Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest

Arch Intern Med. 2009 Jan 12;169(1):15-24. doi: 10.1001/archinternmed.2008.509.


Background: Animal data on cardiac arrest showed improved long-term survival with combined vasopressin-epinephrine. In cardiac arrest, cortisol levels are relatively low during and after cardiopulmonary resuscitation. We hypothesized that combined vasopressin-epinephrine and corticosteroid supplementation during and after resuscitation may improve survival in refractory in-hospital cardiac arrest.

Methods: We conducted a single-center, prospective, randomized, double-blind, placebo-controlled, parallel-group trial. We enrolled 100 consecutive patients with cardiac arrest requiring epinephrine according to current resuscitation guidelines. Patients received either vasopressin (20 IU per cardiopulmonary resuscitation cycle) plus epinephrine (1 mg per resuscitation cycle) (study group; n = 48) or isotonic sodium chloride solution placebo plus epinephrine (1 mg per resuscitation cycle) (control group; n = 52) for the first 5 resuscitation cycles after randomization, followed by additional epinephrine if needed. On the first resuscitation cycle, study group patients received methylprednisolone sodium succinate (40 mg) and controls received saline placebo. Postresuscitation shock was treated with stress-dose hydrocortisone sodium succinate (300 mg daily for 7 days maximum, with gradual taper) (27 patients in the study group) or saline placebo (15 patients in the control group). Primary end points were return of spontaneous circulation for 15 minutes or longer and survival to hospital discharge.

Results: Study group patients vs controls had more frequent return of spontaneous circulation (39 of 48 patients [81%] vs 27 of 52 [52%]; P = .003) and improved survival to hospital discharge (9 [19%] vs 2 [4%]; P = .02). Study group patients with postresuscitation shock vs corresponding controls had improved survival to hospital discharge (8 of 27 patients [30%] vs 0 of 15 [0%]; P = .02), improved hemodynamics and central venous oxygen saturation, and more organ failure-free days. Adverse events were similar in the 2 groups.

Conclusion: In this single-center trial, combined vasopressin-epinephrine and methylprednisolone during resuscitation and stress-dose hydrocortisone in postresuscitation shock improved survival in refractory in-hospital cardiac arrest.

Trial registration: Identifier: NCT00411879.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiopulmonary Resuscitation / methods
  • Cause of Death
  • Confidence Intervals
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Emergency Service, Hospital
  • Epinephrine / administration & dosage*
  • Female
  • Follow-Up Studies
  • Heart Arrest / drug therapy*
  • Heart Arrest / mortality*
  • Heart Arrest / therapy
  • Hospital Mortality / trends*
  • Hospitalization
  • Humans
  • Infusions, Intravenous
  • Intensive Care Units
  • Kaplan-Meier Estimate
  • Male
  • Methylprednisolone / administration & dosage*
  • Middle Aged
  • Probability
  • Proportional Hazards Models
  • Prospective Studies
  • Reference Values
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome
  • Vasopressins / administration & dosage*


  • Vasopressins
  • Methylprednisolone
  • Epinephrine

Associated data