Maximum Dose of Norepinephrine
The maximum recommended dose of norepinephrine is 3.0 mg/hour, as recommended by the American College of Cardiology. 1
Standard Dosing Guidelines
- Norepinephrine is typically initiated as a continuous IV infusion starting at 0.1–0.5 mcg/kg/min (approximately 7–35 mcg/min in a 70-kg adult) 2
- The American College of Cardiology recommends starting at 0.5 mg/hour and increasing by 0.5 mg/hour every 4 hours to a maximum of 3.0 mg/hour 1
- Doses should be titrated to achieve the minimum effective dose that maintains adequate mean arterial pressure (typically ≥65 mmHg), improves tissue perfusion, ensures adequate urine output, and decreases lactate levels 1
High-Dose Considerations
- When high doses of norepinephrine are required, consider adding a second vasopressor agent (such as vasopressin or epinephrine) rather than continuing to escalate norepinephrine 1
- Vasopressin (up to 0.03 U/min) can be added to either raise MAP to target or to decrease the required norepinephrine dose 1
- Research suggests that norepinephrine doses exceeding 1 μg/kg/min are associated with significantly increased mortality risk 3, 4
- A 2024 study identified 1.13 μg/kg/min as the threshold dose of norepinephrine that best predicts early ICU mortality (within 5 days) in patients with circulatory shock 4
Administration Considerations
- Central venous access is preferred for norepinephrine administration 5
- Standard adult concentration: 4 mg of norepinephrine in 250 mL of D5W (16 μg/mL) 5
- For extravasation, phentolamine (0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride) should be injected intradermally at the site 5
- Avoid mixing norepinephrine solutions with alkali-labile drugs due to compatibility concerns 6
Prognostic Implications of High Doses
- Mortality rates increase significantly with higher norepinephrine doses 7, 3, 8, 4
- A retrospective study found that doses >1 μg/kg/min were associated with 90% mortality in septic shock patients 3
- Another study identified that maximum norepinephrine dosage within 24 hours of ICU admission ≥0.6 μg/kg/min was significantly associated with 7-day mortality in septic shock patients 8
- In trauma patients, mortality rates increase with higher doses, with doses greater than 20 mcg/min associated with 79% mortality 9
Monitoring and Titration
- Blood pressure and heart rate should be monitored every 5-15 minutes during initial titration 5
- Watch for signs of excessive vasoconstriction such as cold extremities and decreased urine output 5
- Ensure adequate volume resuscitation before and during norepinephrine administration to optimize cardiac output 5