What is the recommended initial dose of noradrenaline (norepinephrine) in shock?

Norepinephrine Dosing in Shock

Start norepinephrine at 0.05-0.1 mcg/kg/min (approximately 5-10 mcg/min in a 70 kg adult) and titrate to achieve a mean arterial pressure (MAP) of 65 mmHg. 1, 2

Initial Dosing Strategy

• Begin with 0.05-0.1 mcg/kg/min as your starting dose, which translates to approximately 5-10 mcg/min for an average adult 1, 2
• Alternative dosing from guidelines suggests starting at 0.5 mg/hour (approximately 8 mcg/min), titrating up to 3 mg/hour based on response 2
• The typical therapeutic range extends from 0.1-2 mcg/kg/min for most patients with septic shock 2

Titration Protocol

• Increase dose every 5-15 minutes during initial titration based on blood pressure and perfusion markers 3, 2
• For patients not responding adequately, increase by 0.5 mg/hour every 4 hours up to a maximum of 3 mg/hour 2
• Target MAP of ≥65 mmHg as your primary hemodynamic goal 4, 1, 3

Administration Requirements

• Central venous access is strongly preferred to minimize extravasation risk, though peripheral IV can be used temporarily if central access is delayed 3, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors 4, 1, 3
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 3, 2

High-Dose Considerations

• Doses >4 mcg/kg/min are considered very high but can be safe and effective in catecholamine-resistant septic shock 5
• In refractory cases, very high doses have been associated with improved survival (33.4%) compared to expected mortality without escalation 5
• Do not hesitate to escalate if lower doses fail to achieve target MAP, as prolonged hypotension significantly worsens outcomes 6

Timing of Initiation

Early administration matters critically for outcomes. Recent evidence suggests starting norepinephrine earlier rather than waiting to complete full fluid resuscitation in specific circumstances 6, 7:

• Profound hypotension with diastolic blood pressure ≤40 mmHg or diastolic shock index (HR/DBP) ≥3 6
• Life-threatening hypotension with systolic BP <80 mmHg 3
• Patients at risk for fluid overload (ARDS, intra-abdominal hypertension) 6

A randomized trial showed that early norepinephrine (median 93 minutes from ER arrival) achieved shock control by 6 hours in 76.1% of patients versus 48.4% with standard delayed administration, with lower rates of pulmonary edema and arrhythmias 7. However, one observational study showed increased mortality with norepinephrine within the first hour, highlighting the importance of concurrent adequate fluid resuscitation 6.

Fluid Resuscitation Context

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 2
• Address hypovolemia first in most cases, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 2
• The exception: do not delay norepinephrine if life-threatening hypotension is present while completing fluid resuscitation 3

When to Add Second-Line Agents

Add vasopressin 0.03 units/minute when norepinephrine requirements remain elevated or you need to decrease norepinephrine dosage while maintaining MAP ≥65 mmHg 1, 3:

• Vasopressin should never be used as monotherapy—only add to norepinephrine 1, 3
• Consider adding when norepinephrine exceeds 15 mcg/min, based on VASST trial subgroup analysis 4
• Do not exceed vasopressin 0.03-0.04 units/minute except as salvage therapy, as higher doses risk cardiac, digital, and splanchnic ischemia 4, 3

If targets remain unmet despite norepinephrine plus vasopressin, add epinephrine as a third agent rather than increasing vasopressin further 3.

Monitoring Beyond Blood Pressure

Assess perfusion markers beyond MAP alone 3, 2:

• Capillary refill time
• Urine output (target >0.5 mL/kg/hour)
• Lactate clearance (≥10% decrease from baseline)
• Mental status
• Skin temperature and mottling

Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate despite adequate MAP 1, 3, 2.

Critical Pitfalls to Avoid

• Never use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine 4, 1, 3
• Never use low-dose dopamine for renal protection—this is strongly discouraged with no demonstrated benefit 4, 1, 3
• Avoid phenylephrine except in specific circumstances: norepinephrine-induced serious arrhythmias, high cardiac output with persistent hypotension, or salvage therapy 4, 1, 3
• Do not mix with alkaline solutions (sodium bicarbonate) in the IV line, as catecholamines are inactivated in alkaline solutions 2

Extravasation Management

If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline intradermally at the site (pediatric dose: 0.1-0.2 mg/kg up to 10 mg) 2.