Meta-analysis finds very uncertain evidence for CO therapy in wound healing

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PeerJ Published May 11, 2026 Medically reviewed May 11, 2026 Study authors: Chen Shaodong, Tong Jia Ying, Aslam Muhammad Shahzad PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Interpret CO therapy evidence for wound healing as very uncertain; larger trials are needed.

This meta-analysis assessed highly concentrated carbon dioxide (CO) therapy (bathing and non-bathing methods) for treating diabetic foot ulcers and pressure injuries. The analysis included 127 wounds/participants from studies that were not further specified. The primary outcome was complete ulcer healing, with secondary outcomes including microvascular perfusion, skin temperature, VEGF, TNF-α, and wound area reduction.

For complete ulcer healing, the pooled relative risk was 5.33 (95% CI 0.23-126.05), indicating a very wide confidence interval that crosses 1, making the result very uncertain. For microvascular perfusion, the standardized mean difference was 0.61 (95% CI 0.23-0.99), suggesting a moderate improvement with low certainty. Other secondary outcomes were not reported with effect sizes.

The authors note several limitations: heterogeneity among studies, imprecision of estimates, and small sample size. They emphasize the need for further large-scale trials. Adverse events, serious adverse events, and discontinuations were not reported. The certainty of evidence was rated very low for complete healing and low for microvascular perfusion.

Clinicians should interpret these findings with caution. The evidence does not support definitive efficacy of CO therapy for wound healing due to very low certainty. The association is based on limited data, and no causal conclusions can be drawn.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJan 2026

PMID42111815

View Original Abstract ↓

BACKGROUND: Wound healing poses a persistent clinical challenge, especially in chronic wounds like diabetic foot ulcers and pressure injuries. Highly concentrated carbon dioxide (CO) therapy has emerged as a non-invasive approach to promote healing, but its effectiveness remains uncertain. OBJECTIVE: To evaluate the efficacy of highly concentrated CO therapy, bathing and non-bathing methods, on wound healing outcomes. METHODS: 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 CO 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. RESULTS: Five trials ( = 127 wounds/participants) were included. Meta-analysis of two trials indicated that CO therapy increased the likelihood of complete ulcer healing (RR = 5.33; 95% CI [0.23-126.05]; = 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]; = 0%), rated as low certainty. Individual studies reported improvements in skin temperature, VEGF, TNF-α, and wound area reduction. CONCLUSION: Highly concentrated CO therapy shows promise in enhancing wound healing. However, further large-scale, high-quality trials across diverse settings are needed to validate its clinical applicability.