Metabolic Profiles Associate with Mortality and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients.

Abstract

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.