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Glucocorticoids mitigate inflammation but also impact the cells beyond the immune response. This study aims to identify glucocorticoid effects on plasma metabolites.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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\u00a0mg of methylprednisolone or a placebo in the prehospital setting. Blood samples were collected upon hospital admission and 48\u00a0h later. Sixty metabolites were quantified in the plasma using mass spectrometry and compared between groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the modified intention-to-treat population, 68 patients received methylprednisolone, and 69 received placebo [median age was 66\u00a0years (IQR: 56\u201374) and 83% were men]. Blood samples were available for 130 patients, 121 (88%) at admission and 117 patients (94% of patients alive) after 48\u00a0h. Although a nominal difference was observed at admission, no significant metabolic effects were found after correcting for multiple testing. After 48\u00a0h, the placebo group had 83.4% (95% CI 16.9\u2013187.6%) 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\u201370.2%), arginine, and propionylcarnitine (C3).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In this exploratory study, early administration of 250\u00a0mg of methylprednisolone after resuscitation appeared to drive sustained metabolic effects over 48\u00a0h. Specifically, methylprednisolone led to reductions in \u03c9-6 fatty acids and increases in several amino acids, with a notable rise in tryptophan.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40635-025-00754-8","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T14:44:50Z","timestamp":1745678690000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic effects of high-dose glucocorticoid following out-of-hospital cardiac arrest"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5880-3733","authenticated-orcid":false,"given":"Rasmus Paulin","family":"Beske","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laust Emil Roelsgaard","family":"Obling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Abild Stengaard","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob Eifer","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"Kjaergaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e4r Ingemar","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hassager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"754_CR1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.resuscitation.2021.02.007","volume":"161","author":"JT Gr\u00e4sner","year":"2021","unstructured":"Gr\u00e4sner JT, Herlitz J, Tjelmeland IBM, Wnent J, Masterson S, Lilja G, Bein B, B\u00f6ttiger BW, Rosell-Ortiz F, Nolan JP, Bossaert L, Perkins GD (2021) European resuscitation council guidelines 2021: epidemiology of cardiac arrest in Europe. 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In addition, a legal data handling agreement was secured from the Capital Region of Denmark (ID: 2020-866). In compliance with Danish legislation, informed consent was initially provided by an independent primary trial guardian before a patient's inclusion and was later confirmed by a secondary trial guardian.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent, including consent for publication, was also obtained from a surrogate, and from the patient themselves if they were deemed cognitively capable after regaining consciousness, as soon as possible following their admission. The trial was monitored for safety and overall conduct by a Data and Safety Monitoring Board and adherence to national and international guidelines was overseen by the Good Clinical Practice unit of Copenhagen. The trial was conducted under the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46"}}