The effect of vasopressin, epinephrine and methylprednisolone on survival after inhospital cardiac arrest

Background Animal data on cardiac arrest showed improved long-term survivalwith combined vasopressin-epinephrine. In cardiac arrest, cortisol levels arerelatively low during and after cardiopulmonary resuscitation. We hypothesized thatcombined vasopressin-epinephrine and corticosteroid supplementation during andafter 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 withcardiac 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 isotonicsodium 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, studygroup patients received methylprednisolone sodium succinate (40 mg) and controlsreceived saline placebo. Postresuscitation shock was treated with stress-dosehydrocortisone sodium succinate (300 mg daily for 7 days maximum, with gradualtaper) (27 patients in the study group) or saline placebo (15 patients in the controlgroup). Primary end points were return of spontaneous circulation for 15 minutes orlonger and survival to hospital discharge.Results Study group patients vs controls had more frequent return of spontaneouscirculation (39 of 48 patients [81%] vs 27 of 52 [52%]; P = .003) and improvedsurvival to hospital discharge (9 [19%] vs 2 [4%]; P = .02). Study group patientswith postresuscitation shock vs corresponding controls had improved survival tohospital discharge (8 of 27 patients [30%] vs 0 of 15 [0%]; P = .02), improvedhemodynamics and central venous oxygen saturation, and more organ failure–freedays. Adverse events were similar in the 2 groups.111Conclusion In this single-center trial, combined vasopressin-epinephrine andmethylprednisolone during resuscitation and stress-dose hydrocortisone inpostresuscitation shock improved survival in refractory in-hospital cardiac arrest.΢ΥΔΣΗΚΔ΢ ΓΖΜΟ΢ΗΔΤ΢ΔΗ΢-ΑΝΑΚΟΗΝΧ΢ΔΗ΢1) The 20th Annual Congress of the European Society of Intensive Care Medicine,Berlin, Germany, October 7-10, 2007. Oral Presentation. S. D. Mentzelopoulos, N.Katsios, A. Papastylianou, S. Gisioti, A. Stathopoulos, E. Stamataki, M. Tzoufi, S.Zakynthinos. Vasopressin, epinephrine, and methylprednisolone for in-hospital cardiacarrest. Intensive Care Med 2007;33 [suppl 2]:S186.2) The 11th State of the art Interdisciplinary Review Course on Pulmonary diseasesCritical care, Emergency medicine & Nursing care, Athens, Greece, April 20-22, 2007.S Metzelopoylos, N Katsios, A Papastylianou, S Gisioti, A Stathopoylos, E Stamataki,M Tzoufi, S Zakynthinos. Combined Vasopressin, epinephrine and methylprednisolonefor inhospital cardiac arrest.3) The 22nd European Society of Intensive Care Medicine Annual Congress – Vienna,Austria – 11–14 October 2009. S. Mentzelopoulos, S. Kokkoris, K. Mpougia, V.Dimtsa, X. Ieropoulos, E. Zakynthinos, S. Aloizos, A. Papastylianou, N. Katsios, A.Stathopoulos, S. Malachias. Vasopressin, epinephrine, and corticosteroids for inhospitalcardiac arrest: results on patients with postresuscitation shock.Intensive Care Med 2009;35 [suppl]:S283.1124) Vasopresin, Epinephrine, and Corticosteroids for In-Hospital Cardiac ArrestMentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, GkisiotiS, Stathopoulos A, Kollintza A, Stamataki E, Roussos C.Arch Intern Med. 2009 Jan 12;169(1):15-24.5) Advances in Post-Resuscitation Care : the Role of Therapeutic Hypothermia.Androula Papastylianou,MD, Spyros D. Mentzelopoulos,MDHospital Chronicles 2010,vol 5.6) The 23rd Annual Congress of the European Society of Intensive Care Medicine,Barcelona, Spain, October 9-13, 2010. A. Papastylianou, S. Malachias, S. Zakynthinos,E. Zakynthinos, D. Makris, S. Sourlas, S. Aloizos, S. Mentzelopoulos. Predictors ofneurological recovery in refractory in hospital cardiac arrest.Intensive Care Med 2010;36 [suppl 2]:S122.7) Current pharmacological advances in the treatment of cardiac arrest.Androula Papastylianou,MD, Spyros D. Mentzelopoulos,MD.Emergency Medicine International, 20118) The 24th Annual Congress of the European Society of Intensive Care Medicine,Berlin, Germany, October 1-5, 2011. Best Abstract Award Winner; Oral Presentation. S.Mentzelopoulos, A. Papastylianou, C. Chamos, D. Konstantopoulos, T. Ntaidou, I.Kolliantzaki, D. Makris, E. Zakynthinos, S. Sourlas, S. Aloizos, C. Roussos, A. Lomaka,M. Theodoridi, S. Zakynthinos, S. Malachias. Vasopressin, epinephrine, and113corticosteroids for inhospital cardiac arrest: results from a three-center, randomized,controlled trial.Intensive Care Med 2011;37 [suppl]:S109