Department of Internal Medicine, Turku University Hospital, University of Turku, Turku, Finland.
Department of Perioperative Services, Intensive Care and Pain Management, Turku University Hospital, University of Turku, Turku, Finland.
PLoS One. 2024 Jun 4;19(6):e0304966. doi: 10.1371/journal.pone.0304966. eCollection 2024.
Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown.
In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33°C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h.
At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p<0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p<0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups.
In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients.
Trial Registry number: ClinicalTrials.gov Identifier: NCT00879892.
院外心脏骤停（OHCA）预后相对较差，需要多模式预后评估来指导临床决策。识别与患者预后相关的先前未被认识的代谢途径可能有助于未来的生物标志物发现。在 OHCA 中，吸入氙气可引起神经和心脏保护。然而，其代谢作用仍不清楚。
在这项随机、2 组、单盲、2 期 Xe-Hypotheca 试验的事后研究中，110 名 OHCA 幸存者以 1:1 的比例随机分为两组，分别接受目标温度管理（TTM）在 33°C 下，持续 24 小时，或在 TTM 期间吸入氙气。在入院时、24 小时和 72 小时采集用于磁共振波谱代谢分析的血样。
在 24 小时时，乳酸水平升高，调整后的危险比为 2.25，95%CI [1.53; 3.30]，p<0.001，支链氨基酸（BCAA）亮氨酸降低 0.64 [0.5; 0.82]，p = 0.007，缬氨酸降低 0.37 [0.22; 0.63]，p = 0.003，与 6 个月死亡率相关。在 72 小时时，乳酸升高 2.77 [1.76; 4.36]，p<0.001，丙氨酸升高 2.43 [1.56; 3.78]，p = 0.001，小高密度脂蛋白胆固醇酯含量（S-HDL-CE）降低 0.36 [0.19; 0.68]，p = 0.021，与死亡率相关。氙气组和对照组之间未观察到差异。
在接受 TTM 治疗的 OHCA 患者中，无论是否吸入氙气，高乳酸和丙氨酸水平以及降低的支链氨基酸和 S-HDL-CE 与死亡率增加相关。目前关于支链氨基酸，以及可能的丙氨酸和乳酸的观察结果是否可以通过它们在神经递质谷氨酸代谢中的作用反映神经损伤，仍有待确定。氙气并未显著改变所测量的代谢谱，这在 ICU 患者病情恶化的情况下是一个潜在有益的特征。
临床试验注册号：ClinicalTrials.gov 标识符：NCT00879892。
