What is the initial dose of noradrenaline (norepinephrine) in a patient with cardiogenic shock?

Norepinephrine Dosing in Cardiogenic Shock

Start norepinephrine at 0.2-1 mcg/kg/min (or 8-12 mcg/min absolute dose) as a second-line agent only after optimizing volume status and initiating inotropic therapy, targeting a mean arterial pressure ≥65 mmHg. 1, 2, 3

Critical First Principle: Norepinephrine is NOT First-Line

Do not start norepinephrine as your initial vasopressor in cardiogenic shock. This is a fundamental error that can worsen outcomes by increasing afterload on an already failing heart. 2

The correct sequence is:

• First: Optimize volume status with fluid challenge (250 mL over 10 minutes if no overt overload) 2
• Second: Initiate inotropic therapy (dobutamine 2.5-10 mcg/kg/min is preferred first-line) 4, 1, 2
• Third: Add norepinephrine only if systolic BP remains <90 mmHg despite the above measures 1, 2

Specific Dosing Protocol

Initial Dose

Start at 8-12 mcg/min (absolute dose) or 0.2-1 mcg/kg/min, per FDA labeling and European Society of Cardiology guidelines. 2, 3

Titration Strategy

• Monitor blood pressure every 2 minutes until target MAP ≥65 mmHg is achieved 3
• Once stable, monitor every 5 minutes 3
• Typical maintenance dose: 2-4 mcg/min (absolute) 3

Administration Details

• Administer through a central line to minimize risk of tissue necrosis from extravasation 2, 3
• Dilute 4 mg in 1000 mL of 5% dextrose (produces 4 mcg/mL solution) 3
• Avoid infusion into leg veins, especially in elderly or those with peripheral vascular disease 3

Why This Approach Matters for Outcomes

The evidence strongly suggests that premature or excessive norepinephrine use worsens mortality in cardiogenic shock:

• A 2016 multinational CardShock study found that among vasopressors, only adrenaline (not norepinephrine when used appropriately) was independently associated with increased 90-day mortality (OR 5.2), along with worsening cardiac and renal biomarkers 5
• However, a 2022 MIMIC-III database study showed norepinephrine use was associated with 41% vs 30% 30-day mortality compared to non-norepinephrine treatment, suggesting inappropriate early use as first-line therapy 6
• Importantly, a 2010 study demonstrated that norepinephrine up-titration in cardiogenic shock patients already on inotropes was well-tolerated, with stable cardiac output and no lactate elevation 7

The key distinction: norepinephrine is safe and effective when used as a second-line agent after inotropic optimization, but harmful when used as first-line therapy. 2, 7, 6

Hemodynamic Targets

Monitor these parameters to guide therapy:

• Mean arterial pressure ≥65 mmHg 1, 2
• Systolic blood pressure >90 mmHg 2
• Cardiac index >2 L/min/m² 8
• Perfusion markers: urine output, lactate clearance, mental status, skin perfusion 2

Common Pitfalls to Avoid

1. Using norepinephrine before inotropes: This increases afterload on a failing ventricle, potentially worsening cardiac output and organ perfusion 2

2. Inadequate volume assessment: Always assess fluid responsiveness (passive leg raise test) before adding vasopressors 1

3. Peripheral administration: Extravasation causes tissue necrosis; if it occurs, infiltrate the area immediately with 10-15 mL saline containing 5-10 mg of an alpha-blocker 3

4. Abrupt discontinuation: Taper gradually to avoid rebound hypotension 3

5. Ignoring very high doses: At doses >0.6 mcg/kg/min, non-invasive blood pressure measurements become unreliable; use arterial line monitoring 9

When to Consider Alternatives or Escalation

• If norepinephrine requirements are escalating, consider adding vasopressin up to 0.03 units/min to reduce norepinephrine dose 2
• Evaluate for mechanical circulatory support (IABP, ventricular assist devices) as vasopressors are only bridge therapy 2
• Consider milrinone as an alternative inotrope if patient is on beta-blockers, as it works independently of beta-receptors 4

Special Monitoring Considerations

Discontinue all vasopressors as soon as clinically possible due to their propensity to increase myocardial oxygen demand and arrhythmia risk. 2 This is not a long-term solution but a temporizing measure while addressing the underlying cause of cardiogenic shock.