The clinical effect of topical phenytoin on wound healing: a systematic review

Oral phenytoin was first introduced as an antiseizure medication in 1937. Over 60 years investigators have shown an interest in how topical phenytoin may be used to promote wound healing in a variety of chronic wounds.

Systematically to identify, summarize and critically appraise the clinical evidence available on the effects of topical phenytoin on wound healing.

Systematic searches were carried out in PubMed (1963-2005), Medline (1966-2005) and Cinahl (1982-2005) for the years listed and in the Cochrane Library and the University of York NHS Centre for Reviews and Dissemination. The search terms used the following key words alone and in combination: phenytoin, wounds and injuries, wound healing, and wound care. Secondary hand searching was also carried out using relevant journal articles and reference lists, historical books, conference proceedings and theses in the area of wound healing. Papers were included if they described randomized controlled trials (RCTs) on humans and if the primary aim was wound closure, with a secondary aim of measuring wound healing over time. The methodological quality of the papers in this systematic review was assessed using the van Tulder method and in addition best-evidence synthesis was carried out. The magnitude of the effect of phenytoin therapy in the studies included in the systematic review was investigated in four of the 14 trials.

Fourteen RCTs were included in the systematic review. Two papers were of high and 12 papers of low to moderate methodological quality. Most papers failed to describe randomization, treatment allocation and blinding techniques adequately. There was moderate evidence presented to support the use of phenytoin for the treatment of leg ulcers, leprosy wounds, chronic wounds and diabetic foot ulcers. There was a positive percentage treatment effect in favour of the phenytoin-treated group in one study investigating diabetic foot wounds and one study on chronic wounds. There was limited evidence for the use of phenytoin on burns and war wounds.

Overall it would appear that studies investigating the effect of topical phenytoin on wound healing are of moderate methodological quality, and these suggest that there may be a positive effect on wound healing in a variety of wounds.