Abstract Background Hyperbaric oxygen therapy (HBOT) corrects tissue hypoxia, mobilizes stem cells and has immunomodulatory effects, all of which are key mechanisms for healing wounds. A number of studies have suggested that HBOT may be effective for healing inflammatory bowel disease (IBD). Aims Our systematic review aimed to quantify the effectiveness and safety of HBOT in IBD and its associated conditions. Methods We performed a proportional meta-analysis. MEDLINE, EMBASE, Web of Knowledge and The Cochrane Central Register of Controlled Trials were systematically searched from inception through November 2020 with no language restriction. We included randomized controlled studies, cohort studies and case series that contained a minimum of three patients and reported effectiveness and/or safety outcomes for HBOT in patients with IBD. Studies were stratified by IBD phenotype and weighted summary estimates with 95% confidence intervals (CI) were calculated for clinical response and remission using random-effects models. Study quality was assessed using the Cochrane risk-of-bias tool for randomized trials and a modified version of the National Institutes of Health (NIH) checklist for observational studies. Results Nineteen studies met our study criteria: 3 randomized controlled trials and 16 case series. The studies reported outcomes for luminal ulcerative colitis (UC) (n=373), luminal Crohn’s disease (CD) (n=250), enterocutaneous fistulae (ECF) (n=21), perianal CD (n=115), pouch disorders (n=60), pyoderma gangrenosum (PG) (n=5) and perianal sinus/metastatic CD (n=7). Rates of clinical response were 86% (95% CI, 66–95%) for luminal UC, 86% (95% CI, 81–90%) for luminal CD, 85% (95% CI, 61–95%) for ECF, 80% (95% CI, 70–87%) for perianal CD, 65% (95% CI, 52–76%) for pouch disorders, 92% (95% CI, 38–99%) for PG and 79% (95% CI, 36–96%) for perianal sinus/metastatic CD. Rates of clinical remission were 87% (95% CI, 10–100%) for luminal UC, 88% for luminal CD (95% CI, 46–98%), 50% for ECF (95% CI, 12–88%), 64% (95% CI, 52–75%) for perianal CD, 31% (95% CI, 16–50%) for pouch disorders, 92% (95% CI, 38–100%) for PG and 65% (95% CI, 10–97%) for perianal sinus/metastatic CD. Of the ten studies that reported on safety of HBOT, 19 patients (10.5%) had minor adverse events and no major event was reported. Study quality was low in the majority of studies due to an absence of comparator arms, inadequate description of interventions, and poorly defined outcomes. Conclusions Limited high-quality evidence suggest that HBOT is safe and associated with high rates of clinical response and remission for luminal IBD, perianal CD and pouch disorders. A well-designed large multicenter randomized controlled trial is warranted to confirm the benefit of HBOT in IBD. doi:10.17605/osf.io/gpz6d Funding Agencies None
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