# Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period.
> 心停止後の神経保護における吸入ガス療法の最新知見：レビュー


## Abstract

This review consolidates current knowledge on inhaled gases as neuroprotective candidates in the post-resuscitation setting. Nitric oxide (NO), molecular hydrogen (H2), xenon (Xe), and argon (Ar) have each demonstrated the capacity to reduce neuronal degeneration and support neurological recovery following cardiac arrest, operating through distinct pathophysiological mechanisms. Evidence from both cell-based experiments and animal cardiac arrest models supports these protective properties. Phase 1 clinical trials have established acceptable safety profiles for Xe and H2 in this context. A phase 2 randomized trial further demonstrated that Xe combined with targeted temperature management preserves white matter integrity, as quantified by fractional anisotropy on diffusion tensor MRI after 24 hours of inhalation. The authors conclude that larger phase 2 and phase 3 trials are necessary to determine clinical efficacy for post-cardiac arrest brain injury.

### Mechanism

Xe, Ar, NO, and H2 each act through distinct pathophysiological pathways to attenuate neuronal degeneration and support neurological function recovery following resuscitation from cardiac arrest.

## Bibliographic

- **Authors**: Magliocca A, Fries M
- **Journal**: Curr Opin Crit Care
- **Year**: 2021 (2021-06-01)
- **PMID**: [33769417](https://pubmed.ncbi.nlm.nih.gov/33769417/)
- **DOI**: [10.1097/MCC.0000000000000820](https://doi.org/10.1097/MCC.0000000000000820)
- **Study type**: review
- **Delivery route**: inhalation
- **Effect reported**: not assessed

## 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 33769417. https://h2-papers.org/en/papers/33769417
> **Source**: PubMed PMID [33769417](https://pubmed.ncbi.nlm.nih.gov/33769417/)