Managing Patients With Diabetic Foot Ulcers

Diabetic foot ulcers (DFUs) remain a challenge for clinicians despite decades of study. Clinicians now realize that healing strategies should focus on the patient as well as the ulcer. The search continues for interventions that affected individuals and their care providers can count on to heal and manage these challenging wounds, stopping the dreaded progression to amputation and death. The path to healing a patient’s DFU often requires multidisciplinary care, including consistent offloading of insensate areas, endocrinologic and metabolic control, and improved circulation. The studies reviewed in this month’s Evidence Corner suggest clinicians should consider adding tissue oxygenation¹ and foot care knowledge and practice for patients with diabetes mellitus² to improve diabetic foot care management.

Related Content

Foot Sensation Testing in the Patient With Diabetes: Introduction of the Quick & Easy Assessment Tool

An Innovative Literacy-supportive Education Pilot for Wound Self-care

Reference: Niederauer MQ, Michalek JE, Armstrong DG. A prospective, randomized, double-blind multicenter study comparing continuous diffusion of oxygen therapy to sham therapy in the treatment of diabetic foot ulcers [published online February 15, 2017]. J Diabetes Sci Technol. 2017;11(5):883–891.

Rationale: Adequate tissue oxygen is required for healing to progress, and oxygen gradients stimulate local angiogenesis. Interventions designed to improve tissue oxygenation, such as hyperbaric oxygen or topically applied oxygen systems, usually are applied intermittently, limiting patient mobility during treatment. Effects of continuously diffused oxygen (CDO) have shown promise in preclinical and clinical research, but CDO remains to be tested on chronic diabetic foot ulcers (DFUs) in a blind-evaluated, sham-controlled study.

Objective: Conduct a double-blind, sham-controlled, randomized clinical trial (RCT) to test healing efficacy and safety of a US Food and Drug Administration-cleared topical device that continuously delivers a controlled amount of humidified oxygen to a DFU when sealed over the DFU beneath a moisture-retentive dressing.

Methods: Twenty-three clinical centers enrolled patients (age range, 30–90 years) with a chronic DFU measuring 1.5 cm² to 10 cm² who received 30 to 365 days of standard of care (SOC) treatment (initial debridement as appropriate, moist wound therapy, and consistent offloading). Nonhealing wounds (N = 146), defined as decreasing in area < 25% ± 5% in week 1 or 2 or as < 40% ± 10% during an initial 2-week run-in SOC treatment period, were randomly assigned to receive CDO (maintained at 3 mL of oxygen/hour) or sham therapy (same device with no oxygen delivered to the wound). Treatments were applied and outcomes were evaluated by those unaware of treatment assignment. Patients or their caregivers changed the wound dressings between clinic visits. After 12 weeks of treatment, during which 23 patients withdrew from each group, a planned interim analysis tested the significance of differences between the first 50 CDO and 50 sham patients with evaluable data. Fisher’s exact test was used with 2-tailed P < .05 to test statistical significance of group differences between the percent of patients completely healed in 12 weeks as the primary outcome. The CDO and sham contrasts were tested for continuous variables (rate of healing based on weekly planimetric measurements of the wound’s longest length and width and deepest depth as well as standardized measures of wound pain, reepithelization, granulation, and patient-reported quality of life) using t tests uncorrected for multiple comparisons. Planned analyses also included effects of baseline wound area and rate of healing during the run-in period on the primary outcome.

Results: Patients in the 2 groups were comparable on enrollment for age, ethnicity, gender, hemoglobin A_1c, ischemia (as measured by ankle-to-brachial index), wound size, and absence of wound pain. After 12 weeks, 46% of those receiving CDO and 22% receiving sham treatment healed (P = .02). Overall, those receiving CDO treatment healed completely more than 20 days sooner than sham-treated patients (P = .026 for CDO vs. sham). The CDO-sham difference in relative performance (percent of CDO patients healed at 12 weeks divided by that for sham patients) was significant (P < .02) for all patients, but it was most pronounced among patients healing most slowly during the run-in period, where those receiving CDO were 3.15 times more likely to heal in 12 weeks than sham patients (P = .006). This effect persisted or increased in larger or more chronic wounds.

Authors’ Conclusions: While other studies have reported improved healing with CDO, this is the first double-blind, sham-controlled study to confirm healing effects on DFUs and to note that it may be especially effective in those healing most slowly. These effects merit further double-blind RCT confirmation

Reference: Rahaman HS, Jyotsna VP, Sreenivas V, Krishnan A, Tandon N. Effectiveness of a patient education module on diabetic foot care in outpatient setting: an open-label randomized controlled study. Indian J Endocrinol Metab. 2018;22(1):74–78.

Rationale: Physician consultations for patients with diabetes in developing countries are often < 5 minutes and rarely focus on preventing complications. Up to 95% of outpatients in one diabetic foot clinic in India had never received foot care advice, despite evidence that simple foot care education reduces diabetic foot complications and promotes DFU healing.

Objective: Test the effectiveness of a diabetic foot care education module developed for use in an outpatient clinic on improving patient diabetic foot care knowledge and practice.

Methods: Patients meeting the American Diabetes Association (ADA) diagnostic criteria for diabetes mellitus without impaired cognition, vision, or hearing or current or past foot ulcers and capable of 3-month follow-up were randomly assigned to receive routine standardized diabetic foot care with (n = 63) or without (n = 64) an educational module. The module was a 9-minute YouTube-linked audio-visual display covering all important aspects of DFU prevention advised by the ADA and the National Diabetes Education Program as well as a pamphlet on diabetic foot care prepared with help from the All India Institute of Medical Sciences and the New Delhi Center on Community Medicine. All patients received routine education on glycemic control, diet, and exercise plus medications and foot care provided by the hospital outpatient department. Patients completed a standardized questionnaire on knowledge and practice of diabetic foot management at baseline and after 1 and 3 months of study. Separate knowledge (14 questions) and foot care behavior (5 questions) scores were compared for the 2 groups at baseline and after 1 and 3 months of study using Student’s t test, with P < .05 to indicate statistical significance.

Results: The 2 groups were similar at baseline on duration and control of diabetes; baseline knowledge and practice scores for diabetic foot care also were similar. The scores of the group receiving the extra educational module increased (P < .001) from baseline to the final visit in knowledge and practice, while the group receiving only routine care only increased in practice scores (P = .004). This increase in self-managed foot care behavior resulting from routine outpatient consults was less than half the improvement reported for those receiving the educational module.

Authors’ Conclusions: This study demonstrates significant improvement in diabetic foot knowledge and foot care behavior in patients who received standardized audio-visual education during their waiting time in the outpatient department

These 2 studies each advance richly cited prior literature and technology for improving diabetic foot management through tissue oxygenation^3-5 and through patient education.^6-8 As the authors of both studies note, more research is needed to optimize clinical outcomes. Niederauer et al¹ significantly improved DFU healing in 12 weeks by continuously providing 3 mL of humidified oxygen per hour to DFU surface tissue. They invite replications and refinement of the dose response, noting the CDO is capable of sustained delivery of up to 15 mL of humidified oxygen per hour. One question that merits study is whether it was the oxygen or humidity that caused the effect. More important, they set a benchmark for wound study quality by conducting a prospective RCT treatment blinded to patients, investigators, and outcome evaluators. This is the only way investigators can prevent bias, expectations, or placebo effects from altering study results. Rahaman et al² used familiar YouTube technology and patient pamphlets to engage patients in learning during their waiting time in the outpatient clinic. This saved the care provider time, standardized education, and empowered patients to take an active role in their self-care between office visits. The next step is to link the improved knowledge and behavior reported using this educational tool to improved patient outcomes such as reduced DFU incidence or related infections or amputations.