What is the best vasopressor to use after norepinephrine (Levophed) in a patient with hypotension?

Best Vasopressor After Norepinephrine

Add vasopressin at 0.03 units/minute as the second-line vasopressor when norepinephrine alone fails to maintain a mean arterial pressure (MAP) of 65 mmHg despite adequate fluid resuscitation. 1

Second-Line Vasopressor Selection

Vasopressin as Preferred Second Agent

• Vasopressin is the recommended second-line vasopressor to add to norepinephrine rather than escalating norepinephrine dose further. 1
• The standard dose is 0.03 units/minute when added to norepinephrine, with a dose range of 0.01-0.07 units/minute for septic shock. 1, 2
• Vasopressin should never be used as monotherapy—it must be added to norepinephrine, not used alone. 1
• The FDA-approved dosing for post-cardiotomy shock is 0.03 to 0.1 units/minute, and for septic shock is 0.01 to 0.07 units/minute. 2

When to Add Vasopressin

• Add vasopressin when norepinephrine requirements remain elevated (typically when reaching 0.25 mcg/kg/min) and MAP target of 65 mmHg cannot be achieved. 1
• Once vasopressin is added, you can either raise MAP to target OR decrease norepinephrine dosage while maintaining hemodynamic stability. 1

Critical Dosing Limitations

• Do not increase vasopressin beyond 0.03-0.04 units/minute for routine management. 1
• Doses higher than 0.03-0.04 units/minute should be reserved only for salvage therapy when other vasopressors have failed to achieve target MAP. 1
• Higher vasopressin doses are associated with cardiac, digital, and splanchnic ischemia. 1

Alternative Second-Line Options

Epinephrine

• Epinephrine can be added to norepinephrine as an alternative second-line agent, particularly when vasopressin is unavailable or in settings with myocardial dysfunction. 1, 3
• The dosing range is 0.05-2 mcg/kg/min IV infusion or 0.1-0.5 mcg/kg/min. 1, 4
• Epinephrine should be considered when norepinephrine requirements remain high despite vasopressin addition, rather than increasing vasopressin beyond 0.03-0.04 units/minute. 1
• However, epinephrine is associated with higher rates of metabolic and cardiac adverse effects compared to norepinephrine. 3

Third-Line Considerations

When to Add Inotropic Support

• Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressor support, particularly when myocardial dysfunction is evident. 1, 4
• Dobutamine should be added rather than escalating vasopressors further when tissue perfusion markers remain poor. 1

Angiotensin II

• Angiotensin II may be useful in profoundly hypotensive patients or those with acute kidney injury requiring renal replacement therapy. 3, 5
• However, due to limited evidence and safety concerns regarding potential adverse effects from marked vasopressor activity, it is not currently recommended as routine second-line therapy. 3

Agents to Avoid

Dopamine

• Dopamine should NOT be used as a second-line agent. 1
• Dopamine is associated with higher mortality and more arrhythmias compared to norepinephrine. 1, 3
• Use dopamine only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia. 1
• Low-dose dopamine for renal protection is strongly discouraged and has no benefit. 1

Phenylephrine

• Phenylephrine is NOT recommended except in specific circumstances. 1
• Use phenylephrine only 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
• Phenylephrine may raise blood pressure on the monitor while actually worsening tissue perfusion through excessive vasoconstriction. 1

Monitoring Requirements

• Arterial catheter placement is recommended for all patients requiring vasopressors as soon as practical for continuous blood pressure monitoring. 1
• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 1
• Titrate to adequate perfusion markers (lactate clearance, urine output, mental status, capillary refill), not just to supranormal blood pressure targets. 1

Common Pitfalls

• Never escalate norepinephrine indefinitely without adding a second agent. Norepinephrine doses above 15 mcg/min (approximately 0.25 mcg/kg/min in a 70 kg patient) are associated with increased mortality and indicate the need for additional vasopressor support. 1
• Never use vasopressin as monotherapy—it must always be added to norepinephrine. 1
• Never exceed vasopressin 0.03-0.04 units/minute for routine management due to ischemic complications. 1
• Ensure adequate fluid resuscitation (minimum 30 mL/kg crystalloid) before or concurrent with vasopressor therapy. 1