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Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation 2017 Nov 28;136(22):2119-2131 PMID: 28904070 PMCID: PMC5705566

Pubmed ID





BACKGROUND: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation.

METHODS: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects.

RESULTS: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), =0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), =0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent.

CONCLUSIONS: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation.

CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT01401647.

Author List

Kudenchuk PJ, Leroux BG, Daya M, Rea T, Vaillancourt C, Morrison LJ, Callaway CW, Christenson J, Ornato JP, Dunford JV, Wittwer L, Weisfeldt ML, Aufderheide TP, Vilke GM, Idris AH, Stiell IG, Colella MR, Kayea T, Egan D, Desvigne-Nickens P, Gray P, Gray R, Straight R, Dorian P, Resuscitation Outcomes Consortium Investigators


Tom P. Aufderheide MD Professor in the Emergency Medicine department at Medical College of Wisconsin
Mario R. Colella DO, MPH Professor in the Emergency Medicine department at Medical College of Wisconsin


2-s2.0-85037378186   4 Citations

MESH terms used to index this publication - Major topics in bold

Aged, 80 and over
Anti-Arrhythmia Agents
Cardiopulmonary Resuscitation
Double-Blind Method
Electric Countershock
Hospital Mortality
Middle Aged
North America
Out-of-Hospital Cardiac Arrest
Patient Discharge
Prospective Studies
Recovery of Function
Tachycardia, Ventricular
Time Factors
Treatment Outcome
Ventricular Fibrillation
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5