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 |
| Dose | Weight-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 vary | Weight-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 |
| Pharmacokinetics | Onset: Immediate Distribution: 1-2 minutes to reach peak Metabolism: rapid hepatic degradation Elimination: urine (inactive metabolites) Half-life: <5 minutes | Onset: Immediate Distribution: 1-2 minutes to reach peak 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 | Tachyarrhythmias, myocardial ischemia, extravasation leading to necrosis, |
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 |
| Overview of Evidence | |||
| Author (Year) | Study Design/Patient Population | Intervention | Results |
| Bougouin, 2022 | Retrospective N=766 | • Norepinephrine infusion • Epinephrine infusion | • All-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, 2021 | Retrospective N=93 | • Norepinephrine infusion • Epinephrine infusion | • Significantly 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, 2014 | Case 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.
