What is the recommended dose of noradrenaline (norepinephrine) for a patient with hypotension?

Norepinephrine Dosing for Hypotension

Start norepinephrine at 8-12 mcg/min (0.1-0.5 mcg/kg/min) via continuous IV infusion, preferably through central venous access, while simultaneously ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus, targeting a mean arterial pressure of 65 mmHg. 1, 2, 3

Preparation and Standard Concentration

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 mcg/mL 1, 2
• This standard preparation allows for precise titration and is recommended across multiple guidelines 1

Initial Dosing Protocol

Starting Dose

• Begin at 8-12 mcg/min (equivalent to 0.1-0.5 mcg/kg/min for a 70 kg adult) 1, 2, 3
• The FDA label specifies an initial dose range of 0.25-0.375 mL/min from the standard concentration (8-12 mcg of base per minute) 3
• For hepatorenal syndrome specifically, start at 0.5 mg/h (approximately 8 mcg/min) 1, 2

Maintenance Dosing

• Average maintenance dose ranges from 2-4 mcg/min 2, 3
• The FDA label confirms this range as 0.0625-0.125 mL/min from standard concentration 3

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1, 2. This is a strong recommendation with moderate quality evidence from the Surviving Sepsis Campaign. 1

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1
• Avoid norepinephrine in hypovolemic patients without concurrent fluid resuscitation, as vasoconstriction in this setting causes severe organ hypoperfusion despite "normal" blood pressure 1, 4

Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 4, 2. This is a strong recommendation with moderate quality evidence. 1

• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily 1
• The FDA label emphasizes infusing into a large vein to prevent tissue necrosis 3
• Plan for central line placement if norepinephrine will be needed beyond initial resuscitation 1

Target Blood Pressure

Target mean arterial pressure (MAP) of 65 mmHg for most patients 1, 4, 2. This is a strong recommendation with moderate quality evidence from the Surviving Sepsis Campaign. 1

• Patients with chronic hypertension may require higher MAP targets 1, 4
• Younger normotensive patients may tolerate lower pressures 1
• Titrate based on both MAP and markers of tissue perfusion: lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1, 2

Titration Strategy

Monitoring During Initial Titration

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 4

Dose Adjustments

• Increase dose by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h 1, 2
• For hepatorenal syndrome, titrate with goal of increasing MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1
• Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output 1

Escalation Strategy for Refractory Hypotension

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy 1, 2. This is a weak recommendation with moderate quality evidence. 1

• Do not increase vasopressin above 0.03-0.04 units/min; reserve higher doses for salvage therapy only 1
• Recent evidence suggests vasopressin is most effective when baseline norepinephrine dose exceeds 0.38 mcg/kg/min 5
• Alternative second agents include epinephrine 0.1-0.5 mcg/kg/min 1, 2
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min, particularly with myocardial dysfunction 1

Agents to Avoid

• Do not use dopamine as first-line agent; it is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 4
• Do not use low-dose dopamine for renal protection; it has no benefit 1
• Avoid phenylephrine as first-line therapy; it may raise blood pressure while worsening tissue perfusion 1

Special Populations

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 in obese patients to avoid underdosing 6

Pregnant Patients

• Start at 0.02 mcg/kg/min targeting MAP of 65 mmHg 1, 2
• Consider more restrictive initial fluid boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk 1
• Norepinephrine is approximately 13 times more potent than phenylephrine when given as infusion for cesarean delivery 7

Pediatric Patients

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect 1, 2
• Typical range: 0.1-1.0 mcg/kg/min 1
• Maximum doses up to 5 mcg/kg/min may be necessary in exceptional circumstances 1
• Use "Rule of 6" for preparation: 0.6 × body weight (kg) = mg diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 1

Management of Extravasation

If extravasation occurs, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site as soon as possible to prevent tissue necrosis 1, 4, 3

• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 1
• The FDA label emphasizes immediate treatment to prevent tissue death and sloughing 3

Weaning Protocol

Decrease norepinephrine dose by 25% of current dose every 30 minutes as tolerated 4

• Avoid sudden cessation; gradual reduction prevents marked rebound hypotension 3

Important Precautions

Drug Interactions

• Do not mix with sodium bicarbonate or other alkaline solutions in the IV line; norepinephrine is inactivated in alkaline solutions 1, 4
• Use with caution in patients on MAO inhibitors or tricyclic antidepressants due to risk of hypertension 3
• Cyclopropane and halothane anesthetics increase cardiac autonomic irritability 3

Adverse Effects to Monitor

• Arrhythmias, particularly at higher doses 4, 2, 3
• Increased myocardial oxygen consumption 4, 2
• Tissue ischemia and end-organ hypoperfusion 4, 3
• Sulfite-containing formulation may cause allergic reactions 3

High-Dose Considerations

• Doses >0.4 mcg/kg/min are associated with significantly increased mortality (40% hospital mortality) 8
• Recent data suggest cutoffs of 0.2 mcg/kg/min (low dose) and 0.4 mcg/kg/min (high dose) correlate with mortality risk 8
• Higher doses (>10 mcg/min) in elderly patients are associated with increased mortality and should be avoided if possible 4