In which clinical situations should norepinephrine (noradrenaline) and adrenaline (epinephrine) be used?

Clinical Situations for Norepinephrine and Adrenaline (Epinephrine)

Norepinephrine: First-Line Vasopressor

Norepinephrine is the first-choice vasopressor for septic shock and most forms of distributive shock after adequate fluid resuscitation. 1, 2

Primary Indications for Norepinephrine:

• Septic Shock: Norepinephrine is strongly recommended as the initial vasopressor to target a mean arterial pressure (MAP) of 65 mmHg after crystalloid resuscitation (minimum 30 mL/kg) 1, 2

• Distributive Shock: First-line agent for vasodilatory shock states including sepsis, pancreatitis, and other causes of peripheral vasodilation 3

• Post-Cardiac Arrest Shock: Preferred over epinephrine for post-resuscitation shock, with observational data showing lower all-cause mortality (OR 2.6 for epinephrine vs norepinephrine; P=0.002) and lower cardiovascular-specific mortality (aOR 5.5; P<0.001) 4

• Cardiogenic Shock with Hypotension: Recommended in persistently hypotensive cardiogenic shock, particularly when tachycardia is present 3

• Severe Hypotension: Used when systolic blood pressure is <70 mmHg with low total peripheral resistance 5

Key Advantages:

• Lower mortality compared to dopamine in septic shock (RR 0.91; 95% CI 0.83-0.99) 6
• Fewer arrhythmias than dopamine (supraventricular: RR 0.47; ventricular: RR 0.35) 6
• In sepsis, norepinephrine improves renal blood flow and urine output despite theoretical concerns about renal vasoconstriction 5

Adrenaline (Epinephrine): Second-Line and Specific Situations

Epinephrine should be added to (or potentially substituted for) norepinephrine when additional vasopressor support is needed to maintain adequate blood pressure in septic shock. 1, 2

Primary Indications for Epinephrine:

• Refractory Septic Shock: Add epinephrine when norepinephrine alone fails to achieve MAP target of 65 mmHg, typically when norepinephrine-equivalent dose reaches 37-133 μg/min 1, 2, 7

• Anaphylaxis: Epinephrine 0.3-0.5 mg intramuscularly (adults ≥30 kg) or 0.01 mg/kg up to 0.3 mg (children <30 kg) into anterolateral thigh every 5-10 minutes as the definitive emergency treatment 5, 8

• Cardiac Arrest: Epinephrine 1 mg IV every 3-5 minutes during CPR increases return of spontaneous circulation (ROSC) and short-term survival; for shockable rhythms, give after third shock 9

• Symptomatic Bradycardia: When atropine and transcutaneous pacing fail or are unavailable 5

• Resource-Limited Settings: Acceptable alternative to norepinephrine in septic shock when norepinephrine is unavailable, though dopamine may be preferred due to cost and side effect profile 10

Critical Warnings for Epinephrine:

• Cardiogenic Shock: In acute myocardial infarction with cardiogenic shock, epinephrine was associated with significantly higher refractory shock (37% vs 7%; P=0.008) compared to norepinephrine, leading to early trial termination 11

• Metabolic Effects: Epinephrine increases heart rate, cardiac double product (P=0.0002), and lactic acidosis (P<0.0001) more than norepinephrine 11

• Pediatric Septic Shock: Recent data suggests norepinephrine may be superior, with epinephrine associated with greater 30-day mortality (3.7% vs 0%; risk difference 3.7%) 12

Algorithmic Approach to Vasopressor Selection:

Step 1: Identify Shock Type

• Septic/Distributive Shock → Start norepinephrine 1, 2, 3
• Cardiogenic Shock → Start norepinephrine (avoid epinephrine) 3, 11
• Post-Cardiac Arrest → Start norepinephrine 4
• Anaphylaxis → Epinephrine IM immediately 8
• Cardiac Arrest → Epinephrine IV during CPR 9

Step 2: Escalation in Septic Shock

• If MAP <65 mmHg on norepinephrine alone at 37-133 μg/min equivalent dose → Add epinephrine 1, 2, 7
• Alternative: Add vasopressin 0.03 units/min to reduce norepinephrine dose 1, 2

Step 3: Special Populations

• Bradycardia with hypotension → Consider dopamine over norepinephrine 1, 2
• Known cardiac dysfunction → Avoid epinephrine; use norepinephrine with dobutamine if needed 3
• Sulfite allergy → Epinephrine still indicated for anaphylaxis despite bisulfite content 8

Common Pitfalls to Avoid:

• Never use epinephrine as first-line in cardiogenic shock - associated with worse outcomes including refractory shock 11
• Never inject epinephrine into buttocks - risk of Clostridial infection (gas gangrene) and ineffective treatment 8
• Never inject epinephrine into digits, hands, or feet - risk of tissue necrosis from vasoconstriction 8
• Do not use dopamine for renal protection - no benefit demonstrated 1, 2
• Avoid epinephrine monotherapy in post-cardiac arrest shock - higher mortality than norepinephrine 4
• Do not delay epinephrine in anaphylaxis - it is the definitive treatment regardless of other conditions 8