An Evidence-Based Algorithm for Treating Venous Leg Ulcers Utilizing the Cochrane Database of Systematic Reviews

Howard M. Kimmel, DPM, MBA, FACFAS; Angela L. Robin, DPM


Wounds. 2013;25(9):242-250. 

In This Article

Systemic Therapy

The use of systemic agents should be considered in patients with chronic or recurrent VLUs and in those with negative prognostic factors. Systemic agents may be used alone or in combination with compression and other mechanical modalities. Despite a number of studies designed to examine the efficacy and safety of adjunctive systemic therapy in patients with VLUs, and possibly as monotherapy, the cost-effectiveness of this approach has not been established. Pentoxifylline is an inhibitor of platelet aggregation which reduces blood viscosity and, in turn, improves microcirculation. The Cochrane Database reported an extensive review of randomized trials comparing pentoxifylline with placebo or other therapy in the presence or absence of compression in patients with VLU.[40] The authors found that pentoxifylline is more effective than placebo in terms of complete ulcer healing or significant improvement (RR, 1.70). Pentoxifylline plus compression proved more effective than placebo plus compression (RR, 1.56), and pentoxifylline in the absence of compression was more effective than placebo or no treatment (RR 2.25). More adverse effects were reported in patients receiving pentoxifylline (RR 1.56) and most of the reported adverse effects were gastrointestinal.[40]

Like pentoxifylline therapy, aspirin (300 mg per day) combined with compression therapy has been shown to decrease ulcer healing time and reduce ulcer size compared with compression therapy alone.[41] The therapeutic role of aspirin in VLUs is supported by observed increases in levels of fibrinogen, coagulation factor VIII, von Willebrand factor, and plasminogen activator inhibitor-1 in patients with VLUs compared with healthy controls.[42] The addition of aspirin therapy to compression bandages may be useful in the treatment of VLUs as long as there are no contraindications to its use.

Bacterial colonization and superimposed bacterial infections are common in VLUs and contribute to poor wound healing. However, a recent Cochrane Review of 22 randomized control trials of systemic and topical antibiotics and antiseptics for VLU treatment found no evidence that routine use of oral antibiotics improves healing rates.[43] Oral antibiotics may be indicated in patients with VLUs and suspected cellulitis. Suspected osteomyelitis warrants an evaluation for arterial disease and consideration of intravenous antibiotics to treat the underlying infection. Only topical cadexomer iodine showed promising results.[43]

Oxygen is essential to wound healing. Local tissue hypoxia, caused by disrupted or compromised vasculature, is a key factor that limits wound healing.[44] Clinical use of oxygen to promote wound healing began in the 1960s with the administration of systemic full body hyperbaric oxygen therapy (HBOT) to treat wounds.[45] Today, HBOT is usually administered in single- or multiplace chambers utilizing pressures of 2,500 mb and higher. There has been only 1 study on VLUs that indicated a significant reduction in wound area at 6 weeks following the administration of HBOT.[46] The problem with HBOT is the possible complications such as damage to the ears, sinuses, and lungs from the effects of pressure, temporary worsening of short-sightedness, claustrophobia, and oxygen poisoning. Although serious adverse events are rare, HBOT cannot be regarded as an entirely benign intervention. Furthermore, as an adjunct to standard therapy HBOT may be associated with increased costs, and any cost/benefit advantage should be carefully considered.[47]