Therapeutic use of highly concentrated CO₂ for wound healing: bathing and non-bathing modalities in a systematic review and meta-analysis

Wound healing poses a persistent clinical challenge, especially in chronic wounds like diabetic foot ulcers and pressure injuries. Highly concentrated carbon dioxide (CO₂) therapy has emerged as a non-invasive approach to promote healing, but its effectiveness remains uncertain.

To evaluate the efficacy of highly concentrated CO₂ therapy, via bathing and non-bathing methods, on wound healing outcomes.

This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251035698). Six databases were searched, identifying 10,348 records. Five randomized controlled trials met the inclusion criteria, involving participants with wounds treated using highly concentrated CO₂ through bathing or non-bathing methods. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2.0 tool. Meta-analyses were conducted with fixed- or random-effects models, and the certainty of evidence was evaluated using the GRADE approach.

Five trials (N = 127 wounds/participants) were included. Meta-analysis of two trials indicated that CO₂ therapy increased the likelihood of complete ulcer healing (RR = 5.33; 95% CI [0.23-126.05]; I ² = 81.3%), though the evidence was very uncertain due to heterogeneity and imprecision. Another meta-analysis of two trials found moderate improvement in microvascular perfusion (SMD = 0.61; 95% CI [0.23-0.99]; I ² = 0%), rated as low certainty. Individual studies reported improvements in skin temperature, VEGF, TNF-α, and wound area reduction.

Highly concentrated CO₂ therapy shows promise in enhancing wound healing. However, further large-scale, high-quality trials across diverse settings are needed to validate its clinical applicability.