Metabolic effects of high-dose glucocorticoid following out-of-hospital cardiac arrest.

BACKGROUND AND AIM: Patients resuscitated after out-of-hospital cardiac arrest (OHCA) face high morbidity and mortality rates, primarily due to ischemia-reperfusion injury, a complex metabolic disorder that triggers a significant systemic inflammatory response. Glucocorticoids mitigate inflammation but also impact the cells beyond the immune response. This study aims to identify glucocorticoid effects on plasma metabolites.

METHODS

This explorative sub-study is part of a two-center, blinded, randomized controlled trial (NCT04624776) examining the effects of high-dose glucocorticoid on comatose patients resuscitated from OHCA of presumed cardiac origin. Following resuscitation, patients received 250 mg of methylprednisolone or a placebo in the prehospital setting. Blood samples were collected upon hospital admission and 48 h later. Sixty metabolites were quantified in the plasma using mass spectrometry and compared between groups.

RESULTS

In the modified intention-to-treat population, 68 patients received methylprednisolone, and 69 received placebo [median age was 66 years (IQR: 56-74) and 83% were men]. Blood samples were available for 130 patients, 121 (88%) at admission and 117 patients (94% of patients alive) after 48 h. Although a nominal difference was observed at admission, no significant metabolic effects were found after correcting for multiple testing. After 48 h, the placebo group had 83.4% (95% CI 16.9-187.6%) higher prostaglandin E2 and higher levels of linolenic acid and arachidonic acid. The methylprednisolone group had higher levels of tryptophan (47.6%; 95% CI 27.9-70.2%), arginine, and propionylcarnitine (C3).

CONCLUSIONS

In this exploratory study, early administration of 250 mg of methylprednisolone after resuscitation appeared to drive sustained metabolic effects over 48 h. Specifically, methylprednisolone led to reductions in ω-6 fatty acids and increases in several amino acids, with a notable rise in tryptophan.