What is the best second vasopressor to add to norepinephrine (Levophed) for a patient with septic shock and hypotension?

Vasopressin is the Best Second Vasopressor for Septic Shock

For a patient with septic shock who remains hypotensive (MAP <65 mmHg) despite adequate fluid resuscitation and norepinephrine infusion, vasopressin should be added as the second-line vasopressor at a fixed dose of up to 0.03 U/min. 1, 2

Rationale for Vasopressin as Second-Line Agent

Vasopressin offers several advantages as a second vasopressor in septic shock:

1. Complementary mechanism of action: Vasopressin works through V1 receptors rather than adrenergic receptors, making it effective when catecholamine receptors are downregulated in septic shock 2

2. Relative vasopressin deficiency: Patients with septic shock often have relative vasopressin deficiency, making replacement logical 2

3. Norepinephrine-sparing effect: Adding vasopressin can help reduce high-dose norepinephrine requirements and associated adverse effects 2

4. Fixed dosing: Unlike other vasopressors, vasopressin is administered at a fixed dose (up to 0.03 U/min) rather than weight-based titration 1, 2

Clinical Decision Algorithm

1. First-line vasopressor: Start with norepinephrine (0.05-0.1 μg/kg/min initially, titrated to effect) 1, 2

2. When to add vasopressin:

   • When MAP remains <65 mmHg despite adequate norepinephrine dosing
   • Particularly beneficial when norepinephrine requirements are high (≥15 μg/min) 2

3. Vasopressin dosing:

   • Fixed dose up to 0.03 U/min (not weight-based)
   • Do not exceed 0.03 U/min as higher doses may cause tissue ischemia 1, 2

4. Monitoring after addition:

   • Continuous arterial pressure monitoring
   • Tissue perfusion markers (lactate clearance, urine output, skin perfusion, mental status)
   • Watch for signs of digital, cardiac, or splanchnic ischemia 2

Alternative Second Vasopressors

While vasopressin is recommended as the preferred second agent, epinephrine is an acceptable alternative:

• Epinephrine: Can be added at 0.05-2 μg/kg/min when additional support is needed 1, 3
• Caution with epinephrine: Causes more tachycardia than norepinephrine and may worsen tachyarrhythmias 2, 4

Important Considerations and Pitfalls

• Vasopressin should not be used as the initial vasopressor - always add it to norepinephrine 2
• Avoid excessive doses of vasopressin (>0.03 U/min) as they can cause tissue ischemia 2
• Continuous arterial pressure monitoring is essential for patients receiving vasopressors 2
• Consider underlying causes of refractory shock (e.g., inadequate source control, ongoing bleeding, cardiac dysfunction) 2
• Dobutamine should be considered only when there is evidence of cardiac dysfunction with decreased cardiac output, not as a second vasopressor for hypotension 1

Application to the Case

For DR, the 54-year-old male with septic shock on high-dose norepinephrine with MAP of 59 mmHg:

• His cardiac index is adequate at 4.1 L/min/m², indicating good cardiac function
• His persistent hypotension despite norepinephrine makes him an ideal candidate for vasopressin addition
• Adding vasopressin at 0.03 U/min is the most appropriate next step to raise his MAP above 65 mmHg

The evidence strongly supports vasopressin as the optimal second vasopressor in this scenario, with the goal of either achieving target MAP or reducing norepinephrine requirements and associated adverse effects.