Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial

Abstract

BackgroundThe purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock.MethodsWe conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal.ResultsFifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95 % CI: 0.40–1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52 % vs. 60 %, p = 0.57), good neurological outcome (24 % vs. 32 %, p = 0.53) or survival to discharge (28 % vs. 36 %, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100 % (6/6) in the hydrocortisone group achieved shock reversal compared to 33 % (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100 %; 3/3) whereas 50 % (3/6) died in the hydrocortisone group (p = 0.43).ConclusionsIn a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo.Clinical trial registrationClinicaltrials.gov: NCT00676585, registration date: May 9, 2008.

Is cardiac arrest an inflammatory state? Adding steroid into ACLS guidelines will save more lives?

“…Patients who survive after 24 hours of cardiac arrest, a cytokine IL-6 increases significantly 2 . A study by Donnino et al showed that the steroid use decreased IL-6 level post cardiac arrest 19 . However, the reduction in IL-6 did not result in better clinical outcome 19 .…”

“…A study by Donnino et al showed that the steroid use decreased IL-6 level post cardiac arrest 19 . However, the reduction in IL-6 did not result in better clinical outcome 19 . This contradictory result may be explained by the relative small sample size used in that study.…”

Surrogate endpoints and competing risk of death in cardiac arrest research

“…We urgently need new therapies to improve survival with good neurological outcomes after cardiac arrest [ 1 ]. Cardiac arrest is a major global health problem, with approximately 424,000 patients experiencing an out-of-hospital cardiac arrest each year in the USA [ 2 ].…”

“…In this issue of Critical Care , Donnino and colleagues present the results of a randomized controlled trial targeting one such surrogate endpoint, the reversal of shock after cardiac arrest [ 1 ]. Specifically, they tested whether corticosteroids—in doses similar to those used in sepsis trials—could shorten duration of vasopressor administration [ 5 ].…”

“…Another possible explanation is that many patients died before they could achieve shock reversal, rendering this surrogate endpoint unable to discriminate between responders and non-responders. Indeed, more than two-thirds (34/50) of patients died before hospital discharge, and it is unclear how many died before shock reversal [ 1 ]. The researchers used appropriate analytical techniques to account for this competing risk, but even the most sophisticated analyses cannot detect a change in a surrogate endpoint when most patients die before they can experience it.…”