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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 LU ; Meyer, Martin Abild Steengaard ; Kjaergaard, Jesper ; Johansson, Pär Ingemar and Hassager, Christian (2023) In Therapeutic hypothermia and temperature management 13(4). p.208-215
Abstract

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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
metabolism, out-of-hospital cardiac arrest, targeted temperature management
in
Therapeutic hypothermia and temperature management
volume
13
issue
4
pages
8 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:37219970
  • scopus:85178650405
ISSN
2153-7658
DOI
10.1089/ther.2022.0065
language
English
LU publication?
yes
id
7b78c4f9-d181-4e39-a4e4-1bcac79e64d4
date added to LUP
2024-01-04 11:04:03
date last changed
2025-04-19 18:32:16
@article{7b78c4f9-d181-4e39-a4e4-1bcac79e64d4,
  abstract     = {{<p>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 (T<sub>0</sub>) and 48 hours later (T<sub>48</sub>). From T<sub>0</sub> to T<sub>48,</sub> 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 &lt;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.</p>}},
  author       = {{Beske, Rasmus Paulin and Obling, Laust Emil Roelsgaard and Bro-Jeppesen, John and Nielsen, Niklas and Meyer, Martin Abild Steengaard and Kjaergaard, Jesper and Johansson, Pär Ingemar and Hassager, Christian}},
  issn         = {{2153-7658}},
  keywords     = {{metabolism; out-of-hospital cardiac arrest; targeted temperature management}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{208--215}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Therapeutic hypothermia and temperature management}},
  title        = {{The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest}},
  url          = {{http://dx.doi.org/10.1089/ther.2022.0065}},
  doi          = {{10.1089/ther.2022.0065}},
  volume       = {{13}},
  year         = {{2023}},
}