Topical Phenytoin Demonstrates Improved Wound Healing

Dr. Kaiser O'Sahil Sadiq shares key details from his paper, “Topical phenytoin demonstrates improved wound healing, analgesic and antibacterial properties with minimal side effects: a systematic review”; coauthors include Yogamba Mysore Shivakumar, MBBS, MPH; Eshwar Kumar Burra, MBBS; Kamran Shahid, MBBS; Yonas Teferra Tamene, MD, MSN; Shefali Piyush Mody, MBBS; and Tuheen Sankar Nath, MBBS. Read the full paper here.

Transcript

Kaiser O'Sahil Sadiq, MBBS:

My name is Dr. Kaiser Sadiq, and the systematic review that I will be discussing today was conducted while I was a research student with California Institute of Behavioral Neurosciences and Psychology. I earned my medical degree from Jipmer, which is an institute of national importance in India, and I'm currently pursuing a surgical residency in the United States. It's my utmost pleasure to share our work titled “Topical phenytoin demonstrates improved wound healing, analgesic and antibacterial properties with minimal side effects: A systematic review.”

Phenytoin was first developed in 1937 as an anticonvulsant. Its wound healing and analgesic properties were first observed by Shapiro, who published his findings in 1958.

We conducted a systematic review, and we searched PubMed, PubMed Central, Medline, and the Cochrane Library for control trials, both randomized control trials and non-randomized control trials. We included only human studies that were published in English. We excluded studies of other design types as well as in vitro studies, animal studies, and studies that were published in languages other than English. Our search strategy yielded a total of 101 studies, out of which 28 were retrieved and assessed for quality using the RoB 2 tool and the ROBINS-I tool, which were used for randomized control studies and non-randomized control studies respectively. We were left with a total of 17 randomized control studies and 8 non-randomized control studies. After our quality assessment, 5 of these looked at wounds of various etiologies and 20 looked at wounds of single etiologies, namely diabetic foot ulcers, pressure ulcers, leprotic trophic ulcers, traumatic wounds, burns, abscess cavities, and surgical wounds, including oral biopsy wounds, sutured episiotomies, anal fistulotomies, split skin graft donor sites, and the wounds left from excision of melanocytic knee.

Sixty-four percent of studies compared Phenytoin to inert controls, most commonly normal saline, while 36% compared Phenytoin to potentially pharmacologically active compounds such as USOL, framycetin, honey, and aloe vera, to name a few. Seventy percent showed that Phenytoin resulted in accelerated wound healing. There was increased granulation in 89%, a reduction of bacterial contamination in 75%, and an alleviation of pain in 54%. Seventy-one percent reported no side effects, while the remaining 29% reported fairly minimal side effects of a burning sensation, pruritus, or local irritation at the site of administration, some of which were transient, and 2 studies reported excessive granulation tissue, which was reversible.

During my internship in India, while I was rotating in the general surgery department, a large proportion of our patients had chronic wounds due to necrotizing fasciitis, diabetic ulcers, burns, and Fournier’s gangrene. One of the residents at that time applied Phenytoin as part of the wound dressing, and I observed that this led to increased granulation tissue. This inspired me to lead this systematic review to investigate the merits of this relatively inexpensive medicine as an adjunct to wound care.

The most surprising result was Phenytoin’s apparent antibacterial properties in studies that assessed bacterial contamination using wound cultures, 75% resulted in culture negativity. The exact mechanism is unknown at this time, but it has been postulated to be either due to an increase in the local microcirculation or as a result of a direct antibacterial effect of Phenytoin.

The studies in our review varied with regard to dosage and frequency of topical Phenytoin administration. We believe that further trials investigating the optimal dose and frequency would be beneficial to propose guidelines for clinical usage. We also believe that further trials should be conducted looking into Phenytoin usage for postoperative wounds, particularly whether it has any effect on wound complications.