procedures or investigations, such as acute myocardial infarction (3.90% increase), acute cerebrovascular disease (2.15% increase), cardiac dysrhythmias (1.39% increase), nonspecific chest pain (7.14% increase), and biliary tract disease (4.88% increase). As hospitals often do not provide certain nonemergent procedures or investigations on weekends, delay in procedures or investigations may explain the increase in length of stay. These include percutaneous coronary intervention or stress testing for evaluation of cardiac ischemia and endoscopic procedures for biliary tract disease and gastrointestinal hemorrhage. It must, however, be noted in conjunction that numerous studies have established higher complication rates when nonemergent surgeries are performed out of hours or on weekends.^25-28 Therefore, we suggest further studies to compare the effect of weekends on increased procedural complications as to any morbidity caused by increased length of stay, which the present dataset was unable to capture. Another potential explanation for the heterogeneity in length of stay could be the greater availability of caregivers to assist with discharge on weekends, such as for patients admitted for mood disorders.

Surprisingly, weekend admissions appeared to be less costly than weekday admissions overall. Because of the large sample size, very minor differences in cost are likely to be statistically significant. Indeed, for the absolute difference of 0.45%, given a median cost of $6562 on weekends, this only represents a cost saving of approximately $30 per patient admission. There was also heterogeneity observed amongst the different diagnosis groups, and cerebrovascular disease, biliary tract disease and gastrointestinal hemorrhage, which were also associated with increase length of stay, were associated with an increased cost. However, our study is unable to establish causation, and differences in staffing numbers and reimbursement on weekends may confound cost estimates. We propose that further studies using hospital databases with greater granularity in data are necessary to determine the etiology of cost differences between weekends and weekdays.

Our study’s key strengths are the large sample size and generalizability to the US. As a large administrative database, we recognize the likelihood of inconsistencies in hospital coding for covariates, diagnoses, and charges, which may lead to misclassification bias. The NIS definition of weekend (Friday midnight to Sunday midnight) may differ from other definitions of weekend; ideally Friday 5 pm to Monday 8 am may be more clinically representative. This cohort of hospital admissions also does not account for the day of presentation to the emergency department, but rather only the day that ward admission was documented. The variable delays in emergency department, for example if emergency departments are busier on weekends, leading to delays in ward admission, may confound our results. Our exclusion of elective admissions was dependent on the administrative coding of elective versus emergency admissions, of which the definition may differ between hospitals. Finally, despite adjustment on clinical and sociodemographic covariates, there is a possibility of residual confounding in this retrospective comparison between weekend and weekday admissions.

Our study does not suggest that system-wide policies to increase weekend service coverage will impact mortality, although effects on length of stay and cost are inconclusive. Hospitals wishing to improve coverage may consider focusing on procedural diagnoses as listed above which may shorten length of stay, although the out-of-hours complication rate should be carefully monitored.

Disclosure

The authors declare no conflicts of interest.

The “weekend effect” refers to the association between weekend hospital admissions and poorer outcomes, such as higher mortality rates. Analysis of National Health Service claims data from the United Kingdom suggested a 10% increase in 30-day mortality in patients admitted on Saturdays and 15% in patients admitted on Sundays,¹ leading to the push for a 7-day work week and invoking controversial changes in their junior doctor (residency) working contract. Studies in the United States highlighting differences in outcomes for patients admitted on weekends compared to weekdays have mostly focused on specific diagnoses and results have been variable. Few have gone on to look at the association of weekend hospital admissions on cost^2,3 and length of stay³ but results are overall inconclusive. Some have suggested that such poorer outcomes for patients admitted on weekends are due to reduced staffing and delayed procedures on weekends compared to weekdays, although this has been debated.⁴ The lack of consensus has made it difficult for hospitals to plan if and how to expand weekend manpower or services.

In the United States, increase in mortality rate for patients admitted on weekends has been demonstrated for a range of diagnoses, including pulmonary embolism,⁵ intracerebral hemorrhage,⁶ upper gastrointestinal hemorrhage,^7,8 ruptured aortic aneurysm,⁹ heart failure,¹⁰ and acute kidney injury.¹¹ However, other diagnoses such as atrial flutter or fibrillation,² hip fractures,¹² ischemic stroke,¹³ and esophageal variceal hemorrhage,¹⁴ show no difference in mortality between weekday and weekend admissions. Yet, other conditions such as myocardial infarction^15,16 and subarachnoid hemorrhage^17,18 have multiple studies with conflicting results. None of these studies have comprehensively looked at the effect of weekend admissions across all diagnoses nor compared the effect size between common diagnoses in the United States using the same risk adjustment. Reporting of differences in length of stay and cost is also rare.

We postulated that the weekend admissions are associated with increased mortality and length of stay, but that the effect would be heterogeneous between different diagnosis groups. Using a large nationally representative inpatient database, we investigated the association between weekend versus weekday admissions on in-hospital mortality, length of stay, and cost for acute hospitalizations in the United States. We performed subgroup analyses of the top 20 diagnoses to determine which diagnoses, if any, should be targeted for expanded weekend manpower or services.

Data Sources

We used information from the National Inpatient Sample (NIS) database for this study,¹⁹ which is the largest all-payer inpatient healthcare database in the United States. It contains administrative claims information on a 20% stratified sample of discharges from all hospitals participating in the Healthcare Cost and Utilization Project (HCUP), which includes over 90% of hospitals and 95% of discharges in the country. The NIS contains clinical and nonclinical data elements, including diagnoses, severity and comorbidity measures, demographics, admission characteristics, and charges.

Study Patients

The study included all patients who were 18 years or older and were admitted to hospitals participating in HCUP from 2012 to 2014. Elective or planned admissions were excluded from this study because of the anticipated degree of unmeasured confounding that would be present between patients electively admitted on weekends compared to weekdays.

Study Variables

The primary exposure variable was admission on weekends (defined as Friday midnight to Sunday midnight) compared to the rest of the week. The primary outcome variable was in-hospital mortality. The secondary outcome variables were length of stay (measured in integer days) and cost. Length of stay was compared only using only patients who survived the hospital admission to eliminate the effect of death in shortening the length of stay. Cost was calculated by using charges available in the NIS and multiplied by the accompanying cost-to-charge ratios. Charges reflect total amount that hospitals billed for services but do not reflect how much these services actually cost. The HCUP cost-to-charge ratios are hospital-specific data based on hospital accounting reports collected by the Centers for Medicare & Medicaid Services.¹⁹

Covariates included age, sex, race, income, payer, presence or absence of comorbidities as defined by the Elixhauser comorbidity index,²⁰ risk of mortality, and severity of illness scores as defined by the 3M Health Information Systems.²¹ Mortality risk and severity of illness groups are defined by using a proprietary iterative process developed by 3M Health Information Systems using International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) principal and secondary diagnosis codes and procedure codes, age, sex, and discharge disposition, evaluated with historical data.²¹ Severity of illness refers to the extent of physiologic decompensation or loss of function of an organ system, whereas risk of mortality refers to the likelihood of dying.

Statistical Analysis

We compared patient characteristics and other covariates between patients emergently admitted on weekends and weekdays. Continuous variables that were not normally distributed were either categorized (age, risk of mortality, and severity of illness scores) or log-transformed if right skewed (length of stay and cost). Categorical data were reported as percentages and continuous data as medians (interquartile range). We compared the inpatient mortality rate between weekend and weekday admissions by using χ² tests. Multivariable logistic regression was used to adjust for covariates of age, gender, race, payer, income, risk of mortality and severity of illness scores, number of comorbidities, and the presence or absence of each of the 29 comorbidities available in the database to determine an adjusted odds ratio (OR), P values, and confidence intervals (CIs).

We also compared the length of stay amongst survivors and costs between weekend and weekday admissions. Multivariable linear regression was applied to the natural log of these outcome variables and the coefficients exponentiated to determine the difference in length of stay and cost of weekend admissions as compared to weekday. Covariates in the model were the same as those used for the primary outcome.

To determine if particular diagnoses had a pronounced weekend effect, the above analyses were repeated in subgroups of the top 20 most prevalent diagnoses on weekends by using the Clinical Classifications Software for ICD-9-CM diagnosis groups. For subgroup analyses, a Bonferroni correction was used, so P values of <.0025 were considered significant.

Statistical analyses were performed by using SAS version 9.4 (SAS Institute Inc, Cary, NC). All regression models were run using PROC SURVEYREG for continuous outcomes and PROC SURVEYLOGISTIC for binary outcomes to account for the sampling structure of NIS. Two-sided P values of .05 were considered significant, apart from the Bonferroni correction applied to the subgroup analysis. As this study involved publicly available deidentified data, our study was exempt from institutional board review.

Patient Characteristics

Mortality

The crude in-hospital mortality rate was 2.8% for patients admitted on weekends and 2.5% for patients admitted on weekdays (unadjusted OR, 1.110; 95% CI, 1.105-1.113; P < .0001). This relationship was attenuated after adjustment for demographics, severity, and comorbidities, but remained statistically significant (OR 1.029; 95% CI, 1.020-1.039; P < .0001; Table 2), which corresponds to an adjusted risk difference of 0.07% increase in mortality of weekend admissions. The OR for mortality on weekends compared to weekdays was further calculated for each of the top 20 diagnoses (Table 3). Out of all the diagnosis groups, only 1 (urinary tract infection) had a statistically significant P value after Bonferroni correction. We also looked separately at patients who were electively admitted—there was a highly significant OR of mortality of 1.67 (95% CI, 1.60-1.74). Patients classified as elective admissions were excluded for subsequent analyses.

Length of Stay

Cost

The magnitude of association between weekend admissions and mortality in this large administrative database contradicts existing literature, which some believe conclusively proves the international phenomenon of the weekend effect.^22,23 However, our results support a minimal increase in odds of death of 2.9%, with no consistent effect amongst the top 20 diagnoses. Only 1 diagnosis group (urinary tract infection) showed a statistically significant increase in mortality, which could be due to chance. In contrast, the policy-influencing paper in the United Kingdom reports that patients admitted on Saturdays and Sundays have an increased risk of death of 10% and 15%, respectively, compared to patients admitted on Wednesdays.²⁴ They also repeated their measurements on a United Health Care Systems database, comprising 254 leading managed care hospitals in the US, over a time period of 3 months in 2010, and found a hazard ratio of 1.18 (95% CI, 1.11-1.26). Ruiz et al.²² combined almost 3 million medical records from 28 metropolitan hospitals in 5 different countries in the Global Comparators Project, including 5 in the United States, and showed increased mortality on weekends in all countries, concluding that the weekend effect is a systematic phenomenon.

There are several possible explanations for differences in our findings. Freemantle’s study differed to ours by comparing outcomes of weekends to an index of Wednesday; they also found an increased mortality on Mondays and Fridays, which could suggest the presence of residual confounding and doubt as to whether Wednesday is the ideal control group. A further difference is the definition of mortality—we looked at in-hospital mortality, as compared to 30-day mortality. In addition, Freemantle’s study included elective admissions. When we looked at the effect of weekend admissions on mortality, we found a highly significant OR of 1.67, compared to 1.03 in emergency admissions. We attributed this discrepancy to unmeasured confounding, such as preference of physicians or difference in classification of elective admissions in different hospitals. Because of significant effect modification of elective compared to emergency admissions, we decided to restrict our analysis to emergency admissions only. This also enabled direct associations with potential policy recommendations on whether to expand weekend clinical care, which is most relevant to emergency admissions. Finally, the Global Comparators Project only samples a small proportion of hospitals in each country, leading to limited generalizability; in addition, international comparisons are difficult to interpret due to differing health systems.

The overall and diagnosis-specific difference in length of stay was small and of doubtful clinical significance. With an adjusted decrease in length of stay in patients admitted on weekends of 2.24%, when applied to a median length of stay of 3 days, it translates into a 1.7-hour difference in length of stay. However, there was striking heterogeneity noted between diagnoses, with a difference ranging from 8.91% decrease in length of stay (mood disorders) to 7.14% increase in length of stay (nonspecific chest pain), which is likely to explain the overall small magnitude of effect. We noted that the diagnoses associated with increased length of stay for weekend admissions tended to be those requiring inpatient procedures or investigations, such as acute myocardial infarction (3.90% increase), acute cerebrovascular disease (2.15% increase), cardiac dysrhythmias (1.39% increase), nonspecific chest pain (7.14% increase), and biliary tract disease (4.88% increase). As hospitals often do not provide certain nonemergent procedures or investigations on weekends, delay in procedures or investigations may explain the increase in length of stay. These include percutaneous coronary intervention or stress testing for evaluation of cardiac ischemia and endoscopic procedures for biliary tract disease and gastrointestinal hemorrhage. It must, however, be noted in conjunction that numerous studies have established higher complication rates when nonemergent surgeries are performed out of hours or on weekends.^25-28 Therefore, we suggest further studies to compare the effect of weekends on increased procedural complications as to any morbidity caused by increased length of stay, which the present dataset was unable to capture. Another potential explanation for the heterogeneity in length of stay could be the greater availability of caregivers to assist with discharge on weekends, such as for patients admitted for mood disorders.

Surprisingly, weekend admissions appeared to be less costly than weekday admissions overall. Because of the large sample size, very minor differences in cost are likely to be statistically significant. Indeed, for the absolute difference of 0.45%, given a median cost of $6562 on weekends, this only represents a cost saving of approximately $30 per patient admission. There was also heterogeneity observed amongst the different diagnosis groups, and cerebrovascular disease, biliary tract disease and gastrointestinal hemorrhage, which were also associated with increase length of stay, were associated with an increased cost. However, our study is unable to establish causation, and differences in staffing numbers and reimbursement on weekends may confound cost estimates. We propose that further studies using hospital databases with greater granularity in data are necessary to determine the etiology of cost differences between weekends and weekdays.

Our study’s key strengths are the large sample size and generalizability to the US. As a large administrative database, we recognize the likelihood of inconsistencies in hospital coding for covariates, diagnoses, and charges, which may lead to misclassification bias. The NIS definition of weekend (Friday midnight to Sunday midnight) may differ from other definitions of weekend; ideally Friday 5 pm to Monday 8 am may be more clinically representative. This cohort of hospital admissions also does not account for the day of presentation to the emergency department, but rather only the day that ward admission was documented. The variable delays in emergency department, for example if emergency departments are busier on weekends, leading to delays in ward admission, may confound our results. Our exclusion of elective admissions was dependent on the administrative coding of elective versus emergency admissions, of which the definition may differ between hospitals. Finally, despite adjustment on clinical and sociodemographic covariates, there is a possibility of residual confounding in this retrospective comparison between weekend and weekday admissions.

Our study does not suggest that system-wide policies to increase weekend service coverage will impact mortality, although effects on length of stay and cost are inconclusive. Hospitals wishing to improve coverage may consider focusing on procedural diagnoses as listed above which may shorten length of stay, although the out-of-hours complication rate should be carefully monitored.

Disclosure

The authors declare no conflicts of interest.

Alcohol use disorders (AUDs) are common, with an estimated lifetime prevalence of 17.8% for alcohol dependence.¹ Alcohol misuse is costly, accounting for $24.6 billion in annual healthcare expenditures, including $5.1 billion for alcohol-related hospitalizations.² A number of trials have demonstrated that naltrexone can help patients with AUDs maintain abstinence or diminish heavy drinking.^3-10 A recent meta-analysis of pharmacotherapy trials for patients with AUDs reported that for patients using 50 mg of naltrexone daily, the number needed to treat was 12 to prevent a return to heavy drinking and 20 to prevent a return to any drinking.¹¹ Despite good evidence for its effectiveness, naltrexone is not prescribed to the majority of patients with AUDs. In a study of veterans with AUDs cared for in the Veterans Affairs health system, only 1.9% of patients were prescribed naltrexone over the 6-month study period.¹² A 2003 survey of 2 professional organizations for addiction treatment specialists reported that a mean of 13% of providers prescribed naltrexone to their patients.¹³

When naltrexone is prescribed, it is most frequently in the outpatient setting.^3-10 Data for initiation of naltrexone in the inpatient setting are more limited. Wei et al.¹⁴ reported on the implementation of a discharge protocol, including counseling about naltrexone, for hospitalized patients with AUDs at an urban academic medical center. They reported a significant increase in the prescription of naltrexone to eligible patients by the time of discharge that was associated with a significant decrease in 30-day readmissions. Initiation of naltrexone in the inpatient versus the outpatient setting has some potential advantages. First, patients hospitalized for alcohol withdrawal have AUDs, obviating the need for screening. Second, the outpatient trials of naltrexone typically required 3 days of sobriety before initiation, which is generally achieved during hospitalization for detoxification or withdrawal.

Previous work at our institution centered on standardizing the process of evaluating patients needing alcohol detoxification at the time of referral for admission.¹⁵ The use of a standardized protocol reduced the number of inpatient admissions for alcohol-related diagnoses but had no effect on the 30-day readmission rate (28%) for those patients who were hospitalized. Our hospitalist group had no standardized process for discharging hospitalized patients with AUDs, and the discharge process rarely included counseling on medications for maintenance of sobriety. In this manuscript, we describe the implementation and impact of a process for counseling patients hospitalized for alcohol detoxification or withdrawal about naltrexone for maintenance of sobriety by the time of hospital discharge.

Study Setting

The University of North Carolina (UNC) Hospitals is an 803-bed tertiary academic center. UNC Hospital Medicine is staffed by 29 physicians and 3 advanced practice providers (APPs). During the study period, there were 3 hospital medicine services at UNC Hospitals with a combined average daily census of approximately 40 patients, and each service was staffed by one attending physician every day of the week and one APP Monday through Friday.

Study Design

We used a pre-post study design, in which we implemented a new process for standardizing the discharge of hospitalized patients with AUDs, including a process for counseling about naltrexone by the time of discharge. We sought and received institutional review board (IRB) approval for this study (UNC IRB 15-1441).

Interventions

We formed an improvement team that included 3 physicians and an APP in hospital medicine, a general internist and a psychiatrist, both with expertise in the use of medications for maintenance of sobriety, the director of UNC’s Alcohol and Substance Abuse Program, and 2 case managers. The team developed a number of interventions, including group education, a process for patient identification, and algorithms for counseling about, prescribing, and documenting the discussion of naltrexone.

Group Education

We presented evidence about medications for the maintenance of sobriety at a regularly scheduled hospitalist meeting. An hour-long session on motivational interviewing techniques was also presented at a separate meeting. All created algorithms were circulated to the group electronically and posted at workstations in the hospitalist work area. As data were generated postimplementation, control charts of process measures were created, posted in the hospitalist work area, and presented at subsequent group meetings.

Identification of Patients

We focused our interventions on patients admitted for alcohol detoxification or withdrawal (including withdrawal seizures). We asked our group to preferentially admit these patients to 1 of our 3 hospitalists services, on which the service APP (K.S.) was also an improvement team member.

Creation of Algorithms and Scripts for Counseling

We created a simple algorithm for evaluating patients for naltrexone. We recommended that all patients admitted for alcohol detoxification or withdrawal be counseled about naltrexone for the maintenance of sobriety before discharge. The contraindications to naltrexone we included were (1) concurrent opioid use, (2) documented cirrhosis, and/or (3) liver function tests greater than 3 times the upper limit of normal by the time of hospital discharge.

We also created a suggested script for motivational interviewing (supplemental Appendix 1). This was presented at a group meeting and circulated via e-mail. The actual counseling technique and process was left up to individual providers. In practice, counseling took place in the course of daily rounds, generally the day before or day of hospital discharge.

Prescription of Medication

For interested patients without contraindications, we recommended a prescription of naltrexone at 50 mg daily for 3 months. For patients prescribed naltrexone without medical insurance (n = 17), we utilized our existing pharmacy assistance program, whereby discharging patients can obtain an initial 14-day supply after applying to the program and then can fill subsequent prescriptions if they meet program financial requirements.

Follow-up Appointments

For patients with established outpatient providers, we asked patients to schedule follow-up appointments within a month of discharge. Patients prescribed naltrexone without primary providers (n = 16) were eligible for an existing program, the UNC Transitions Program, whereby patients identified as having moderate-to-high risk of hospital readmission can receive a follow-up appointment at UNC Internal Medicine or UNC Family Medicine within 2 weeks of discharge.

Creation of “Smart Phrases”

To aid in documentation, we created “smart phrases” (easily accessed, previously created phrases that can be adopted by all users) within the hospital electronic health record. We created one smart phrase for documentation of counseling about naltrexone, which included dropdown menus for contraindications and the patient’s preference and one for discharge instructions for patients started on naltrexone (supplemental Appendix 2).

Implementation

After the presentation of suggested interventions in July 2015 and the subsequent dissemination of educational materials, we implemented our new process on August 1, 2015.

Data Collection

Patients were identified for inclusion in the study analysis by querying UNC Hospitals’ billing database for the inpatient diagnosis codes (diagnosis-related groupings) 896 and 897, “alcohol/drug abuse or dependence without rehabilitation therapy,” with and without major comorbidity or complication, respectively, and with hospital medicine as the discharging service. All encounters were then manually reviewed by 2 investigators (J.S. and C.M.). Encounters were included if the history and physical indicated that the primary reason for admission was alcohol detoxification or withdrawal. Encounters with other primary reasons for admission (eg, pancreatitis, gastrointestinal bleeding) were excluded. For patients with multiple encounters, only the first eligible encounter in the pre- and/or postimplementation period was included. Comorbidities for identified patients were assessed via the search of study encounters for the International Classification of Diseases, 9th Revision-Clinical Modification codes for hypertension, anxiety, depression, cirrhosis, diabetes, and congestive heart failure.

Process, Outcomes, and Balancing Measures

The study process measures included the percentage of patients hospitalized for alcohol detoxification or withdrawal with documentation of counseling about naltrexone by the time of discharge, before and after process intervention. Documentation was defined as the description of counseling about naltrexone in the discharge summary or progress notes of identified encounters. We also measured the percentage of patients started on naltrexone before and after intervention. Lastly, we measured the percentage of patients prescribed naltrexone who filled at least 1 prescription for the medication, assessed by calls to the pharmacy where the medication was prescribed. Prescriptions that could not be confirmed (ie, paper rather than electronic prescriptions) were counted as not filled.

For outcome measures, we recorded the percentages of study patients who returned to the emergency department (ED) and were readmitted to UNC Hospitals (inpatient or observation) for any reason within 30 days of discharge. These outcomes were determined by a manual chart review.

In order to ensure the new process was not associated with delays in patient discharge, we measured the mean length of stay in days for study patient encounters before and after intervention as a balancing measure.

Statistical Analysis

Demographic and clinical characteristics for included patients were compared for the 16 months preimplementation (April 1, 2014 through July 31, 2015) and the 19 months postimplementation (August 1, 2015 through February 28, 2017). Descriptive statistics were calculated by using the Student t test for continuous variables and the χ² test for dichotomous variables. We used multivariate logistic regression to evaluate the associations between the intervention arms (pre- vs postintervention) and study outcomes, adjusting for age, gender, race, insurance type, and medical comorbidities. We chose these variables for inclusion based on their association with study outcomes at the P ≤ .20 level in bivariate analyses. P < .05 was considered statistically significant. All analyses were performed by using Stata version 13.1 (StataCorp LLC, College Station, TX).

For 2 process measures, the percentages of patients counseled about and started on naltrexone, we plotted consecutive samples of 10 patients before and after intervention on a control chart, using preintervention data to calculate means and control limits.

Subgroup Analysis

We used multivariate logistic regression to evaluate the associations between counseling versus no counseling and prescription of naltrexone versus no prescription for study outcomes in the postintervention subgroup, adjusting for age, gender, race, insurance type, and medical comorbidities.

Patients

We identified 188 preimplementation encounters and excluded 12 patients (6.4%) for primary admission reasons other than alcohol withdrawal or detoxification and 48 (25.5%) repeat hospitalizations, leaving 128 unique patient encounters. We identified 166 postimplementation encounters and excluded 25 (15.1%) hospitalizations for admission reason and 27 repeat hospitalizations (16.3%), leaving 114 unique patient encounters (flow diagram in supplemental Appendix 3). The most common admission reason for the exclusion of encounters was withdrawal from a substance other than alcohol (supplemental Appendix 4). The percentages of encounters excluded in preimplementation and postimplementation periods were similar at 31.9% and 31.4%, respectively.

The majority of patients were male and white, and almost half were uninsured (Table 1). There were no demographic differences between patients in the pre- versus postimplementation groups. For studied comorbidities, postintervention patients were more likely to have hypertension, anxiety, and depression.

Process Measures

Among those counseled about naltrexone before discharge, 34 of 74 patients (45.9%) had no contraindications to naltrexone and were interested in taking the medication. Among the 40 patients who were counseled about but not prescribed naltrexone, 19 (47.5%) declined, 9 (22.5%) had liver function tests elevated more than 3 times the upper limit of the reference range, 9 (22.5%) had concurrent opiate use, and 3 (7.5%) had multiple contraindications.

Among the 34 patients who were prescribed naltrexone, 25 (73.5%) filled at least 1 prescription as confirmed by phone call to the relevant pharmacy.

Outcome Measures

Subgroup Analysis

Balancing Measure

The mean length of stay for all patient encounters was 3.3 days. There were no differences in length of stay comparing pre- with postintervention patient encounters (Table 1) or those postintervention patients counseled versus not counseled (Table 2).

Our study demonstrates that counseling about medications for the maintenance of sobriety can be implemented as part of the routine care of hospitalized patients with AUDs. In our experience, about half of the patients counseled had no contraindications to naltrexone and were willing to take it at discharge. Almost three-fourths of those who were prescribed naltrexone filled the prescription at least once. The counseling process was not associated with increased length of stay. In the adjusted analysis, postintervention patients had significantly lower odds of 30-day ED returns. Additionally, in subgroup analysis, postintervention patients counseled about naltrexone had significantly lower rates of subsequent healthcare utilization compared with those not counseled, with absolute differences of 26% for ED revisits and 22% for rehospitalizations within 30 days.

The failure to demonstrate a difference in adjusted rehospitalization rates in the postintervention versus the preintervention group has several possible explanations. First, we had incomplete fidelity to our interventions, documenting counseling about naltrexone before discharge in over 60% of postintervention patients, raising the possibility that better fidelity may have resulted in improved outcomes. Related to this, only 28% of postintervention patients were prescribed naltrexone, which may be an inadequate sample size to demonstrate positive effects from the medication. Another possible explanation is that the postintervention group had higher rates of some of the comorbidities we assessed, namely, anxiety, depression, and hypertension, which could have negatively impacted the effectiveness of the interventions to prevent rehospitalization; however, after adjusting for comorbidities, the odds of rehospitalization were still not significantly different. It is interesting that the odds of postintervention ED revisits (but not rehospitalizations) were lower in the adjusted analysis. It may be that patients who revisit the ED and are not rehospitalized are different in important ways from those who are readmitted. Alternately, the larger number of ED revisits overall (about twice the rate of rehospitalization) may have made it easier to identify positive effects from the intervention for this outcome than rehospitalization (ie, the study may have been underpowered to detect a relatively small reduction in rehospitalization). It is also possible, however, that the interventions were simply insufficient to prevent rehospitalization.

The subgroup analysis, however, did find significant differences in both outcome measures for postintervention patients counseled versus not counseled about naltrexone before discharge. There are several possible explanations for these results. First, there may have been unmeasured differences in those counseled versus not counseled that explain the reductions observed in subsequent healthcare utilization. For example, the counseled patients could have been more motivated to change and, thus, more readily approached by providers for counseling. The lack of any demographic differences between the 2 groups and the relative simplicity of the counseling part of the intervention occurring as part of daily rounds argue against this hypothesis, but there are many potential unmeasured confounders (eg, homelessness, ability to afford medications), and this possibility remains. A second possible explanation is that patients counseled about naltrexone could have been more likely than those not counseled to seek subsequent care at other institutions. A third possibility is that that the counseling about (and prescribing when appropriate) naltrexone itself led to the observed decreases in subsequent ED visits and hospitalizations. This hypothesis would have been more supported had we been able to demonstrate a statistically significant reduction in healthcare utilization in those prescribed versus not prescribed naltrexone. But there were nonsignificant trends in the reduction of ED revisits and rehospitalizations among those prescribed the medication, suggesting we may have been able to demonstrate statistically significant reductions with a larger sample size.

Comparing our results with existing literature is challenging. The majority of randomized trials of naltrexone for AUDs were conducted in the outpatient setting.^3-10 Most of these trials utilized some type of psychosocial intervention in addition to naltrexone.^3-5,8-10 The 1 prior naltrexone study we identified conducted in the inpatient setting by Wei et al.¹⁴ is the most similar to our study. The authors reported the effects of a new process for assessing hospitalized patients with AUDs, including the use of a discharge planning tool for all patients admitted with alcohol dependence. The discharge tool included prompts for naltrexone in appropriate patients. The measured outcomes included the percentage of eligible patients prescribed naltrexone at discharge and the percentages of ED revisits and rehospitalizations within 30 days. Postintervention, 64% of eligible patients were prescribed naltrexone compared with 0% before, very similar to our results. There were significant decreases among all discharged patients with alcohol dependence for 30-day ED revisits (18.8% pre- vs 6.1% postimplementation) and rehospitalizations (23.4% vs 8.2%). The study differed from ours in a number of important respects, including a location in a large urban setting and implementation on a teaching service rather than an attending-only hospitalist service. Additionally, the authors studied 1 month of process implementation and compared it to another month 1 year before the new process, with an overall smaller sample size of 64 patients before and 49 patients after implementation. Potential reasons why Wei et al.¹⁴ were able to document lower rehospitalization rates postintervention when we did not include the differences in patient population (eg, high homeless rate, lower percentage of female patients in Wei study) and secular trends unrelated to interventions in either study.

Limitations of our study include the nonrandomized and uncontrolled design, which introduces the possibility of unmeasured confounding factors leading to the decrease we observed in healthcare utilization. Additionally, the single-center design precludes our ability to assess for healthcare utilization outcomes in other nearby facilities. We had incomplete implementation of our new process, counseling just over 60% of patients. As our primary outcomes relied on documentation in the medical record, both undersampling (not documenting some interventions) and reporting bias (being more likely to record positive sessions from intervention) are possible. Lastly, despite a moderate total sample size of almost 250 patients, the relatively small numbers of patients who were actually prescribed naltrexone in our study lessens our ability to show direct impact.

In conclusion, our study demonstrates a practical process for counseling about and prescribing naltrexone to patients hospitalized for alcohol detoxification or withdrawal. We demonstrate that many of these patients will be interested in starting naltrexone at discharge and will reliably fill the prescriptions if written. Counseling was associated with a significant reduction in subsequent healthcare utilization. These results have a wide potential impact given the ubiquitous nature of AUDs among hospitalized patients in community and academic settings.

Disclosure

The authors have no conflicts of interest relevant to this article to disclose. There were no sources of funding for this work.

Alcohol use disorders (AUDs) are common, with an estimated lifetime prevalence of 17.8% for alcohol dependence.¹ Alcohol misuse is costly, accounting for $24.6 billion in annual healthcare expenditures, including $5.1 billion for alcohol-related hospitalizations.² A number of trials have demonstrated that naltrexone can help patients with AUDs maintain abstinence or diminish heavy drinking.^3-10 A recent meta-analysis of pharmacotherapy trials for patients with AUDs reported that for patients using 50 mg of naltrexone daily, the number needed to treat was 12 to prevent a return to heavy drinking and 20 to prevent a return to any drinking.¹¹ Despite good evidence for its effectiveness, naltrexone is not prescribed to the majority of patients with AUDs. In a study of veterans with AUDs cared for in the Veterans Affairs health system, only 1.9% of patients were prescribed naltrexone over the 6-month study period.¹² A 2003 survey of 2 professional organizations for addiction treatment specialists reported that a mean of 13% of providers prescribed naltrexone to their patients.¹³

When naltrexone is prescribed, it is most frequently in the outpatient setting.^3-10 Data for initiation of naltrexone in the inpatient setting are more limited. Wei et al.¹⁴ reported on the implementation of a discharge protocol, including counseling about naltrexone, for hospitalized patients with AUDs at an urban academic medical center. They reported a significant increase in the prescription of naltrexone to eligible patients by the time of discharge that was associated with a significant decrease in 30-day readmissions. Initiation of naltrexone in the inpatient versus the outpatient setting has some potential advantages. First, patients hospitalized for alcohol withdrawal have AUDs, obviating the need for screening. Second, the outpatient trials of naltrexone typically required 3 days of sobriety before initiation, which is generally achieved during hospitalization for detoxification or withdrawal.

Previous work at our institution centered on standardizing the process of evaluating patients needing alcohol detoxification at the time of referral for admission.¹⁵ The use of a standardized protocol reduced the number of inpatient admissions for alcohol-related diagnoses but had no effect on the 30-day readmission rate (28%) for those patients who were hospitalized. Our hospitalist group had no standardized process for discharging hospitalized patients with AUDs, and the discharge process rarely included counseling on medications for maintenance of sobriety. In this manuscript, we describe the implementation and impact of a process for counseling patients hospitalized for alcohol detoxification or withdrawal about naltrexone for maintenance of sobriety by the time of hospital discharge.

Study Setting

The University of North Carolina (UNC) Hospitals is an 803-bed tertiary academic center. UNC Hospital Medicine is staffed by 29 physicians and 3 advanced practice providers (APPs). During the study period, there were 3 hospital medicine services at UNC Hospitals with a combined average daily census of approximately 40 patients, and each service was staffed by one attending physician every day of the week and one APP Monday through Friday.

Study Design

We used a pre-post study design, in which we implemented a new process for standardizing the discharge of hospitalized patients with AUDs, including a process for counseling about naltrexone by the time of discharge. We sought and received institutional review board (IRB) approval for this study (UNC IRB 15-1441).

Interventions

We formed an improvement team that included 3 physicians and an APP in hospital medicine, a general internist and a psychiatrist, both with expertise in the use of medications for maintenance of sobriety, the director of UNC’s Alcohol and Substance Abuse Program, and 2 case managers. The team developed a number of interventions, including group education, a process for patient identification, and algorithms for counseling about, prescribing, and documenting the discussion of naltrexone.

Group Education

We presented evidence about medications for the maintenance of sobriety at a regularly scheduled hospitalist meeting. An hour-long session on motivational interviewing techniques was also presented at a separate meeting. All created algorithms were circulated to the group electronically and posted at workstations in the hospitalist work area. As data were generated postimplementation, control charts of process measures were created, posted in the hospitalist work area, and presented at subsequent group meetings.

Identification of Patients

We focused our interventions on patients admitted for alcohol detoxification or withdrawal (including withdrawal seizures). We asked our group to preferentially admit these patients to 1 of our 3 hospitalists services, on which the service APP (K.S.) was also an improvement team member.

Creation of Algorithms and Scripts for Counseling

We created a simple algorithm for evaluating patients for naltrexone. We recommended that all patients admitted for alcohol detoxification or withdrawal be counseled about naltrexone for the maintenance of sobriety before discharge. The contraindications to naltrexone we included were (1) concurrent opioid use, (2) documented cirrhosis, and/or (3) liver function tests greater than 3 times the upper limit of normal by the time of hospital discharge.

We also created a suggested script for motivational interviewing (supplemental Appendix 1). This was presented at a group meeting and circulated via e-mail. The actual counseling technique and process was left up to individual providers. In practice, counseling took place in the course of daily rounds, generally the day before or day of hospital discharge.

Prescription of Medication

For interested patients without contraindications, we recommended a prescription of naltrexone at 50 mg daily for 3 months. For patients prescribed naltrexone without medical insurance (n = 17), we utilized our existing pharmacy assistance program, whereby discharging patients can obtain an initial 14-day supply after applying to the program and then can fill subsequent prescriptions if they meet program financial requirements.

Follow-up Appointments

For patients with established outpatient providers, we asked patients to schedule follow-up appointments within a month of discharge. Patients prescribed naltrexone without primary providers (n = 16) were eligible for an existing program, the UNC Transitions Program, whereby patients identified as having moderate-to-high risk of hospital readmission can receive a follow-up appointment at UNC Internal Medicine or UNC Family Medicine within 2 weeks of discharge.

Creation of “Smart Phrases”

To aid in documentation, we created “smart phrases” (easily accessed, previously created phrases that can be adopted by all users) within the hospital electronic health record. We created one smart phrase for documentation of counseling about naltrexone, which included dropdown menus for contraindications and the patient’s preference and one for discharge instructions for patients started on naltrexone (supplemental Appendix 2).

Implementation

After the presentation of suggested interventions in July 2015 and the subsequent dissemination of educational materials, we implemented our new process on August 1, 2015.

Data Collection

Patients were identified for inclusion in the study analysis by querying UNC Hospitals’ billing database for the inpatient diagnosis codes (diagnosis-related groupings) 896 and 897, “alcohol/drug abuse or dependence without rehabilitation therapy,” with and without major comorbidity or complication, respectively, and with hospital medicine as the discharging service. All encounters were then manually reviewed by 2 investigators (J.S. and C.M.). Encounters were included if the history and physical indicated that the primary reason for admission was alcohol detoxification or withdrawal. Encounters with other primary reasons for admission (eg, pancreatitis, gastrointestinal bleeding) were excluded. For patients with multiple encounters, only the first eligible encounter in the pre- and/or postimplementation period was included. Comorbidities for identified patients were assessed via the search of study encounters for the International Classification of Diseases, 9th Revision-Clinical Modification codes for hypertension, anxiety, depression, cirrhosis, diabetes, and congestive heart failure.

Process, Outcomes, and Balancing Measures

The study process measures included the percentage of patients hospitalized for alcohol detoxification or withdrawal with documentation of counseling about naltrexone by the time of discharge, before and after process intervention. Documentation was defined as the description of counseling about naltrexone in the discharge summary or progress notes of identified encounters. We also measured the percentage of patients started on naltrexone before and after intervention. Lastly, we measured the percentage of patients prescribed naltrexone who filled at least 1 prescription for the medication, assessed by calls to the pharmacy where the medication was prescribed. Prescriptions that could not be confirmed (ie, paper rather than electronic prescriptions) were counted as not filled.

For outcome measures, we recorded the percentages of study patients who returned to the emergency department (ED) and were readmitted to UNC Hospitals (inpatient or observation) for any reason within 30 days of discharge. These outcomes were determined by a manual chart review.

In order to ensure the new process was not associated with delays in patient discharge, we measured the mean length of stay in days for study patient encounters before and after intervention as a balancing measure.

Statistical Analysis

Demographic and clinical characteristics for included patients were compared for the 16 months preimplementation (April 1, 2014 through July 31, 2015) and the 19 months postimplementation (August 1, 2015 through February 28, 2017). Descriptive statistics were calculated by using the Student t test for continuous variables and the χ² test for dichotomous variables. We used multivariate logistic regression to evaluate the associations between the intervention arms (pre- vs postintervention) and study outcomes, adjusting for age, gender, race, insurance type, and medical comorbidities. We chose these variables for inclusion based on their association with study outcomes at the P ≤ .20 level in bivariate analyses. P < .05 was considered statistically significant. All analyses were performed by using Stata version 13.1 (StataCorp LLC, College Station, TX).

For 2 process measures, the percentages of patients counseled about and started on naltrexone, we plotted consecutive samples of 10 patients before and after intervention on a control chart, using preintervention data to calculate means and control limits.

Subgroup Analysis

We used multivariate logistic regression to evaluate the associations between counseling versus no counseling and prescription of naltrexone versus no prescription for study outcomes in the postintervention subgroup, adjusting for age, gender, race, insurance type, and medical comorbidities.

Patients

We identified 188 preimplementation encounters and excluded 12 patients (6.4%) for primary admission reasons other than alcohol withdrawal or detoxification and 48 (25.5%) repeat hospitalizations, leaving 128 unique patient encounters. We identified 166 postimplementation encounters and excluded 25 (15.1%) hospitalizations for admission reason and 27 repeat hospitalizations (16.3%), leaving 114 unique patient encounters (flow diagram in supplemental Appendix 3). The most common admission reason for the exclusion of encounters was withdrawal from a substance other than alcohol (supplemental Appendix 4). The percentages of encounters excluded in preimplementation and postimplementation periods were similar at 31.9% and 31.4%, respectively.

The majority of patients were male and white, and almost half were uninsured (Table 1). There were no demographic differences between patients in the pre- versus postimplementation groups. For studied comorbidities, postintervention patients were more likely to have hypertension, anxiety, and depression.

Process Measures

Among those counseled about naltrexone before discharge, 34 of 74 patients (45.9%) had no contraindications to naltrexone and were interested in taking the medication. Among the 40 patients who were counseled about but not prescribed naltrexone, 19 (47.5%) declined, 9 (22.5%) had liver function tests elevated more than 3 times the upper limit of the reference range, 9 (22.5%) had concurrent opiate use, and 3 (7.5%) had multiple contraindications.

Among the 34 patients who were prescribed naltrexone, 25 (73.5%) filled at least 1 prescription as confirmed by phone call to the relevant pharmacy.

Outcome Measures

Subgroup Analysis

Balancing Measure

The mean length of stay for all patient encounters was 3.3 days. There were no differences in length of stay comparing pre- with postintervention patient encounters (Table 1) or those postintervention patients counseled versus not counseled (Table 2).

Our study demonstrates that counseling about medications for the maintenance of sobriety can be implemented as part of the routine care of hospitalized patients with AUDs. In our experience, about half of the patients counseled had no contraindications to naltrexone and were willing to take it at discharge. Almost three-fourths of those who were prescribed naltrexone filled the prescription at least once. The counseling process was not associated with increased length of stay. In the adjusted analysis, postintervention patients had significantly lower odds of 30-day ED returns. Additionally, in subgroup analysis, postintervention patients counseled about naltrexone had significantly lower rates of subsequent healthcare utilization compared with those not counseled, with absolute differences of 26% for ED revisits and 22% for rehospitalizations within 30 days.

The failure to demonstrate a difference in adjusted rehospitalization rates in the postintervention versus the preintervention group has several possible explanations. First, we had incomplete fidelity to our interventions, documenting counseling about naltrexone before discharge in over 60% of postintervention patients, raising the possibility that better fidelity may have resulted in improved outcomes. Related to this, only 28% of postintervention patients were prescribed naltrexone, which may be an inadequate sample size to demonstrate positive effects from the medication. Another possible explanation is that the postintervention group had higher rates of some of the comorbidities we assessed, namely, anxiety, depression, and hypertension, which could have negatively impacted the effectiveness of the interventions to prevent rehospitalization; however, after adjusting for comorbidities, the odds of rehospitalization were still not significantly different. It is interesting that the odds of postintervention ED revisits (but not rehospitalizations) were lower in the adjusted analysis. It may be that patients who revisit the ED and are not rehospitalized are different in important ways from those who are readmitted. Alternately, the larger number of ED revisits overall (about twice the rate of rehospitalization) may have made it easier to identify positive effects from the intervention for this outcome than rehospitalization (ie, the study may have been underpowered to detect a relatively small reduction in rehospitalization). It is also possible, however, that the interventions were simply insufficient to prevent rehospitalization.

The subgroup analysis, however, did find significant differences in both outcome measures for postintervention patients counseled versus not counseled about naltrexone before discharge. There are several possible explanations for these results. First, there may have been unmeasured differences in those counseled versus not counseled that explain the reductions observed in subsequent healthcare utilization. For example, the counseled patients could have been more motivated to change and, thus, more readily approached by providers for counseling. The lack of any demographic differences between the 2 groups and the relative simplicity of the counseling part of the intervention occurring as part of daily rounds argue against this hypothesis, but there are many potential unmeasured confounders (eg, homelessness, ability to afford medications), and this possibility remains. A second possible explanation is that patients counseled about naltrexone could have been more likely than those not counseled to seek subsequent care at other institutions. A third possibility is that that the counseling about (and prescribing when appropriate) naltrexone itself led to the observed decreases in subsequent ED visits and hospitalizations. This hypothesis would have been more supported had we been able to demonstrate a statistically significant reduction in healthcare utilization in those prescribed versus not prescribed naltrexone. But there were nonsignificant trends in the reduction of ED revisits and rehospitalizations among those prescribed the medication, suggesting we may have been able to demonstrate statistically significant reductions with a larger sample size.

Comparing our results with existing literature is challenging. The majority of randomized trials of naltrexone for AUDs were conducted in the outpatient setting.^3-10 Most of these trials utilized some type of psychosocial intervention in addition to naltrexone.^3-5,8-10 The 1 prior naltrexone study we identified conducted in the inpatient setting by Wei et al.¹⁴ is the most similar to our study. The authors reported the effects of a new process for assessing hospitalized patients with AUDs, including the use of a discharge planning tool for all patients admitted with alcohol dependence. The discharge tool included prompts for naltrexone in appropriate patients. The measured outcomes included the percentage of eligible patients prescribed naltrexone at discharge and the percentages of ED revisits and rehospitalizations within 30 days. Postintervention, 64% of eligible patients were prescribed naltrexone compared with 0% before, very similar to our results. There were significant decreases among all discharged patients with alcohol dependence for 30-day ED revisits (18.8% pre- vs 6.1% postimplementation) and rehospitalizations (23.4% vs 8.2%). The study differed from ours in a number of important respects, including a location in a large urban setting and implementation on a teaching service rather than an attending-only hospitalist service. Additionally, the authors studied 1 month of process implementation and compared it to another month 1 year before the new process, with an overall smaller sample size of 64 patients before and 49 patients after implementation. Potential reasons why Wei et al.¹⁴ were able to document lower rehospitalization rates postintervention when we did not include the differences in patient population (eg, high homeless rate, lower percentage of female patients in Wei study) and secular trends unrelated to interventions in either study.

Limitations of our study include the nonrandomized and uncontrolled design, which introduces the possibility of unmeasured confounding factors leading to the decrease we observed in healthcare utilization. Additionally, the single-center design precludes our ability to assess for healthcare utilization outcomes in other nearby facilities. We had incomplete implementation of our new process, counseling just over 60% of patients. As our primary outcomes relied on documentation in the medical record, both undersampling (not documenting some interventions) and reporting bias (being more likely to record positive sessions from intervention) are possible. Lastly, despite a moderate total sample size of almost 250 patients, the relatively small numbers of patients who were actually prescribed naltrexone in our study lessens our ability to show direct impact.

In conclusion, our study demonstrates a practical process for counseling about and prescribing naltrexone to patients hospitalized for alcohol detoxification or withdrawal. We demonstrate that many of these patients will be interested in starting naltrexone at discharge and will reliably fill the prescriptions if written. Counseling was associated with a significant reduction in subsequent healthcare utilization. These results have a wide potential impact given the ubiquitous nature of AUDs among hospitalized patients in community and academic settings.

Disclosure

The authors have no conflicts of interest relevant to this article to disclose. There were no sources of funding for this work.

Alcohol use disorders (AUDs) are common, with an estimated lifetime prevalence of 17.8% for alcohol dependence.¹ Alcohol misuse is costly, accounting for $24.6 billion in annual healthcare expenditures, including $5.1 billion for alcohol-related hospitalizations.² A number of trials have demonstrated that naltrexone can help patients with AUDs maintain abstinence or diminish heavy drinking.^3-10 A recent meta-analysis of pharmacotherapy trials for patients with AUDs reported that for patients using 50 mg of naltrexone daily, the number needed to treat was 12 to prevent a return to heavy drinking and 20 to prevent a return to any drinking.¹¹ Despite good evidence for its effectiveness, naltrexone is not prescribed to the majority of patients with AUDs. In a study of veterans with AUDs cared for in the Veterans Affairs health system, only 1.9% of patients were prescribed naltrexone over the 6-month study period.¹² A 2003 survey of 2 professional organizations for addiction treatment specialists reported that a mean of 13% of providers prescribed naltrexone to their patients.¹³

When naltrexone is prescribed, it is most frequently in the outpatient setting.^3-10 Data for initiation of naltrexone in the inpatient setting are more limited. Wei et al.¹⁴ reported on the implementation of a discharge protocol, including counseling about naltrexone, for hospitalized patients with AUDs at an urban academic medical center. They reported a significant increase in the prescription of naltrexone to eligible patients by the time of discharge that was associated with a significant decrease in 30-day readmissions. Initiation of naltrexone in the inpatient versus the outpatient setting has some potential advantages. First, patients hospitalized for alcohol withdrawal have AUDs, obviating the need for screening. Second, the outpatient trials of naltrexone typically required 3 days of sobriety before initiation, which is generally achieved during hospitalization for detoxification or withdrawal.

Previous work at our institution centered on standardizing the process of evaluating patients needing alcohol detoxification at the time of referral for admission.¹⁵ The use of a standardized protocol reduced the number of inpatient admissions for alcohol-related diagnoses but had no effect on the 30-day readmission rate (28%) for those patients who were hospitalized. Our hospitalist group had no standardized process for discharging hospitalized patients with AUDs, and the discharge process rarely included counseling on medications for maintenance of sobriety. In this manuscript, we describe the implementation and impact of a process for counseling patients hospitalized for alcohol detoxification or withdrawal about naltrexone for maintenance of sobriety by the time of hospital discharge.

Study Setting

The University of North Carolina (UNC) Hospitals is an 803-bed tertiary academic center. UNC Hospital Medicine is staffed by 29 physicians and 3 advanced practice providers (APPs). During the study period, there were 3 hospital medicine services at UNC Hospitals with a combined average daily census of approximately 40 patients, and each service was staffed by one attending physician every day of the week and one APP Monday through Friday.

Study Design

We used a pre-post study design, in which we implemented a new process for standardizing the discharge of hospitalized patients with AUDs, including a process for counseling about naltrexone by the time of discharge. We sought and received institutional review board (IRB) approval for this study (UNC IRB 15-1441).

Interventions

We formed an improvement team that included 3 physicians and an APP in hospital medicine, a general internist and a psychiatrist, both with expertise in the use of medications for maintenance of sobriety, the director of UNC’s Alcohol and Substance Abuse Program, and 2 case managers. The team developed a number of interventions, including group education, a process for patient identification, and algorithms for counseling about, prescribing, and documenting the discussion of naltrexone.

Group Education

We presented evidence about medications for the maintenance of sobriety at a regularly scheduled hospitalist meeting. An hour-long session on motivational interviewing techniques was also presented at a separate meeting. All created algorithms were circulated to the group electronically and posted at workstations in the hospitalist work area. As data were generated postimplementation, control charts of process measures were created, posted in the hospitalist work area, and presented at subsequent group meetings.

Identification of Patients

We focused our interventions on patients admitted for alcohol detoxification or withdrawal (including withdrawal seizures). We asked our group to preferentially admit these patients to 1 of our 3 hospitalists services, on which the service APP (K.S.) was also an improvement team member.

Creation of Algorithms and Scripts for Counseling

We created a simple algorithm for evaluating patients for naltrexone. We recommended that all patients admitted for alcohol detoxification or withdrawal be counseled about naltrexone for the maintenance of sobriety before discharge. The contraindications to naltrexone we included were (1) concurrent opioid use, (2) documented cirrhosis, and/or (3) liver function tests greater than 3 times the upper limit of normal by the time of hospital discharge.

We also created a suggested script for motivational interviewing (supplemental Appendix 1). This was presented at a group meeting and circulated via e-mail. The actual counseling technique and process was left up to individual providers. In practice, counseling took place in the course of daily rounds, generally the day before or day of hospital discharge.

Prescription of Medication

For interested patients without contraindications, we recommended a prescription of naltrexone at 50 mg daily for 3 months. For patients prescribed naltrexone without medical insurance (n = 17), we utilized our existing pharmacy assistance program, whereby discharging patients can obtain an initial 14-day supply after applying to the program and then can fill subsequent prescriptions if they meet program financial requirements.

Follow-up Appointments

For patients with established outpatient providers, we asked patients to schedule follow-up appointments within a month of discharge. Patients prescribed naltrexone without primary providers (n = 16) were eligible for an existing program, the UNC Transitions Program, whereby patients identified as having moderate-to-high risk of hospital readmission can receive a follow-up appointment at UNC Internal Medicine or UNC Family Medicine within 2 weeks of discharge.

Creation of “Smart Phrases”

To aid in documentation, we created “smart phrases” (easily accessed, previously created phrases that can be adopted by all users) within the hospital electronic health record. We created one smart phrase for documentation of counseling about naltrexone, which included dropdown menus for contraindications and the patient’s preference and one for discharge instructions for patients started on naltrexone (supplemental Appendix 2).

Implementation

After the presentation of suggested interventions in July 2015 and the subsequent dissemination of educational materials, we implemented our new process on August 1, 2015.

Data Collection

Patients were identified for inclusion in the study analysis by querying UNC Hospitals’ billing database for the inpatient diagnosis codes (diagnosis-related groupings) 896 and 897, “alcohol/drug abuse or dependence without rehabilitation therapy,” with and without major comorbidity or complication, respectively, and with hospital medicine as the discharging service. All encounters were then manually reviewed by 2 investigators (J.S. and C.M.). Encounters were included if the history and physical indicated that the primary reason for admission was alcohol detoxification or withdrawal. Encounters with other primary reasons for admission (eg, pancreatitis, gastrointestinal bleeding) were excluded. For patients with multiple encounters, only the first eligible encounter in the pre- and/or postimplementation period was included. Comorbidities for identified patients were assessed via the search of study encounters for the International Classification of Diseases, 9th Revision-Clinical Modification codes for hypertension, anxiety, depression, cirrhosis, diabetes, and congestive heart failure.

Process, Outcomes, and Balancing Measures

The study process measures included the percentage of patients hospitalized for alcohol detoxification or withdrawal with documentation of counseling about naltrexone by the time of discharge, before and after process intervention. Documentation was defined as the description of counseling about naltrexone in the discharge summary or progress notes of identified encounters. We also measured the percentage of patients started on naltrexone before and after intervention. Lastly, we measured the percentage of patients prescribed naltrexone who filled at least 1 prescription for the medication, assessed by calls to the pharmacy where the medication was prescribed. Prescriptions that could not be confirmed (ie, paper rather than electronic prescriptions) were counted as not filled.

For outcome measures, we recorded the percentages of study patients who returned to the emergency department (ED) and were readmitted to UNC Hospitals (inpatient or observation) for any reason within 30 days of discharge. These outcomes were determined by a manual chart review.

In order to ensure the new process was not associated with delays in patient discharge, we measured the mean length of stay in days for study patient encounters before and after intervention as a balancing measure.

Statistical Analysis

Demographic and clinical characteristics for included patients were compared for the 16 months preimplementation (April 1, 2014 through July 31, 2015) and the 19 months postimplementation (August 1, 2015 through February 28, 2017). Descriptive statistics were calculated by using the Student t test for continuous variables and the χ² test for dichotomous variables. We used multivariate logistic regression to evaluate the associations between the intervention arms (pre- vs postintervention) and study outcomes, adjusting for age, gender, race, insurance type, and medical comorbidities. We chose these variables for inclusion based on their association with study outcomes at the P ≤ .20 level in bivariate analyses. P < .05 was considered statistically significant. All analyses were performed by using Stata version 13.1 (StataCorp LLC, College Station, TX).

For 2 process measures, the percentages of patients counseled about and started on naltrexone, we plotted consecutive samples of 10 patients before and after intervention on a control chart, using preintervention data to calculate means and control limits.

Subgroup Analysis

We used multivariate logistic regression to evaluate the associations between counseling versus no counseling and prescription of naltrexone versus no prescription for study outcomes in the postintervention subgroup, adjusting for age, gender, race, insurance type, and medical comorbidities.

Patients

We identified 188 preimplementation encounters and excluded 12 patients (6.4%) for primary admission reasons other than alcohol withdrawal or detoxification and 48 (25.5%) repeat hospitalizations, leaving 128 unique patient encounters. We identified 166 postimplementation encounters and excluded 25 (15.1%) hospitalizations for admission reason and 27 repeat hospitalizations (16.3%), leaving 114 unique patient encounters (flow diagram in supplemental Appendix 3). The most common admission reason for the exclusion of encounters was withdrawal from a substance other than alcohol (supplemental Appendix 4). The percentages of encounters excluded in preimplementation and postimplementation periods were similar at 31.9% and 31.4%, respectively.

The majority of patients were male and white, and almost half were uninsured (Table 1). There were no demographic differences between patients in the pre- versus postimplementation groups. For studied comorbidities, postintervention patients were more likely to have hypertension, anxiety, and depression.

Process Measures

Among those counseled about naltrexone before discharge, 34 of 74 patients (45.9%) had no contraindications to naltrexone and were interested in taking the medication. Among the 40 patients who were counseled about but not prescribed naltrexone, 19 (47.5%) declined, 9 (22.5%) had liver function tests elevated more than 3 times the upper limit of the reference range, 9 (22.5%) had concurrent opiate use, and 3 (7.5%) had multiple contraindications.

Among the 34 patients who were prescribed naltrexone, 25 (73.5%) filled at least 1 prescription as confirmed by phone call to the relevant pharmacy.

Outcome Measures

Subgroup Analysis

Balancing Measure

The mean length of stay for all patient encounters was 3.3 days. There were no differences in length of stay comparing pre- with postintervention patient encounters (Table 1) or those postintervention patients counseled versus not counseled (Table 2).

Our study demonstrates that counseling about medications for the maintenance of sobriety can be implemented as part of the routine care of hospitalized patients with AUDs. In our experience, about half of the patients counseled had no contraindications to naltrexone and were willing to take it at discharge. Almost three-fourths of those who were prescribed naltrexone filled the prescription at least once. The counseling process was not associated with increased length of stay. In the adjusted analysis, postintervention patients had significantly lower odds of 30-day ED returns. Additionally, in subgroup analysis, postintervention patients counseled about naltrexone had significantly lower rates of subsequent healthcare utilization compared with those not counseled, with absolute differences of 26% for ED revisits and 22% for rehospitalizations within 30 days.

The failure to demonstrate a difference in adjusted rehospitalization rates in the postintervention versus the preintervention group has several possible explanations. First, we had incomplete fidelity to our interventions, documenting counseling about naltrexone before discharge in over 60% of postintervention patients, raising the possibility that better fidelity may have resulted in improved outcomes. Related to this, only 28% of postintervention patients were prescribed naltrexone, which may be an inadequate sample size to demonstrate positive effects from the medication. Another possible explanation is that the postintervention group had higher rates of some of the comorbidities we assessed, namely, anxiety, depression, and hypertension, which could have negatively impacted the effectiveness of the interventions to prevent rehospitalization; however, after adjusting for comorbidities, the odds of rehospitalization were still not significantly different. It is interesting that the odds of postintervention ED revisits (but not rehospitalizations) were lower in the adjusted analysis. It may be that patients who revisit the ED and are not rehospitalized are different in important ways from those who are readmitted. Alternately, the larger number of ED revisits overall (about twice the rate of rehospitalization) may have made it easier to identify positive effects from the intervention for this outcome than rehospitalization (ie, the study may have been underpowered to detect a relatively small reduction in rehospitalization). It is also possible, however, that the interventions were simply insufficient to prevent rehospitalization.

The subgroup analysis, however, did find significant differences in both outcome measures for postintervention patients counseled versus not counseled about naltrexone before discharge. There are several possible explanations for these results. First, there may have been unmeasured differences in those counseled versus not counseled that explain the reductions observed in subsequent healthcare utilization. For example, the counseled patients could have been more motivated to change and, thus, more readily approached by providers for counseling. The lack of any demographic differences between the 2 groups and the relative simplicity of the counseling part of the intervention occurring as part of daily rounds argue against this hypothesis, but there are many potential unmeasured confounders (eg, homelessness, ability to afford medications), and this possibility remains. A second possible explanation is that patients counseled about naltrexone could have been more likely than those not counseled to seek subsequent care at other institutions. A third possibility is that that the counseling about (and prescribing when appropriate) naltrexone itself led to the observed decreases in subsequent ED visits and hospitalizations. This hypothesis would have been more supported had we been able to demonstrate a statistically significant reduction in healthcare utilization in those prescribed versus not prescribed naltrexone. But there were nonsignificant trends in the reduction of ED revisits and rehospitalizations among those prescribed the medication, suggesting we may have been able to demonstrate statistically significant reductions with a larger sample size.

Comparing our results with existing literature is challenging. The majority of randomized trials of naltrexone for AUDs were conducted in the outpatient setting.^3-10 Most of these trials utilized some type of psychosocial intervention in addition to naltrexone.^3-5,8-10 The 1 prior naltrexone study we identified conducted in the inpatient setting by Wei et al.¹⁴ is the most similar to our study. The authors reported the effects of a new process for assessing hospitalized patients with AUDs, including the use of a discharge planning tool for all patients admitted with alcohol dependence. The discharge tool included prompts for naltrexone in appropriate patients. The measured outcomes included the percentage of eligible patients prescribed naltrexone at discharge and the percentages of ED revisits and rehospitalizations within 30 days. Postintervention, 64% of eligible patients were prescribed naltrexone compared with 0% before, very similar to our results. There were significant decreases among all discharged patients with alcohol dependence for 30-day ED revisits (18.8% pre- vs 6.1% postimplementation) and rehospitalizations (23.4% vs 8.2%). The study differed from ours in a number of important respects, including a location in a large urban setting and implementation on a teaching service rather than an attending-only hospitalist service. Additionally, the authors studied 1 month of process implementation and compared it to another month 1 year before the new process, with an overall smaller sample size of 64 patients before and 49 patients after implementation. Potential reasons why Wei et al.¹⁴ were able to document lower rehospitalization rates postintervention when we did not include the differences in patient population (eg, high homeless rate, lower percentage of female patients in Wei study) and secular trends unrelated to interventions in either study.

Limitations of our study include the nonrandomized and uncontrolled design, which introduces the possibility of unmeasured confounding factors leading to the decrease we observed in healthcare utilization. Additionally, the single-center design precludes our ability to assess for healthcare utilization outcomes in other nearby facilities. We had incomplete implementation of our new process, counseling just over 60% of patients. As our primary outcomes relied on documentation in the medical record, both undersampling (not documenting some interventions) and reporting bias (being more likely to record positive sessions from intervention) are possible. Lastly, despite a moderate total sample size of almost 250 patients, the relatively small numbers of patients who were actually prescribed naltrexone in our study lessens our ability to show direct impact.

In conclusion, our study demonstrates a practical process for counseling about and prescribing naltrexone to patients hospitalized for alcohol detoxification or withdrawal. We demonstrate that many of these patients will be interested in starting naltrexone at discharge and will reliably fill the prescriptions if written. Counseling was associated with a significant reduction in subsequent healthcare utilization. These results have a wide potential impact given the ubiquitous nature of AUDs among hospitalized patients in community and academic settings.

Disclosure

The authors have no conflicts of interest relevant to this article to disclose. There were no sources of funding for this work.

Academic hospital medicine is a young specialty, with most faculty at the rank of instructor or assistant professor.¹ Traditional markers of academic success for clinical and translational investigators emphasize progressive, externally funded grants, achievements in basic science research, and prolific publication in the peer-reviewed literature.² Promotion is often used as a proxy measure for academic success.

Conceptual models of career success derived from nonhealthcare industries and for physician-scientists include both extrinsic and intrinsic domains.^3,4 Extrinsic domains of career success include financial rewards (compensation) and progression in hierarchical status (advancement).^3,4 Intrinsic domains of career success include pleasure derived from daily work (job satisfaction) and satisfaction derived from aspects of the career over time (career satisfaction).^3,4

Research is limited regarding hospitalist faculty beliefs about career success. A better understanding of hospitalist perspectives can inform program development to support junior faculty in academic hospital medicine. In this phenomenological, qualitative study, we explore the global concept of career success as perceived by early-career clinician-educator hospitalists.

Study Design, Setting, and Participants

We conducted interviews with hospitalists from 3 academic medical centers between May 2016 and October 2016. Purposeful sampling was used.⁵ Leaders within each hospital medicine group identified early-career faculty with approximately 2 to 5 years in academic medicine with a rank of instructor or assistant professor at each institution likely to self-identify as clinician-educators for targeted solicitation to enroll. Additional subjects were recruited until thematic saturation had been achieved on the personal definition of career success. Participants received disclosure and consent documents prior to enrollment. No compensation was provided to participants. This study was approved by the Colorado Multiple Institutional Review Board.

Interview Guide Development and Content

The semistructured interview format was developed and validated through an iterative process. Proposed questions were developed by study investigators on the basis of review of the literature on career success in nonhealthcare industries and academic hospitalist promotion. The questions were assessed for content validity through a review of interview domains by an academic hospitalist program director (R. P.). Cognitive interviewing with 3 representative academic hospitalists who were not part of the study cohort was done as an additional face-validation step of the question probe structure. As a result of the cognitive interviews, 1 question was eliminated, and a framework for clarifications and answer probes was derived prior to the enrollment of the first study subject. No changes were made to the interview format during the study period.

Data Collection

The principal investigator (E.C.) performed all interviews by using the interview tool consisting of 7 demographic questions and 11 open-ended questions and exploring aspects of the concept of career success. The initial open-ended question, “How would you personally define career success as an academic hospitalist at this stage in your career?” represented the primary question of interest. Follow-up questions were used to better understand responses to the primary question. All interviews were audio recorded, deidentified, and transcribed by the principal investigator. Transcripts were randomly audited by a second investigator (E.Y.) for accuracy and completeness.

Sample Size Determination

Interviews were continued to thematic saturation. After the first 3 interviews were transcribed, 2 members of the research team (E.C. and P.K.) reviewed the transcripts and developed a preliminary thematic codebook for the primary question. Subsequent interviews were reviewed and analyzed against these themes. Interviews were continued to thematic saturation, which was defined as more than 3 sequential interviews with no new identified themes.⁶

Data Analysis

By using qualitative data analysis software (ATLAS.ti version 7; ATLAS.ti Scientific Software Development GmbH, Berlin, Germany), transcriptions were analyzed with a team-based, mixed inductive-deductive approach. An inductive approach was utilized to allow basic theme codes to emerge from the raw text, and thus remaining open to unanticipated themes. Investigators assessed each distinct quote for new themes, confirmatory themes, and challenges to previously developed concepts. Basic themes were then discussed among research team members to determine prominent themes, with basic theme codes added, removed, or combined at this stage of the analysis. Responses to each follow-up question were subsequently assessed for new themes, confirmatory themes, or challenges to previously developed concepts related to the personal definition of career success. A deductive approach was then used to map our inductively generated themes back to the organizing themes of the existing conceptual framework.

Thematic Mapping to Organizing Themes of the Conceptual Model (Table)

The single most dominant theme, “excitement about daily work” was connected to an intrinsic sense of job satisfaction. Career satisfaction emerged from interviews more frequently than extrinsic organizing themes, such as advancement or compensation. Advancement through promotion was infrequently referenced as part of success, and tenure was never raised despite being available for clinician-educators at 2 of the 3 institutions. Compensation was not referenced in any interviewee’s initial definition of career success, although in 1 interview, it came up in response to a follow-up question. The Figure visually represents the relative weighting (shown by the sizes of the boxes) of organizing themes to the early-career hospitalists’ self-concepts of career success. Relationships among organizing themes as they emerged from interviews are represented by arrows.

Intrinsic—Job Satisfaction

With regard to job satisfaction, early-career faculty often invoked words such as “excitement,” “enjoyment,” and “passionate” to describe an overall theme of “excitement about daily work.” A positive affective state created by the nature of daily work was described as integral to the personal sense of career success. It was also strongly associated with perception of sustainability in a hospitalist career.

“I think [career success] would be job satisfaction. …So, for me, that would be happiness with my job. I like coming to work. I like doing what I do and at the end of the day going home and saying that was a good day. I like to think that would be success at work…is how I would define it.”

This theme was also related to a negative aspect often referred to as burnout, which many identified as antithetical to career success. More often, they described success as a heightened state of enthusiasm for the daily work experience.

“I am staying engaged and excited. So, I am not just taking care of patients; I am not just teaching. Having enough excitement from my work to come home and talk about it at dinner. To enjoy my days off but at the same time being excited to get back to work.”

This description of passion toward the work of being a hospitalist was often linked to a sense of deeper purpose found through the delivery of clinical care and education of learners.

“I really feel that we have the opportunity to very meaningfully and powerfully impact people’s lives, and that to me is meaningful. …That’s value. ...That’s coming home at the end of the day and thinking that you have had a positive impact.”

The interviews reflected that core to meaningful work was a sense of personal efficacy as a clinician, which was reflected in the themes of clinical proficiency and practicing high-quality care.

“I think developing clinical expertise, both through experience and studying. Getting to the point to where you can take really excellent care of your patient through expertise would be a sense of success that a lot of academic hospitalists would strive for.”

Intrinsic—Career Satisfaction

Within career satisfaction, participants described that “being respected and recognized” and “dissemination of work” were important contributors to career success. Reputation was frequently referenced as a measure of career success. Reputation was defined by some in a local context of having the respect of learners, peers, and others as a national renown. As a prerequisite for developing a reputation beyond the local academic environment, dissemination of work was often referenced as an important component of satisfaction in the career. This dissemination extended beyond peer-reviewed publications and included other forms of scholarship, presentations at conferences, and sharing clinical innovations between hospitals.

“For me personally, I have less of an emphasis on research and some of the more, I don’t want to say ‘academic’ because I think education is academic, but maybe some of the more scholarly practice of medicine, doing research and the writing of papers and things like that, although I certainly view some of that as a part of career success.”

Within career satisfaction, participants also described a diverse set of themes, including progressive improvement in skills, developing a self-perception of excellence in 1 or more arenas of academic medicine, leadership, work–life integration, innovation, and relationships. The concept of developing a niche, or becoming an expert in a particular domain of hospital medicine, was frequently referenced.

“I think part of [success] is ‘Have they identified a niche?’ Because I think if you want to be in an academic center, as much as I value teaching and taking care of patients, I think 1 of the advantages is the opportunity to potentially identify an area of expertise.”

Participants frequently alluded to the idea that the most important aspects of career satisfaction are not static phenomena but rather values that could evolve over the course of a career. For instance, in the early-career, making a difference with individual learners or patients could have greater valence, but as the career progressed, finding a niche, disseminating work, and building a national reputation would gain importance to a personal sense of career satisfaction.

Extrinsic—Advancement

Promotion was typically referenced when discussing career success, but it was not uniformly valued by early career hospitalists. Some expressed significant ambivalence about its effect on their personal sense of career success. Academic hospitalists identified a number of organizations with definitions of success that influence them. Definitions of success for the university were more relevant to interviewees compared to those of the hospital or professional societies. Interviewees were able to describe a variety of criteria by which their universities define or recognize career success. These commonly included promotion, publications and/or scholarship, and research. The list of factors perceived as success by the hospital were often distinct from those of the university and included cost-effective care, patient safety, and clinical leadership roles.

Participants described a sense of internal conflict when external-stakeholder definitions of success diverged from internal motivators. This was particularly true when this divergence led academic hospitalists to engage in activities for advancement that they did not find personally fulfilling. Academic hospitalists recognized that advancement was central to the concept of career success for organizations even if this was not identified as being core to their personal definitions of success.

“I think that for me, the idea of being promoted and being a leader in the field is less important to me than...for the organization.”

Hospitalists expressed that objective markers, such as promotion and publications, were perceived as more important at higher levels of the academic organization, whereas more subjective aspects of success, aligned with intrinsic personal definitions, were more valued within the hospital medicine group.

Extrinsic—Compensation

Compensation was notable for its absence in participants’ discussion of career success. When asked about their definitions of career success, academic hospitalists did not spontaneously raise the topic of compensation. The only mention of compensation was in response to a question about how personal and external definitions of career success differ.

Unexpected Findings

While it was almost universally recognized by participants as important, ambivalence toward the “academic value of clinical work,” “scholarship,” and especially “promotion” represented an unexpected thematic family.

“I can’t quite get excited about a title attached to my name or the number of times my name pops up when I enter it into PubMed. My personal definition is more…where do I have something that I am interested [in] that someone else values. And that value is not shown as an associate professorship or an assistant professorship next to my name. …When you push me on it, you could call me clinical instructor forever, and I don’t think I would care too much.”

The interaction between work and personal activities as representing complementary aspects of a global sense of success was also unexpected and ran contrary to a simplistic conception of work and life in conflict. Academic hospitalists referenced that the ability to participate in aspects of life external to the workplace was important to their sense of career success. Participants frequently used phrases such as “work–life balance” to encompass a larger sense that work and nonwork life needed to merge to form a holistic sense of having a positive impact.

“Personal success is becoming what I have termed a ‘man of worth.’ I think [that is] someone who feels as though they make a positive impact in the world. Through both my career, but I guess the things that I do that are external to my career. Those would be defined by being a good husband, a good son, a philanthropist out in the community…sometimes, these are not things that can necessarily go on a [curriculum vitae].”

Conflict Among Organizing Themes

At times, academic hospitalists described a tension between day-to-day job satisfaction and what would be necessary to accomplish longer-term career success in the other organizing themes. This was reflected by a sense of trade-off. For instance, activities that lead to some aspects of career satisfaction or advancement would take time away from the direct exposure to learners and clinical care that currently drive job satisfaction.

“If the institution wanted me to be more productive from a research standpoint or…advocate that I receive funding so I could buy down clinical time and interactions I have with my students and my patients, then I can see my satisfaction going down.”

Many described a sense of engaging in activities they did not find personally fulfilling because of a sense of expectation that those activities were considered successful by others. Some described a state in which the drive toward advancement as an extrinsic incentive could come at the expense of the intrinsic rewards of being an academic hospitalist.

Career success has been defined as “the positive psychological or work-related outcomes or achievements one accumulates as a result of work experiences.”^4,7,8 Academic career success for hospitalist faculty isn’t as well defined and has not been examined from the perspectives of early-career clinician-educator hospitalist faculty themselves.

The themes that emerged in this study describe a definition of success anchored in the daily work of striving to become an exceptional clinician and teacher. The major themes included (1) having excitement about daily work, (2) having meaningful impact, (3) development of a niche (4) a sense of respect within the sphere of academic medicine, and (5) disseminating work.

Success was very much internally defined as having a positive, meaningful impact on patients, learners, and the systems in which they practice. The faculty had a conception of what promotion committees value and often internalized aspects of this, such as developing a national reputation and giving talks at national meetings. Participants typically self-identified as clinician-educators, and yet dissemination of work remained an important component of personal success. While promotion was clearly identified as a marker of success, academic hospitalists often rejected the supposition of promotion itself as a professional goal. They expressed hope, and some skepticism, that external recognition of career success would follow the pursuit of internally meaningful goals.

While promotion and peer-reviewed publications represent easily measured markers often used as proxies for individual career and programmatic success, our research demonstrates that there is a deep well of externally imperceptible influences on an individual’s sense of success as an academic hospitalist. In our analysis, intrinsic elements of career success received far greater weight with early-career academic hospitalists. Our findings are supported by a prior survey of academic physicians that similarly found that faculty with >50% of their time devoted to clinical care placed greater career value in patient care, relationships with patients, and recognition by patients and residents compared to national reputation.⁹ Similar to our own findings, highly clinical faculty in that study were also less likely to value promotion and tenure as indicators of career success.⁹

The main focus of our questions was how early-career faculty define success at this point in their careers. When asked to extrapolate to a future state of career success, the concept of progression was repeatedly raised. This included successive promotions to higher academic ranks, increasing responsibility, titles, leadership, and achieving competitive roles or awards. It also included a progressively increasing impact of scholarship, growing national reputation, and becoming part of a network of accomplished academic hospitalists across the country. Looking forward, our early-career hospitalists felt that long-term career success would represent accomplishing these things and still being able to be focused on being excellent clinicians to patients, having a work–life balance, and keeping joy and excitement in daily activities.

Our work has limitations, including a focus on early-career clinician-educator hospitalists. The perception of career success may evolve over time, and future work to examine perceptions in more advanced academic hospitalists would be of interest. Our work used purposeful sampling to capture individuals who were likely to self-identify as academic clinician-educators, and results may not generalize to hospitalist physician-scientists or hospitalists in community practices.

Our analysis suggests that external organizations influence internal perceptions of career success. However, success is ultimately defined by the individual and not the institution. Efforts to measure and improve academic hospitalists’ attainment of career success should attend to intrinsic aspects of satisfaction in addition to objective measures, such as publications and promotion. This may provide a mechanism to address burnout and improve retention. As important as commonality in themes is the variation in self-definitions of career success among individuals. This suggests the value of inquiry by academic leadership in exploring and understanding what success is from the individual faculty perspective. This may enhance the alignment among personal definitions, organizational values, and, ultimately, sustainable, successful careers.

Disclosure: The authors have nothing to disclose.

Academic hospital medicine is a young specialty, with most faculty at the rank of instructor or assistant professor.¹ Traditional markers of academic success for clinical and translational investigators emphasize progressive, externally funded grants, achievements in basic science research, and prolific publication in the peer-reviewed literature.² Promotion is often used as a proxy measure for academic success.

Conceptual models of career success derived from nonhealthcare industries and for physician-scientists include both extrinsic and intrinsic domains.^3,4 Extrinsic domains of career success include financial rewards (compensation) and progression in hierarchical status (advancement).^3,4 Intrinsic domains of career success include pleasure derived from daily work (job satisfaction) and satisfaction derived from aspects of the career over time (career satisfaction).^3,4

Research is limited regarding hospitalist faculty beliefs about career success. A better understanding of hospitalist perspectives can inform program development to support junior faculty in academic hospital medicine. In this phenomenological, qualitative study, we explore the global concept of career success as perceived by early-career clinician-educator hospitalists.

Study Design, Setting, and Participants

We conducted interviews with hospitalists from 3 academic medical centers between May 2016 and October 2016. Purposeful sampling was used.⁵ Leaders within each hospital medicine group identified early-career faculty with approximately 2 to 5 years in academic medicine with a rank of instructor or assistant professor at each institution likely to self-identify as clinician-educators for targeted solicitation to enroll. Additional subjects were recruited until thematic saturation had been achieved on the personal definition of career success. Participants received disclosure and consent documents prior to enrollment. No compensation was provided to participants. This study was approved by the Colorado Multiple Institutional Review Board.

Interview Guide Development and Content

The semistructured interview format was developed and validated through an iterative process. Proposed questions were developed by study investigators on the basis of review of the literature on career success in nonhealthcare industries and academic hospitalist promotion. The questions were assessed for content validity through a review of interview domains by an academic hospitalist program director (R. P.). Cognitive interviewing with 3 representative academic hospitalists who were not part of the study cohort was done as an additional face-validation step of the question probe structure. As a result of the cognitive interviews, 1 question was eliminated, and a framework for clarifications and answer probes was derived prior to the enrollment of the first study subject. No changes were made to the interview format during the study period.

Data Collection

The principal investigator (E.C.) performed all interviews by using the interview tool consisting of 7 demographic questions and 11 open-ended questions and exploring aspects of the concept of career success. The initial open-ended question, “How would you personally define career success as an academic hospitalist at this stage in your career?” represented the primary question of interest. Follow-up questions were used to better understand responses to the primary question. All interviews were audio recorded, deidentified, and transcribed by the principal investigator. Transcripts were randomly audited by a second investigator (E.Y.) for accuracy and completeness.

Sample Size Determination

Interviews were continued to thematic saturation. After the first 3 interviews were transcribed, 2 members of the research team (E.C. and P.K.) reviewed the transcripts and developed a preliminary thematic codebook for the primary question. Subsequent interviews were reviewed and analyzed against these themes. Interviews were continued to thematic saturation, which was defined as more than 3 sequential interviews with no new identified themes.⁶

Data Analysis

By using qualitative data analysis software (ATLAS.ti version 7; ATLAS.ti Scientific Software Development GmbH, Berlin, Germany), transcriptions were analyzed with a team-based, mixed inductive-deductive approach. An inductive approach was utilized to allow basic theme codes to emerge from the raw text, and thus remaining open to unanticipated themes. Investigators assessed each distinct quote for new themes, confirmatory themes, and challenges to previously developed concepts. Basic themes were then discussed among research team members to determine prominent themes, with basic theme codes added, removed, or combined at this stage of the analysis. Responses to each follow-up question were subsequently assessed for new themes, confirmatory themes, or challenges to previously developed concepts related to the personal definition of career success. A deductive approach was then used to map our inductively generated themes back to the organizing themes of the existing conceptual framework.

Thematic Mapping to Organizing Themes of the Conceptual Model (Table)

The single most dominant theme, “excitement about daily work” was connected to an intrinsic sense of job satisfaction. Career satisfaction emerged from interviews more frequently than extrinsic organizing themes, such as advancement or compensation. Advancement through promotion was infrequently referenced as part of success, and tenure was never raised despite being available for clinician-educators at 2 of the 3 institutions. Compensation was not referenced in any interviewee’s initial definition of career success, although in 1 interview, it came up in response to a follow-up question. The Figure visually represents the relative weighting (shown by the sizes of the boxes) of organizing themes to the early-career hospitalists’ self-concepts of career success. Relationships among organizing themes as they emerged from interviews are represented by arrows.

Intrinsic—Job Satisfaction

With regard to job satisfaction, early-career faculty often invoked words such as “excitement,” “enjoyment,” and “passionate” to describe an overall theme of “excitement about daily work.” A positive affective state created by the nature of daily work was described as integral to the personal sense of career success. It was also strongly associated with perception of sustainability in a hospitalist career.

“I think [career success] would be job satisfaction. …So, for me, that would be happiness with my job. I like coming to work. I like doing what I do and at the end of the day going home and saying that was a good day. I like to think that would be success at work…is how I would define it.”

This theme was also related to a negative aspect often referred to as burnout, which many identified as antithetical to career success. More often, they described success as a heightened state of enthusiasm for the daily work experience.

“I am staying engaged and excited. So, I am not just taking care of patients; I am not just teaching. Having enough excitement from my work to come home and talk about it at dinner. To enjoy my days off but at the same time being excited to get back to work.”

This description of passion toward the work of being a hospitalist was often linked to a sense of deeper purpose found through the delivery of clinical care and education of learners.

“I really feel that we have the opportunity to very meaningfully and powerfully impact people’s lives, and that to me is meaningful. …That’s value. ...That’s coming home at the end of the day and thinking that you have had a positive impact.”

The interviews reflected that core to meaningful work was a sense of personal efficacy as a clinician, which was reflected in the themes of clinical proficiency and practicing high-quality care.

“I think developing clinical expertise, both through experience and studying. Getting to the point to where you can take really excellent care of your patient through expertise would be a sense of success that a lot of academic hospitalists would strive for.”

Intrinsic—Career Satisfaction

Within career satisfaction, participants described that “being respected and recognized” and “dissemination of work” were important contributors to career success. Reputation was frequently referenced as a measure of career success. Reputation was defined by some in a local context of having the respect of learners, peers, and others as a national renown. As a prerequisite for developing a reputation beyond the local academic environment, dissemination of work was often referenced as an important component of satisfaction in the career. This dissemination extended beyond peer-reviewed publications and included other forms of scholarship, presentations at conferences, and sharing clinical innovations between hospitals.

“For me personally, I have less of an emphasis on research and some of the more, I don’t want to say ‘academic’ because I think education is academic, but maybe some of the more scholarly practice of medicine, doing research and the writing of papers and things like that, although I certainly view some of that as a part of career success.”

Within career satisfaction, participants also described a diverse set of themes, including progressive improvement in skills, developing a self-perception of excellence in 1 or more arenas of academic medicine, leadership, work–life integration, innovation, and relationships. The concept of developing a niche, or becoming an expert in a particular domain of hospital medicine, was frequently referenced.

“I think part of [success] is ‘Have they identified a niche?’ Because I think if you want to be in an academic center, as much as I value teaching and taking care of patients, I think 1 of the advantages is the opportunity to potentially identify an area of expertise.”

Participants frequently alluded to the idea that the most important aspects of career satisfaction are not static phenomena but rather values that could evolve over the course of a career. For instance, in the early-career, making a difference with individual learners or patients could have greater valence, but as the career progressed, finding a niche, disseminating work, and building a national reputation would gain importance to a personal sense of career satisfaction.

Extrinsic—Advancement

Promotion was typically referenced when discussing career success, but it was not uniformly valued by early career hospitalists. Some expressed significant ambivalence about its effect on their personal sense of career success. Academic hospitalists identified a number of organizations with definitions of success that influence them. Definitions of success for the university were more relevant to interviewees compared to those of the hospital or professional societies. Interviewees were able to describe a variety of criteria by which their universities define or recognize career success. These commonly included promotion, publications and/or scholarship, and research. The list of factors perceived as success by the hospital were often distinct from those of the university and included cost-effective care, patient safety, and clinical leadership roles.

Participants described a sense of internal conflict when external-stakeholder definitions of success diverged from internal motivators. This was particularly true when this divergence led academic hospitalists to engage in activities for advancement that they did not find personally fulfilling. Academic hospitalists recognized that advancement was central to the concept of career success for organizations even if this was not identified as being core to their personal definitions of success.

“I think that for me, the idea of being promoted and being a leader in the field is less important to me than...for the organization.”

Hospitalists expressed that objective markers, such as promotion and publications, were perceived as more important at higher levels of the academic organization, whereas more subjective aspects of success, aligned with intrinsic personal definitions, were more valued within the hospital medicine group.

Extrinsic—Compensation

Compensation was notable for its absence in participants’ discussion of career success. When asked about their definitions of career success, academic hospitalists did not spontaneously raise the topic of compensation. The only mention of compensation was in response to a question about how personal and external definitions of career success differ.

Unexpected Findings

While it was almost universally recognized by participants as important, ambivalence toward the “academic value of clinical work,” “scholarship,” and especially “promotion” represented an unexpected thematic family.

“I can’t quite get excited about a title attached to my name or the number of times my name pops up when I enter it into PubMed. My personal definition is more…where do I have something that I am interested [in] that someone else values. And that value is not shown as an associate professorship or an assistant professorship next to my name. …When you push me on it, you could call me clinical instructor forever, and I don’t think I would care too much.”

The interaction between work and personal activities as representing complementary aspects of a global sense of success was also unexpected and ran contrary to a simplistic conception of work and life in conflict. Academic hospitalists referenced that the ability to participate in aspects of life external to the workplace was important to their sense of career success. Participants frequently used phrases such as “work–life balance” to encompass a larger sense that work and nonwork life needed to merge to form a holistic sense of having a positive impact.

“Personal success is becoming what I have termed a ‘man of worth.’ I think [that is] someone who feels as though they make a positive impact in the world. Through both my career, but I guess the things that I do that are external to my career. Those would be defined by being a good husband, a good son, a philanthropist out in the community…sometimes, these are not things that can necessarily go on a [curriculum vitae].”

Conflict Among Organizing Themes

At times, academic hospitalists described a tension between day-to-day job satisfaction and what would be necessary to accomplish longer-term career success in the other organizing themes. This was reflected by a sense of trade-off. For instance, activities that lead to some aspects of career satisfaction or advancement would take time away from the direct exposure to learners and clinical care that currently drive job satisfaction.

“If the institution wanted me to be more productive from a research standpoint or…advocate that I receive funding so I could buy down clinical time and interactions I have with my students and my patients, then I can see my satisfaction going down.”

Many described a sense of engaging in activities they did not find personally fulfilling because of a sense of expectation that those activities were considered successful by others. Some described a state in which the drive toward advancement as an extrinsic incentive could come at the expense of the intrinsic rewards of being an academic hospitalist.

Career success has been defined as “the positive psychological or work-related outcomes or achievements one accumulates as a result of work experiences.”^4,7,8 Academic career success for hospitalist faculty isn’t as well defined and has not been examined from the perspectives of early-career clinician-educator hospitalist faculty themselves.

The themes that emerged in this study describe a definition of success anchored in the daily work of striving to become an exceptional clinician and teacher. The major themes included (1) having excitement about daily work, (2) having meaningful impact, (3) development of a niche (4) a sense of respect within the sphere of academic medicine, and (5) disseminating work.

Success was very much internally defined as having a positive, meaningful impact on patients, learners, and the systems in which they practice. The faculty had a conception of what promotion committees value and often internalized aspects of this, such as developing a national reputation and giving talks at national meetings. Participants typically self-identified as clinician-educators, and yet dissemination of work remained an important component of personal success. While promotion was clearly identified as a marker of success, academic hospitalists often rejected the supposition of promotion itself as a professional goal. They expressed hope, and some skepticism, that external recognition of career success would follow the pursuit of internally meaningful goals.

While promotion and peer-reviewed publications represent easily measured markers often used as proxies for individual career and programmatic success, our research demonstrates that there is a deep well of externally imperceptible influences on an individual’s sense of success as an academic hospitalist. In our analysis, intrinsic elements of career success received far greater weight with early-career academic hospitalists. Our findings are supported by a prior survey of academic physicians that similarly found that faculty with >50% of their time devoted to clinical care placed greater career value in patient care, relationships with patients, and recognition by patients and residents compared to national reputation.⁹ Similar to our own findings, highly clinical faculty in that study were also less likely to value promotion and tenure as indicators of career success.⁹

The main focus of our questions was how early-career faculty define success at this point in their careers. When asked to extrapolate to a future state of career success, the concept of progression was repeatedly raised. This included successive promotions to higher academic ranks, increasing responsibility, titles, leadership, and achieving competitive roles or awards. It also included a progressively increasing impact of scholarship, growing national reputation, and becoming part of a network of accomplished academic hospitalists across the country. Looking forward, our early-career hospitalists felt that long-term career success would represent accomplishing these things and still being able to be focused on being excellent clinicians to patients, having a work–life balance, and keeping joy and excitement in daily activities.

Our work has limitations, including a focus on early-career clinician-educator hospitalists. The perception of career success may evolve over time, and future work to examine perceptions in more advanced academic hospitalists would be of interest. Our work used purposeful sampling to capture individuals who were likely to self-identify as academic clinician-educators, and results may not generalize to hospitalist physician-scientists or hospitalists in community practices.

Our analysis suggests that external organizations influence internal perceptions of career success. However, success is ultimately defined by the individual and not the institution. Efforts to measure and improve academic hospitalists’ attainment of career success should attend to intrinsic aspects of satisfaction in addition to objective measures, such as publications and promotion. This may provide a mechanism to address burnout and improve retention. As important as commonality in themes is the variation in self-definitions of career success among individuals. This suggests the value of inquiry by academic leadership in exploring and understanding what success is from the individual faculty perspective. This may enhance the alignment among personal definitions, organizational values, and, ultimately, sustainable, successful careers.

Disclosure: The authors have nothing to disclose.

Academic hospital medicine is a young specialty, with most faculty at the rank of instructor or assistant professor.¹ Traditional markers of academic success for clinical and translational investigators emphasize progressive, externally funded grants, achievements in basic science research, and prolific publication in the peer-reviewed literature.² Promotion is often used as a proxy measure for academic success.

Conceptual models of career success derived from nonhealthcare industries and for physician-scientists include both extrinsic and intrinsic domains.^3,4 Extrinsic domains of career success include financial rewards (compensation) and progression in hierarchical status (advancement).^3,4 Intrinsic domains of career success include pleasure derived from daily work (job satisfaction) and satisfaction derived from aspects of the career over time (career satisfaction).^3,4

Research is limited regarding hospitalist faculty beliefs about career success. A better understanding of hospitalist perspectives can inform program development to support junior faculty in academic hospital medicine. In this phenomenological, qualitative study, we explore the global concept of career success as perceived by early-career clinician-educator hospitalists.

Study Design, Setting, and Participants

We conducted interviews with hospitalists from 3 academic medical centers between May 2016 and October 2016. Purposeful sampling was used.⁵ Leaders within each hospital medicine group identified early-career faculty with approximately 2 to 5 years in academic medicine with a rank of instructor or assistant professor at each institution likely to self-identify as clinician-educators for targeted solicitation to enroll. Additional subjects were recruited until thematic saturation had been achieved on the personal definition of career success. Participants received disclosure and consent documents prior to enrollment. No compensation was provided to participants. This study was approved by the Colorado Multiple Institutional Review Board.