Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest - PARAMEDIC2

Contribution To Literature:

The PARAMEDIC2 trial showed that epinephrine use for OOHCA results in higher rates of return of spontaneous circulation, with a small but significant increase in survival at 30 days compared with placebo, but without increasing the proportion with a favorable neurological outcome among survivors.


The goal of the trial was to compare the safety and efficacy of epinephrine compared with placebo among patients with out-of-hospital cardiac arrest (OOHCA).

Study Design

Adult patients with OOHCA were randomized in a 1:1 fashion to receive either parenteral epinephrine (n = 4,015) or saline placebo (n = 3,999). Each syringe contained 1 mg of epinephrine or 0.9% saline. Single doses of epinephrine or saline were administered every 3-5 minutes (median administered dose, 4.9 mg). Resuscitation protocols were standard. An initial attempt at cardiopulmonary resuscitation (CPR) and defibrillation was required.

  • Total number of enrollees: 8,014
  • Duration of follow-up: 30 days
  • Mean patient age: 69.8 years
  • Percentage female: 35%

Inclusion criteria:

  • Adult patients
  • OOHCA for which advanced life support was provided by trial-trained paramedics

Exclusion criteria:

  • Known or apparent pregnancy
  • Age <16 years
  • Cardiac arrest from anaphylaxis or asthma
  • Administration of epinephrine before the arrival of the trial-trained paramedic

Other salient features/characteristics:

  • Initial rhythm shockable: 19% (ventricular fibrillation, 17%); nonshockable: 78% (asystole, 54%)
  • Bystander witnessed arrest: 50%
  • CPR performed: 70%
  • Interval between emergency call and administration of drug: 21.3 minutes

Principal Findings:

The primary outcome, being alive at 30 days, for epinephrine vs. placebo, was 3.2% vs. 2.4%, p = 0.02 (number needed to treat, 112).

Secondary outcomes:

  • Survival until hospital admission: 23.8% vs. 8.0%, p < 0.05
  • Favorable neurological outcome at hospital discharge: 2.2% vs. 1.9%, p > 0.05
  • Severe neurological impairment among survivors: 31.0% vs. 17.8%, p < 0.05
  • Survival at 3 months: 3.0% vs. 2.2%, p < 0.05


The results of this trial indicate that the use of epinephrine for OOHCA results in higher rates of return of spontaneous circulation with resultant higher rate of survival until hospital admission. There was also a small but significant increase in survival at 30 days and at 3 months. However, the proportion of alive patients with severe neurological impairments was higher in the epinephrine arm with no difference in the patients with favorable neurological outcome at hospital discharge between the two arms.

OOHCA has a dismal prognosis, with only about 3% of patients remaining alive at 30 days following the index event in this trial. Although the use of epinephrine in these patients seems reasonable, other issues such as prompt recognition, early bystander CPR, and prompt defibrillation are much more important for achieving a favorable outcome. It is also unknown if earlier administration of epinephrine (median time in this trial was 21 minutes), particularly among patients with nonshockable rhythms, would be associated with an improvement in outcomes.


Perkins GD, Ji C, Deakin CD, et al., on behalf of the PARAMEDIC2 Collaborators. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018;379:711-21.

Editorial: Callaway CW, Donnino MW. Testing Epinephrine for Out-of-Hospital Cardiac Arrest. N Engl J Med 2018;379:787-8.

Clinical Topics: Arrhythmias and Clinical EP, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Advanced Cardiac Life Support, Arrhythmias, Cardiac, Cardiopulmonary Resuscitation, Defibrillators, Electric Countershock, Epinephrine, Heart Arrest, Out-of-Hospital Cardiac Arrest, Secondary Prevention, Survival Rate, Ventricular Fibrillation

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