What is the difference between epinephrine (adrenaline) and norepinephrine usage in emergency medicine?

Epinephrine vs. Norepinephrine Usage in Emergency Medicine

Norepinephrine should be preferred as the first-line vasopressor in septic shock and post-resuscitation shock due to its more favorable safety profile and mortality outcomes compared to epinephrine. 1, 2

Pharmacological Differences

• Mechanism of Action: Epinephrine has both α and β adrenergic effects, while norepinephrine has predominantly α-adrenergic effects with some β1 activity but minimal β2 effects 3, 4
• Hemodynamic Effects: Norepinephrine increases mean arterial pressure (MAP) primarily through vasoconstriction with minimal changes in heart rate and stroke volume, while epinephrine increases MAP and cardiac output through increased stroke volume and heart rate 1
• Metabolic Effects: Epinephrine may increase aerobic lactate production via stimulation of skeletal muscles' β2-adrenergic receptors, potentially interfering with the use of lactate clearance to guide resuscitation 1

Clinical Applications in Septic Shock

First-line Vasopressor Choice

• Norepinephrine is recommended as the first-line vasopressor for septic shock based on evidence showing lower mortality and fewer adverse events compared to dopamine 1
• Norepinephrine is more potent than dopamine and more effective at reversing hypotension in septic shock patients 1
• Norepinephrine is associated with significantly fewer arrhythmias compared to dopamine (RR 0.35; 95% CI 0.19-0.66 for ventricular arrhythmias) 1

Role of Epinephrine

• Epinephrine should be considered the first alternative to norepinephrine in septic shock when norepinephrine is unavailable or ineffective 1
• Despite concerns about splanchnic circulation effects, randomized trials (n=540) comparing norepinephrine to epinephrine found no significant differences in mortality (RR 0.96; 95% CI 0.77-1.21) 1
• In resource-limited settings, epinephrine may be used as an alternative to norepinephrine, particularly when norepinephrine is unavailable 1

Cardiac Arrest Management

• Epinephrine is recommended during cardiopulmonary resuscitation to increase return of spontaneous circulation (ROSC) 1
• Epinephrine increases short-term survival (ROSC) in cardiac arrest but has not been conclusively shown to improve long-term survival or neurological outcomes 5, 6
• The 2015 International Consensus on Cardiopulmonary Resuscitation recommends standard-dose epinephrine (1 mg) for cardiac arrest (weak recommendation, very low-quality evidence) 1

Post-Resuscitation Shock

• Norepinephrine is preferred over epinephrine for post-resuscitation shock management 7, 2
• Patients receiving epinephrine infusions after ROSC experienced significantly higher rates of prehospital rearrest compared to those receiving norepinephrine (55% vs 25%, adjusted OR 3.28,95% CI 2.25-5.08) 7
• All-cause hospital mortality was significantly higher with epinephrine compared to norepinephrine in post-resuscitation shock (adjusted OR 2.6; 95% CI 1.4-4.7) 2

Pediatric Considerations

• In pediatric septic shock, epinephrine may be more effective than dopamine for shock resolution in the first hour (OR 4.8; 95% CI 1.3-17.2) 1
• Current evidence is insufficient to recommend a specific inotrope or vasopressor to improve mortality in pediatric distributive shock 1
• Selection of vasopressors in pediatric patients should be tailored to individual physiology and clinical response 1

Practical Considerations and Dosing

• Norepinephrine is typically administered as an intravenous infusion into a large vein, preferably through a central venous catheter 1
• Epinephrine for hypotension in septic shock: IV infusion rate of 0.05 mcg/kg/min to 2 mcg/kg/min, titrated to achieve desired mean arterial pressure 3
• When infusion pumps are unavailable (resource-limited settings), dopamine or epinephrine can be diluted in crystalloid solution and administered using a drop regulator with frequent monitoring of blood pressure and heart rate 1

Adverse Effects and Precautions

• Epinephrine: Headache, anxiety, restlessness, tremor, dizziness, diaphoresis, nausea/vomiting, respiratory difficulties, arrhythmias (including fatal ventricular fibrillation), rapid blood pressure rises, and cerebral hemorrhage 3
• Norepinephrine: Generally fewer arrhythmias compared to epinephrine or dopamine, but still requires careful monitoring for hypertension and tissue ischemia 1
• Extravasation of either agent can cause local tissue necrosis; infusion sites should be frequently checked 1, 3