Introduction

The effects of epinephrine on animal hemodynamics have been studied since the late 1800s with recent concern regarding deleterious complications with cerebral and myocardial oxygen supply. Recently, norepinephrine has been considered as an alternative vasopressor post-cardiac arrest to minimize complications associated with epinephrine use.

Key Concept

  • Epinephrine has known deleterious effects on cerebral and myocardial oxygen supply post-arrest
  • Norepinephrine is being considered as an alternative vasopressor post-cardiac arrest
  • Both agents share alpha and beta agonist properties but differ in relative receptor activity
  • Current evidence suggests norepinephrine may offer hemodynamic advantages in certain post-arrest scenarios

Pharmacology of Epinephrine & Norepinephrine

Category Epinephrine Norepinephrine
Dose

Weight-based: 0.01–1 mcg/kg/min

Non-weight-based: 1–80 mcg/min

Institutional infusion rates may vary

Weight-based: 0.05–1 mcg/kg/min (initiate 0.05–0.15)

Non-weight-based: 5–80 mcg/min (initiate 5–15)

Institutional infusion rates may vary
PK/PD
Onset: Immediate Peak: 1–2 min Metabolism: Hepatic Half-life: <5 min Elimination: Urine (inactive metabolites)
Adverse Effects
Tachyarrhythmias Myocardial ischemia Extravasation → necrosis
Mechanism of Action

α Agonist Effect

Peripheral vasoconstriction → ↑ myocardial & cerebral blood flow

β Agonist Effect

↑ Heart rate & contractility → ↑ myocardial oxygen demand
Compatibility
Refer to institutional policies for line compatibility and Y-site administration.

Clinical Pearl

Norepinephrine may offer a hemodynamic advantage over epinephrine in certain post-arrest scenarios due to less beta-1 stimulation and reduced myocardial oxygen demand.

Overview of Key Evidence

Author / Year Design (n) Key Findings
Bougouin, 20227 Retrospective
N=766
↑ Hospital mortality w/ EPI (OR 2.6)

95% CI 1.4–4.7; P=0.002. More CPC 3–5 at discharge in epinephrine group.
Weiss, 20216 Retrospective
N=93
EPI: more adverse events (50% vs 22.2%)

Adjusted OR 3.94 (P=0.013). More refractory hypotension, rearrest, or death in ED.
Mion, 20145 Case Report
N=1
NE → ROSC & full recovery

After recurrent VF with epinephrine, transition to norepinephrine led to sustained ROSC and full recovery post-ICU.
Kim, 20124 Retrospective
N=90
Survivors more likely received NE

NE use: 34.8% in survivors vs 22.6% in non-survivors; 42.85% vs 25% in prolonged arrest.

Clinical Conclusions

Bottom Line

It remains controversial whether epinephrine is the preferred vasopressor post-cardiac arrest. Norepinephrine is a reasonable alternative, particularly when adverse effects from epinephrine are of concern.

It remains controversial whether epinephrine is the preferred vasopressor post-cardiac arrest due to concerns about increased myocardial oxygen demand and adverse outcomes.

Norepinephrine is a reasonable alternative post-arrest vasopressor, particularly when adverse effects from epinephrine — such as tachyarrhythmias and myocardial ischemia — are of concern.

Retrospective data suggest epinephrine use post-ROSC is associated with higher mortality (OR 2.6) and more adverse events (OR 3.94) compared to norepinephrine.

Prospective, randomized trials are needed to definitively establish the optimal vasopressor strategy in post-cardiac arrest shock.

Full Reference List

  1. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Accessed 2022, March 15.
  2. Callaway C. Epinephrine for cardiac arrest. Current Opinion in Cardiology. 2013;28(1):36–42.
  3. Epinephrine [package insert]. Lake Forest, IL: Hospira, Inc.; 2019.
  4. Kim et al. The benefit of norepinephrine infusion for hemodynamic support following cardiopulmonary arrest and resuscitation. Critical Care Medicine. 2012;40(12):1–328.
  5. Mion G, et al. Cardiac arrest: should we consider norepinephrine instead of epinephrine? Am J Emerg Med. 2014;32(12):1560.e1–2. PMID: 24997106.
  6. Weiss A, et al. Comparison of clinical outcomes with initial norepinephrine or epinephrine for hemodynamic support after return of spontaneous circulation. Shock. 2021;56(6):988–993. PMID: 34172611.
  7. Bougouin W, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med. 2022;48(3):300–310. PMID: 35129643.
Tags: Advanced Cardiac Life Support Cardiology Hemodynamic Support Post-Cardiac Arrest Shock Vasopressor Therapy

Never Miss a Pearl

Get Pharmacy Pearls delivered weekly

Join 3,000+ pharmacists who receive curated clinical insights every Friday.

Start Free Trial