Abstract Su206: Early Metabolic Effects of Prehospitally Administered High-Dose Glucocorticoids in Comatose Patients Resuscitated from Out-of-Hospital Cardiac Arrest

Background: Administration of glucocorticoid in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) mitigate the inflammatory response within the first 24 hours. The anti-inflammatory action is mediated through genomic effects, taking hours to days to set in, but glucocorticoids may also exert acute, non-genomic effects. The interplay between inflammation and metabolism is becoming more evident and emerging evidence suggests that early metabolic interventions can reduce reactive oxygen species, thus preventing cell apoptosis and necrosis. Hence, it is pivotal to investigate whether glucocorticoids cause significant metabolic effects in this context. Methods: Sub-study of a two-center, blinded, randomized controlled trial (NCT04624776) examining the effects of prehospital administration of 250 mg methylprednisolone versus placebo in comatose patients resuscitated from OHCA of presumed cardiac cause. Blood samples were collected upon hospital arrival (T0) and 48 hours later (T48). A total of 60 metabolites were quantified by mass-spectrometry and compared between groups following adjustment for sex, age, time to return of spontaneous circulation (ROSC), ST-elevation myocardial infarction, and time from intervention to sampling (only at T0). All results were corrected using the false-discovery rate method to account for multiple tests. Results: In the modified intention to treat population (mITT) 68 (50%) had been randomized to glucocorticoid and 69 (50%) to placebo. Blood samples were available for 121 (88%) and 117 (82%) patients at T0 and T48, respectively. Median age was 66 years (IQR: 56- 74) and 100 (83%) patients were men. Median time to ROSC was 16 min (10-20), and study medicine was administered prehospital 20 min (13-29) following ROSC with blood samples at T0 being drawn after 107 min (64-180). Though a nominal difference was observed at hospital arrival (Figure 1 left), we found no metabolic effects following correction for multiple testing. At T48, glucocorticoid showed increased plasma levels of many amino acids, especially tryptophan (Figure 1 right), while prostaglandin E2 and free fatty acids associated with inflammation were higher in the placebo group. Discussion: We did not find evidence for early metabolic effects of glucocorticoid treatment after OHCA. In contrast, several metabolites were affected at T48, including an increase in plasma tryptophan levels in the glucocorticoid group and lower levels of prostaglandin E2.