Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.
Htun Y, Nakamura S, Nakao Y, Mitsuie T, Nakamura M, Yamato S, Jinnai W, Koyano K, Ohta K, Morimoto A, Wakabayashi T, Sugino M, Fujioka K, Kato I, Kondo S, Yasuda S, Miki T, Ueno M, Kusaka T. · 2019.
What kind of evidence is this?
Preclinical
Controlled neonatal-piglet study
Other neurological conditions
Inhaled H₂
Positive preclinical combination signal with incomplete arm separation.
Animal functional and histological outcomes.
Methods at a glance
Newborn piglets after hypoxic-ischemic injury.
Three groups with five-day survival; group counts were checked in the full article.
24-hour treatment with five-day neurological and histological follow-up.
2.1–2.7% H₂ ventilation combined with therapeutic hypothermia for 24 hours.
Inhaled molecular H₂ with mechanical ventilation.
Delivered H₂ varied from 2.1% to 2.7% as oxygen requirements changed.
Absolute H₂ flow was not reported separately.
Oxygen concentration was adjusted within the ventilation protocol.
Normothermia and therapeutic-hypothermia groups without H₂.
Outcomes and reported result
Neurological scores, walking ability and brain histology.
The hypothermia-plus-H₂ group had better short-term neurological scores than normothermia and favorable histological trends; the design does not isolate H₂ from hypothermia.
The full article was checked for methods, intervention details, outcomes, positive and null findings, funding and conflicts. This record does not imply medical efficacy.
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
Preclinical piglet model, small groups and no H₂-without-hypothermia arm.
The reported neonatal-piglet injury and combined-treatment protocol only.
SYRCLE animal-study tool — preliminary
Some concerns
Controlled groups were present, but the missing H₂-alone arm, small samples and incomplete blinding create concerns.
Sequence generation checked where reported · Allocation concealment generally unclear · Personnel blinding generally unclear · Outcome-assessor blinding generally unclear · No prospectively registered analysis plan identified
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: 30858437 · DOI: 10.1038/s41598-019-40674-8
A free full article is available through PubMed Central.
Official PubMed Central full article and PubMed bibliographic record; source identity, methods, intervention, results, funding and conflicts checked 10 August 2026.
2026-08-10