Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients
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Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients. / Paulin Beske, Rasmus; Henriksen, Hanne H.; Obling, Laust; Kjærgaard, Jesper; Bro-Jeppesen, John; Nielsen, Niklas; Johansson, Pär I.; Hassager, Christian.
In: Resuscitation, Vol. 179, 2022, p. 163-171.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 323996827