What is the recommended starting infusion rate for noradrenaline (norepinephrine) in a patient with hypotension?

Norepinephrine Starting Infusion Rate for Hypotension

Start norepinephrine at 8-12 mcg/min (0.1-0.2 mcg/kg/min) via continuous intravenous infusion, titrating to achieve a mean arterial pressure (MAP) of 65 mmHg or higher. 1

Initial Dosing

• The FDA-approved starting dose is 8-12 mcg/min (equivalent to 0.25-0.375 mL/min of the standard dilution), which corresponds to approximately 0.1-0.2 mcg/kg/min in a 70 kg adult 1
• After initiation, assess patient response and adjust dosage every 2 minutes until the desired hemodynamic effect is achieved, then monitor blood pressure every 5 minutes for the duration of infusion 1
• The typical maintenance dose ranges from 2-4 mcg/min once blood pressure is stabilized 1

Critical Pre-Administration Requirements

• Address hypovolemia FIRST with a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 2, 3, 1
• In severe, life-threatening hypotension (systolic BP ≤70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues simultaneously rather than waiting for complete volume repletion 2, 4
• Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure readings 4

Administration Route and Preparation

• Administer through a central venous line whenever possible to prevent tissue necrosis from extravasation 2, 3, 1
• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring 3, 4
• Standard dilution: Add 4 mg norepinephrine to 1000 mL of 5% Dextrose to produce a 4 mcg/mL concentration 1
• Alternative concentration: Add 4 mg to 250 mL D5W for 16 mcg/mL in patients requiring fluid restriction 3

Target Blood Pressure and Titration

• Target MAP of 65 mmHg as the primary endpoint for septic shock and most hypotensive states 2, 4
• Titrate to achieve MAP 65-100 mmHg sufficient to maintain vital organ perfusion 2, 4
• Patients with chronic hypertension or atherosclerosis may require higher MAP targets, while younger normotensive patients may tolerate lower pressures 4
• Guide titration by both MAP and markers of tissue perfusion: lactate clearance, urine output (goal >50 mL/h), mental status, and capillary refill 3, 4

Escalation Strategy

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 4
• Consider adding hydrocortisone 50 mg IV every 6 hours for refractory shock requiring high-dose vasopressors 4
• Higher doses of norepinephrine (>10 mcg/min or >0.7 mcg/kg/min) are associated with increased mortality and should prompt consideration of additional vasopressors 2

Monitoring Requirements

• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors 2, 4
• Monitor blood pressure every 2 minutes during initial titration until target achieved, then every 5 minutes 3, 1
• Assess peripheral perfusion regularly: skin temperature, capillary refill, urine output 2, 4
• Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate 3

Special Considerations

Septic Shock Context:

• Norepinephrine is the first-choice vasopressor over dopamine, epinephrine, or phenylephrine based on moderate quality evidence showing superior outcomes 2, 4
• Early administration of norepinephrine (simultaneously with fluid resuscitation) should be considered in patients with profound hypotension, particularly when diastolic BP ≤40 mmHg or diastolic shock index (HR/diastolic BP) ≥3 5

Obese Patients:

• Obese patients require lower weight-based doses (approximately 0.09 mcg/kg/min) but similar total doses (8-9 mcg/min) compared to non-obese patients 6
• Consider using non-weight-based dosing (absolute mcg/min) rather than weight-based dosing in obese patients 6

Cirrhosis/Hepatorenal Syndrome:

• Start at lower doses with more gradual titration: increase by 0.5 mg/h every 4 hours to a maximum of 3 mg/h 3, 4

Critical Safety Precautions

• If extravasation occurs, immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the affected site to prevent tissue necrosis 2, 3, 1
• Do not mix with sodium bicarbonate or other alkaline solutions, as norepinephrine is inactivated in alkaline environments 2, 1
• Use with caution in patients with ischemic heart disease as it increases myocardial oxygen demand 2, 4
• When discontinuing, reduce the infusion rate gradually rather than abruptly to avoid rebound hypotension 1

Common Pitfalls to Avoid

• Starting norepinephrine without adequate fluid resuscitation leads to severe organ hypoperfusion despite normalized blood pressure 4, 1
• Delaying norepinephrine in profound hypotension while waiting for complete volume repletion unnecessarily prolongs hypotension and worsens outcomes 5
• Using leg veins in elderly or patients with peripheral vascular disease increases extravasation risk 1
• Continuing to escalate norepinephrine alone beyond 0.25 mcg/kg/min without adding second-line agents 4