Author response: Venous ulcer treatment

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Author response: Venous ulcer treatment

My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.1

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis1 and a 2012 update2 found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.3 Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. O’Meara S, Cullum N, Nelson EA, et al. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;(11):CD000265.

3. Mayberry JC, Moneta GL, Taylor LM Jr, et al. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery. 1991;109:575-581.

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My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.1

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis1 and a 2012 update2 found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.3 Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.1

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis1 and a 2012 update2 found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.3 Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. O’Meara S, Cullum N, Nelson EA, et al. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;(11):CD000265.

3. Mayberry JC, Moneta GL, Taylor LM Jr, et al. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery. 1991;109:575-581.

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. O’Meara S, Cullum N, Nelson EA, et al. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;(11):CD000265.

3. Mayberry JC, Moneta GL, Taylor LM Jr, et al. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery. 1991;109:575-581.

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What is the best initial treatment for venous stasis ulcers?

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EVIDENCE-BASED ANSWER

THE MAINSTAY OF INITIAL TREATMENT of venous stasis ulcers is compression therapy (strength of recommendation [SOR]: A, systematic review of randomized controlled trials [RCTs]). Multicomponent compression therapy is slightly superior to single-component therapy (SOR: B, systematic review of RCTs with inconsistent results). The various types of dressings available for managing venous stasis ulcers aresimilarly efficacious (SOR: A, systematic review of RCTs).

Systemic therapies such as aspirin (SOR: B, single RCT) and pentoxifylline (SOR: A, systematic review of RCTs) improve healing rates whereas antibiotics don’t (SOR: A, systematic review of RCTs). Cadexomer iodine, a topical antiseptic, improves ulcer healing but may not be feasible in most clinical settings because of the frequent dressing changes required (SOR: B, single RCT).

 

Evidence summary

A systematic review found 7 RCTs with a total of 686 subjects that compared compression with no compression for venous leg ulcers.1  Although the outcome data were too heterogeneous for a meta-analysis, the 4 studies in which statistical analysis was possible showed that compression healed venous leg ulcers faster than no compression (relative risk [RR] range=1.2 to 4 in favor of compression), as detailed in the TABLE. Notably, only 2 of the studies achieved statistical significance (P<.05).

Two other studies in this review, with 20 and 245 patients, compared 4-component with single-component compression. In the smaller study, multicomponent compression produced more completely healed ulcers at 12 weeks, but the difference wasn’t statistically significant.

In the larger study, nonhealing at 24 weeks was much less common among patients treated with multicomponent compression than single-component therapy (RR=0.74; 95% confidence interval [CI], 0.59-0.92; number needed to treat [NNT]=5.7; P=.009), and median time to healing was shorter(78 vs 168 days; statistical significance not reported).

The reviewers concluded that compression increases ulcer healing rates compared with no compression and that multicomponent systems are more effective than single component systems.1

Similar results, different costs among dressing types
A systematic review and meta-analysis of 42 RCTs that included 3001 patients compared multiple dressing types, including hydrocolloid, foam, alginate, and low-adherent dressings, used beneath compression.2 The study found no significant differences in healing rates among the dressings, although costs varied widely.

Systemic therapy: Aspirin and pentoxifylline help
Systemic or topical treatments are an alternative for patients with contraindications or intolerance to compression. An RCT of 20 patients that compared aspirin 300 mg/day with placebo found higher ulcer healing rates in the aspirin group after 4 months (38% vs 0%; NNT=2.6; P<.007). Improvement, defined as reduction in ulcer size, occurred in 52%of patients treated with aspirin but only 26%treated with placebo(NNT=3.8;P<.007).3

A systematic review of 11 trials (N=841) found that pentoxifylline accelerated healing rates vs placebo (NNT=4; 95% CI, 3-6); the authors recommended its use in conjunction with compression therapy when possible.4

Another systematic review of 5 RCTs (N=232) found that systemic antibiotics didn’t improve outcomes significantly more than placebo.5

Topical cadexomer iodine: Effective, but is it feasible?
One of the 5 reviewed RCTs (60 patients) found that topical cadexomer iodine produced more frequent healing than standard care at 6 weeks (NNT=3;95%CI,2-19).5 However, the cadexomer regimen involved daily dressing changes, which might limit feasibility in many clinical settings.

Systemic aspirin and pentoxifylline improve healing rates, but systemic antibiotics don’t. Other interventions to consider for venous ulcers include hyperbaric oxygen and venous surgery. 

Recommendations

The Association for the Advancement of Wound Care recommends compression therapy and limb elevation to reduce edema.  They also recommend cleaning the ulcer with a safe cleanser, debriding nonvital tissue, maintaining a moist wound environment, and managing pain and odor.6

The Wound, Ostomy, and Continence Nurses Society and the American Society of Plastic Surgeons make similar recommendations: ulcer debridement, edema management, infection control, and pain management.7,8

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. Palfreyman SJ, Nelson EA, Lochiel R, et al. Dressings for healing venous leg ulcers. Cochrane Database Syst Rev. 2006;(3):CD001103.

3. Layton AM, Ibbotson SH, Davies JA, et al. Randomized trial of oral aspirin for chronic venous leg ulcers. Lancet. 1994;344:164-165.

4. JullAB,ArrollB, ParagV, et al. Pentoxifylline fortreating venous leg ulcers. Cochrane Database Syst Rev. 2007;(3):CD001733.

5. O’Meara S, Al-Kurdi D, Ovington LG, et al. Antibiotics and antiseptics for venous leg ulcers. CochraneDatabase Syst Rev. 2010;(1):CD003557.

6. Association fortheAdvancement of WoundCare (AAWC) venous ulcer guideline. 2010. Available at: http://aawconline.org/wpcontent/uploads/2012/03/AAWC-Venous-UlcerGuideline-Update+Algorithm-v28.pdf. Accessed November 16, 2012.

7. Wound, Ostomy, and Continence Nurses Society. Guideline for management of wounds in patients with lower-extremity venous disease. 2011. Available at: http://guideline.gov/content.aspx?id=38249. Accessed November 16, 2012.

8. American Society of Plastic Surgeons. Evidence-based clinicalpracticeguideline:Chronicwoundsofthelowerextremity. 2007. Available at: http://www.plasticsurgery.org/Documents/medical-professionals/health-policy/evidencepractice/Evidence-based-Clinical-Practice-GuidelineChronic-Wounds-of-the-Lower-Extremity.pdf. Accessed November 16, 2012.

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Elisha Poynter, MD;
Mark Andrews, MD

Department of Family Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC

Wendi Ackerman, MLS
Upstate Medical University, Syracuse, NY

ASSISTANT EDITOR
Carmen Strickland, MD
Wake Forest University School of Medicine, Winston-Salem, NC

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Elisha Poynter, MD;
Mark Andrews, MD

Department of Family Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC

Wendi Ackerman, MLS
Upstate Medical University, Syracuse, NY

ASSISTANT EDITOR
Carmen Strickland, MD
Wake Forest University School of Medicine, Winston-Salem, NC

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Elisha Poynter, MD;
Mark Andrews, MD

Department of Family Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC

Wendi Ackerman, MLS
Upstate Medical University, Syracuse, NY

ASSISTANT EDITOR
Carmen Strickland, MD
Wake Forest University School of Medicine, Winston-Salem, NC

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EVIDENCE-BASED ANSWER

THE MAINSTAY OF INITIAL TREATMENT of venous stasis ulcers is compression therapy (strength of recommendation [SOR]: A, systematic review of randomized controlled trials [RCTs]). Multicomponent compression therapy is slightly superior to single-component therapy (SOR: B, systematic review of RCTs with inconsistent results). The various types of dressings available for managing venous stasis ulcers aresimilarly efficacious (SOR: A, systematic review of RCTs).

Systemic therapies such as aspirin (SOR: B, single RCT) and pentoxifylline (SOR: A, systematic review of RCTs) improve healing rates whereas antibiotics don’t (SOR: A, systematic review of RCTs). Cadexomer iodine, a topical antiseptic, improves ulcer healing but may not be feasible in most clinical settings because of the frequent dressing changes required (SOR: B, single RCT).

 

Evidence summary

A systematic review found 7 RCTs with a total of 686 subjects that compared compression with no compression for venous leg ulcers.1  Although the outcome data were too heterogeneous for a meta-analysis, the 4 studies in which statistical analysis was possible showed that compression healed venous leg ulcers faster than no compression (relative risk [RR] range=1.2 to 4 in favor of compression), as detailed in the TABLE. Notably, only 2 of the studies achieved statistical significance (P<.05).

Two other studies in this review, with 20 and 245 patients, compared 4-component with single-component compression. In the smaller study, multicomponent compression produced more completely healed ulcers at 12 weeks, but the difference wasn’t statistically significant.

In the larger study, nonhealing at 24 weeks was much less common among patients treated with multicomponent compression than single-component therapy (RR=0.74; 95% confidence interval [CI], 0.59-0.92; number needed to treat [NNT]=5.7; P=.009), and median time to healing was shorter(78 vs 168 days; statistical significance not reported).

The reviewers concluded that compression increases ulcer healing rates compared with no compression and that multicomponent systems are more effective than single component systems.1

Similar results, different costs among dressing types
A systematic review and meta-analysis of 42 RCTs that included 3001 patients compared multiple dressing types, including hydrocolloid, foam, alginate, and low-adherent dressings, used beneath compression.2 The study found no significant differences in healing rates among the dressings, although costs varied widely.

Systemic therapy: Aspirin and pentoxifylline help
Systemic or topical treatments are an alternative for patients with contraindications or intolerance to compression. An RCT of 20 patients that compared aspirin 300 mg/day with placebo found higher ulcer healing rates in the aspirin group after 4 months (38% vs 0%; NNT=2.6; P<.007). Improvement, defined as reduction in ulcer size, occurred in 52%of patients treated with aspirin but only 26%treated with placebo(NNT=3.8;P<.007).3

A systematic review of 11 trials (N=841) found that pentoxifylline accelerated healing rates vs placebo (NNT=4; 95% CI, 3-6); the authors recommended its use in conjunction with compression therapy when possible.4

Another systematic review of 5 RCTs (N=232) found that systemic antibiotics didn’t improve outcomes significantly more than placebo.5

Topical cadexomer iodine: Effective, but is it feasible?
One of the 5 reviewed RCTs (60 patients) found that topical cadexomer iodine produced more frequent healing than standard care at 6 weeks (NNT=3;95%CI,2-19).5 However, the cadexomer regimen involved daily dressing changes, which might limit feasibility in many clinical settings.

Systemic aspirin and pentoxifylline improve healing rates, but systemic antibiotics don’t. Other interventions to consider for venous ulcers include hyperbaric oxygen and venous surgery. 

Recommendations

The Association for the Advancement of Wound Care recommends compression therapy and limb elevation to reduce edema.  They also recommend cleaning the ulcer with a safe cleanser, debriding nonvital tissue, maintaining a moist wound environment, and managing pain and odor.6

The Wound, Ostomy, and Continence Nurses Society and the American Society of Plastic Surgeons make similar recommendations: ulcer debridement, edema management, infection control, and pain management.7,8

EVIDENCE-BASED ANSWER

THE MAINSTAY OF INITIAL TREATMENT of venous stasis ulcers is compression therapy (strength of recommendation [SOR]: A, systematic review of randomized controlled trials [RCTs]). Multicomponent compression therapy is slightly superior to single-component therapy (SOR: B, systematic review of RCTs with inconsistent results). The various types of dressings available for managing venous stasis ulcers aresimilarly efficacious (SOR: A, systematic review of RCTs).

Systemic therapies such as aspirin (SOR: B, single RCT) and pentoxifylline (SOR: A, systematic review of RCTs) improve healing rates whereas antibiotics don’t (SOR: A, systematic review of RCTs). Cadexomer iodine, a topical antiseptic, improves ulcer healing but may not be feasible in most clinical settings because of the frequent dressing changes required (SOR: B, single RCT).

 

Evidence summary

A systematic review found 7 RCTs with a total of 686 subjects that compared compression with no compression for venous leg ulcers.1  Although the outcome data were too heterogeneous for a meta-analysis, the 4 studies in which statistical analysis was possible showed that compression healed venous leg ulcers faster than no compression (relative risk [RR] range=1.2 to 4 in favor of compression), as detailed in the TABLE. Notably, only 2 of the studies achieved statistical significance (P<.05).

Two other studies in this review, with 20 and 245 patients, compared 4-component with single-component compression. In the smaller study, multicomponent compression produced more completely healed ulcers at 12 weeks, but the difference wasn’t statistically significant.

In the larger study, nonhealing at 24 weeks was much less common among patients treated with multicomponent compression than single-component therapy (RR=0.74; 95% confidence interval [CI], 0.59-0.92; number needed to treat [NNT]=5.7; P=.009), and median time to healing was shorter(78 vs 168 days; statistical significance not reported).

The reviewers concluded that compression increases ulcer healing rates compared with no compression and that multicomponent systems are more effective than single component systems.1

Similar results, different costs among dressing types
A systematic review and meta-analysis of 42 RCTs that included 3001 patients compared multiple dressing types, including hydrocolloid, foam, alginate, and low-adherent dressings, used beneath compression.2 The study found no significant differences in healing rates among the dressings, although costs varied widely.

Systemic therapy: Aspirin and pentoxifylline help
Systemic or topical treatments are an alternative for patients with contraindications or intolerance to compression. An RCT of 20 patients that compared aspirin 300 mg/day with placebo found higher ulcer healing rates in the aspirin group after 4 months (38% vs 0%; NNT=2.6; P<.007). Improvement, defined as reduction in ulcer size, occurred in 52%of patients treated with aspirin but only 26%treated with placebo(NNT=3.8;P<.007).3

A systematic review of 11 trials (N=841) found that pentoxifylline accelerated healing rates vs placebo (NNT=4; 95% CI, 3-6); the authors recommended its use in conjunction with compression therapy when possible.4

Another systematic review of 5 RCTs (N=232) found that systemic antibiotics didn’t improve outcomes significantly more than placebo.5

Topical cadexomer iodine: Effective, but is it feasible?
One of the 5 reviewed RCTs (60 patients) found that topical cadexomer iodine produced more frequent healing than standard care at 6 weeks (NNT=3;95%CI,2-19).5 However, the cadexomer regimen involved daily dressing changes, which might limit feasibility in many clinical settings.

Systemic aspirin and pentoxifylline improve healing rates, but systemic antibiotics don’t. Other interventions to consider for venous ulcers include hyperbaric oxygen and venous surgery. 

Recommendations

The Association for the Advancement of Wound Care recommends compression therapy and limb elevation to reduce edema.  They also recommend cleaning the ulcer with a safe cleanser, debriding nonvital tissue, maintaining a moist wound environment, and managing pain and odor.6

The Wound, Ostomy, and Continence Nurses Society and the American Society of Plastic Surgeons make similar recommendations: ulcer debridement, edema management, infection control, and pain management.7,8

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. Palfreyman SJ, Nelson EA, Lochiel R, et al. Dressings for healing venous leg ulcers. Cochrane Database Syst Rev. 2006;(3):CD001103.

3. Layton AM, Ibbotson SH, Davies JA, et al. Randomized trial of oral aspirin for chronic venous leg ulcers. Lancet. 1994;344:164-165.

4. JullAB,ArrollB, ParagV, et al. Pentoxifylline fortreating venous leg ulcers. Cochrane Database Syst Rev. 2007;(3):CD001733.

5. O’Meara S, Al-Kurdi D, Ovington LG, et al. Antibiotics and antiseptics for venous leg ulcers. CochraneDatabase Syst Rev. 2010;(1):CD003557.

6. Association fortheAdvancement of WoundCare (AAWC) venous ulcer guideline. 2010. Available at: http://aawconline.org/wpcontent/uploads/2012/03/AAWC-Venous-UlcerGuideline-Update+Algorithm-v28.pdf. Accessed November 16, 2012.

7. Wound, Ostomy, and Continence Nurses Society. Guideline for management of wounds in patients with lower-extremity venous disease. 2011. Available at: http://guideline.gov/content.aspx?id=38249. Accessed November 16, 2012.

8. American Society of Plastic Surgeons. Evidence-based clinicalpracticeguideline:Chronicwoundsofthelowerextremity. 2007. Available at: http://www.plasticsurgery.org/Documents/medical-professionals/health-policy/evidencepractice/Evidence-based-Clinical-Practice-GuidelineChronic-Wounds-of-the-Lower-Extremity.pdf. Accessed November 16, 2012.

References

1. O’Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2009;(1):CD000265.

2. Palfreyman SJ, Nelson EA, Lochiel R, et al. Dressings for healing venous leg ulcers. Cochrane Database Syst Rev. 2006;(3):CD001103.

3. Layton AM, Ibbotson SH, Davies JA, et al. Randomized trial of oral aspirin for chronic venous leg ulcers. Lancet. 1994;344:164-165.

4. JullAB,ArrollB, ParagV, et al. Pentoxifylline fortreating venous leg ulcers. Cochrane Database Syst Rev. 2007;(3):CD001733.

5. O’Meara S, Al-Kurdi D, Ovington LG, et al. Antibiotics and antiseptics for venous leg ulcers. CochraneDatabase Syst Rev. 2010;(1):CD003557.

6. Association fortheAdvancement of WoundCare (AAWC) venous ulcer guideline. 2010. Available at: http://aawconline.org/wpcontent/uploads/2012/03/AAWC-Venous-UlcerGuideline-Update+Algorithm-v28.pdf. Accessed November 16, 2012.

7. Wound, Ostomy, and Continence Nurses Society. Guideline for management of wounds in patients with lower-extremity venous disease. 2011. Available at: http://guideline.gov/content.aspx?id=38249. Accessed November 16, 2012.

8. American Society of Plastic Surgeons. Evidence-based clinicalpracticeguideline:Chronicwoundsofthelowerextremity. 2007. Available at: http://www.plasticsurgery.org/Documents/medical-professionals/health-policy/evidencepractice/Evidence-based-Clinical-Practice-GuidelineChronic-Wounds-of-the-Lower-Extremity.pdf. Accessed November 16, 2012.

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What is the best initial treatment for venous stasis ulcers?
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