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

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发表日期：

2024年1月24日

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Toui Tsuchiya,
Shinji Nakamura,
Yuichiro Sugiyama,
Yasuhiro Nakao,
Tsutomu Mitsuie,
Kota Inoue,
Eri Inoue,
Yinmon Htun,
Makoto Arioka,
Kenichi Ohta,
Hirosuke Morita,
Noriko Fuke,
Sonoko Kondo,
Kosuke Koyano,
Takanori Miki,
Masaki Ueno,
Takashi Kusaka

摘要

Background

We previously reported that hydrogen (H₂) 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 + H₂ 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 + H₂ (2.1–2.7% H₂ 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 + H₂ than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H₂ and significantly shorter than with NT.

Conclusions

H₂ 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.

H₂ 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.