Abstract 212: The Effect Of 33 °C Vs. 36 °C Targeted Temperature Management To The Metabolism Following Out-of-hospital Cardiac Arrest.

Abstract

Targeted Temperature Management (TTM) following shockable out-of-hospital cardiac arrest (OHCA) has been recommended. The effect of different targeted temperatures on the human metabolome has not been compared. Elevated levels of metabolites from the Krebs cycle have recently been associated with a poor outcome in OHCA patients. Similarly, decreased levels of the amino acids valine and leucine have been linked with a poor outcome in septic shock patients. Method: From a single center in the randomized clinical TTM trial, we analyzed blood samples from resuscitated unconscious OHCA patients at two timepoints (hospital arrival and 48 hours later) using ultra-performance liquid mass-spectrometry. Patients were randomized to either 33°C or 36°C hypothermia for the first 28 hours. Sixty-one metabolites of the ~3000 compounds detected were prespecified for quantification and analyzed in the current study. Differences (95% CI) in metabolite concentrations from a constrained linear mixed model are reported, and p-values from the interaction term timepoint x TTM arm. Results: Of the 146 patients, 70 (48 %) were randomized to TTM 33°C. The baseline characteristics (age, gender, shockable rhythm, time to return of spontaneous circulation) and outcome (180 days mortality) were similar in the TTM groups. After 48 hours, approx. 24 hours from the cessation of TTM, fourteen metabolites differed significantly between the two groups. Among these, lactate acid (190 μM (74-305 μM), p<0.001 ), pyruvic acid (26 μM (8-44 μM), p<0. 0 1 ), 2-oxoglutaric acid (2.7 μM (1.0-4.4 μM), p<0.01 ) and prostaglandin E2 (0.60 nM (0.24-1.0 nM), p<0.01 ) were increased in the TTM 33 °C arm whereas valine (25 μM (15-35 μM), p<0.001 ) and leucine (14 μM (8.3 - 20 μM), p<0.001 ) were decreased. Conclusion: TTM at 33°C for 24 hours after OHCA results in a prognostically poorer metabolome even 24 hours later compared with TTM at 36°C.