Abstract / Summary
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.