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

Rasmus Paulin Beske*, Laust Emil Roelsgaard Obling, Martin Abild Stengaard Meyer, Jacob Eifer Møller, Jesper Kjaergaard, Pär Ingemar Johansson, Christian Hassager

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
Artikelnummer46
TidsskriftIntensive Care Medicine Experimental
Vol/bind13
Antal sider12
ISSN2197-425X
DOI
StatusUdgivet - 26. apr. 2025

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