What is the recommended dosage of noradrenaline (norepinephrine) for blood pressure support?

Norepinephrine Dosing for Blood Pressure Support

Start norepinephrine at 0.25-0.375 mL/min (8-12 mcg/min of base) and titrate to maintain mean arterial pressure (MAP) of 65 mmHg, with typical maintenance doses of 2-4 mcg/min (0.0625-0.125 mL/min). 1

Standard Adult Dosing Protocol

Initial Dose and Preparation

• Begin with 8-12 mcg/min of norepinephrine base (0.25-0.375 mL/min from standard 4 mg/4 mL concentration), titrating to achieve MAP of 65 mmHg. 1
• Standard concentration: Add 4 mg norepinephrine to 250 mL D5W to yield 16 μg/mL. 2
• Alternative weight-based dosing: Start at 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult). 2

Maintenance Dosing

• Average maintenance dose ranges from 2-4 mcg/min of base (0.0625-0.125 mL/min). 1
• Typical therapeutic range in septic shock: 0.1-2 mcg/kg/min. 2
• Titrate every 4 hours by 0.5 mg/h increments (approximately 8 mcg/min) up to maximum 3 mg/h (50 mcg/min). 2

Target Blood Pressure

• Target MAP of 65 mmHg for most patients with septic shock (strong recommendation, moderate quality evidence). 3, 4
• Systolic blood pressure target: 80-100 mmHg sufficient to maintain circulation of vital organs. 1
• Consider higher MAP targets (>65 mmHg) in patients with chronic hypertension. 2, 5

Administration Route and Monitoring

Vascular Access

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 3, 2, 5, 1
• Peripheral IV or intraosseous administration can be used temporarily if central access is unavailable or delayed. 2
• Place arterial catheter as soon as practical for continuous blood pressure monitoring (weak recommendation, very low quality evidence). 3, 4

Monitoring Parameters

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 2
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill. 2
• Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate. 2

Critical Pre-Administration Requirements

Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to optimize cardiac output. 2, 4 Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 2

Escalation Strategy for Refractory Hypotension

Second-Line Agents

• Add vasopressin 0.03 units/min when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists (weak recommendation, moderate quality evidence). 3, 2, 4
• Alternative: Add epinephrine 0.1-0.5 mcg/kg/min to norepinephrine (weak recommendation, low quality evidence). 3, 4
• Do NOT increase vasopressin above 0.03-0.04 units/min—reserve higher doses for salvage therapy only. 3, 4

Inotropic Support

• Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with myocardial dysfunction (weak recommendation, low quality evidence). 3, 4

Dose Thresholds Indicating Severity

• Low dose: <0.2 mcg/kg/min (hospital mortality 14%). 6
• Intermediate dose: 0.2-0.4 mcg/kg/min (hospital mortality 26.4%). 6
• High dose: >0.4 mcg/kg/min (hospital mortality 40.2%). 6
• Doses ≥15 mcg/min (approximately 0.2 mcg/kg/min) indicate severe shock and warrant addition of vasopressin. 4

Pediatric Dosing

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect. 3, 2
• Typical range: 0.1-1.0 mcg/kg/min. 2
• Maximum doses up to 5 mcg/kg/min may be necessary in some children. 2, 7
• "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. 2

Special Populations

Obese Patients

• Obese patients require lower weight-based doses (mean 0.09 mcg/kg/min) compared to non-obese patients (0.13 mcg/kg/min). 8
• Non-weight-based total doses are similar between obese and non-obese patients (approximately 8-9 mcg/min). 8
• Consider using non-weight-based dosing (absolute mcg/min) rather than mcg/kg/min in obese patients. 8

Pregnant Patients (Cesarean Delivery)

• For spinal hypotension prevention: Start at 1.9-3.8 mcg/min as variable rate infusion. 9
• ED50 for maintaining blood pressure: 1.01 mcg/min (95% CI: 0.84-1.18). 9

Critical Pitfalls to Avoid

Agents NOT to Use

• Do NOT use dopamine as first-line agent—associated with higher mortality and more arrhythmias compared to norepinephrine (weak recommendation, low quality evidence). 3, 4, 5
• Dopamine only acceptable in highly selected patients with low risk of tachyarrhythmias and absolute/relative bradycardia. 3, 4
• Do NOT use low-dose dopamine for renal protection—no benefit and strongly discouraged (strong recommendation, high quality evidence). 3, 4
• Do NOT use phenylephrine as first-line therapy—may raise blood pressure while worsening tissue perfusion. 4, 5
• Phenylephrine only acceptable when norepinephrine causes serious arrhythmias, cardiac output is high with persistent hypotension, or as salvage therapy. 3, 4

Administration Errors

• Do NOT mix norepinephrine with sodium bicarbonate or alkaline solutions—adrenergic drugs are inactivated in alkaline solutions. 2
• Do NOT abruptly discontinue infusion—sudden cessation may result in marked hypotension; reduce rate gradually. 1
• Do NOT delay fluid resuscitation—inadequate volume repletion before norepinephrine causes severe organ hypoperfusion. 2, 4

Management of Extravasation

If extravasation occurs, immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline intradermally at the site to prevent tissue necrosis and sloughing. 2, 5, 1 Pediatric dose: 0.1-0.2 mg/kg up to 10 mg. 2

Adverse Effects

• Ischemic injury and tissue necrosis with extravasation. 1
• Cardiac arrhythmias, particularly at higher doses. 1
• Bradycardia (paradoxical reflex response). 1
• Hypertension with excessive dosing (resolves with dose reduction). 7
• Increased myocardial oxygen consumption. 5