Medication for Out-of-Hospital Cardiac Arrest: For Which Patients Is It Effective?
BY JEFF BAUER
FROM N ENGL J MED
A recent double-blind, randomized trial that compared parenteral amiodarone, lidocaine, and saline placebo for patients who experienced out-of-hospital cardiac arrest found that overall, neither medication resulted in a significantly higher survival rate nor better neurological outcomes.1 However, among a subgroup of patients whose cardiac arrest was witnessed by a bystander, the rate of survival to hospital discharge was significantly higher with amiodarone or lidocaine than with placebo.
Researchers studied 3,026 adults who had nontraumatic out-of-hospital cardiac arrest and shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. These patients were treated in accordance with local emergency medical service (EMS) protocols that complied with American Heart Association (AHA) guidelines for advanced life support. After one or more shocks failed to end ventricular fibrillation or pulseless ventricular tachycardia, patients were randomly treated with one of three parenteral preparations: lidocaine (993 patients), a recently approved cyclodextrin-based formulation of amiodarone that is designed to reduce hypotensive effects (974 patients), or a normal saline placebo (1,059 patients). The initial treatment consisted of two syringes that were administered by rapid bolus. If the ventricular fibrillation or pulseless ventricular tachycardia persisted after this initial dose, a supplemental dose (one syringe) of the same drug was administered. The average time to treatment with these drugs was 19 minutes from the initial call to EMS. On arrival at the hospital, patients were treated with usual postcardiac arrest care in accordance with AHA guidelines.
The primary outcome was survival to hospital discharge. The secondary outcome was survival with favorable neurological status at discharge, which was defined as a score of ≤3 on the modified Rankin scale, indicating the ability to conduct daily activities independently or with minimal assistance.
The hospital survival rates were 23.7% for patients who received lidocaine, 24.4% for those who received amiodarone, and 21.0% for those who received placebo. The differences in survival rates for each drug compared to placebo, and one drug compared to the other drug, were not statistically significant. Rates of survival with favorable neurological status were similar among all three groups.
However, among 1,934 patients who experienced a witnessed out-of-hospital cardiac arrest, each drug was associated with a significantly higher rate of survival (5 percentage points) compared to placebo. In these patients, the survival rate was 27.8% with lidocaine, 27.7% with amiodarone, and 22.7% with placebo. This absolute risk difference was significant for lidocaine versus placebo and for amiodarone versus placebo, but not for lidocaine versus amiodarone.
Researchers said patients who have a witnessed out-of-hospital cardiac arrest presumably have “early recognition of cardiac arrest, a short interval between the patient’s collapse from cardiac arrest and the initiation of treatment, and a greater likelihood of therapeutic responsiveness.” In an accompanying editorial, Joglar and Page2 said EMS personnel should consider using lidocaine or amiodarone when a patient’s cardiac arrest is witnessed.
1. Kudenchuk PJ, Brown SP, Daya M, et al; Resuscitation Outcomes Consortium Investigators. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;374(18):1711-1722.
2. Joglar JA, Page RL. Out-of-hospital cardiac arrest--are drugs ever the answer? N Engl J Med. 2016;374(18):1781-1782.