Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial.

Abstract

The HYBRID II trial examined whether 18-hour inhalation of 2% molecular hydrogen gas improves outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA) of cardiogenic origin. Conducted across 15 Japanese hospitals from 2017 to 2021, the study enrolled 73 patients randomised to hydrogen (n=39) or control (n=34) groups. The primary endpoint—proportion achieving Cerebral Performance Category (CPC) 1 or 2 at 90 days—was 56% in the hydrogen group versus 39% in controls, a difference that did not reach statistical significance (relative risk 0.72; 95% CI 0.46–1.13; P=0.15). Secondary endpoints showed statistically significant advantages for hydrogen: median modified Rankin Scale scores were 1 versus 5 (P=0.01), and 90-day survival rates were 85% versus 61% (P=0.02). Enrolment was curtailed prematurely due to COVID-19 restrictions, limiting statistical power. The findings suggest a potential benefit of hydrogen inhalation on survival and functional recovery, warranting further adequately powered investigation.

Mechanism

Molecular hydrogen is proposed to selectively scavenge hydroxyl radicals and peroxynitrite generated during ischaemia-reperfusion following cardiac arrest, thereby reducing oxidative neuronal injury and supporting neurological recovery.