Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients,Resuscitation

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Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients
Resuscitation ( IF 6.5 ) Pub Date : 2022-06-23 , DOI: 10.1016/j.resuscitation.2022.06.010
Rasmus Paulin Beske ₁ , Hanne H Henriksen ₂ , Laust Obling ₁ , Jesper Kjærgaard ₁ , John Bro-Jeppesen ₃ , Niklas Nielsen ₄ , Pär I Johansson ₅ , Christian Hassager ₆

Affiliation

Background

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury.

Aim

To describe metabolic derangement in patients following resuscitated OHCA.

Methods

Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance-liquid-mass-spectrometry. Sixty-one metabolites were prespecified for quantification and studied.

Results

In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53-68). All measured metabolites from the tricarboxylic acid (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four clusters (A-D) of patients with distinct metabolic profiles. Cluster A and B had higher levels of TCA metabolites, amino acids and acylcarnitine species compared to C and D. The mortality was significantly higher in cluster A and B (A:62% and B:59% vs. C:21 % and D:24%, p<0.001). Cluster A and B had longer time to return of spontaneous circulation (A:33 min (21-43), B:27 min (24-35), C:18 min (13-28), and D:18 min (12-25), p<0.001).

Conclusion

Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes with significantly different mortality were identified.

中文翻译：

复苏昏迷的院外心脏骤停患者的靶向血浆代谢组学

背景

院外心脏骤停 (OHCA) 是导致死亡的主要原因。即使成功复苏，由于缺血和再灌注损伤 (I/R)，死亡率仍然很高。缺氧导致再灌注时放大的代谢紊乱，导致线粒体中活性氧物质的不受控制地产生，从而触发细胞死亡机制。对 OHCA 后人类 I/R 损伤的了解仍然很少，没有现有的治疗方法可以减轻再灌注损伤。

目标

描述复苏 OHCA 后患者的代谢紊乱。

方法

使用超高性能液体质谱法分析了在入院时抽取的连续复苏的昏迷 OHCA 患者的血浆。预先指定了 61 种代谢物进行定量和研究。

结果

共纳入 163 名患者，其中 143 名（88%）为男性，中位年龄为 62 岁（53-68 岁）。非幸存者与幸存者（180 天生存期）相比，三羧酸 (TCA) 循环中所有测量的代谢物均显着更高。分层聚类确定了四个具有不同代谢特征的患者群 (AD)。与 C 和 D 相比，A 组和 B 组具有更高水平的 TCA 代谢物、氨基酸和酰基肉碱种类。A 组和 B 组的死亡率显着更高（A：62% 和 B：59% 对比 C：21% 和 D :24%，p<0.001 )。A组和B组恢复自主循环的时间更长（A：33分钟（21-43），B：27分钟（24-35），C：18分钟（13-28），D：18分钟（12 -25)，p<0.001 )。