What are the maximum recommended doses of noradrenaline (norepinephrine) and vasopressin in septic shock?

Maximum Inotropic Dosage of Noradrenaline and Vasopressin in Septic Shock

For norepinephrine, there is no absolute maximum dose defined in guidelines, but doses above 1 µg/kg/min are associated with mortality rates exceeding 80%, and you should add vasopressin before reaching 0.25-0.50 µg/kg/min of norepinephrine base to avoid excessive catecholamine exposure. 1, 2 For vasopressin, the maximum recommended dose is 0.03-0.04 units/minute, with doses beyond this reserved only for salvage therapy when all other vasopressors have failed. 1

Norepinephrine Dosing Strategy

Initial Approach

• Start norepinephrine as the first-line vasopressor immediately when hypotension persists after adequate fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours), targeting a MAP of 65 mmHg 1, 3, 4
• Administer through central venous access with continuous arterial blood pressure monitoring 1, 3, 4

When to Add Second-Line Agents

• The Society of Critical Care Medicine recommends adding vasopressin when norepinephrine requirements exceed 0.25-0.50 µg/kg/min (norepinephrine base), rather than continuing to escalate norepinephrine alone 1, 5
• This threshold is critical because high-dose norepinephrine (>1 µg/kg/min) carries mortality rates exceeding 80%, suggesting the need for adjunctive strategies before reaching this level 2
• Research suggests that patients requiring norepinephrine doses above 0.38 mcg/kg/min have a 53% probability of microcirculatory improvement with vasopressin addition 6

Vasopressin Dosing Protocol

Standard Dosing

• Add vasopressin at a fixed dose of 0.03 units/minute when norepinephrine alone fails to maintain target MAP 1, 3, 4
• The acceptable dose range is 0.01-0.03 units/minute for routine use 1, 3, 4

Maximum Dose Limitations

• Do not exceed 0.03-0.04 units/minute except as salvage therapy when other vasopressors have failed to achieve target MAP 1, 3
• Vasopressin must never be used as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor 1, 3, 4
• The landmark VASST trial used doses of 0.01-0.03 U/minute and found no mortality benefit compared to norepinephrine alone, though there was a trend toward benefit in less severe septic shock 7

Escalation Algorithm for Refractory Shock

Third-Line Options

If target MAP remains unachieved despite norepinephrine plus vasopressin at maximum doses:

• Add epinephrine as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute 1, 4
• Consider dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressor support, particularly when myocardial dysfunction is evident 1, 3, 4
• Consider low-dose corticosteroids (hydrocortisone 200 mg/day IV) for shock reversal if hypotension remains refractory 1

Critical Pitfalls to Avoid

Agents to Avoid

• Do not use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine, and should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 3, 4
• Do not use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit 1, 3
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is documented to be high with persistently low blood pressure, or as salvage therapy 1, 3, 4

Monitoring Considerations

• Do not rely solely on blood pressure numbers—monitor markers of tissue perfusion including lactate clearance, urine output, mental status, and skin perfusion 3, 4
• Avoid excessive vasoconstriction by watching for signs of digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 1
• The goal is adequate tissue perfusion, not supranormal blood pressure targets 1