Abstract
Diabetic foot ulcers (DFUs) are severe complications of diabetes mellitus that often lead to nontraumatic limb amputation. This systematic review aimed to assess the primary clinical evidence supporting hyperbaric oxygen therapy (HBOT) in the management of DFUs. A literature search was conducted using PubMed, Scopus, and Web of Science from June to August 2024, and six studies with a total of 391 patients were included in the final analysis, after applying relevant inclusion and exclusion criteria. The majority of the studies indicated reduced major amputation rates, improved ulcer healing rates, and decreased ulcer size and depth with HBOT compared to standard care (SC). To assess the risk of bias, this review used the Cochrane Risk of Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for observational studies. This evaluation uncovered variations in methodological rigor across the included studies in the review. Most studies indicate that HBOT leads to lower rates of major amputations, better ulcer healing, and reduced ulcer dimensions than SC. However, one study found no significant differences in amputation rates or long-term wound healing between groups. Selection bias from inconsistent patient allocation is a common limitation in observational studies, potentially distorting comparisons. Performance bias, particularly insufficient blinding, could have influenced treatment adherence and wound care practices, thereby affecting outcome evaluations. These biases, coupled with differences in SC practices, make it challenging to interpret the true efficacy of HBOT and restrict its clinical applicability. While most studies showed a low risk of bias in certain areas, moderate-to-high bias in key aspects necessitated careful interpretation. Future high-quality RCTs with stringent blinding, standardized protocols, and defined patient selection criteria are crucial to confirm the effectiveness of HBOT, improve guidelines, and establish its long-term viability. Although this review suggests that HBOT may be valuable for DFUs, additional rigorous research is needed to reduce bias, enhance methodological consistency, and improve the reliability of the findings for clinical implementation.