Topical oxygen therapy for healing diabetic foot ulcers: A systematic review and meta-analysis of randomised control trials

Abstract

• Diabetic foot ulcers (DFU) are notoriously difficult to heal with studies suggesting over half fail to heal within the first 12 weeks. • Topical oxygen therapy (TOT) is a new advanced wound care technique which has shown potential to improve healing potential of DFU. • Our meta-analysis found that TOT increased the likelihood of healing by 59% within 12 weeks in superficial, relatively well-vascularised DFU. There was no significant impact on amputation. • Most studies were at moderate to high risk of bias; therefore, the strength of the findings can be considered low. Exclusion of the study at highest risk of bias eliminated the benefit observed in the metanalysis. • Cost-effectiveness could not be calculated as none of the studies clearly reported on costs. Topical oxygen therapy (TOT) has been suggested to improve the likelihood of complete wound healing. A systematic review of PUBMED, Embase and clinicaltrials.gov databases from inception until December 2021 for eligible randomised controlled studies. The primary outcome measure was 12-week complete wound healing rate. Seven studies papers ( n = 627 participants) met our eligibility criteria, of which four ( n = 492) were used in the final qualitative synthesis. Use of adjuvant TOT significantly more complete wound healing in comparison to SC (RR 1.59 95% confidence interval 1.07, 2.37 p = 0.02; NNT 6.3) in superficial, relatively well-vascularised DFU with no difference in adverse events between the groups. However, this effect was lost on sensitivity analysis. No amputation benefit was identified. However, larger DFU (>3cm 2 ) apparently derived greater benefit and two studies reported benefit in DFU time to healing. Five out of six studies were at moderate or high risk of bias and clear conclusions on cost-effectiveness could not be drawn. The provision of adjuvant TOT in DFU was safe and associated with a higher rate of complete wound healing when added to standard care. These findings require cautious interpretation as the available evidence was deemed at significant risk of bias so the strength of findings can only be considered low.