Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial

Intensive Care Med. 2023 Dec;49(12):1467-1478. doi: 10.1007/s00134-023-07247-w. Epub 2023 Nov 9.

Abstract

Purpose: Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients.

Methods: The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up.

Results: We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group.

Conclusion: Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.

Trial registration: ClinicalTrials.gov NCT04624776.

Keywords: Inflammation; Intensive cardiovascular care; Neuroprotection; Out-of-hospital cardiac arrest; Post-cardiac arrest syndrome.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Biomarkers
  • Coma
  • Emergency Medical Services*
  • Humans
  • Inflammation / complications
  • Interleukin-6
  • Methylprednisolone / therapeutic use
  • Out-of-Hospital Cardiac Arrest* / complications
  • Out-of-Hospital Cardiac Arrest* / drug therapy
  • Phosphopyruvate Hydratase

Substances

  • Methylprednisolone
  • Interleukin-6
  • Biomarkers
  • Phosphopyruvate Hydratase

Associated data

  • ClinicalTrials.gov/NCT04624776