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

Michael W Donnino, Lars W Andersen, Katherine M Berg, Maureen Chase, Robert Sherwin, Howard Smithline, Erin Carney, Long Ngo, Parth V Patel, Xiaowen Liu, Donald Cutlip, Peter Zimetbaum, Michael N Cocchi, Collaborating Authors from the Beth Israel Deaconess Medical Center’s Center for Resuscitation Science Research Group, Tyler Giberson, Brandon Giberson, Justin Salciccioli, Amanda DeBrule, Amy Uber, Michael Rogan, Caitlin Jones-Bamman, Ari Moskowitz, Julia Balkema, Michael W Donnino, Lars W Andersen, Katherine M Berg, Maureen Chase, Robert Sherwin, Howard Smithline, Erin Carney, Long Ngo, Parth V Patel, Xiaowen Liu, Donald Cutlip, Peter Zimetbaum, Michael N Cocchi, Collaborating Authors from the Beth Israel Deaconess Medical Center’s Center for Resuscitation Science Research Group, Tyler Giberson, Brandon Giberson, Justin Salciccioli, Amanda DeBrule, Amy Uber, Michael Rogan, Caitlin Jones-Bamman, Ari Moskowitz, Julia Balkema

Abstract

Background: The 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.

Methods: We 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.

Results: Fifty 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).

Conclusions: In 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 registration: Clinicaltrials.gov: NCT00676585, registration date: May 9, 2008.

Keywords: Adrenal; Cardiac arrest; Hydrocortisone; Shock; Steroids; Vasopressors.

Figures

Fig. 1
Fig. 1
Cytokine levels at 24 hours. Log-transformed interleukin (IL)-6 (left) and IL-10 (right) levels 24 hours after study drug administration. There was significantly lower IL-6 levels at 24 hours in the hydrocortisone group compared to the placebo group (p = 0.008) but no difference in IL-10 levels (p = 0.22). The dots indicate the means and the error bars the standard deviation

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