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Sun L, Mohr NM, Rajwani H, Fietsam AC, Wagner B, Bates ML, Vasilyev M, Doerschug KC, Sharma A.

Hyperbaric Oxygen Therapy in Septic Shock: A First-in-Human Pilot Trial. Undersea Hyperb Med.

2026 Third Quarter; 53(3):511-522.

Introduction: Septic shock, a severe, life-threatening infection resulting in organ failure, has seen

no successful, novel therapies emerge in the past two decades. In addition to hypoperfusion and

inflammation, organ dysfunction in septic shock is caused by microvascular, mitochondrial, and immune

dysfunction. Animal studies support the use of hyperbaric oxygen treatment to improve mitochondrial

function and reduce the inflammatory cascade, suggesting a potential role for hyperbaric oxygen in

treating septic shock.

Methods: A phase I open-label matched clinical trial was conducted to measure the effect of hyperbaric

oxygen on microvascular function, mitochondrial function, and inflammatory cytokines. Four

experimental subjects who received 60 minutes of hyperbaric oxygen (2.5 ATA, 25-min descent and

ascent) plus standard sepsis management, then four age-matched (ages 29–75) and vasopressor dose-

matched (norepinephrine equivalents of 0.05-0.35 ug/kg/min at enrollment) controls were enrolled. The

primary outcome was microvascular function, measured using the rate of reoxygenation after upper-limb

ischemia by real-time near-infrared spectroscopy. Secondary outcomes included mitochondrial function

(ex vivo neutrophils and monocytes) and serum inflammatory cytokine levels (IL-6, IL-10, TNF-alpha). The

data were analyzed graphically to identify trends in matched subjects.

Results: Hyperbaric oxygen treatment led to transient improvements in microvascular function in two

subjects and no change in the other two experimental subjects. In contrast, all control subjects had

declines in microvascular function. No differences were observed in mitochondrial function or cytokine

profiles between the groups. No adverse events occurred in any septic shock subjects in the intervention

arm.

Discussion: Our study did not find a statistically or clinically significant benefit of hyperbaric oxygen

in septic shock. Future adequately powered trials are needed to assess efficacy better and identify

subgroups most likely to benefit.

Keywords: clinical trial; hyperbaric oxygenation; microvascular function; mitochondria; septic; shock