Epinephrine Dose: Optimal Versus Standard Evaluation Trial

This study is designed as a prospective, multicentre, single-blinded randomized controlled trial (RCT) where eligible OHCA patients are randomized to receive a low cumulative dose of epinephrine (low dose epinephrine, up to 2mg total) or a standard cumulative dose of epinephrine (standard dose epinephrine, up to 8mg total) in a 1:1 fashion.

Eligible OHCA patients will be treated by emergency medical service (EMS) providers who will initiate cardiopulmonary resuscitation (CPR) and the delivery of defibrillation shocks per EMS treatment protocols. After one defibrillation and when feasible, EMS providers will establish peripheral intravenous (IV) access, and patients will be randomly allocated to 1 of the 2 study arms. Subsequent study drug doses will be administered every 3-5 minutes, based on current guidelines and paramedic protocols, during resuscitation until the first return of spontaneous circulation (ROSC) is achieved or if resuscitation has been terminated by the base hospital physician. Other medications (e.g. antiarrhythmics, magnesium, beta blockers) and interventions (e.g. intubation) may be interposed as required. Follow-up will take place using a combination of administrative databases (e.g. the Discharge Abstract Database and the National Ambulatory Care Reporting System) and telephone interviews.

This RCT will evaluate a fundamental change in the treatment of OHCA. The investigators hypothesize that a low cumulative dose of epinephrine will improve patient survival to hospital discharge compared to a standard cumulative dose of epinephrine.

• Cardiac Arrest, Out-Of-Hospital
• Sudden Cardiac Arrest
• Ventricular Fibrillation
• Ventricular Tachycardia-Pulseless

• Active Comparator: Low Dose Epinephrine
  Epinephrine up to 2mg total
  Intervention: Drug: Epinephrine
• Active Comparator: Standard Dose Epinephrine
  Epinephrine up to 8mg total
  Intervention: Drug: Epinephrine

Inclusion Criteria:

1. Out-of-hospital cardiac arrest treated by paramedics
2. Initial EMS recorded cardiac rhythm of VF or pulseless VT, or EMS AED shock
3. Established intravenous vascular access

Exclusion Criteria:

1. Known or apparent age <18 years
2. Initial recorded cardiac rhythm of pulseless electrical activity (PEA) or asystole
3. Cardiac arrest due to an obvious non-cardiac primary cause (e.g. blunt or penetrating trauma, exsanguination, burns, drug overdose, drowning, anaphylaxis, sudden asphyxiation, etc.)
4. Prior receipt of open-label intravenous or intramuscular epinephrine during resuscitation

• Canadian Institutes of Health Research (CIHR)
• Pfizer