DOI: http://dx.doi.org/10.18203/2349-2902.isj20174174

The efficacy of phenytoin dressing in healing of diabetic ulcer: a randomized control study

Vijay Gunasekaran, Saravanakumar Subbaraj, Tirou Aroul

Abstract


Background: Diabetic foot infection constitutes up to 10 percent of diabetes-related hospital admissions and the prevalence of diabetes is 2.4% in rural and 12-17% in urban settings. The quest for better wound healing agents for diabetic ulcers is perhaps one of the oldest challenges for medical practice. One such agent that has been tried in wound healing is phenytoin. A common side effect of phenytoin (diphenylhydantoin) treatment for epilepsy is gingival hyperplasia. This stimulatory effect of phenytoin on connective tissue suggested a possibility for its use in wound healing.

Methods: 60 patients with diabetic foot ulcer admitted in General Surgery at Mahatma Gandhi Medical College and Research Institute, Puducherry, India were randomly assigned into two groups, the study group consisting of 30 patients who were treated with phenytoin dressing and 30 patients into control group who were treated with conventional saline dressing. Both groups underwent initial debridement and were started on parenteral antibiotics according to wound swab culture and sensitivity. Study group were treated with phenytoin dressing and the wound was assessed based on the rate of ulcer size reduction, the rate of granulation tissue, duration of hospital stays and antibacterial property of phenytoin. Patients were assessed weekly up to 21 days.

Results: The rate of granulation tissue in phenytoin group was 90.36% which was statistically significant (p = 0.0011) as compared to control group which was 82.03%. Wound swab cultures repeated on day 21 revealed that there was 50% negative culture in phenytoin group when compared to control group of 24% which also was statistically significant. The mean hospital stay for the patient in phenytoin group was 29.2 days and in control group, it was 26.1 days. It was observed that surface area reduction in phenytoin group was 41.25cm2 to 18.38cm2 and in control group was 40.28cm2 to 20.23cm2 by the end of 21 days, but this was not statistically significant.

Conclusions: Phenytoin dressing is effective in increasing the rate of granulation tissue by virtue of its action on stimulating fibroblast proliferation and decreasing collagenase activity. It not only hastens granulation tissue but also decreases bacterial load as compared to conventional dressing by virtue of its intrinsic antibacterial activity and indirectly through their effects on anti-inflammatory cells and neovascularization. Phenytoin prepares the foot ulcer for early grafting thereby improving the overall outcome.


Keywords


Diabetic foot ulcer, Granulation tissue, Moist dressing, Topical phenytoin dressing, Wound healing

Full Text:

PDF

References


Jyothylekshmy V, Menon AS, Abraham S. Epidemiology of diabetic foot complications in a podiatry clinic of a tertiary hospital in South India. Indian J Health Sci. 2015;8(1):48-51.

Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:217-28.

Calhoun JH, Overgaard KA, Stevens CM, Dowling JP, Mader JT. Diabetic foot ulcers and infections: current concepts. Adv Skin Wound Care. 2002;15:31-42.

Younes N, Albsoul A, Badran D, and Obedi S. Wound bed preparation with 10 percent phenytoin ointment increases the take of split-thickness skin graft in large diabetic ulcers. Dermatol Online J. 2006;12(6):5.

Meritt HH, Putnam TJ. Sodium diphenyl hydantoinate in the treatment of convulsive disorders. JAMA. 11938;11:1068-73.

Silverman AK, Fairley J, Wongs RC. Cutaneous and Immunologic reactions to phenytoin. J Am Acad Dermatol. 1988;18:721-41.

Zayat SG. Preliminary experience with topical phenytoin in wound healing in a war zone. Mil Med. 1989;154:178-80.

Rhodes RS, Heyneman CA, Culbersten VL, Wilson SE, Phatak HM. Topical phenytoin treatment of stage II decubitus ulcers in the elderly. Ann Pharmaco Ther. 2001;35:675-81.

Simpson GM, Kunz E, Slafta J. Use of diphenylhydantoin in treatment of leg ulcers, N Y State J Med. 1965;65:886-8.

Modaghegh S, Salchian B, Tavassoli M, Djamshidi A, Rezai AS. Use of phenytoin in healing of war and non war wounds, a pilot study of 25 cases. Int J Dermatol. 1989;28:347-50.

Pendse AK, Sharma A, Sodani A, Hada S. Topical phenytoin in wound healing. Int J Dermatol. 1993;32:214-7.

Lodha SC. New application of an old drug: topical phenytoin for burns. J Burn Care Rehabil. 1991;12(1):96.

Bansal NK, Mukul. Comparison of topical phenytoin with normal saline in the treatment of chronic trophic ulcers in leprosy. Int J Dermatol. 1993;34:210-3.

Bethedsa MD. ASHP drug information 2001, American Society of Health System Pharmacists. 2001:2081.

DaCosta ML, Regan MC, al Sader M, Leader M, Bouchier-Hayes D. Diphenylhydantoin sodium promotes early and marked angiogenesis and results in increased collagen deposition and tensile strength in healing wounds. Surg. 1998;123:287-93.

Kato T, Okahashi N, Kawai S, Kato T, Inaba H, Morisaki I, et al. Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin. J Periodontol. 2005;76:941-50.

Moy LS, Tan EM, Holness R, Uitto J. Phenytoin modulates connective tissue metabolism and cell proliferation in human skin fibroblast cultures. Arch Dermatol. 1985;121:79-83.

Genever PG, Cunliffe WJ, Wood EJ. Influence of the extracellular matrix on fibroblast responsiveness to phenytoin using in vitro wound healing models. Br J Dermatol. 1995;133:231-5.

Swamy SM, Tan P, Zhu YZ, Lu J, Achuth HN, Moochhala S. Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004;314:661-6.

Richard JL, Sotto A, Lavigne JP. New insights in diabetic foot infection. World J Diabetes. 2011;2(2):24-32.

Kodela SR, Prasanna Kumar TJ, Vivek. Out come of topical phenytoin in the management of diabetic ulcers. IOSR-JDMS. 2016;15(7):39-54.

Tauro LF, Shetty P, Dsouza NT, Mohammed S, Sucharitha S. A comparative study of efficacy of topical phenytoin vs conventional wound care in diabetic ulcers. Int J Mol Med Sci. 2013;3:8.

Patil V, Patil R, Kariholu PL, Patil LS, Shahapur P. Topical phenytoin application in grade i and ii diabetic foot ulcers: a prospective study. JCDR. 2013;7(10):2238-40.

Muthukumarasamy MG, Sivakumar G, Manoharan G. Topical phenytoin in diabetic foot ulcers; diabetes care. 1991;14(10):909-11.

Aplqvist J. Long term prognosis for diabetic patients with foot ulcers. J Int Med. 1993;233:485-91.

Nouvong A. Evaluation of diabetic foot ulcer healing with hyperspectral imaging of oxyhemoglobin and deoxyhemoglobin. Diabet Care. 2009;32(11):2056-61.

Green W. Cost-effectiveness analysis of d-nav for people with diabetes at high risk of neuropathic foot ulcers. Diabetes Ther. 2016;7:511-25.

Modaghegh S, Salchian B, Tavassoli M, Djamshidi A, Rezai AS. Use of phenytoin in healing of war and non-war wounds, a pilot study of 25 cases, Int J Dermatol. 1989;28:347-50.

Rituraj, Aggarwal S, Chatterjee S. Topical phenytoin: role in diabetic ulcer care. IJIMS. 2015;2(6):93-7.