# 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.
> 院外心停止後における水素吸入と低体温目標体温管理の併用効果：HYBRID II試験の事後解析


## 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.

## Bibliographic

- **Authors**: Tamura T, Narumiya H, Homma K, Suzuki M
- **Journal**: Crit Care Med
- **Year**: 2024 (2024-10-01)
- **PMID**: [39133068](https://pubmed.ncbi.nlm.nih.gov/39133068/)
- **DOI**: [10.1097/CCM.0000000000006395](https://doi.org/10.1097/CCM.0000000000006395)
- **PMC**: [PMC11392137](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392137/)
- **Study type**: human randomized controlled trial
- **Delivery route**: inhalation
- **Effect reported**: mixed

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 39133068. https://h2-papers.org/en/papers/39133068
> **Source**: PubMed PMID [39133068](https://pubmed.ncbi.nlm.nih.gov/39133068/)