Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II)
Tamura T et al.; HYBRID II Study Group · EClinicalMedicine. 2023;58:101907.
What kind of evidence is this?
Human
Multicenter randomized double-blind placebo-controlled trial
Critical care and ischemia-reperfusion
Other forms
Not reported in this record.
Not reported in this record.
Methods at a glance
Comatose adults aged 20–80 after cardiogenic out-of-hospital cardiac arrest
73 randomized: H₂ n=39; control n=34
18 hours after admission; outcomes assessed through 90 days
2% H₂ added to supplementary oxygen through mechanical ventilation
H₂ added to ventilator gas with supplemental O₂ — not Brown’s gas.
2% H₂ with clinically adjusted inspired O₂ reported in the protocol as 24–50%.
Not reported — ventilator flow varied by patient, so no single absolute H₂ flow can be calculated.
O₂ was co-delivered at a clinically adjusted concentration; absolute O₂ flow in mL/min was not reported.
Supplementary oxygen without H₂ using blinded gas cylinders
Outcomes and reported result
Primary: CPC 1–2 at 90 days. Secondary: modified Rankin scale, survival and safety
The primary outcome was not statistically significant: CPC 1–2 occurred in 56% with H₂ and 39% with control (p=0.15). Several secondary mRS and survival results favored H₂, but the trial was stopped early and was underpowered.
Full methods, outcomes, registration, funding and conflicts checked in the open-access full text; independent appraisal remains incomplete.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Stopped early because of pandemic enrollment restrictions, with 73 of 360 planned participants. The prespecified primary endpoint was null; positive secondary findings require cautious interpretation. Taiyo Nippon Sanso funded the trial.
Selected comatose adults after cardiogenic out-of-hospital cardiac arrest receiving intensive post-arrest care.
Not reported in this record.
Not reported in this record.
Not reported in this record.
No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 36969346 · DOI: 10.1016/j.eclinm.2023.101907
Open-access full text is available through PMC and the publisher.
Open-access PMC and publisher full texts plus PubMed record.
2026-08-10