Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial

Study Questions:

What is the impact of combined vasopressin-steroids-epinephrine (VSE) during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR on survival to hospital discharge?

Methods:

This was a randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in three Greek tertiary care centers (2,400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). The main outcome measures were the return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a cerebral performance category (CPC) score of 1 or 2.

Results:

Follow-up was completed in all resuscitated patients. Patients in the VSE group versus patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs. 91/138 [65.9%]; odds ratio [OR], 2.98; 95% confidence interval [CI], 1.39-6.40; p = 0.005) and survival to hospital discharge with a CPC score of 1 or 2 (18/130 [13.9%] vs. 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; p = 0.02). Patients in the VSE group with postresuscitation shock versus corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs. 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; p = 0.02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the two groups.

Conclusions:

The authors concluded that among patients with cardiac arrest, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status.

Perspective:

In this study of patients with cardiac arrest requiring vasopressors, the combination of vasopressin and epinephrine, along with methylprednisolone during CPR and hydrocortisone in postresuscitation shock, resulted in improved survival to hospital discharge with favorable neurological status, compared with epinephrine/saline placebo. These results are consistent with increased efficacy of the VSE combination versus epinephrine alone during CPR for in-hospital, vasopressor-requiring cardiac arrest. The improved peri-arrest hemodynamics and shorter advanced life support duration of VSE patients versus control patients may reflect attenuated peri-arrest cerebral ischemia, possibly contributing to improved neurological recovery. Based on these data, it appears that combined vasopressin-epinephrine and methylprednisolone during CPR may be the preferred regimen for patients with in-hospital cardiac arrest.

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, SCD/Ventricular Arrhythmias

Keywords: Tertiary Care Centers, Odds Ratio, Follow-Up Studies, Methylprednisolone, Shock, Vasoconstrictor Agents, Cardiopulmonary Resuscitation, Heart Arrest, Brain Ischemia, Hemodynamics, Epinephrine, Oxygen, Confidence Intervals, Hydrocortisone


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