The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest
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The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest. / Beske, Rasmus Paulin; Obling, Laust Emil Roelsgaard; Bro-Jeppesen, John; Nielsen, Niklas; Meyer, Martin Abild Steengaard; Kjaergaard, Jesper; Johansson, Pär Ingemar; Hassager, Christian.
In: Therapeutic Hypothermia and Temperature Management, Vol. 13, No. 4, 2023, p. 208-215.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest
AU - Beske, Rasmus Paulin
AU - Obling, Laust Emil Roelsgaard
AU - Bro-Jeppesen, John
AU - Nielsen, Niklas
AU - Meyer, Martin Abild Steengaard
AU - Kjaergaard, Jesper
AU - Johansson, Pär Ingemar
AU - Hassager, Christian
N1 - Publisher Copyright: © 2023 Mary Ann Liebert Inc.. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Targeted temperature management (TTM) may moderate the injury from out-of-hospital cardiac arrest. Slowing the metabolism has been a suggested effect. Nevertheless, studies have found higher lactate levels in patients cooled to 33°C compared with 36°C even days from TTM cessation. Larger studies have not been performed on the TTM's effect on the metabolome. Accordingly, to explore the effect of TTM, we used ultra-performance liquid-mass spectrometry in a substudy of 146 patients randomized in the TTM trial to either 33°C or 36°C for 24 hours and quantified 60 circulating metabolites at the time of hospital arrival (T0) and 48 hours later (T48). From T0 to T48, profound changes to the metabolome were observed: tricarboxylic acid (TCA) cycle metabolites, amino acids, uric acid, and carnitine species all decreased. TTM significantly modified these changes in nine metabolites (Benjamini-Hochberg corrected false discovery rate <0.05): branched amino acids valine and leucine levels dropped more in the 33°C arm (change [95% confidence interval]: −60.9μM [−70.8 to −50.9] vs. −36.0μM [−45.8 to −26.3] and −35.5μM [−43.1 to −27.8] vs. −21.2μM [−28.7 to −13.6], respectively), whereas the TCA metabolites including malic acid and 2-oxoglutaric acid remained higher for the first 48 hours (−7.7μM [−9.7 to −5.7] vs. −10.4μM [−12.4 to −8.4] and −3μM [−4.3 to −1.7] vs. −3.7μM [−5 to −2.3]). Prostaglandin E2 only dropped in the TTM 36°C group. The results show that TTM affects the metabolism hours after normothermia have been reached.
AB - Targeted temperature management (TTM) may moderate the injury from out-of-hospital cardiac arrest. Slowing the metabolism has been a suggested effect. Nevertheless, studies have found higher lactate levels in patients cooled to 33°C compared with 36°C even days from TTM cessation. Larger studies have not been performed on the TTM's effect on the metabolome. Accordingly, to explore the effect of TTM, we used ultra-performance liquid-mass spectrometry in a substudy of 146 patients randomized in the TTM trial to either 33°C or 36°C for 24 hours and quantified 60 circulating metabolites at the time of hospital arrival (T0) and 48 hours later (T48). From T0 to T48, profound changes to the metabolome were observed: tricarboxylic acid (TCA) cycle metabolites, amino acids, uric acid, and carnitine species all decreased. TTM significantly modified these changes in nine metabolites (Benjamini-Hochberg corrected false discovery rate <0.05): branched amino acids valine and leucine levels dropped more in the 33°C arm (change [95% confidence interval]: −60.9μM [−70.8 to −50.9] vs. −36.0μM [−45.8 to −26.3] and −35.5μM [−43.1 to −27.8] vs. −21.2μM [−28.7 to −13.6], respectively), whereas the TCA metabolites including malic acid and 2-oxoglutaric acid remained higher for the first 48 hours (−7.7μM [−9.7 to −5.7] vs. −10.4μM [−12.4 to −8.4] and −3μM [−4.3 to −1.7] vs. −3.7μM [−5 to −2.3]). Prostaglandin E2 only dropped in the TTM 36°C group. The results show that TTM affects the metabolism hours after normothermia have been reached.
KW - metabolism
KW - out-of-hospital cardiac arrest
KW - targeted temperature management
U2 - 10.1089/ther.2022.0065
DO - 10.1089/ther.2022.0065
M3 - Journal article
C2 - 37219970
AN - SCOPUS:85178650405
VL - 13
SP - 208
EP - 215
JO - Therapeutic Hypothermia and Temperature Management
JF - Therapeutic Hypothermia and Temperature Management
SN - 2153-7658
IS - 4
ER -
ID: 377993512