TY - JOUR

T1 - Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients

AU - Paulin Beske, Rasmus

AU - Henriksen, Hanne H.

AU - Obling, Laust

AU - Kjærgaard, Jesper

AU - Bro-Jeppesen, John

AU - Nielsen, Niklas

AU - Johansson, Pär I.

AU - Hassager, Christian

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Lipid metabolites

KW - Metabolomics

KW - Out-of-hospital cardiac arrest

KW - Tricarboxylic acid

U2 - 10.1016/j.resuscitation.2022.06.010

DO - 10.1016/j.resuscitation.2022.06.010

M3 - Journal article

C2 - 35753507

AN - SCOPUS:85133399006

VL - 179

SP - 163

EP - 171

JO - Resuscitation

JF - Resuscitation

SN - 0300-9572

ER -