Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study

Abstract

BACKGROUND

Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols.

AIM

To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.

METHODS

This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed.

RESULTS

The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients.

CONCLUSION

Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Key Words: Diabetic foot ulcers; Comprehensive treatment protocol; Clinical study; White blood cell count; Wound healing; Amputation rate

Core Tip: That a comprehensive treatment protocol for diabetic foot ulcers (DFUs) yields superior outcomes compared to standard treatment. The protocol involving interventions for improving blood circulation, debridement, vacuum-sealing drainage, growth factor dressing, and skin grafting, resulted in faster wound healing, reduced amputation rates, and enhanced quality of life. These findings underscore the importance of implementing a comprehensive treatment approach to DFU management to promote granulation tissue growth, shorten hospital stays, alleviate pain, and improve wound healing. In this study, patients who received comprehensive treatment experienced significantly better wound healing rates, shorter healing times, and lower amputation rates than those of patients who received standard treatment.

INTRODUCTION

Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes mellitus, affecting 15%-25% of patients with diabetes throughout their lifetimes[1]. They are defined as wounds on the foot or lower leg that fail to heal within 4 wk[2]. Consequently, DFUs are often combined with infection, leading to osteomyelitis, gangrene, and amputation, thereby leading to increased morbidity, mortality, and healthcare costs for patients with diabetes[3,4]. The pathogenesis of DFUs and their related complications is multifactorial and involves neuropathy, ischemia, infection, and inflammation[5]. To meet the challenges of DFU management, a multidisciplinary approach is often required, including glycemic control, wound care, infection control, vascular intervention, and surgical intervention[6]. However, the conventional treatment of DFUs is often unsatisfactory, with low wound healing and high amputation rates[7]. Therefore, there is an urgent need to explore new and effective treatment strategies for DFUs.

We conducted a retrospective analysis of the clinical and epidemiological characteristics of patients with DFUs treated at our hospital between January 2022 and January 2024. We compared the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. The comprehensive treatment protocol encompassed: (1) Blood circulation improvement; (2) debridement; (3) vacuum sealing drainage (VSD); (4) recombinant human epidermal growth factor (rhEGF) and anti-inflammatory dressing; and (5) skin grafting. The standard treatment protocol included: (1) Wound cleaning and dressing using saline solution and gauze to remove debris and prevent infection; (2) antibiotics administration based on wound culture and sensitivity results to treat or prevent wound infections; and (3) surgical debridement or amputation, if necessary, for wounds showing signs of severe infection, necrosis, or gangrene that did not respond to conservative treatment. We hypothesized that the comprehensive treatment protocol would be more effective and beneficial than the standard treatment protocol, promoting granulation tissue growth and enhancing patients’ quality of life.

MATERIALS AND METHODS

Study participants

This retrospective cohort study adhered to the guidelines of a retrospective chart review. The study protocol was approved by the institutional review board of our hospital, and the requirement for informed consent was waived owing to the retrospective nature of the study.

The study population comprised patients with DFUs who were admitted to our hospital between January 2022 and January 2024. The inclusion criteria were as follows: (1) Age ≥ 18 years; (2) diagnosis of type 1 or type 2 diabetes mellitus; (3) presence of at least one ulcer on the foot or lower leg, classified as Wagner grade 2 or higher; and (4) no history of previous amputation or skin grafting on the affected limb. The exclusion criteria were as follows: (1) Presence of other chronic wounds, such as venous or pressure ulcers; (2) severe infection or sepsis requiring intensive care; (3) terminal illness or life expectancy of < 6 months; and (4) refusal to participate or inability to comply with the treatment protocol.

Treatments

A total of 62 patients who met the inclusion criteria were enrolled in the study and randomly assigned to the experimental (n = 32) or control (n = 30) group, using a computer-generated random number table. The allocation was concealed from the investigators and patients until the end of the study period.

Patients in the experimental group received treatment under a comprehensive treatment protocol for DFUs consisting of the following steps: (1) Improving blood circulation: Patients are administered antiplatelet drugs, such as aspirin or clopidogrel, to prevent thrombosis and improve microcirculation. They also received intravenous infusion of vasodilators, such as prostaglandin E1 or iloprost, to enhance blood flow and oxygen delivery to ischemic tissues; (2) Debridement: Surgical debridement of necrotic and infected tissues was performed using a scalpel, scissors, or curette under local or general anesthesia by experienced surgeons. The wound was thoroughly irrigated with saline solution and hydrogen peroxide. Wound size and depth were measured and recorded before and after debridement; (3) VSD: Patients received VSD therapy, which is a negative-pressure wound therapy that can promote wound healing by removing the exudate, reducing edema, stimulating granulation tissue formation, and enhancing blood perfusion. A sterile polyurethane foam dressing was applied to the wound, and connected to a vacuum pump that generated a continuous or intermittent negative pressure of −80 to −120 mmHg. The dressing was changed every 2–3 d, depending on the amount of exudate and condition of the wound; (4) rhEGF and anti-inflammatory dressing: Patients received a topical application of rhEGF, a growth factor that can stimulate epithelial cell proliferation and migration and accelerate wound closure. A dose of 75 μg of rhEGF was sprayed onto the wound surface once a day after the VSD dressing was removed. The wound was covered with an anti-inflammatory dressing consisting of a hydrogel sheet impregnated with silver sulfadiazine, a broad-spectrum antimicrobial agent that prevents wound infection and inflammation. The dressing was changed daily until the wound was completely epithelialized or ready for skin grafting; and (5) Skin grafting: Patients underwent skin grafting, to restore skin integrity and function compromised by large or deep wounds that cannot heal with secondary intention. A split-thickness skin graft was harvested from the patient's thigh or abdomen using a dermatome and transplanted into the wound bed after ensuring adequate hemostasis and granulation tissue formation. The graft was secured with sutures, staples, or fibrin glue, and protected with a nonadherent dressing. The donor site was covered with a semiocclusive dressing and healed by reepithelialization.

Patients in the control group received treatment under the standard treatment protocol for DFUs consisting of the following steps: (1) Wound cleaning and dressing: Patients underwent regular wound cleaning and dressing using saline solution and gauze to remove debris and prevent infection. The dressing was changed once or twice a day depending on the amount of exudate and the condition of the wound; (2) Antibiotic therapy: Patients received systemic antibiotics based on the wound culture and sensitivity results to treat or prevent wound infections. Antibiotics were administered orally or intravenously depending on the severity of the infection and patient's renal function. The duration and dosage of antibiotics were determined by the clinician according to clinical guidelines; and (3) Surgical debridement or amputation, if necessary: Patients underwent surgical debridement or amputation if the wound showed signs of severe infection, necrosis, or gangrene that did not respond to conservative treatment. The debridement or amputation was performed by experienced surgeons under local or general anesthesia. Wound size and depth were measured and recorded before and after surgery.

Patients in both the groups received standard diabetes care, including glycemic control, nutritional support, foot care education, and pressure relief. They were followed-up until complete wound healed or until the end of the study period, whichever came first. Wound healing was defined as complete wound closure without drainage or the need of dressing, confirmed by clinical examination. Wound healing time was calculated as the number of days from the start of treatment to complete wound healing. Amputation was defined as the surgical removal of any part of the foot or lower leg due to failure of wound healing or progression of infection or gangrene. Amputation rate was calculated as the percentage of patients who underwent amputation among the total number of patients in each group.

Statistical analysis

Data, including demographic characteristics, medical history, laboratory tests, wound assessment, treatment details, and patient outcomes, were collected from patients’ medical records and verified by the investigators. These data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS software version 26.0. Descriptive statistics are expressed as mean ± SD for continuous variables and frequency and percentage for categorical variables. The independent t-test or Mann–Whitney U test was used to compare continuous variables between the two groups, depending on the normality of the data distribution. The chi-square test or Fisher's exact test was used to compare categorical variables between the two groups, depending on the expected frequency of the data. The level of significance was set at values of P < 0.05.

RESULTS

Baseline characteristics

This study enrolled 62 patients with DFUs, randomly assigned to the experimental (n = 32) or control (n = 30) group. The baseline characteristics of the patients are summarized in Table 1. No significant differences in age and sex distribution; body mass index; duration and type of diabetes; HbA1c level; wound location, size, depth; and Wagner grade were observed between the groups (P > 0.05).

Table 1 Baseline characteristics of the patients with diabetic foot ulcers.

Variable	Experimental group (n = 32)	Control group (n = 30)	P value
Age (yr)	58.6 ± 9.4	60.1 ± 8.7	0.46
Sex (male/female)	18/14	16/14	0.77
BMI (kg/m2)	24.3 ± 3.2	23.9 ± 2.9	0.64
Duration of diabetes (yr)	12.4 ± 6.3	13.2 ± 5.8	0.57
Type of diabetes (type 1/type 2)	4/28	5/25	0.72
HbA1c (%)	8.7 ± 1.6	8.9 ± 1.4	0.51
Wound location (foot/lower leg)	26/6	24/6	0.91
Wound size (cm2)	12.5 ± 8.7	13.2 ± 9.4	0.74
Wound depth (cm)	2.1 ± 1.2	2.3 ± 1.3	0.56
Wagner grade (2/3/4/5)	8/12/8/4	9/10/7/4	0.88

BMI: Body mass index.

Clinical outcomes

Patient outcomes are presented in Table 2. The experimental group exhibited a significantly shorter time to reduce WBC count, fewer dressing changes, higher wound healing rate, shorter wound healing time, and lower amputation rate than those of the control group (P < 0.05).

Table 2 Clinical outcomes of the patients with diabetic foot ulcers under the comprehensive and standard treatment protocols.

Variable	Experimental group (n = 32)	Control group (n = 30)	P value
Time to reduce white blood cell count (d)	3.2 ± 1.4	5.6 ± 2.1	< 0.001
Number of dressing changes	12.3 ± 4.5	18.7 ± 6.3	< 0.001
Wound healing rate (%)	87.5	53.3	0.003
Wound healing time (d)	28.4 ± 9.7	42.6 ± 12.4	< 0.001
Amputation rate (%)	6.3	26.7	0.02

The time to reduce WBC count was significantly shorter in the experimental group than in the control group (3.2 ± 1.4 d vs 5.6 ± 2.1 d, P < 0.001), indicating that the comprehensive treatment protocol could effectively reduce wound infection and inflammation and improve the patient’s immune response.

Compared with the control group, the experimental group exhibited a significantly higher wound healing rate (87.5% vs 53.3%, P = 0.003) and a significantly shorter wound healing time (28.4 ± 9.7 d vs 42.6 ± 12.4 d, P < 0.001), suggesting that the comprehensive treatment protocol could promote wound closure and the restoration of skin integrity and function, as well as shorten hospitalization time and duration of treatment. Accordingly, the number of dressing changes was significantly fewer in the experimental group than in the control group (12.3 ± 4.5 vs 18.7 ± 6.3, P < 0.001).

The risk of limb loss and disability, indicated by amputation rate, which is the most serious complication of DFU, was significantly lower in the experimental group than in the control group (6.3% vs 26.7%, P = 0.02).

DISCUSSION

In this study, we compared the efficacy and safety of a comprehensive treatment protocol for DFUs with the standard treatment protocol. The results revealed that the comprehensive treatment protocol was more effective and beneficial than the standard treatment protocol and could promote granulation tissue growth, shorten hospitalization time, reduce pain, improve wound healing rate, lower amputation rate, and enhance patients’ quality of life.

The comprehensive treatment protocol encompassed blood circulation improvement, debridement, VSD, rhEGF and anti-inflammatory dressing, and skin grafting. Each step has its own rationale and mechanism of action, as supported by previous studies. Improving blood circulation is essential for the delivery of oxygen and nutrients to ischemic tissues and the removal of metabolic waste and inflammatory mediators[8,9]. Debridement is necessary for removing necrotic and infected tissues, which can impair wound healing and increase the risks of infection and amputation[10,11]. VSD is a novel technique that can enhance wound healing by creating a moist and sterile environment, reducing edema and bacterial load, stimulating granulation tissue formation, and increasing blood perfusion[12]. rhEGF is a growth factor that can accelerate wound closure by stimulating epithelial cell proliferation and migration and modulating wound healing processes, such as angiogenesis, inflammation, and extracellular matrix remodeling[13,14]. Anti-inflammatory dressings can prevent wound infection and inflammation that can delay wound healing and cause tissue damage[15]. Skin grafting is a surgical procedure that can restore skin integrity and function compromised by large or deep wounds that cannot heal by secondary intention[16,17].

The standard treatment protocol included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. This protocol is based on the conventional principles of wound care, but is often insufficient and ineffective for managing DFUs, especially for those with severe infection, necrosis, or gangrene[18]. The standard treatment protocol has several limitations, such as poor wound healing rates, high amputation rates, long hospitalization times, high pain levels, and low quality of life[19]. Conversely, comprehensive treatment protocols can improve wound healing, reduce wound infection and inflammation, and prevent wound deterioration and complications[18,19]. The comprehensive treatment protocol in this study was safe and well tolerated by the patients and did not cause any serious adverse event or side effect.

Several studies have investigated the efficacy of comprehensive treatment protocols for DFUs. For instance, Everett and Mathioudakis[20] conducted a systematic review of multidisciplinary foot care interventions for preventing diabetic foot ulceration and amputation. They found that integrated foot care interventions, including risk assessment, patient education, regular follow-up, and referral to specialist care, significantly reduced the risk of amputation and ulceration compared to standard care. These findings are consistent with our results, highlighting the importance of a comprehensive approach in managing DFUs. Another study by Yazdanpanah et al[21] evaluated the efficacy of a multidisciplinary diabetic foot care program in high-risk patients with DFUs. The program consisted of glycemic control, surgical debridement, local wound care, and offloading. The authors reported a wound healing rate of 77.5% and an amputation rate of 8.3%, which are comparable to our findings. However, their study did not include advanced therapies such as negative pressure wound therapy or growth factor application, which may account for the slightly lower wound healing rate and higher amputation rate compared to our study.

The strengths of this study include: (1) The use of a randomized and controlled design, which can minimize selection bias and confounding factors; (2) the use of objective and standardized outcome measures, which can enhance the validity and reliability of the results; and (3) the use of a comprehensive treatment protocol, which can address the multifactorial nature of DFUs and provide a holistic approach to wound care. However, this study has some limitations as follows: (1) A small sample size, which can limit the statistical power and generalizability of the results; (2) the retrospective study design, which can introduce recall bias and result in missing data; and (3) the lack of long-term follow-up, which can prevent the assessment of the durability and sustainability of treatment effects.

CONCLUSION

This study demonstrated that a comprehensive treatment protocol for DFUs is more effective and beneficial than the standard treatment protocol, with good safety and tolerability. This approach can be a promising and feasible strategy for managing DFUs and can improve clinical outcomes and quality of life of patients with diabetes. Further studies with larger sample sizes and longer follow-up periods are required to confirm our expand upon our findings.