What is the recommended dose of noradrenaline (norepinephrine) infusion for a typical adult patient with hypotension, particularly in cases of severe septic shock?

Norepinephrine Dosing for Septic Shock

For adults with septic shock, start norepinephrine at 0.05-0.1 mcg/kg/min (approximately 3.5-7 mcg/min for a 70 kg patient) and titrate to achieve a mean arterial pressure (MAP) of 65 mmHg, with no absolute maximum dose but practical limits around 0.5-1 mcg/kg/min (35-70 mcg/min) before adding second-line agents. 1

Initial Dosing Strategy

• Begin norepinephrine at 0.05-0.1 mcg/kg/min after or concurrent with at least 30 mL/kg crystalloid resuscitation in the first 3 hours 1, 2
• Target MAP ≥65 mmHg as the initial hemodynamic goal; consider higher targets (70-75 mmHg) only in patients with chronic hypertension 1, 2
• Administer through central venous access whenever possible, though peripheral access is acceptable in emergencies with close monitoring for extravasation 1, 3
• Establish continuous arterial blood pressure monitoring via arterial catheter as soon as practical 1

Dose Titration and Escalation

• Titrate norepinephrine in increments based on hemodynamic response, recognizing that doses quoted in textbooks are approximations and must be adjusted to individual patient response 4
• Historical studies used doses of 0.5-1 mcg/kg/min (35-70 mcg/min for 70 kg patient) successfully in hyperdynamic septic shock 3
• Doses exceeding 0.38 mcg/kg/min (approximately 27 mcg/min for 70 kg patient) indicate severe shock and should trigger consideration of adding vasopressin 5
• Doses ≥15 mcg/min (absolute dose, not weight-based) represent a critical threshold associated with significantly elevated mortality and should prompt immediate addition of second-line agents 1

When to Add Second-Line Vasopressors

Add vasopressin 0.03 units/min when norepinephrine requirements remain elevated or exceed moderate doses, rather than continuing to escalate norepinephrine indefinitely 1, 2:

• Start vasopressin at 0.01 units/min and titrate by 0.005 units/min every 10-15 minutes to maximum 0.03-0.04 units/min 1
• Never use vasopressin as monotherapy—it must be added to norepinephrine, not substituted for it 1
• Vasopressin is particularly effective when baseline norepinephrine dose exceeds 0.38 mcg/kg/min, with 53% probability of improving microcirculatory perfusion 5

If target MAP not achieved with norepinephrine plus vasopressin, add epinephrine at 0.05 mcg/kg/min, titrating up to 0.3 mcg/kg/min 1:

• Epinephrine serves as third-line agent when dual vasopressor therapy fails 1
• Be aware that epinephrine causes transient lactic acidosis through β2-adrenergic stimulation, making lactate less reliable as a resuscitation endpoint 1

Critical Timing Considerations

Early norepinephrine administration is beneficial and should not be delayed in patients with profound hypotension 2, 6:

• Consider starting norepinephrine early (simultaneously with fluid resuscitation) when diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3 6
• Duration and depth of hypotension strongly worsen outcomes; relying solely on fluids may unduly prolong hypotension 6
• Norepinephrine rapidly increases and better stabilizes arterial pressure compared to fluid resuscitation alone 6

Monitoring Beyond Blood Pressure

Assess tissue perfusion using multiple parameters, not just MAP 1:

• Urine output ≥0.5 mL/kg/h
• Lactate clearance every 2-4 hours
• Mental status and peripheral perfusion (capillary refill, skin temperature)
• Heart rate and rhythm

Common Pitfalls to Avoid

• Do not use dopamine as first-line therapy—it increases 28-day mortality by 11% absolute risk and causes significantly more arrhythmias compared to norepinephrine 1
• Avoid phenylephrine except in specific circumstances (norepinephrine-induced arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy) as it may compromise microcirculatory flow despite raising blood pressure 1
• Do not escalate vasopressin beyond 0.03-0.04 units/min for routine use, as higher doses cause cardiac, digital, and splanchnic ischemia 1
• Recognize that extremely high norepinephrine doses (>175 mcg/min or 2.5 mcg/kg/min) indicate irreversible circulatory failure with complete vascular collapse and dismal prognosis 1

Adjunctive Therapies for Refractory Shock

When shock remains refractory despite escalating vasopressors 1, 7:

• Add hydrocortisone 200 mg/day IV when hemodynamic stability cannot be achieved despite adequate fluid resuscitation and vasopressor therapy 7
• Consider dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP, particularly when myocardial dysfunction is evident 1
• Taper hydrocortisone when vasopressors are no longer required 7

Special Population Considerations

Pediatric dosing differs substantially from adult dosing 4:

• Children with fluid-refractory septic shock predominantly have low cardiac output, unlike adults who typically have high cardiac output and low systemic vascular resistance 4
• Adult data favoring norepinephrine as first-line may not directly apply to pediatric populations 4

Elderly patients tolerate norepinephrine well even when administered peripherally in intermediate care settings, with observed mortality better than predicted by APACHE-II scores 8