TY - JOUR

T1 - Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest

T2 - a randomized clinical trial

AU - Obling, Laust Emil Roelsgaard

AU - Beske, Rasmus Paulin

AU - Wiberg, Sebastian

AU - Folke, Fredrik

AU - Moeller, Jacob Eifer

AU - Kjaergaard, Jesper

AU - Hassager, Christian

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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

AB - 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

KW - Acute cardiac care

KW - Hemodynamics

KW - Inflammation

KW - Neuroprotection

KW - Out-of-hospital cardiac arrest

KW - Post cardiac arrest syndrome

KW - Pre-hospital intervention

KW - Randomized controlled trial

KW - Steroid

U2 - 10.1186/s13063-022-06838-0

DO - 10.1186/s13063-022-06838-0

M3 - Journal article

C2 - 36414975

AN - SCOPUS:85142249830

VL - 23

JO - Trials

JF - Trials

SN - 1745-6215

M1 - 952

ER -