# Effect of hydrogen gas inhalation on patient QOL after hepatectomy: protocol for a randomized controlled trial.
> 肝切除後患者のQOLに対する水素ガス吸入の効果：無作為化対照試験プロトコル


## Abstract

This document describes the protocol for a double-blind, randomized, superiority trial evaluating whether hydrogen gas inhalation improves quality of life (QOL) in patients following hepatectomy. Hepatic resection involves repeated ischemia-reperfusion cycles that generate reactive oxygen species (ROS), potentially impairing liver function. Because molecular hydrogen selectively neutralizes highly toxic ROS, early postoperative inhalation may limit hepatic dysfunction. Participants will be randomly assigned to inhale either hydrogen gas or air after surgery. The primary endpoint is the QoR40 score on postoperative day 3. Secondary endpoints include additional QoR40 assessments, Clavien-Dindo complication grading, pain intensity via Numerical Rating Scale, dietary intake, liver function markers, systemic inflammation indices, urinary 8-hydroxydeoxyguanosine (8-OHdG) as an oxidative stress biomarker, and pedometer-recorded step counts. The trial is registered under jRCTs03220332 and was approved by the Niigata University Central Review Board of Clinical Research.

### Mechanism

Molecular hydrogen is proposed to selectively scavenge highly toxic reactive oxygen species generated during hepatic ischemia-reperfusion, thereby limiting oxidative stress-mediated liver dysfunction in the postoperative period.

## Bibliographic

- **Authors**: Kaibori M, Kosaka H
- **Journal**: Trials
- **Year**: 2021 (2021-10-21)
- **PMID**: [34674744](https://pubmed.ncbi.nlm.nih.gov/34674744/)
- **DOI**: [10.1186/s13063-021-05697-5](https://doi.org/10.1186/s13063-021-05697-5)
- **PMC**: [PMC8529823](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529823/)
- **Study type**: human randomized controlled trial
- **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 34674744. https://h2-papers.org/en/papers/34674744
> **Source**: PubMed PMID [34674744](https://pubmed.ncbi.nlm.nih.gov/34674744/)