PHILADELPHIA – Methylprednisolone significantly reduced interleukin (IL)-6 levels in patients resuscitated after out-of-hospital cardiac arrest (OHCA) compared to placebo, new trial results show. Whether this translates to clinical benefit is unclear, however. Laust E.R. Obling, MD, PhD, of Rigshospitalet, Copenhagen, Denmark, presented these findings as featured science Monday at the American Heart Association Scientific Sessions 2023. A manuscript reporting the results was published Thursday online in Intensive Care Medicine. According to the National Danish Cardiac Arrest Registry, the 30-day survival rate of OHCA improved from 4% in 2001 to 13% in 2021, and the rate of OHCA patients who were resuscitated improved from 8% to 27% over the same period. However, the survival rate of resuscitated OHCA patients held steady at about 50% over those 20 years. Post-cardiac arrest patients can suffer myocardial injury, hemodynamic instability, cerebral injury and systemic inflammation, but it is unclear whether there is a link between inflammation and cerebral injury. Methylprednisolone is a well-known and cheap steroid that reduces inflammation. It works both genomically, over the long term, and non-genomically, with rapid onset, within seconds or minutes. Previous in-hospital cardiac arrest studies have shown promising results for methylprednisolone. STEROHCA (STERoid for Out-of-Hospital Cardiac Arrest) is a randomized, placebo-controlled phase II trial that randomly assigned 158 patients with resuscitated prehospital OHCA patients to receive either 250 mg of methylprednisolone (intravenously or intraosseously) or placebo. Of the randomized patients, 137 were included in the modified intention-to-treat analysis (methylprednisolone n=68, placebo n=69). Inclusion criteria included adults ages 18 years or older with cardiac etiology, Glasgow Coma Scale score ≤8, and return of spontaneous circulation (ROSC) time of at least 5 minutes. Primary asystole was an exclusion criterion. The primary outcome was the level of IL-6 at 24 hours post-randomization. At 24 hours, patients in the placebo group had 40 times the IL-6 level of those in the methylprednisolone group (median: methylprednisolone 2.1 pg/mL [interquartile range (IQR): 1.0, 7.1] vs. placebo 30.7 pg/mL [IQR: 14.2, 59]; p<0.0001). However, there was no difference in neuron-specific enolase levels at 48 hours (median: methylprednisolone 14.4 μg/L [IQR: 14.4, 24.6] vs. placebo 14.8 μg/L [IQR: 11.2, 19.4]; p=0.22). There was no significant difference in crude survival between groups, 75% in the methylprednisolone and 64% in the placebo group (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.35-1.20; p=0.17), but once the groups were adjusted for sex, age, time to ROSC, shockable rhythm and whether they underwent primary percutaneous coronary intervention, the placebo group did show a significantly lower survival rate by Kaplan-Meier estimate (adjusted HR: 0.35; 95% CI: 0.18-0.67; p=0.002). However, Obling noted that the study was not powered to detect differences in clinical outcomes. Obling said further study is planned. Rigshospitalet’s PULSE-MI registry has collected data on more than 700 patients with STEMI who received prehospital pulse glucocorticoid therapy. Treatment is the same as the STEROHCA trial, and 250 mg of methylprednisolone. The primary outcome is infarct size at 3 months as measured by cardiac magnetic resonance imaging. He said these results are expected to be released in spring 2024. Obling concluded that the administration of methylprednisolone mitigated biomarkers of inflammation in resuscitated OHCA patients, but it did not show effects on brain or cardiac injury biomarkers. And compared to placebo, methylprednisolone resulted in a more hemodynamically stable profile. Source: Obling LER, Beske RP, Meyer MAS, et al. Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial. Intensive Care Med. 2023 Nov 9 (Article in press). Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Laust E.R. Obling, MD, PhD, presents findings from the STEROHCA trial during a Featured Science session Monday at the American Heart Association Scientific Sessions 2023 in Philadelphia.