What is the maximum dose of norepinephrine (vasopressor)?

Maximum Dose of Norepinephrine

The maximum recommended dose of norepinephrine is 3.0 mg/hour (approximately 0.5 mcg/kg/min in a 70 kg adult), with doses exceeding 1.0 mcg/kg/min associated with mortality rates approaching 90% and serving as a threshold for refractory shock requiring addition of second-line vasopressors. 1, 2

Standard Dosing Protocol

• Start norepinephrine at 0.5 mg/hour via continuous IV infusion 1
• Titrate upward by 0.5 mg/hour increments every 4 hours as needed 1, 2
• The absolute maximum dose is 3.0 mg/hour (approximately 50 mcg/min or 0.5 mcg/kg/min in a 70 kg adult) 1, 2
• Target mean arterial pressure (MAP) of 65 mmHg or adequate tissue perfusion markers (urine output >50 mL/hour, lactate clearance, improved mental status, capillary refill) 1, 2

Critical Thresholds for Escalation

When norepinephrine reaches 0.25 mcg/kg/min (approximately 1.0-1.2 mg/hour in a 70 kg adult) and hypotension persists, add a second vasopressor rather than continuing to escalate norepinephrine alone. 1, 2

Evidence-Based Mortality Thresholds:

• Doses >0.6 mcg/kg/min are associated with significantly increased 7-day mortality (sensitivity 47%, specificity 93%) 3
• Doses >1.0 mcg/kg/min predict ICU mortality rates approaching 90% 4
• Doses >1.13 mcg/kg/min have a hazard ratio of 7.40 for day-5 mortality (sensitivity 67%, specificity 80%) 5

Second-Line Vasopressor Strategy

When norepinephrine reaches 0.25 mcg/kg/min with persistent hypotension:

• Add vasopressin 0.03-0.04 units/min as the preferred second agent 1, 2
• Alternatively, add epinephrine 0.1-0.5 mcg/kg/min if vasopressin is unavailable 2
• Do NOT increase vasopressin above 0.04 units/min except as salvage therapy 2

Pediatric Dosing

• Start at 0.1 mcg/kg/min and titrate to effect 1, 2
• Typical range: 0.1-1.0 mcg/kg/min 1, 2
• Maximum doses up to 5 mcg/kg/min may be necessary in exceptional circumstances, requiring central venous access 2

Administration Requirements

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 2
• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site 1, 2
• Ensure adequate fluid resuscitation (minimum 30 mL/kg crystalloid bolus) before or concurrent with norepinephrine initiation 2

Common Pitfalls to Avoid

• Never escalate norepinephrine beyond 0.25 mcg/kg/min without adding a second vasopressor - this significantly increases mortality risk 1, 2, 5, 4
• Do not use dopamine as first-line agent (associated with higher mortality and arrhythmias compared to norepinephrine) 2
• Avoid phenylephrine as first-line therapy (may raise blood pressure while worsening tissue perfusion) 2
• Do not delay norepinephrine initiation in profound hypotension (systolic <70 mmHg or diastolic ≤40 mmHg) while waiting for complete volume repletion 2, 6

Practical Dose Severity Classification

Based on recent validation studies, norepinephrine doses can be categorized as: 7

• Low dose: <0.2 mcg/kg/min (hospital mortality ~14%)
• Intermediate dose: 0.2-0.4 mcg/kg/min (hospital mortality ~26%)
• High dose: >0.4 mcg/kg/min (hospital mortality ~40%)

These thresholds provide a rational framework for assessing cardiovascular failure severity and guiding escalation decisions. 7