European Journal of Cardiovascular Medicine

Diabetes mellitus refers to a group of metabolic disorders characterised by hyperglycemia. An enigmatic challenge of this millennium remains chronic non-healing wound management, which is one of the most common surgical conditions a surgeon encounters. The tremendous burden on individuals with diabetes mellitus is due to metabolic dysregulation causing secondary pathophysiologic changes in multiple organ systems.[1]

The characteristic of chronic wounds is that they refuse to heal, especially diabetic ulcers, pressure ulcers, or bed sores despite daily dressing with expensive local applications. Previously dry dressing for wounds was considered but now we know that re-epithelialization is much faster or the development of granulation tissue  faster when moist/wet dressings are done for wound healing. We recognize that occluding wounds do not lead to infection. There are many modalities of wound care to assist a surgeon, for example, the use of compression bandages to treat venous ulcers, but the problem of chronic wounds remains.[2]

A revolution in wound care management is currently in the making. Various non-conventional topical therapies in wound healing during the last two decades  but still there exists no ideal dressing. Surgical dressing of both open and closed wounds is based mainly on tradition, training, and surgeons' philosophy. Diabetic peripheral neuropathy is a precipitating factor for diabetic foot ulcers.[3,4,5]

Non-conventional topical therapies in wound healing, such as antacids, Benzoyl peroxide, aloe vera, collagen, impregnated gauze, mercurochrome, insulin, oxygen therapy, sugar, vinegar, and phenytoin have been tried by many people.[6] 

Studies have also shown that topical phenytoin was found to be superior in the management of diabetic ulcers and promotes the healing of decubitus ulcers, venous stasis ulcers, traumatic wounds, burns, leprosy, trophic ulcers, The present study was conducted to compare the efficacy of topical phenytoin dressing with conventional wound dressing in the healing process in Diabetic ulcers and to prove that topical phenytoin can be used as a much better alternative option in the management of Diabetic ulcers.[7.

Study Design: Comparative Study

This is a hospital-based prospective randomized comparative study that included 106 patients with diabetic ulcers admitted to Gadag institute of medical sciences, Gadag  from November 2020 to November 2022 satisfying all the inclusion criteria mentioned below after obtaining clearance from the ethical committee.

The main inclusion criteria were as follows 

• Grade I and II foot ulcers according to Meggit-Wagner classification.
• Ulcer surface area 15cm2
• Patients giving consent for topical phenytoin therapy.

The main exclusion criteria for the study included       

• Grade III, IV, and V foot ulcers according to the Meggit-Wagner classification.
• Ulcer surface area >15cm2
• Chronic non-healing wounds of other etiology.
• Diabetes mellitus with gangrenous changes.
• Wounds with osteomyelitis.
• Patients with allergy to phenytoin.
• Other co-morbid conditions like renal failure and generalized debility affect wound healing.

The data was collected from 106 patients who are having diabetic ulcers satisfying all the inclusion criteria mentioned above. The whole sample population was divided into two equal and comparable groups based on willingness for undergoing topical phenytoin therapy for wounds. Those who were not willing were subjected to conventional wound care, forming the control group. The selection of patients was done by purposive sampling method.

Table 1: Patient characteristics in the control group and study group

106 patients admitted to the study were divided into equal and comparable groups. Patients subjected to topical phenytoin dressing were classified under the Study group and those who underwent conventional wound dressings were classified as the control group.

                                     Table 2: Age-wise distribution of patients in the control group and study group

The age of the patients varied from 25 to 80 years. The maximum number of cases belongs to the age group of 51 to 60 (33.02%). The average diabetic foot lesion in our country is 60 years. The mean age in the study group was   56.08 ± 12.40    years and in the control group was 57.81 ± 10.75   years.

Table 3: Gender-wise distribution of patients in the control group and study group

In both the study and control group diabetes is more common among males compared to females. Among them 75.47% of the patients were male and 24.53% were female. 

A total of 53 patients received conventional dressings in the control group, 43 were males and 10 were females and out of 53 patients in the Phenytoin dressings study group,  37 were males and 16 were females.

Table 4: Comparison of the control group and study group with a rate of granulation tissue formation (%) by independent t test

The rate of granulation tissue formation was assessed. It was found to be  between 66% to 88% in  the study group and 43% to 69% in the control group and was found to be statistically significant by independent t test.  

Wound dressings have evolved from the status of providing physical protection to the raw surface, absorbing exudates, and controlling local infections with local medications to the level of providing an adequate environment promoting wound healing. This has been achieved by modern wound dressing techniques promoting granulation tissue formation.[9]

Phenytoin is an antiepileptic drug that is being used for wound-healing properties in diabetic foot ulcers. Studies have shown that topical phenytoin can improve the healing rate of diabetic foot ulcers, reduce the size of the ulcer and decrease the healing time compared to conventional wound care. [10]

In our study, the mean age in the study group was 56.08 years, and 57.81 years in the control group. In both the study and control group diabetes was more common in males compared to females. Among them 75.47% of the patients were male and 24.53% were female.   In the study group, 37 patients were males and 16 were females. In the control group, males were 43 and females 10. In both the study and control group, the most common site of diabetic ulcer presentation was in the Plantar aspect of the foot (Total - 51.89%). The duration of hospital stay was 35.06 days in the study group and 45.36 days in the control group. [11]

During the study, there was an excellent progression of granulation tissue in the topical phenytoin group when compared to the control group. There was high statistical significance (p=0.0001). Speeding up of granulation tissue thus provides faster healing and faster wound bed preparation which was shown in the study. The rate of granulation tissue formation was found to be 77.79% in the study group and 62.04% in the control group. The amount of good granulation tissue is a major indicator of healthy healing. Culture and sensitivity from the wound discharge revealed that Staphylococcus Aureus was the most common organism isolated from the diabetic foot ulcer in both the study and control group. [12] Other common organisms were E Coli, Pseudomonas Aeruginosa, and Klebsiella. It was observed that there was a 58.49% conversion of a negative culture in the study group when compared to 43.40% in the control group.

No statistical difference in the baseline characteristics like age, sex, and initial wound area of ulcer between the two groups. Increased rate of granulation tissue formation and rate of reduction in the  mean ulcer surface area was found to be better in our study group using topical phenytoin than the conventional dressing group using betadine.  Thus, topical phenytoin dressing was found to be a safe, effective, inexpensive, and widely available therapeutic agent in the healing of diabetic foot ulcers.

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Patil V, Patil R, Kariholu PL, Patil LS, Shahapur P. Topical Phenytoin Application in Grade I and II Diabetic Foot Ulcers: A Prospective Study. J Clin Diagn Res. 2013;7(10):2238-40.