What vasopressor can we start if blood pressure (BP) is not increasing with noradrenaline at double strength?

Second-Line Vasopressor for Refractory Hypotension on High-Dose Norepinephrine

Add vasopressin at 0.03 units/minute to your norepinephrine infusion when blood pressure remains inadequate despite high-dose norepinephrine (double strength). 1, 2

Immediate Action Protocol

• Start vasopressin at 0.03 units/minute (range 0.01-0.03 units/minute) as your second-line agent when norepinephrine alone fails to achieve target MAP of 65 mmHg 1, 2, 3
• Vasopressin should be added to—not substituted for—norepinephrine, as it must never be used as monotherapy 1, 2, 3
• Once vasopressin is initiated, you can either raise MAP to target OR decrease norepinephrine dosage while maintaining hemodynamic stability 2, 3

Alternative Second-Line Options

If vasopressin is unavailable or contraindicated, consider these alternatives in order of preference:

• Epinephrine can be added to norepinephrine as an alternative second agent, with FDA-approved dosing of 0.05-2 mcg/kg/min IV infusion 2, 4
• Dobutamine (up to 20 mcg/kg/min) should be added if persistent hypoperfusion exists despite adequate vasopressor therapy, particularly when myocardial dysfunction is evident 1, 2, 4

Critical Monitoring Requirements

• Ensure central venous access is established for safe vasopressor administration 2, 3
• Place arterial catheter for continuous blood pressure monitoring as soon as practical 1, 2, 3
• Monitor beyond just MAP numbers—assess capillary refill, urine output, lactate clearance, and mental status to evaluate actual tissue perfusion 3
• Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate, digital ischemia 3, 5

Third-Line Escalation Strategy

If hemodynamic targets remain unmet despite norepinephrine plus vasopressin:

• Add epinephrine as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute 2, 3
• Do not exceed vasopressin doses of 0.03-0.04 units/minute except for salvage therapy when all other options have failed 1, 2

Agents to Absolutely Avoid

• Never use dopamine as your second-line agent—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, 2, 3
• Never use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit 1, 2, 3
• Avoid phenylephrine except in specific circumstances: when norepinephrine causes serious arrhythmias, cardiac output is documented to be high with persistently low blood pressure, or as salvage therapy when all other agents have failed 1, 2, 3

Evidence Supporting Early Vasopressin Addition

• Recent research demonstrates that adding vasopressin within 3 hours of norepinephrine initiation significantly decreases time to shock resolution (37.6 hours vs 60.7 hours) and reduces ICU length of stay 6
• Vasopressin works through V1 receptor-mediated vasoconstriction and reaches peak pressor effect within 15 minutes, with effects fading within 20 minutes after stopping infusion 7
• The majority of clinical studies show that vasopressin infusion increases blood pressure, increases urine output, and decreases norepinephrine dose requirements 5

Common Pitfalls to Avoid

• Do not delay vasopressin addition waiting for maximum norepinephrine doses—earlier addition (within 3 hours) is associated with better outcomes 6
• Do not use vasopressin as your initial single vasopressor—it must be added to norepinephrine 1, 2, 4
• Do not increase vasopressin beyond 0.03-0.04 units/minute in routine practice—escalate with epinephrine instead 1, 2, 3
• Avoid excessive focus on blood pressure numbers alone—phenylephrine may raise MAP on the monitor while actually worsening tissue perfusion through excessive vasoconstriction 2