The DAMO2CLES [Does Applying More Oxygen (O2) Cure Lower Extremity Sores?] study (1) is the only prospective multicenter trial evaluating the effectiveness of hyperbaric oxygen therapy (HBOT) in the treatment of ischemic diabetic foot ulcers (DFUs). By involving 10 hyperbaric facilities across the Netherlands and Belgium, this protocol captures a cross-section of the standard care (SC) in the region with regard to ischemic DFUs but falls victim to variable clinical practice patterns. The authors state that there was adherence to DFU best practice management (2) but did not state how different sites used transcutaneous oxygen monitoring, cellular tissue products, or total contact casting. Recruitment was difficult, which prompted a change in the sample size calculations and included a major deficiency in the randomization process—five patients randomized to the HBOT group refused HBOT and another four patients were medically ineligible for HBOT, resulting in a 15% dropout before a single treatment was given. Only 65% of patients completed the prescribed course of 30 HBOT treatments, which is important as the per-protocol analysis of patients who completed 30 HBOT sessions (SC group 78% vs. SC+HBOT group 95%) had a statistically significant improvement in limb salvage as opposed to the intention-to-treat group (SC group 78% vs. SC+HBOT group 88%).
Patient selection remains the Achilles heel of all DFU studies to date, and this study is no exception. Nonischemic patients who may not require HBOT for wound healing were excluded, but the authors did not stratify patients where HBOT failed to produce a significant rise in transcutaneous oxygen monitoring. In this situation, HBOT is less likely to be beneficial (3,4). The Undersea and Hyperbaric Medical Society clinical practice guideline recommends against using HBOT for the treatment of Wagner grade II DFUs (5); however, 56% of the SC group and 45% of the SC+HBOT group were in this category. The guideline suggests using HBOT for Wagner grade III or IV DFUs, especially after surgical intervention in a gangrenous foot (e.g., Wagner IV DFU); however, there was no reported outcome data stratified by Wagner grades for further subgroup analysis. Although 25% of the patients in both groups were status post transmetatarsal amputation, there was no mention of the time delay between the surgical intervention and initiation of HBOT. The average age of the DFU in both groups was over 6 months, so it can be extrapolated that HBOT was not used in the acute postoperative period.
Although some would conclude that this is another negative study of the use of HBOT for DFUs, I believe that the most appropriate conclusion is that HBOT remains a viable adjunctive treatment for enhancing amputation-free survival in the ischemic DFU if it is used correctly as a therapeutic modality. Given the cumulative deficiencies described above, I believe that this study is underpowered and cannot make a definitive statement concluding that HBOT is ineffective. Furthermore, it highlights the need for better patient selection criteria as we conduct future studies to determine which DFUs will benefit from HBOT.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.