All Pharmacy Pearls

Introduction

  • 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.

    Epinephrine [Adrenalin®]

    Dose

    Cardiac arrest: 1 mg IV/IO every 3 to 5 minutes

    Mechanism of Action

    Receptor Activity

    Pharmacological Action

    Effect

    α agonist

    Peripheral

    vasoconstriction

    increased myocardial and cerebral blood

    flow

    β agonist

    increased heart rate and

    contractility

    increased myocardial oxygen demand

    Indications

    Asystole/pulseless electrical activity (PEA)

    Pulseless ventricular tachycardia/fibrillation

Clinical Detail

Clinical Detail

Mechanism of Action

Receptor ActivityPharmacological ActionEffect
α agonistPeripheral vasoconstriction↑ myocardial and cerebral blood flow
β agonist↑ heart rate and contractility↑ myocardial oxygen demand

Drug Profile

ParameterDetail
IndicationsAsystole/pulseless electrical activity (PEA); pulseless ventricular tachycardia/fibrillation
OnsetImmediate
Distribution1-2 minutes to reach central circulation during CPR
MetabolismRapid hepatic degradation
EliminationUrine (inactive metabolites)
Half-life<5 minutes
Adverse EffectsTachyarrhythmias, myocardial ischemia, may decrease cerebral perfusion, mesenteric ischemia, extravasation leading to necrosis, lactic acidosis
Dosage FormsVial: 1 mg/mL (1 mL & 30 mL); pre-filled syringe: 1 mg/10 mL (10 mL)
CompatibilityCompatible with: NS, D5W, and LR. Incompatible with sodium bicarbonate

Evidence

Evidence

Author (Year)Study Design / Patient PopulationInterventionResults
Pearson, 1963Animal study (n=80); asphyxiated dogs with asystole and ventricular fibrillationEpinephrine 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, 1992RCT (650); out-of-hospital cardiac arrestEpinephrine 7 mg every 5 min vs. epinephrine 1 mg every 5 minNo difference in survival to hospital admission or discharge and neurologic outcomes between low- and high-dose epinephrine
Brown, 1992RCT (n=1280); out-of-hospital cardiac arrestEpinephrine 0.2 mg/kg vs. epinephrine 0.02 mg/kgNo difference in ROSC, survival to hospital admission and discharge, or neurological outcomes between low- and high-dose epinephrine
Choux, 1995RCT (n=536); out-of-hospital cardiac arrestEpinephrine 5 mg every 5 min vs. epinephrine 1 mg every 5 minNo difference in ROSC at any time, admission to hospital, or neurological outcomes between low- and high-dose epinephrine
Sherman, 1997RCT (n=140); out-of-hospital cardiac arrestEpinephrine 0.1 mg/kg vs. epinephrine 0.01 mg/kgNo difference in rhythm improvement, ROSC, neurologic outcomes, or discharge from hospital between low- and high-dose epinephrine
Gueugniaud, 1998RCT (n=3327); out-of-hospital cardiac arrestEpinephrine 5 mg every 3 min vs. epinephrine 1 mg every 3 min↑ ROSC in high-dose epinephrine group. No difference in admission to hospital, 24-hour survival, discharge from hospital, or neurological outcomes between low- and high-dose epinephrine
Fisk, 2018Pre-post study (n=2255); out-of-hospital cardiac arrestEpinephrine 1 mg at 4 min, then 1 mg every 8 min (2 min for non-shockable rhythms) vs. epinephrine 0.5 mg at 4 min and 8 min, then 0.5 mg every 8 min (2 min for non-shockable 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 arrestRapid 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, 2009RCT (n=851); out-of-hospital cardiac arrestACLS with IV medications vs. ACLS without IV medications79% 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
Jacobs, 2011RCT (n=534); out-of-hospital cardiac arrestEpinephrine vs. placebo↑ ROSC and survival to hospital admission in group receiving epinephrine. No difference in survival to hospital discharge or neurological outcomes
Hagihara, 2012Observational study (n=417,188); out-of-hospital cardiac arrestEpinephrine vs. 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 arrestEpinephrine 1 mg every 3-5 min vs. 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

Conclusions

  • 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.

References

    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-of-

    hospital 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.

Tags:epinephrine cardiac arrest ROSC ACLS

Source PDF

Epinephrine for Cardiac Arrest. Pharmacy friday Pearls. 08-21-20 (1).pdf