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Topical wound therapies have unclear benefits for patients with pressure ulcers, venous leg ulcers (VLUs), and arterial ulcers. There is slightly more evidence supporting the use of systemic therapies. Used with compression therapy or alone, oral pentoxifylline has been shown to be more effective than placebo or no therapy in improving and healing VLUs. (This is an off-label use of pentoxifylline.) To prevent bacterial resistance, most guidelines recommend use of antimicrobial dressings, antiseptics, and antibiotics only for patients with infected wounds. There is insufficient evidence to conclude that antiseptics or topical antibiotics improve or heal pressure ulcers and VLUs more effectively than nonmedicated dressings. Systemic antibiotics are used for patients with nonhealing wounds when the clinical infection is not improving with antiseptics or topical antibiotics. After the underlying cause of a chronic wound is addressed, pain management should start with topical drugs. When pain is not managed with topical drugs, systemic drugs should be considered. Opioids should be used only if the overall benefits outweigh the risks. Nutritional supplementation has not been clearly shown to prevent or manage chronic ulcers.

Case 3. Priya is a 67-year-old Indian-American woman with hypertension and dyslipidemia. She presents to your office with a 4-month history of nonhealing bilateral venous leg ulcers. She reports ulcer pain during dressing changes and finds it difficult to apply compression stockings over the thick dressings.

Topical

Phenytoin, an antiepileptic drug, has been used topically to manage wounds. A Cochrane review based on three small randomized controlled trials (RCTs) showed insufficient evidence for the effectiveness of topical phenytoin compared with hydrocolloid dressings, triple antibiotic ointment, and simple dressings in the management of stage 1 and 2 pressure ulcers.67 (This is an off-label use of phenytoin.)

A 2019 RCT performed in Iran that included 200 critically ill patients evaluated topical nifedipine for management of stage 1 and 2 pressure ulcers.68 It showed that topical nifedipine, at 1 and 2 weeks, was more effective than placebo in decreasing the depth and size of ulcers. The dropout rate was 17% in each group and the authors did not use intention-to-treat analysis. More rigorous trials are needed before strong recommendations can be made for use of topical nifedipine. (This is an off-label use of nifedipine.)

A study was conducted with 112 critically ill adult patients using topical pentoxifylline for management of stage 1 and 2 pressure ulcers.69 It showed that topical pentoxifylline was more effective than placebo at 1 and 2 weeks in decreasing the severity (ie, stage) and size of ulcers. The study was limited by its small size, single location (ie, intensive care unit in a tertiary center), and short follow-up. (This is an off-label use of pentoxifylline.)

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