What is the difference between Adrenaline (epinephrine) and Noradrenaline (norepinephrine) in a critical care setting, particularly for treating hypotension and cardiac arrest?

Adrenaline vs Noradrenaline in Critical Care

Norepinephrine is the preferred first-line vasopressor for septic shock and post-resuscitation shock, while epinephrine is reserved for cardiac arrest resuscitation and as a second-line agent when norepinephrine fails or is unavailable. 1, 2

Pharmacological Differences

Norepinephrine increases mean arterial pressure primarily through alpha-adrenergic vasoconstriction with minimal effects on heart rate and stroke volume, making it a "pure" vasopressor 2. In contrast, epinephrine increases both MAP and cardiac output through combined alpha and beta-adrenergic stimulation, increasing stroke volume and heart rate 2.

A critical distinction is that epinephrine stimulates β2-adrenergic receptors in skeletal muscle, which increases aerobic lactate production independent of tissue hypoperfusion 2. This can interfere with using lactate clearance to guide resuscitation—a significant clinical pitfall 2.

Post-Cardiac Arrest and Post-Resuscitation Shock

Norepinephrine is strongly preferred over epinephrine for post-resuscitation shock. 1, 3

• Epinephrine use in post-resuscitation shock is associated with significantly higher mortality (adjusted OR 2.6; 95% CI 1.4-4.7) compared to norepinephrine 3
• Cardiovascular-specific mortality is markedly increased with epinephrine (adjusted OR 5.5; 95% CI 3.0-10.3) 3
• Unfavorable neurological outcomes (CPC 3-5) are more common with epinephrine 3
• Guidelines explicitly state that epinephrine alone is associated with higher mortality in ECPR patients, and norepinephrine should be preferred 1

Upon achieving return of spontaneous circulation after cardiac arrest, vasoactive support should be weaned as tolerated, with norepinephrine as the preferred agent if vasopressor support remains necessary 1.

Septic Shock Management

Norepinephrine is the recommended first-line vasopressor for septic shock based on superior efficacy and safety profile 1, 2.

• Norepinephrine is more potent and effective at reversing hypotension in septic shock compared to dopamine 2
• Norepinephrine causes significantly fewer arrhythmias than dopamine (RR 0.35; 95% CI 0.19-0.66 for ventricular arrhythmias) 2
• Epinephrine should be considered the first alternative when norepinephrine is unavailable or ineffective 2
• Despite theoretical concerns about splanchnic perfusion, randomized trials show no mortality difference between norepinephrine and epinephrine (RR 0.96; 95% CI 0.77-1.21) 2

If hypotension persists despite norepinephrine, vasopressin (up to 0.03 units/min) can be added to reduce norepinephrine requirements 1.

Cardiac Arrest Resuscitation

Epinephrine (1 mg IV/IO every 3-5 minutes) is the standard vasopressor during active cardiac arrest 1, 4.

• Epinephrine significantly increases return of spontaneous circulation (ROSC): 151 more patients per 1,000 achieve ROSC compared to placebo (RR 2.80; 95% CI 1.78-4.41) 1, 4
• Survival to hospital admission increases by 124 more patients per 1,000 (RR 1.95; 95% CI 1.34-2.84) 1, 4
• For non-shockable rhythms (PEA/asystole), administer epinephrine as soon as feasible 4
• For shockable rhythms (VF/pVT), epinephrine may be given after initial defibrillation attempts fail 4

The unique β2-adrenergic effects of epinephrine may enhance pacemaker cell function and restore contractility in ischemic cardiomyocytes via sodium/potassium pump activation—effects not shared by norepinephrine 5. However, the evidence for long-term benefit remains uncertain, with observational data suggesting potential harm to neurological outcomes despite improved ROSC 1.

High-dose epinephrine (0.1-0.2 mg/kg) is NOT recommended for routine use 4.

Cardiogenic Shock

Norepinephrine is preferred over epinephrine in cardiogenic shock 1.

• Norepinephrine should only be used when inotropic agents and fluid resuscitation fail to restore systolic blood pressure >90 mmHg with adequate organ perfusion 1
• Epinephrine is not recommended as an inotrope or vasopressor in cardiogenic shock and should be restricted to cardiac arrest scenarios 1
• Inotropes (dobutamine, dopamine, phosphodiesterase III inhibitors) are first-line for cardiogenic shock with adequate blood pressure 1

Critical Pitfalls to Avoid

• Never use epinephrine as first-line for post-resuscitation shock—this is associated with doubled mortality 1, 3
• Do not rely on lactate clearance for resuscitation guidance when using epinephrine due to β2-mediated lactate production 2
• Avoid delaying epinephrine in cardiac arrest with non-shockable rhythms—give as soon as feasible 4
• In cardiogenic shock on VA-ECMO, epinephrine increases LV afterload and distension; norepinephrine with inotropic support is preferred 1
• Monitor for transient metabolic effects with epinephrine (hyperglycemia, lactic acidosis) that may prompt drug discontinuation in 13% of patients 6

Administration Considerations

Both agents require infusion into a large vein, preferably via central venous catheter 2, 7. Extravasation of either agent can cause tissue necrosis, requiring frequent site monitoring 2. All patients on vasopressors should have arterial catheter placement as soon as practical 1.