Few diagnoses in emergency medicine move a hospital as fast as necrotizing fasciitis. The flesh-eating infection kills somewhere between 20 and 40 percent of the people it strikes, a figure that has barely budged despite decades of aggressive surgery, broad-spectrum antibiotics and modern intensive care. Against that stubborn number, some trauma centers have long added a third weapon to the standard two: hyperbaric oxygen therapy, delivered as an adjunct once the first debridement is done.
A narrative review published July 17, 2026, in Frontiers in Cellular and Infection Microbiology now offers one of the most organized maps yet of that practice — what the evidence says, where it contradicts itself, and why the hyperbaric community still cannot point to a definitive trial. The authors, Yansong Xu and Chuan Huang of the First Affiliated Hospital of Guangxi Medical University in Nanning, China, are candid from the outset: theirs is a narrative synthesis, not a quantitative meta-analysis, and the literature they surveyed is “predominantly observational.”
What the numbers show — and what they can’t prove
The headline finding in the review comes from the largest prospective cohort to date, reported by Hyldegaard and colleagues in 2025: among 409 patients with necrotizing soft tissue infections, those who received hyperbaric oxygen had a 30-day mortality of 7 percent, compared with 43 percent in those who did not. The 90-day figures told a similar story — 11 versus 46 percent.
Large administrative datasets point the same direction. A U.S. nationwide inpatient analysis by Soh and colleagues, covering more than 45,000 cases after matching, found mortality of 4.5 percent with HBOT against 9.4 percent without it. A 2024 National Inpatient Sample study by Toppen and colleagues put the adjusted odds ratio for in-hospital death at 0.63 in HBOT-treated patients — alongside higher total hospital costs but shorter stays. An earlier multi-institutional analysis by Shaw and colleagues calculated that patients who did not receive HBOT had more than tenfold higher odds of death, with the benefit concentrated in the sickest cases.
Then come the caveats, and the review does not soft-pedal them. Several cohorts — Massey in 2012, Mladenov in 2022, Kariksiz and Ates in 2025 — found no independent survival benefit at all. Confounding by indication runs in both directions: healthier patients may be more likely to be referred for HBOT, while some centers reserve it as a last resort for the critically ill, and almost no study adequately controls for time to first debridement, antibiotic choice or intensity of ICU support. Not a single large randomized controlled trial exists in this space.
The biological argument
The mechanistic case, laid out in detail, is coherent. Flooding tissue with oxygen at pressure raises tissue oxygen tension high enough to restore neutrophil killing capacity, directly suppress anaerobic bacteria, and shrink the edema that strangles microcirculation. The review highlights a molecular pivot: hypoxia-inducible factor 1-alpha, which accumulates in oxygen-starved tissue and drives a maladaptive inflammatory state, is degraded when oxygen tension rises — a plausible explanation for why early HBOT, started right after debridement, shows up in studies as an acute survival effect rather than merely a wound-healing one.
Subgroup signals suggest the therapy may matter most in the worst cases: patients in septic shock, those with APACHE II scores of 18 or higher, and wounds of 450 square centimeters or more. The authors stress, however, that these thresholds come from post-hoc analyses of retrospective data and have never been validated prospectively.
How it is actually used
Where centers do deploy HBOT for these infections, the protocol largely follows the Undersea and Hyperbaric Medical Society’s indications manual: 90-minute sessions of 100 percent oxygen at 2.0 to 2.5 atmospheres absolute, typically twice daily in the first days, continued until the necrosis stops extending. The review is emphatic on one point — hyperbaric oxygen is an adjunct, never a substitute for early, radical surgical debridement and antibiotics. Delay the surgery to arrange the chamber, and any theoretical benefit evaporates.
It is also worth situating this within the regulatory frame. In the United States, the FDA has cleared hyperbaric oxygen therapy for gas gangrene — clostridial myonecrosis, a close relative within the necrotizing soft tissue infection family — but the agency’s consumer guidance is blunt that HBOT is not proven for the long list of conditions marketed by wellness operators, and its 2025 safety letter to providers warned of fires, injuries and deaths tied to improper device use. Hospital-based adjunctive treatment of necrotizing infection sits at the opposite end of that spectrum: prescription therapy in accredited facilities, for an indication with a plausible mechanism and a half-century of clinical use. What it still lacks is the randomized evidence that would turn a reasonable practice into a proven one.
What would settle it
The review closes with a research agenda rather than a verdict: multicenter randomized trials powered to detect a survival effect in defined high-risk subgroups, prospective validation of biomarkers like soluble ICAM-1 and lactate that might one day guide patient selection, and honest cost-effectiveness accounting for a therapy that demands specialized facilities and round-the-clock staffing.
Until those studies arrive, the fairest summary of the evidence is the authors’ own: adjunctive HBOT for necrotizing fasciitis is associated with better outcomes in most of the data we have, association is not causation, and the infections in question kill far too many people for the question to remain unanswered much longer.
Sources
- Xu Y, Huang C. Hyperbaric oxygen therapy for necrotizing fasciitis: a narrative review of mechanisms, clinical evidence, controversies, and practical considerations. Front Cell Infect Microbiol (2026)
- Full text (open access) — PMC
- FDA — Hyperbaric Oxygen Therapy: Get the Facts
- FDA — Follow Instructions for Safe Use of Hyperbaric Oxygen Therapy Devices: Letter to Health Care Providers
- Undersea and Hyperbaric Medical Society (UHMS)