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Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
Peter J Kudenchuk1, Siobhan P Brown1, Mohamud Daya1
1From the Department of Medicine (P.J.K., T.R., G.N.) and Division of Cardiology (P.J.K.), University of Washington, the King County Emergency Medical Services, Public Health (P.J.K., T.R.), the Department of Biostatistics, University of Washington Clinical Trial Center (S.P.B., G.N., B.L.), and University of Washington-Harborview Center for Prehospital Emergency Care (G.N.), Seattle, and Clark County Emergency Medical Services, Vancouver (L.W.) - all in Washington; the Department of Emergency Medicine, Oregon Health and Science University, Portland (M.D.); Rescu, Li Ka Shing Knowledge Institute, St. Michael's Hospital (L.J.M., P.D.), and the Divisions of Emergency Medicine (L.J.M.) and Cardiology (P.D.), Department of Medicine, University of Toronto, Toronto, the Department of Emergency Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa (C.V., I.G.S.), and the Department of Emergency Medicine, Providence Health Care Research Institute, University of British Columbia Faculty of Medicine (J.C.), and Providence Health Care Research Institute and British Columbia Emergency Health Services (R.S.), Vancouver - all in Canada; University of Pittsburgh, Pittsburgh (C.W.C., A.M.B.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda (D.E., P.D.-N.), and Johns Hopkins University, Baltimore (M.L.W.) - both in Maryland; the Department of Emergency Medicine, Virginia Commonwealth University, Richmond (J.P.O.); the Departments of Emergency Medicine and Internal Medicine, University of Texas Southwestern Medical Center (A.H.I.), and Dallas Fire-Rescue Department (N.S.) - both in Dallas; the Departments of Emergency Medicine (T.P.A.) and Pediatrics (M.R.C.), Medical College of Wisconsin, Milwaukee; the Department of Emergency Medicine, University of California San Diego (J.V.D., G.M.V.), and San Diego Fire-Rescue Department (J.V.D.) - both in San Diego; and University of Alabama at Birmingham, Birmingham (P.C.G., R.G.).
Background:
Antiarrhythmic drugs are used commonly in out-of-hospital cardiac arrest for shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, but without proven survival benefit.
Methods:
In this randomized, double-blind trial, we compared parenteral amiodarone, lidocaine, and saline placebo, along with standard care, in adults who had nontraumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia after at least one shock, and vascular access. Paramedics enrolled patients at 10 North American sites. The primary outcome was survival to hospital discharge; the secondary outcome was favorable neurologic function at discharge. The per-protocol (primary analysis) population included all randomly assigned participants who met eligibility criteria and received any dose of a trial drug and whose initial cardiac-arrest rhythm of ventricular fibrillation or pulseless ventricular tachycardia was refractory to shock.
Results:
In the per-protocol population, 3026 patients were randomly assigned to amiodarone (974), lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%, respectively, survived to hospital discharge. The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], -0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points (95% CI, -1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7 percentage points (95% CI, -3.2 to 4.7; P=0.70). Neurologic outcome at discharge was similar in the three groups. There was heterogeneity of treatment effect with respect to whether the arrest was witnessed (P=0.05); active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing than did recipients of lidocaine or placebo.
Conclusions:
Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT01401647.).
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