title: Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial.
abstract: OBJECTIVE
  Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination.
  
  
  OBJECTIVE
  To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility).
  
  
  METHODS
  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).
  
  
  METHODS
  Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2.
  
  
  RESULTS
  Follow-up was completed in all resuscitated patients. Patients in the VSE group vs 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% CI, 1.39-6.40; P = .005) and survival to hospital discharge with 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 = .02). Patients in the VSE group with postresuscitation shock vs 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 = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups.
  
  
  CONCLUSIONS
  Among patients with cardiac arrest requiring vasopressors, 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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00729794.
authors.affiliation: First Department of Intensive Care Medicine, University of Athens Medical School, Athens, Greece. sdmentzelopoulos@yahoo.com
authors.forename: Spyros D
authors.initials: SD
authors.lastname: Mentzelopoulos
authors.forename: Sotirios
authors.initials: S
authors.lastname: Malachias
authors.forename: Christos
authors.initials: C
authors.lastname: Chamos
authors.forename: Demetrios
authors.initials: D
authors.lastname: Konstantopoulos
authors.forename: Theodora
authors.initials: T
authors.lastname: Ntaidou
authors.forename: Androula
authors.initials: A
authors.lastname: Papastylianou
authors.forename: Iosifinia
authors.initials: I
authors.lastname: Kolliantzaki
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoridi
authors.forename: Helen
authors.initials: H
authors.lastname: Ischaki
authors.forename: Dimosthemis
authors.initials: D
authors.lastname: Makris
authors.forename: Epaminondas
authors.initials: E
authors.lastname: Zakynthinos
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
authors.forename: Sotirios
authors.initials: S
authors.lastname: Sourlas
authors.forename: Stavros
authors.initials: S
authors.lastname: Aloizos
authors.forename: Spyros G
authors.initials: SG
authors.lastname: Zakynthinos
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000627:therapeutic use*; D005260:Female; D023261:Glasgow Outcome Scale; D006323:Heart Arrest / Q000150:complications* / Q000628:therapy*; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007297:Inpatients; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010351:Patient Discharge; D012769:Shock / Q000188:drug therapy / Q000209:etiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014667:Vasopressins / Q000627:therapeutic use*
chemical_list: D000318:Adrenergic beta-Agonists; D006490:Hemostatics; D018696:Neuroprotective Agents; D014667:Vasopressins; D006854:Hydrocortisone; D008775:Methylprednisolone; D004837:Epinephrine