Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial.

Abstract

This post hoc analysis examined data from the multicenter HYBRID II randomized controlled trial, focusing on 72 patients with cardiogenic out-of-hospital cardiac arrest (OHCA) managed across 15 Japanese ICUs. Patients received either hydrogen-oxygen mixture or oxygen alone, with target temperature management (TTM) set at either 32–34°C or 35–36°C per institutional protocol. Among patients managed at TTM32–34°C, 68% in the hydrogen group achieved favorable 90-day neurological outcomes versus 38% in the control group (relative risk 1.81; 95% CI 1.05–3.66). Multivariable analysis confirmed that the combination of hydrogen inhalation with TTM32–34°C was independently associated with good neurological outcomes (adjusted odds ratio 16.10; 95% CI 1.88–138.17; p = 0.01). No statistically significant improvement in 90-day survival was observed with the combined approach compared to TTM32–34°C alone (adjusted hazard ratio 0.22; 95% CI 0.05–1.06; p = 0.06). These findings suggest that hydrogen inhalation combined with deeper hypothermia may reduce post-cardiac arrest brain injury.

Mechanism

The combination of hydrogen inhalation, which selectively scavenges reactive oxygen species, and hypothermic temperature management, which suppresses cerebral metabolic demand, is proposed to synergistically reduce post-cardiac arrest brain injury.