What is the recommended starting dose of noradrenaline (norepinephrine) for a patient with severe hypotension or septic shock?

Norepinephrine Dosing in Severe Hypotension and Septic Shock

Starting Dose

Start norepinephrine at 0.25-0.375 mL per minute (8-12 mcg of base per minute), which translates to approximately 0.05-0.1 mcg/kg/min, and titrate rapidly to achieve a mean arterial pressure (MAP) of 65 mmHg. 1

• The FDA-approved initial dosing is 8-12 mcg of base per minute, with adjustments made to establish and maintain systolic blood pressure of 80-100 mmHg sufficient to maintain circulation of vital organs 1
• Norepinephrine is the mandatory first-choice vasopressor for septic shock, recommended with Grade 1B evidence by the Surviving Sepsis Campaign 2, 3
• The target MAP should be 65 mmHg in most patients, though higher targets (70-75 mmHg) may be appropriate in patients with chronic hypertension 2, 3

Maintenance Dosing

• The average maintenance dose ranges from 2-4 mcg of base per minute (0.0625-0.125 mL per minute) 1
• Titrate continuously based on arterial blood pressure monitoring via arterial catheter, which should be placed as soon as practical 3, 4
• Monitor perfusion markers beyond MAP alone: lactate clearance, urine output ≥0.5 mL/kg/hr, mental status, skin perfusion, and capillary refill 2, 3

Administration Requirements

Norepinephrine must be administered through central venous access whenever possible to minimize the risk of 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 (an adrenergic blocking agent) to prevent tissue necrosis 1
• Continuous arterial blood pressure monitoring is mandatory for all patients receiving vasopressors 3, 4

Timing of Initiation

In patients with life-threatening hypotension (systolic BP <80 mmHg or diastolic BP ≤40 mmHg), start norepinephrine immediately alongside fluid resuscitation rather than waiting to complete fluid resuscitation. 5, 6

• Early norepinephrine administration prevents prolonged severe hypotension, which is an independent predictor of mortality 7, 5
• A diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3 indicates profound vascular tone depression and should trigger urgent norepinephrine initiation 5, 6
• Early norepinephrine increases cardiac output by increasing cardiac preload and contractility, even in patients with impaired left ventricular function 8
• Administer at least 30 mL/kg IV crystalloid within the first 3 hours, but do not delay norepinephrine if profound hypotension is present 3, 4

Escalation for Refractory Hypotension

If norepinephrine doses exceed 0.2-0.3 mcg/kg/min (approximately 15 mcg/min in a 70 kg patient) and MAP remains <65 mmHg, add vasopressin at 0.03 units/minute rather than escalating norepinephrine further. 2, 3

• Vasopressin should be added to norepinephrine, never used as monotherapy 2, 3
• The maximum vasopressin dose is 0.03-0.04 units/minute; higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit 2, 3
• If norepinephrine plus vasopressin fail to achieve target MAP, add epinephrine (0.05-2 mcg/kg/min) as a third agent 2, 3
• Consider dobutamine (2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 2, 3

Critical Pitfalls to Avoid

Never use dopamine as first-line therapy—it is associated with significantly higher mortality and more arrhythmias compared to norepinephrine. 2, 3

• Dopamine should only be considered in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 2, 3
• Do not use dopamine for "renal protection"—this practice is strongly discouraged and has no benefit 3, 9
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is documented to be high with persistent hypotension, or as salvage therapy when all other agents have failed 2, 3
• Never abruptly discontinue norepinephrine—sudden cessation may result in marked hypotension; reduce the infusion rate gradually 1

Weaning Protocol

When weaning vasopressors, reduce norepinephrine first while maintaining vasopressin at 0.03 units/minute until hemodynamic stability is achieved. 9

• Ensure MAP ≥65 mmHg is sustained for at least 2-4 hours before initiating weaning 9
• Verify adequate tissue perfusion: lactate clearance, urine output ≥0.5 mL/kg/hr, improving mental status, warm extremities with brisk capillary refill 9
• Reduce norepinephrine by 0.01-0.02 mcg/kg/min (or 1-2 mcg/min) every 15-30 minutes while maintaining vasopressin at 0.03 units/minute 9
• Withdraw vasopressin only after norepinephrine has been successfully weaned, not before 9