Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

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 (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=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), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=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: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

A randomized trial of continuous versus interrupted chest compressions in out-of-hospital cardiac arrest: rationale for and design of the Resuscitation Outcomes Consortium Continuous Chest Compressions Trial.

The Resuscitation Outcomes Consortium is conducting a randomized trial comparing survival with hospital discharge after continuous chest compressions without interruption for ventilation versus currently recommended American Heart Association cardiopulmonary resuscitation with interrupted chest compressions in adult patients with out-of-hospital cardiac arrest without obvious trauma or respiratory cause. Emergency medical services perform study cardiopulmonary resuscitation for 3 intervals of manual chest compressions (each ~2 minutes) or until restoration of spontaneous circulation. Patients randomized to the continuous chest compression intervention receive 200 chest compressions with positive pressure ventilations at a rate of 10/min without interruption in compressions. Those randomized to the interrupted chest compression study arm receive chest compressions interrupted for positive pressure ventilations at a compression:ventilation ratio of 30:2. In either group, each interval of compressions is followed by rhythm analysis and defibrillation as required. Insertion of an advanced airway is deferred for the first ≥6 minutes to reduce interruptions in either study arm. The study uses a cluster randomized design with every-6-month crossovers. The primary outcome is survival to hospital discharge. Secondary outcomes are neurologically intact survival and adverse events. A maximum of 23,600 patients (11,800 per group) enrolled during the post-run-in phase of the study will provide ≥90% power to detect a relative change of 16% in the rate of survival to discharge, 8.1% to 9.4% with overall significance level of 0.05. If this trial demonstrates improved survival with either strategy, >3,000 premature deaths from cardiac arrest would be averted annually.

Sex- and gender-specific research priorities in cardiovascular resuscitation: proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Resuscitation Research Workgroup.

Significant sex and gender differences in both physiology and psychology are readily acknowledged between men and women; however, data are lacking regarding differences in their responses to injury and treatment and in their ultimate recovery and survival. These variations remain particularly poorly defined within the field of cardiovascular resuscitation. A better understanding of the interaction between these important factors may soon allow us to dramatically improve outcomes in disease processes that currently carry a dismal prognosis, such as sudden cardiac arrest. As part of the 2014 Academic Emergency Medicine consensus conference "Gender-Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes," our group sought to identify key research questions and knowledge gaps pertaining to both sex and gender in cardiac resuscitation that could be answered in the near future to inform our understanding of these important issues. We combined a monthly teleconference meeting of interdisciplinary stakeholders from largely academic institutions with a focused interest in cardiovascular outcomes research, an extensive review of the existing literature, and an open breakout session discussion on the recommendations at the consensus conference to establish a prioritization of the knowledge gaps and relevant research questions in this area. We identified six priority research areas: 1) out-of-hospital cardiac arrest epidemiology and outcome, 2) customized resuscitation drugs, 3) treatment role for sex steroids, 4) targeted temperature management and hypothermia, 5) withdrawal of care after cardiac arrest, and 6) cardiopulmonary resuscitation training and implementation. We believe that exploring these key topics and identifying relevant questions may directly lead to improved understanding of sex- and gender-specific issues seen in cardiac resuscitation and ultimately improved patient outcomes.