Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets

• Published in: Pediatric research Vol. 95; no. 6; pp. 1536 - 1542
• Main Authors: Tsuchiya, Toui, Nakamura, Shinji, Sugiyama, Yuichiro, Nakao, Yasuhiro, Mitsuie, Tsutomu, Inoue, Kota, Inoue, Eri, Htun, Yinmon, Arioka, Makoto, Ohta, Kenichi, Morita, Hirosuke, Fuke, Noriko, Kondo, Sonoko, Koyano, Kosuke, Miki, Takanori, Ueno, Masaki, Kusaka, Takashi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-05-2024; Nature Publishing Group
• Subjects: Basic Science Article; Brain damage; Clinical outcomes; Convulsions & seizures; Electroencephalography; Hypothermia; Hypoxia; Ischemia; Medicine; Medicine & Public Health; Neurological disorders; Pediatric Surgery; Pediatrics
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/s41390-024-03041-6

Background
We previously reported that hydrogen (H
2
) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H
2
with TH alone in piglets 24 h after hypoxic–ischemic (HI) insult.
Methods
After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT,
n
 = 14), TH alone (33.5 ± 0.5 °C, 24 h,
n
 = 13), and TH + H
2
(2.1–2.7% H
2
gas, 24 h,
n
 = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal.
Results
The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H
2
than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H
2
and significantly shorter than with NT.
Conclusions
H
2
gas combined with TH ameliorated seizure burden 24 h after HI insult.
Impact
In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE).
Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development.
H
2
gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.