Maximum Norepinephrine Drip Dose
The maximum dose of norepinephrine is 3 mg/hour (approximately 0.7 mcg/kg/min in a 70 kg adult), as recommended by the American College of Gastroenterology for hepatorenal syndrome management. 1, 2
Standard Dosing Parameters
Start at 0.5 mg/hour and increase by 0.5 mg/hour increments every 4 hours up to a maximum of 3 mg/hour, targeting a mean arterial pressure increase of ≥10 mmHg and/or urine output >50 mL/hour for at least 4 hours. 1, 2, 3
The typical dosing range in septic shock is 0.1-2 mcg/kg/min, which translates to approximately 0.5-3 mg/hour in a 70 kg adult. 2
For pediatric patients, dosing ranges from 0.1-1.0 mcg/kg/min, with maximum doses up to 5 mcg/kg/min sometimes necessary in exceptional circumstances. 2, 3
Clinical Context for Maximum Dosing
When norepinephrine reaches 0.25 mcg/kg/min (approximately 1 mg/hour) and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone. 2, 3 This strategy prevents the need for extremely high norepinephrine doses that are associated with significantly worse outcomes.
Doses exceeding 0.6 mcg/kg/min are associated with 93% specificity for predicting 7-day mortality in septic shock. 4
Doses greater than 1 mcg/kg/min are associated with a 90% ICU mortality rate and represent a threshold for refractory septic shock. 5
Evidence on High-Dose Norepinephrine
While the guideline-recommended maximum is 3 mg/hour, research demonstrates that very high doses (>4 mcg/kg/min, approximately >17 mg/hour in a 70 kg adult) have been used in catecholamine-resistant septic shock with a 33% survival rate. 6 However, this should be considered salvage therapy only, as doses >1 mcg/kg/min carry a 9.7-fold increased odds of mortality. 5
Critical Management Points
Always ensure adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to prevent severe organ hypoperfusion from vasoconstriction in hypovolemic patients. 2
Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2
If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site. 2, 3
Monitor for ischemic complications including angina, digital ischemia, skin necrosis, and intestinal ischemia, which can be reduced by starting at the lowest dose and gradually titrating upward. 1
Escalation Strategy Beyond Maximum Dose
Rather than exceeding 3 mg/hour, add additional vasopressor agents:
Add vasopressin 0.03-0.04 units/min when norepinephrine reaches 0.25 mcg/kg/min. 2, 3
Add epinephrine 0.1-0.5 mcg/kg/min if hypotension persists despite norepinephrine and vasopressin. 2
Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with myocardial dysfunction. 2