Neurologically favorable survival after cardiac arrest remains dismal, with a prevalence of severe disability ranging from 25% to 50%. In previous preliminary work by Mentzelopoulos et al, patients resuscitated with vasopressin, steroids, and epinephrine (VSE) had less organ dysfunction and improved survival. The question of whether the addition of steroids is beneficial in terms of neurologically favorable outcomes was addressed in the recent study led by Spyros Mentzelopoulos, MD, and colleagues at three centers in Greece.
This study was a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. Patients with in-hospital cardiac arrest requiring vasopressors were included. The control group was treated according to the European Resuscitation Council (ERC) 2005 Guidelines, with a saline placebo provided in lieu of the steroid. Patients in the experimental group (VSE group) received arginine vasopressin, epinephrine, and one dose of methylprednisolone (40 mg). Surviving patients in the VSE group received stress-dose hydrocortisone (300 mg /day) for up to seven days post-arrest. The primary endpoint was return of spontaneous circulation for 20 minutes or longer and survival to hospital discharge with a favorable neurological recovery as assessed by the Glasgow-Pittsburgh Cerebral Performance Category. Several secondary endpoints were also studied, including complications related to steroids. Multivariable regression techniques, including a Cox regression analysis, were used to analyze data.
Of 364 patients with cardiac arrest, 138 were ultimately included in the control group and 130 were assigned to the VSE group. VSE patients received less epinephrine and had shorter duration of advanced life support compared to the control group. Patients in the VSE group had a lower hazard of poor outcome (hazard ratio, 0.70; 95% confidence interval [CI], 0.54-0.92; P=0.009) and were more likely to be alive at the time of discharge with a favorable neurological status (odds ratio, 3.28; 95% CI, 1.17-9.20; P=0.02). Patients in both groups who survived more than four hours had similar ventilator-free days and duration of hospital stay.
Steroids may help attenuate the systemic inflammatory response syndrome and improve cerebral perfusion, though the exact mechanisms of action remain unclear. Limitations to this study include lack of data regarding pre-arrest endocrine status, post-arrest myocardial function, and the use of 2005 ERC protocols for cardiac arrest compared to more recent guidelines. Moreover, the role of steroids remains unclear for cardiac arrest patients in the pre-hospital environment. Although several studies have cast doubt on the efficacy of epinephrine in terms of improved outcomes for patients with cardiac arrest, when vasopressors are combined with steroids, the effects of vasopressors may be enhanced. The positive results observed in this trial of VSE in cardiac arrest merits further investigation before adoption in the next iteration of advanced cardiac life support guidelines.
Samuel M. Galvagno Jr., DO, PhD, is Editor of Concise Critical Care Appraisal. An assistant professor at the University of Maryland, R Adams Cowley Shock Trauma Center, he is board certified in anesthesiology, critical care medicine, and public health. He earned his PhD in Clinical Investigation from Johns Hopkins in 2012. His major interests include aeromedical critical care, pain management in the ICU, medical education, and patient safety. He teaches FCCS, ACLS, PALS, and ATLS. A major in the United States Air Force, he is the Director of Critical Care Air Transport Team (CCATT) Operations at the 943rd Aerospace Medicine Squadron at the 943rd Rescue Group, Davis-Monthan Air Force Base, Arizona.