Maximum Dose of Norepinephrine in Vasopressor Therapy
There is no absolute maximum dose of norepinephrine for vasopressor therapy; instead, norepinephrine should be titrated based on clinical response with doses typically ranging from 0.1-3.0 mg/hour (approximately 0.01-3.0 μg/kg/min), with higher doses used in refractory cases.
Dosing Guidelines and Classifications
- Norepinephrine is typically administered as a continuous IV infusion starting at 0.5 mg/hour and increased by 0.5 mg/hour every 4 hours to a maximum of 3.0 mg/hour, with the goal of increasing mean arterial pressure (MAP) by 10 mmHg or achieving adequate urine output (>50 mL/h) 1
- For clinical categorization of vasopressor support, norepinephrine doses can be classified as 2:
- Low dose: <0.2 μg/kg/min
- Intermediate dose: 0.2-0.4 μg/kg/min
- High dose: >0.4 μg/kg/min
Clinical Endpoints and Titration
- The primary goal of norepinephrine therapy is to achieve and maintain a target MAP, typically 65 mmHg in most patients with septic shock 1
- Doses should be titrated to the minimum effective dose that achieves the desired clinical endpoints 1, 3:
- Adequate MAP (≥65 mmHg)
- Improved tissue perfusion
- Adequate urine output
- Decreasing lactate levels
Special Considerations for High Doses
- Doses ≥0.6 μg/kg/min within the first 24 hours of ICU admission are associated with significantly higher 7-day mortality (sensitivity 47%, specificity 93%) and may indicate refractory septic shock 4
- When high doses are required, consider adding a second vasopressor agent such as epinephrine or vasopressin rather than continuing to escalate norepinephrine 1
- Vasopressin (up to 0.03 U/min) can be added to norepinephrine to either raise MAP to target or to decrease the required norepinephrine dose 1
Pediatric Dosing
- For pediatric patients, norepinephrine dosing typically ranges from 0.1-1.0 μg/kg/minute 5
- In severe cases, doses as high as 5 μg/kg/minute may be necessary in children 5
- The "rule of 6" can be used for pediatric dosing: 0.6 × body weight (kg) = number of milligrams diluted to total 100 mL of saline; then 1 mL/h delivers 0.1 μg/kg/min 5
Monitoring and Safety Considerations
- Continuous hemodynamic monitoring is essential during norepinephrine administration 3
- Avoid mixing norepinephrine solutions with alkali-labile drugs due to compatibility concerns 6
- 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 extravasation site to counteract dermal vasoconstriction 5
- Monitor for signs of excessive vasoconstriction, which may compromise tissue perfusion 3, 7