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Background 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.
Objectives Systematically to identify, summarize and critically appraise the clinical evidence available on the effects of topical phenytoin on wound healing.
Methods 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.
Results 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.
Conclusions 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.
The impact of topical phenytoin on recalcitrant neuropathic diabetic foot ulceration.
El-Nahas M, Gawish H, Tarshoby M, State O. J Wound Care. 2008 Dec 19;18(1):33-37
Quote:
Objective: To study the impact of topical phenytoin on the healing of recalcitrant neuropathic diabetic foot ulcers in patients with no clinical evidence of ischaemia or infection, and to evaluate its antibacterial effect.
Method: Thirty-two patients were enrolled into the study. Topical phenytoin in the form of 2% aerosol powder was applied once daily in addition to the patient’s usual treatment (weekly sharp debridement, offloading and use of a gauze dressing) for eight weeks. The primary outcome was change in ulcer area over time, measured by grid tracing. Secondary outcomes were the ability of topical phenytoin to eradicate bacterial isolates, and the occurrence of adverse events.
Results: Topical phenytoin significantly improved healing of recalcitrant neuropathic diabetic foot ulcers. Baseline wound area was 319.3 + 340.4mm2, reducing to 286.1 + 341.1mm2 and 269.1 + 341.2mm2 after four and eight weeks respectively. However, the overall reduction in ulcer size was only 18.3% + 27.5% and 25.7% + 38.6 % respectively. Topical phenytoin therapy over eight weeks did not eradicate any of the bacterial wound isolates (Staphylococcus spp., Proteus spp. or Pseudomonas spp.). Of the 32 patients evaluated, only eight (25%) achieved more than 50% reduction in ulcer size after eight weeks of treatment.
Conclusion: Topical phenytoin can enhance wound healing in recalcitrant neuropathic diabetic foot ulcers, although only one-quarter of patients achieved more than 50% reduction in ulcer size after eight weeks of therapy. Further research is needed to characterise those patients who will satisfactorily respond to such therapy
Topical phenytoin and wound healing
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