How do you titrate the dose of noradrenaline (norepinephrine) in a patient with hypotension?

How to Increase the Dose of Noradrenaline

Start norepinephrine at 0.25-0.375 mL/min (8-12 mcg/min of base), then titrate upward in increments every 4 hours by 0.5 mg/h (approximately 8 mcg/min) until achieving a target MAP of 65 mmHg, with typical maintenance doses ranging from 2-4 mcg/min of base. 1, 2

Initial Dosing Strategy

• Begin with an initial infusion rate of 8-12 mcg/min of norepinephrine base (0.25-0.375 mL/min of standard concentration) 1
• Target a mean arterial pressure (MAP) of 65 mmHg as the primary endpoint for septic shock 2
• In patients with cirrhosis and hepatorenal syndrome, start lower at 0.5 mg/h and increase more gradually 2

Titration Protocol

• Increase the dose every 4 hours by 0.5 mg/h increments until MAP reaches 65 mmHg or urine output exceeds 50 mL/h for at least 4 hours 2
• For septic shock, titrate to maintain MAP between 65-100 mmHg sufficient for vital organ perfusion 3, 1
• Monitor hemodynamic response continuously during titration using arterial line monitoring 2, 3
• The average maintenance dose typically ranges from 2-4 mcg/min of base (0.0625-0.125 mL/min) 1

Maximum Dosing Considerations

• In hepatorenal syndrome, the maximum recommended dose is 3 mg/h 2
• Doses exceeding 10 mcg/min are associated with increased mortality and should prompt consideration of adding a second vasopressor rather than continuing to escalate norepinephrine alone 3
• Recent data suggests doses >0.4 mcg/kg/min represent "high-dose" norepinephrine with significantly elevated mortality (40% hospital mortality), while 0.2-0.4 mcg/kg/min represents intermediate dosing (26% mortality) 4

Adding Second-Line Vasopressors

When norepinephrine doses are escalating and MAP remains inadequate:

• Add vasopressin 0.03 units/min (not to exceed 0.03-0.04 units/min) to either raise MAP or allow reduction of norepinephrine dose 2
• Alternatively, add epinephrine when an additional agent is needed to maintain adequate blood pressure 2
• Consider hydrocortisone 50 mg IV every 6 hours (or 200 mg continuous infusion) for refractory shock requiring high-dose vasopressors 2

Critical Monitoring During Titration

• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 2, 3
• Assess end-organ perfusion markers: urine output, lactate levels, skin perfusion (temperature, capillary refill) 2, 3
• Monitor for signs of excessive vasoconstriction: worsening lactate, decreased urine output, cool extremities 3
• Watch for cardiac arrhythmias, particularly at higher doses 1

Administration Safety

• Always administer through a central venous line whenever possible to prevent tissue necrosis from extravasation 3, 1
• If extravasation occurs, immediately infiltrate the area with 10-15 mL of saline containing 5-10 mg of phentolamine 3, 1
• Ensure adequate volume resuscitation is occurring concurrently—norepinephrine is relatively contraindicated in hypovolemic patients 3

Weaning Protocol

• When hemodynamics stabilize and MAP is consistently adequate, decrease norepinephrine by 25% of the current dose every 30 minutes as tolerated 3
• Avoid abrupt discontinuation, as sudden cessation can result in marked hypotension 1

Special Populations

• Patients with previous hypertension: The same MAP target of 65 mmHg is appropriate; increasing MAP to 85-90 mmHg with higher norepinephrine doses improves microcirculatory flow equally in both hypertensive and normotensive patients 5
• Cirrhosis patients: Use more gradual titration (0.5 mg/h increments every 4 hours) with maximum 3 mg/h, and consider vasopressin earlier as second-line agent 2

Common Pitfalls to Avoid

• Do not use dopamine as first-line vasopressor—norepinephrine is superior with moderate quality evidence 2, 3
• Do not continue escalating norepinephrine indefinitely; add second vasopressor when doses exceed 0.4 mcg/kg/min 4
• Do not target MAP >65 mmHg routinely unless specific indications exist (e.g., chronic hypertension with evidence of ongoing hypoperfusion) 2
• Do not administer through peripheral IV if avoidable due to high risk of tissue necrosis 3, 1