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.