- There are greater than 350,000 out-of-hospital cardiac arrests annually, and nearly 90% of them are fatal.
- The effects of epinephrine on animal hemodynamics have been studied since the late 1800s.
- While the first advanced cardiac life support (ACLS) guidelines were first published in 1974, the role of epinephrine remains controversial.
|Dose||Cardiac arrest: 1 mg IV/IO every 3 to 5 minutes|
|Mechanism of Action||Receptor Activity||Pharmacological Action||Effect|
|α agonist||Peripheral vasoconstriction||↑ myocardial and cerebral blood flow|
|β agonist||↑ heart rate and contractility||↑ myocardial oxygen demand|
|Indications||Asystole/pulseless electrical activity (PEA) Pulseless ventricular tachycardia/fibrillation|
|Pharmacokinetics||Onset: immediate Distribution: 1-2 minutes to reach central circulation during CPR Metabolism: rapid hepatic degradation Elimination: urine (inactive metabolites) Half-life: <5 minutes|
|Adverse Effects||Tachyarrhythmias, myocardial ischemia, may decrease cerebral perfusion, mesenteric ischemia, extravasation leading to necrosis, lactic acidosis|
|Dosage Forms||Vial: 1 mg/mL (1 mL & 30 mL) Pre-filled syringe: 1 mg/10 mL (10 mL)|
|Compatibility||Compatible with: NS, D5W, and LR Incompatible with sodium bicarbonate|
|Overview of Evidence|
|Author (Year)||Study Design/Patient Population||Intervention||Results|
|Pearson, 1963||Animal study (n=80) Asphyxiated dogs with asystole and ventricular fibrillation||Epinephrine 1 mg Positive-pressure breathing Chest compressions Defibrillation||↑ ROSC in dogs that received epinephrine 5 min and 10 min after asystole ↑ ROSC in dogs that received epinephrine 1 min after ventricular fibrillation Ventricular fibrillation occurred only in the epinephrine group|
|Stiell, 1992||RCT (650) Out-of-hospital cardiac arrest||Epinephrine 7 mg every 5 min Epinephrine 1 mg every 5 min||No difference in survival to hospital admission or discharge and neurologic outcomes between low- and high-dose epinephrine|
|Brown, 1992||RCT (n=1280) Out-of-hospital cardiac arrest||Epinephrine 0.2 mg/kg Epinephrine 0.02 mg/kg||No difference in ROSC, survival to hospital admission and discharge, or neurological outcomes between low- and high-dose epinephrine|
|Choux, 1995||RCT (n=536) Out-of-hospital cardiac arrest||Epinephrine 5 mg every 5 min Epinephrine 1 mg every 5 min||No difference in ROSC at any time, admission to hospital, or neurological outcomes between low- and high-dose epinephrine|
|Sherman, 1997||RCT (n =140) Out-of-hospital cardiac arrest||Epinephrine 0.1 mg/kg Epinephrine 0.01 mg/kg||No difference in rhythm improvement, ROSC, neurologic outcomes, or discharge from hospital between low- and high-dose epinephrine|
|Gueugniaud, 1998||RCT (n= 3327) Out-of-hospital cardiac arrest||Epinephrine 5 mg every 3 min Epinephrine 1 mg Every 3 min||↑ ROSC in high-dose epinephrine group No difference in admission to hospital, 24hour survival, discharge from hospital, or neurological outcomes between low- and high-dose epinephrine|
|Fisk, 2018||Pre-post study (n= 2255) Out-of-hospital cardiac arrest||Epinephrine 1 mg at 4 min, then 1 mg every 8 min (2 min for non-shockable rhythms) Epinephrine 0.5 mg at 4 min and 8 min, then 0.5 mg every 8 min (2 min for nonshockable rhythms)||No difference in any ROSC, sustained ROSC, survival to discharge, or favorable neurological outcomes between low- and high-dose epinephrine|
|Stiell, 2004 (OPALS)||Pre-Post study (n=5638) Out-of-hospital cardiac arrest||• Rapid defibrillation ACLS (endotracheal intubation & IV medications)||98.5% of ACLS group received epinephrine ↑ ROSC and survival to hospital admission in group receiving epinephrine No difference in survival to hospital discharge and neurological outcomes|
|Olasveengen, 2009||RCT (n=851) Out-of-hospital cardiac arrest||ACLS with IV medications ACLS without IV medications||79% of IV medication group received epinephrine ↑ ROSC at any time and survival to hospital admission in group receiving epinephrine No difference in survival to hospital discharge and neurological outcomes|
|Author (Year)||Study Design/Patient Population||Intervention||Results|
|Jacobs, 2011||RCT (n=534) Out-of-hospital cardiac arrest||Epinephrine Placebo||↑ ROSC and survival to hospital admission in group receiving epinephrine No difference in survival to hospital discharge or neurological outcomes|
|Hagihara, 2012||Observational study (n=417,188) Out-of-hospital cardiac arrest||Epinephrine No epinephrine||↑ ROSC in group receiving epinephrine ↓ 1-month survival and neurological outcomes in epinephrine group|
|Perkins, 2018 (PARAMEDIC- 2)||RCT (n=8007) Out-of-hospital cardiac arrest||Epinephrine 1 mg every 3-5 min Placebo||↑ ROSC, survival to hospital admission, and 30-day survival in epinephrine group No difference in favorable neurologic outcome at hospital discharge ↑ severe neurologic impairment in group receiving epinephrine|
- The dose of epinephrine is based on animal studies from the 1960s, in which epinephrine was administered immediately after the induction of cardiac arrest.
- There have been no differences found between standard and high-dose epinephrine.
- Epinephrine may lead to increased ROSC and survival to hospital admission but has not been found to consistently improve long-term outcomes.
- Bottom Line: Quality chest compressions and early defibrillation continue to be the standard of care in ACLS and should not be delayed for administration of epinephrine.
- Attaran RR, Ewy GA. Epinephrine in resuscitation: curse or cure? Future Cardiology. 2010;6(4).
- Callaway C. Epinephrine for cardiac arrest. Current Opinion in Cardiology. 2013;28(1):36-42.
- Epinephrine [package insert] Lake Forest, IL: Hospira, Inc.; 2019.
- Pearson JW, Redding JS. Epinephrine in cardiac resuscitation. Am Heart J. 1963;66:210-214.
- Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med.
1992;327(15):1045-1050. Choux C, Gueugniaud PY, Barbieux A, et al. Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital. Resuscitation. 1995;29(1):3-9.
- Sherman BW, Munger MA, Foulke GE, Rutherford WF, Panacek EA. High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy. Pharmacotherapy. 1997;17(2):242-247.
- Gueugniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group. N Engl J Med. 1998;339(22):1595-1601.
- Fisk CA, Olsufka M, Yin L, et al. Lower-dose epinephrine administration and out-of-hospital cardiac arrest outcomes. Resuscitation. 2018;124:43-48.
- Stiell IG, Wells GA, Field B, et al. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med. 2004;351(7):647-656.
- Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-ofhospital cardiac arrest: a randomized trial. JAMA. 2009;302(20):2222-2229.
- Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation. 2011;82(9):1138-1143.
- Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012;307(11):1161-1168.
- Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018;379(8):711-721.