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

Abstract

Background Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. Methods The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. Results A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference − 0.04 mcg/kg/min, 95% CI − 0.07 to − 0.01, p = 0.02). Moreover, after 12–24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from − 4.2 to − 3.8, 95% CIs from − 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from − 0.10 to − 0.07, 95% CIs from − 0.16 to − 0.01), while there were no major differences in heart rate (mean differences from − 4 to − 3, 95% CIs from − 11 to 3). These treatment differences between groups were also present 30–48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. Conclusions Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. Trial registration: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776. Graphic Abstract

A critical reappraisal of vasopressin and steroids in in-hospital cardiac arrest

“…Neutral results, primarily on early post-ROSC arterial pressure and inflammatory response, strongly implied a resistance to previously well-documented, circulatory and immunomodulatory effects of steroids [ 3 ]. Nevertheless, single, high-dose (i.e., 250 mg) methylprednisolone within 5–30 min following successful out-of-hospital ALS has been recently associated with lower postresuscitation interleukin-6, improved postresuscitation hemodynamics and higher probability of survival to discharge [ 4 , 5 ]; these benefits might reflect a rapid, nongenomic, high-dose methylprednisolone action [ 4 ].…”