Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest: a randomized clinical trial

Abstract

Background Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality risk and often develop post-cardiac arrest syndrome (PCAS) involving systemic inflammation. The severity of the inflammatory response is associated with adverse outcome, with anoxic irreversible brain injury as the leading cause of death following resuscitated OHCA. The study aimed to investigate the anti-inflammatory and neuroprotective effect of pre-hospital administration of a high-dose glucocorticoid following OHCA. Methods The study is an investigator-initiated, randomized, multicenter, single-blinded, placebo-controlled, clinical trial. Inclusion will continue until one hundred twenty unconscious OHCA patients surviving a minimum of 72 h are randomized. Intervention is a 1:1 randomization to an infusion of methylprednisolone 250 mg following a minimum of 5 min of sustained return of spontaneous circulation in the pre-hospital setting. Methylprednisolone will be given as a bolus infusion of 1 × 250 mg (1 × 4 mL) over a period of 5 min. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%). Main eligibility criteria are OHCA of presumed cardiac cause, age ≥ 18 years, Glasgow Coma Scale ≤ 8, and sustained ROSC for at least 5 min. Co-primary endpoint: Reduction of interleukin-6 and neuron-specific-enolase. Secondary endpoints: Markers of inflammation, brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, safety, neurological function at follow-up, and mortality. A research biobank is set up with blood samples taken daily during the first 72 h from hospitalization to evaluate primary and secondary endpoints. Discussion We hypothesize that early anti-inflammatory steroid treatment in the pre-hospital setting can mitigate the progression of PCAS following resuscitated OHCA. Primary endpoints will be assessed through analyses of biomarkers for inflammation and neurological damage taken during the first 72 h of admission. Trial registration EudraCT number: 2020-000855-11; submitted March 30, 2020 ClinicalTrials.gov Identifier: NCT04624776; submitted October 12, 2020, first posted November 10, 2020

Postresuscitation management

“…The study did not reveal any significant disparities in blood pressure levels, cardiac function, or the inflammatory response, as assessed by interleukin-6 levels [33]. Ongoing investigations are exploring the use of varying doses and types of steroids in this context [34].…”

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial

“…This was a sub-study of the STEROHCA trial, an investigator-initiated randomized placebo-controlled multicenter study investigating the anti-inflammatory and neuroprotective effects of early high-dose glucocorticoid treatment following resuscitated OHCA. The study protocol and the primary results have previously been published [ 12 ]. Prior to initiation, approvals for the study were obtained from the Regional Ethics Committee (ID: H-20022320) and the Danish Medicines Agency (ID: 2020033425).…”

“…To explore the possible advantages of glucocorticoids in post-cardiac arrest treatment, we conducted the “STERoid treatment as anti-inflammatory and neuroprotective agent following OHCA” (STEROHCA) trial [ 12 ]. Here, following a median time of twenty minutes from return of spontaneous circulation (ROSC), one high-dose glucocorticoid injection was administered prehospitally in resuscitated OHCA patients in order to mitigate severity of the post-cardiac arrest syndrome.…”

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

“…Prior to initiation, the trial was registered at https://clinicaltrials.gov (Unique Identifier: NCT04624776). The study protocol has previously been published [ 17 ]. The prehospital inclusion process is displayed in the appendix (supplementary Fig.…”

“…Safety was assessed by the cumulative incidence of adverse events 180 days after randomization. As stated in the study protocol [ 17 ], the following was considered an adverse event: infection, bleeding, dialysis, electrolyte derangement (hypo- or hyperkalemia), metabolic derangement (hypo- or hyperglycemia), cardiac arrhythmia, seizure, and other (for example, other conditions leading to re-hospitalization or death). It was considered a serious adverse event if an adverse event led to prolonged hospitalization or a life-threatening condition requiring re-hospitalization or death.…”