Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: A sub-study of the STEROHCA trial.

Background: The post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized "STERoid for OHCA" (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission.
Methods: The STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences.
Results: The 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49-5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03-0.10), p < 0.001), IL-8 (ratio 0.53 (0.38-0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13-0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18-0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4-0.8), p = 0.01).
Conclusion: Administering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h.
Trial Registration: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www.
Clinicaltrials: gov; Unique Identifier: NCT04624776.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The corresponding author (LERO) received salary support from a grant provided by the Research Foundation of Rigshospitalet (E-22652-04). The study, including the salary of RPB, received backing from a grant from the Novo Nordisk Foundation (NNF20OC0064043) under the supervision of CH. Additionally, CH benefits from an unrestricted grant from the Lundbeck Foundation (R186-2015–2132), received a speaker honorarium from Abiomed during the study, and holds positions as a board member of the European Society of Cardiology and chair of the Danish Heart Foundation. JK is supported by an unrestricted grant from the Novo Nordisk Foundation (NNF17OC0028706) and serves on two Data Safety Monitoring Boards for the IVIO trial (as chair) and the COCA trial without financial compensation. JEM received research grants from Abiomed and the Novo Nordisk Foundation outside the current study, speaker honorariums from Abiomed, Abbott, and Boehringer Ingelheim, and attended meetings with support from Abiomed. FF is backed by a research grant from the Novo Nordisk Foundation (NNF19OC0055142). RFS received grants from the Lundbeck Foundation, Danish Heart Foundation, and Sygeforsikringen Danmark Research Fund, all unrelated to the present study. The remaining authors have no disclosures to report.].
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