Open Access Peer-reviewed

Intravenous Phenytoin: Potential New Therapy for Gastrointestinal Fistlae

Saed A Jaber1,, Basma M Fallatah1, Bader Tayara1, Hassan Yami1, Mahmoud Abdelmoeti1

1Surgery Department, KFMMC, Dhahran, Saudi Arabia

Global Journal of Surgery. 2013, 1(3), 11-14. DOI: 10.12691/js-1-3-1
Published online: August 25, 2017

Abstract

Gastrointestinal fistulae are among the most devastating complications of gastrointestinal surgery and can be lethal. Fistula tract healing consists of several processes, including cell migration and formation of a new extracellular matrix. Multiple studies have demonstrated that phenytoin can promote wound healing and induce faster fibrosis. We postulate that the positive effects of phenytoin can be used to enhance fibrosis of the fistula tract. We treated 16 patients who had developed GI fistulae as a complication of surgical intervention. Five patients developed external small intestinal fistulae, 3 patients developed colonic fistulae, 3 patients developed pancreatic fistulae, 1 patient developed a biliary fistula and 4 patients developed gastrocutaneous fistulae. Patients were started on IV phenytoin for the first 4 days and subsequently switched to oral phenytoin for a total of ten days. A significant drop in output was noticed 3-4 days after treatment. The fistulae healed in a short period averaging 8 days without the need for a surgical intervention in 13 patients (81%), but failed to heal in three patients. Conclusion: intravenous phenytoin may have a positive effect on the treatment of fistulae. Prospective studies are needed to validate this potential effect of phenytoin on fistula healing.

Keywords:

gastrointestinal, fistulae, surgery, phenytoin
[1]  Silverman, A.K., Fairley, J., Wong, R.C. Cutaneous and immunologic reactions to phenytoin. J Am Acad Dermatol. 18, 721-741,1988.View Article
 
[2]  Eisenberg, M., Stevens, L.H., Schofield, P.J. Epidermolysis bullosa--new therapeutic approaches. Australas J Dermatol. 19, 1-8.1978.
 
[3]  Kero, M. Epidermolysis bullosa in Finland - Clinical features, morphology, and relation to collagen metabolism. Acta Derm Venereol Suppl. 110, 1-51.1984.
 
[4]  Bauer, E.A., Gedde-Dahl Jr, T., Eisen, A.Z. The role of human skin collagenase in epidermolysis bullosa. J Invest Dermatol. 68, 119-124.1977.
 
[5]  Talas, G., Adams, T.S., Eastwood, M., Rubio, G., Brown, R.A. Phenytoin reduces the contraction of recessive dystrophic epidermolysis bullosa fibroblast populated collagen gels. Int J Biochem Cell Biol. 29, 261-270.1997.
 
[6]  Genever, P.G., Cunliffe, W.J., Wood, E.J. Influence of the extracellular matrix on fibroblast responsiveness to phenytoin using in vitro wound healing models. Br J Dermatol. 133, 231-235.1995.
 
[7]  Moy, L.S., Tan, E.M., Holness, R., Uitto, J. Phenytoin modulates connective tissue metabolism and cell proliferation in human skin fibroblast cultures. Arch Dermatol. 121, 79-83.1985.
 
[8]  Fischer, J.E. The pathophysiology of enterocutaneous fistulas. World J Surg. 7, 446-450.1983.
 
[9]  González-Pinto, I., Moreno, G.O. Optimising the treatment of upper gastrointestinal fistulae. Gut. 49, iv21-iv28 .2002.
 
[10]  Foster 3rd, C.E., Lefore, A.T. General management of gastrointestinal fistulas - Recognition, stabilization, and correction of fluid and electrolyte imbalances. Surg Clin North Am. 76, 1019-1033.1996.
 
[11]  Cunnane, S.C., Kent, E.T., Mcadoo, K.R., Caldwell, D., Lin, A.N., Carter, D.M. Abnormalities of plasma and erythrocyte essential fatty acid composition in epidermolysis bullosa: influence of treatment with diphenylhydantoin. Invest Dermatol. 89, 395-399.1987.
 
[12]  Muthukumarasamy, M.G., Sivakumar, G., Manoharan, G. Topical phenytoin in diabetic foot ulcers. Diabetes Care. 14, 909-911.1991.
 
[13]  Talas, G., Brown, R.A., Mcgrouther, D.A. Role of phenytoin in wound healing--a wound pharmacology perspective. Biochem Pharmacol. 57, 1085-1094.1999.
 
[14]  Dill, R.E., Miller, E.K., Weil, T., Lesley, S., Farmer, G.R., Iacopino, A.M. Phenytoin increases gene expression for platelet-derived growth factor B chain in macrophages and monocytes. J Periodontol. 64, 169-173.1993.
 
[15]  Pendse, A.K., Sharma, A., Sodani, A., Hada, S. Topical phenytoin in wound healing. Int J Dermatol. 32, 214-217.1993.
 
[16]  Anstead, G.M., Hart, L.M., Sunahara, J.F., Liter, M.E. Phenytoin in wound healing. Ann Pharmacother. 30, 768-775.1996.
 
[17]  Margolis, D.J., Lewis, V.L. A literature assessment of the use of miscellaneous topical agents, growth factors, and skin equivalents for the treatment of pressure ulcers. Dermatol Surg. 21, 145-148.1995.
 
[18]  Rhodes, R.S., Heyneman, C.A., Culbertson, V.L., Wilson, S.E., Phatak, H.M. Topical phenytoin treatment of stage II decubitus ulcers in the elderly. Ann Pharmacother. 35, 675-681.2001.
 
[19]  Oluwatosin, O.M., Olabanji, J.K., Oluwatosin, O.A., Tijani, L.A., Onyechi, H.U. A comparison of topical honey and phenytoin in the treatment of chronic leg ulcers. Afr J Med Med Sci. 29, 31-34.2000.
 
[20]  El Zayat, S.G.. Preliminary experience with topical phenytoin in wound healing in a war zone. Mil Med. 154, 178-180.1998.
 
[21]  Modaghegh, S., Salehian, B., Tavassoli, M., Djamshidi, A., Rezai, A.S. . Use of phenytoin in healing of war- and non-w ar wounds - A pilot study of 25 cases. Int J Dermatol. 28, 347-350.1998{21} El Zayat, S.G.. Preliminary experience with topical phenytoin in wound healing in a war zone. Mil Med. 154, 178-180.1998.
 
[22]  Putignano, P., Kaltsas, G.A., Satta, M.A., Grossman, A.B. The effects of anti-convulsant drugs on adrenal function. Horm Metab Res. 30, 389-397.1998.
 
[23]  Adelson, P.D., Bratton, S.L., Carney, N.A., Chesnut, R.M., Du Coudray, H.E., Goldstein, B., Kochanek, P.M., Miller, H.C., Partington, M.P., Selden, N.R., Warden, C.R., Wright, D.W., American Association for Surgery of Trauma, Child Neurology Society, International Society for Pediatric Neurosurgery, Child Neurology Society, I.S.F.P.N., International Trauma Anesthesia and Critical Care Society, Society of Critical Care Medicine, World Federation of Pediatric Intensive and Critical Care Societies. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 19. The role of anti-seizure prophylaxis following severe pediatric traumatic brain injury. Pediatr Crit Care Med. 4, S72-S74.2003.