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Charleston, SC

jimmy@pharmacyfridaypeals.com

Norepinephrine vs Epinephrine Post Cardiac Arrest

Introduction 

1. The effects of epinephrine on animal hemodynamics have been studied since the late 1800s with recent concern with deleterious complications with cerebral and myocardial oxygen supply. 2. Recently, there has been consideration for norepinephrine post cardiac arrest to minimize the  complications associated with epinephrine

Epinephrine Norepinephrine
DoseWeight-based dosing: • Usual dosage range: 0.01 to 1  mcg/kg/minute; titrate based on  clinical end points (eg, MAP,  end-organ perfusion) Non-weight-based dosing: • Usual dosage range: 1 to 80  mcg/minute; titrate based on  clinical end points (eg, MAP,  end-organ perfusion Institutional infusion rates may varyWeight-based dosing:  • Initial: 0.05 to 0.15 mcg/kg/minute; titrate  based on clinical end points (eg, MAP,  end-organ perfusion); usual dosing range:  0.05 to 1 mcg/kg/minute Non-weight-based dosing (based on ~80 kg  patient): • Initial: 5 to 15 mcg/minute; titrate based on  clinical end points (eg, MAP, end-organ  perfusion); usual dosing range: 5 to 80  mcg/minute Institutional infusion rates may vary
PharmacokineticsOnset: Immediate  Distribution: 1-2 minutes to reach  peak Metabolism: rapid hepatic  degradation Elimination: urine (inactive  metabolites) Half-life: <5 minutesOnset: Immediate  Distribution: 1-2 minutes to reach peak Metabolism: rapid hepatic degradation Elimination: urine (inactive metabolites) Half-life: <5 minutes
Adverse EffectsTachyarrhythmias, myocardial  ischemia, may decrease cerebral  perfusion, mesenteric ischemia,  extravasation leading to necrosis,  lactic acidosisTachyarrhythmias, myocardial ischemia, extravasation leading to necrosis,

Mechanism of Action

Receptor  ActivityPharmacological Action Effect
α agonist Peripheral  vasoconstrictionmyocardial and cerebral blood  flow
β agonist heart rate and  contractilitymyocardial oxygen demand
Overview of Evidence
Author (Year) Study Design/Patient  PopulationIntervention Results
Bougouin,  2022Retrospective N=766• Norepinephrine infusion • Epinephrine infusionAll-cause hospital mortality was  significantly higher in the  epinephrine group (OR 2.6; 95%CI  1.4-4.7; P = 0.002). • Proportion of patients with CPC of 3- 5 at hospital discharge was also  higher with epinephrine
Weiss,  2021Retrospective  N=93• Norepinephrine infusion • Epinephrine infusionSignificantly more EPI patients  had refractory hypotension,  rearrest, or death in the emergency  department (EPI 21/42, 50% vs. NE  10/45, 22.2%; P = 0.008) • In an adjusted regression model, the  odds of reaching the primary  outcome in the ED were 3.94  [95%CI 1.38-12.2] (P = 0.013) times  higher in the EPI group compared  to NE treated patients.
Mion,  2014Case report N=1 • Epinephrine then transition to  norepinephrine• 58 year male, The cardiac rhythm  turned into a ventricular fibrillation  (VF). That had reccurent v fib with  epinephrine • Return of spontaneous circulation  was observed, with the recovering of  sinusal activity. After staying for  several weeks in intensive care unit  because of multiorgan failure, the  patient recovered without sequelae.
Kim, 2012 Retrospective N=90• Norepinephrine infusion • Epinephrine infusion• The survivors (N=46) were more  likely to have received  norepinephrine infusion than the  non-survivors (34.8% vs 22.6%). • Of those who had a prolonged arrest  (more than ten minute down time,  N=28) the survivors were also more  likely to have received  norepinephrine infusion (42.85% vs  25%).

Conclusions 

• It’s controversial as to whether epinephrine is preferred vasopressor post cardiac arrest. • Norepinephrine is a reasonable agent to use post arrest if it is clinically warranted. 


References 

• Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2022,  March 15. 

• http://www.micromedexsolutions.com/ 

• Callaway C. Epinephrine for cardiac arrest. Current Opinion in Cardiology. 2013;28(1):36-42. • Epinephrine [package insert] Lake Forest, IL: Hospira, Inc.; 2019. 

• (poster) Kim et al. THE BENEFIT OF NOREPINEPHRINE INFUSION FOR HEMODYNAMIC  SUPPORT FOLLOWING CARDIOPULMONARY ARREST AND RESUSCITATION. Critical Care  Medicine: December 2012 – Volume 40 – Issue 12 – p 1-328 

• Mion Get al. Cardiac arrest: should we consider norepinephrine instead of epinephrine? Am J  Emerg Med. 2014 Dec;32(12):1560.e1-2. PMID: 24997106. 

• Weiss A, et ql. Comparison of Clinical Outcomes with Initial Norepinephrine or Epinephrine for  Hemodynamic Support After Return of Spontaneous Circulation. Shock. 2021 Dec 1;56(6):988-993.  PMID: 34172611. • Bougouin W, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post resuscitation shock. Intensive Care Med. 2022 Mar;48(3):300-310. PMID: 35129643.

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