TY - JOUR
T1 - Metabolic profiles associate with mortality and neurological outcomes in out-of-hospital cardiac arrest patients
AU - Berg-Hansen, Kristoffer
AU - Wiggers, Henrik
AU - Møller, Niels
AU - Johannsen, Mogens
AU - Johansson, Pär I.
AU - Meyer, Martin Abild Stengaard
AU - Kjærgaard, Jesper
AU - Hassager, Christian
AU - Bro-Jeppesen, John
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/4
Y1 - 2025/4
N2 - Background: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and poor neurological outcome, with significant metabolic changes upon return of spontaneous circulation (ROSC). This study aimed to investigate the association of metabolic derangements with outcomes in patients resuscitated from OHCA. Methods: Blood samples from 156 consecutive unconscious OHCA patients in the Targeted Temperature Management trial were analyzed at hospital admission. Metabolic parameters including free fatty acids (FFAs), glucose, lactate, 3-hydroxybutyrate (3-OHB), and insulin were measured. Hierarchical clustering categorized patients based on metabolic response patterns. Thirty-day mortality and neurological outcomes were compared across these clusters. Results: The median age was 62 years (IQR 54–68) and 87% were male. Hierarchical clustering identified three distinct metabolic profiles. Cluster A showed severe metabolic distress with elevated lactate, high insulin resistance, and modest FFA/3-OHB levels. Cluster B had low FFA/3-OHB levels while Cluster C showed high FFA/3-OHB levels; both were associated with lower lactate and insulin resistance compared with Cluster A. Cluster A was linked to greater cardiac arrest severity, including longer time to ROSC, increased defibrillations, and higher adrenaline use. Thirty-day mortality rates were: Cluster A, 68%; B, 33%; C, 21% (log-rank P < 0.001). Neurological deaths were lowest in Clusters C. Baseline FFA levels were independently associated with neurological death. Conclusion: This study identifies distinct metabolic profiles associated with neurological recovery after cardiac arrest, suggesting a potential link between metabolic states and outcomes that may reflect adaptive brain resilience. These findings highlight the need for further research to explore whether metabolic-targeted interventions could enhance recovery.
AB - Background: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and poor neurological outcome, with significant metabolic changes upon return of spontaneous circulation (ROSC). This study aimed to investigate the association of metabolic derangements with outcomes in patients resuscitated from OHCA. Methods: Blood samples from 156 consecutive unconscious OHCA patients in the Targeted Temperature Management trial were analyzed at hospital admission. Metabolic parameters including free fatty acids (FFAs), glucose, lactate, 3-hydroxybutyrate (3-OHB), and insulin were measured. Hierarchical clustering categorized patients based on metabolic response patterns. Thirty-day mortality and neurological outcomes were compared across these clusters. Results: The median age was 62 years (IQR 54–68) and 87% were male. Hierarchical clustering identified three distinct metabolic profiles. Cluster A showed severe metabolic distress with elevated lactate, high insulin resistance, and modest FFA/3-OHB levels. Cluster B had low FFA/3-OHB levels while Cluster C showed high FFA/3-OHB levels; both were associated with lower lactate and insulin resistance compared with Cluster A. Cluster A was linked to greater cardiac arrest severity, including longer time to ROSC, increased defibrillations, and higher adrenaline use. Thirty-day mortality rates were: Cluster A, 68%; B, 33%; C, 21% (log-rank P < 0.001). Neurological deaths were lowest in Clusters C. Baseline FFA levels were independently associated with neurological death. Conclusion: This study identifies distinct metabolic profiles associated with neurological recovery after cardiac arrest, suggesting a potential link between metabolic states and outcomes that may reflect adaptive brain resilience. These findings highlight the need for further research to explore whether metabolic-targeted interventions could enhance recovery.
KW - 3-hydroxybutyrate
KW - Free fatty acids
KW - Metabolism
KW - Mortality
KW - Neurological outcome
KW - Out-of-hospital cardiac arrest
UR - http://www.scopus.com/inward/record.url?scp=105000514001&partnerID=8YFLogxK
U2 - 10.1016/j.resuscitation.2025.110583
DO - 10.1016/j.resuscitation.2025.110583
M3 - Journal article
C2 - 40090610
AN - SCOPUS:105000514001
SN - 0300-9572
VL - 209
JO - Resuscitation
JF - Resuscitation
M1 - 110583
ER -