open access publication

Article, 2024

Modulation of cytokine response in post-cardiac arrest syndrome through prehospital high-dose glucocorticoid treatment

European Heart Journal Acute Cardiovascular Care, ISSN 2048-8726, 2048-8734, Volume 13, Supplement_1, Page zuae036.159, 10.1093/ehjacc/zuae036.159

Contributors

Obling, Laust Emil Roelsgaard 0000-0003-2927-3670 [1] Beske, Rasmus Paulin P 0000-0002-5880-3733 [1] Meyer, Martin Abild Stengaard 0000-0002-6312-2457 [1] Grand, Johannes 0000-0002-5511-4668 [1] Wiberg, Sebastian C 0000-0002-7062-7189 [1] Bjerre, Mette 0000-0002-5511-8829 [2] Folke, Fredrik F 0000-0002-2284-7857 [3] Møller, Jacob Eifer 0000-0003-2873-5845 [1] Kjaergaard, Jesper 0000-0001-5244-0399 [1] Hassager, Christian 0000-0002-1199-0981 [1]

Affiliations

  1. [1] Rigshospitalet
    2. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Aarhus University
    3. [NORA names: AU Aarhus University; University; Denmark; Europe, EU; Nordic; OECD];
  3. [3] Copenhagen Emergency Medical Services
    4. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Research Foundation of Rigshospitalet. Background Post-cardiac arrest syndrome (PCAS) following out-of-hospital cardiac arrest (OHCA) is a life-threatening condition, characterized by a cascade of pathological events, including the development of a severe cytokine response. This inflammatory response may be associated with secondary brain injury and multi-organ dysfunction. In the randomized STEROHCA trial, high-dose glucocorticoid was administered immediately following resuscitation in the prehospital setting. The intervention exhibited a significant decrease in interleukin (IL) 6 levels, but its effect on other cytokines has yet to be assessed. Purpose We aimed to investigate the effects of high-dose glucocorticoid treatment in mitigating the cytokine response observed in PCAS after OHCA. Methods The modified intention-to-treat population of the double-blind, randomized STEROHCA trial consisted of 137 OHCA patients, who were randomized to a single prehospital injection of methylprednisolone 250 mg or placebo. Of these, this sub-study included 112 patients who were comatose and admitted to an ICU. Cytokine profiling was performed with a 17-plex assay, including pro- and anti-inflammatory cytokines, which were measured at 0, 24, 48, and 72h after admission. We applied mixed-model analyses to assess the effect of the intervention over time with log-transformed data. To maintain an exploratory approach, we chose not to correct for multiple testing. Results The intervention induced a reduction in the levels of several cytokines, with a significant treatment over time effect for IL-4, IL-8, IL-10, Monocyte Chemoattractant Protein-1 (MCP-1), Macrophage Inflammatory Protein-1 Beta (MIP-1β), and Tumor Necrosis Factor Alpha (TNF-α), all p<0.01. These cytokines, except for IL-10, exhibited lower values in the glucocorticoid group after 24h, Figure 1. Higher levels of IL-10 were observed in the glucocorticoid group at 0h. We found no differences in cytokine levels after 48-, and 72h between the two groups. Conclusion High-dose glucocorticoid treatment administered promptly after resuscitation from OHCA reduced several pro-inflammatory cytokines after 24h. TNF-α has previously been associated with poor outcomes following OHCA, whereas the exact role of the other cytokines following OHCA is unclear.Cytokines at 0-, 24-, 48-, and 72 hours

Keywords

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Funders

  • Novo Nordisk Foundation

Data Provider: Digital Science

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