What is the role of vasopressin in treating septic shock refractory to first-line vasopressor therapy, such as norepinephrine?

Vasopressin in Septic Shock

Add vasopressin at 0.03 units/minute to norepinephrine when you cannot achieve a MAP of 65 mmHg with norepinephrine alone or when you need to reduce norepinephrine requirements—never use vasopressin as monotherapy. 1, 2, 3

First-Line Management

• Start norepinephrine as your first-choice vasopressor after adequate fluid resuscitation (minimum 30 mL/kg crystalloid), targeting a MAP of 65 mmHg. 1, 2, 3

• Norepinephrine is superior to dopamine, reducing mortality by 11% (RR 0.89,95% CI 0.81-0.98, NNT=9) and causing fewer arrhythmias. 1, 4

• Place an arterial catheter for continuous blood pressure monitoring as soon as practical in all patients requiring vasopressors. 1, 3

When to Add Vasopressin

Add vasopressin when norepinephrine alone fails to maintain MAP ≥65 mmHg despite appropriate fluid resuscitation. 1, 2, 3

Specific Dosing Protocol

• Start vasopressin at 0.03 units/minute (maximum dose 0.03-0.04 units/minute) as an adjunct to norepinephrine. 1, 2, 3

• The dose range is 0.01-0.03 units/minute, but the standard dose is 0.03 units/minute. 3

• Vasopressin acts through V1 receptors on vascular smooth muscle, causing vasoconstriction independent of catecholamine pathways, which is why it works when norepinephrine is insufficient. 5

• The pressor effect reaches its peak within 15 minutes and fades within 20 minutes after stopping the infusion. 5

Evidence for Vasopressin Use

The landmark VASST trial (778 patients) showed that vasopressin versus norepinephrine had no difference in 28-day mortality overall (35.4% vs 39.3%, P=0.26), but in less severe septic shock, vasopressin reduced mortality (26.5% vs 35.7%, P=0.05). 6

• Vasopressin is relatively deficient during sepsis, making it a rational second-line agent that acts on different vascular receptors than α1-adrenergic receptors. 7, 8

• Vasopressin has a norepinephrine-sparing effect and may benefit renal function. 9

• No evidence exists for tachyphylaxis or tolerance to vasopressin's pressor effect. 5

Critical Pitfalls to Avoid

• Never use vasopressin as the sole initial vasopressor—it must always be added to norepinephrine, not used as monotherapy. 1, 3

• Do not exceed 0.03-0.04 units/minute except as salvage therapy when all other vasopressors have failed to achieve target MAP. 1, 3

• Do not use dopamine for renal protection—this is strongly discouraged and has no benefit, while increasing arrhythmia risk. 1, 3, 10

• Avoid 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

Alternative Escalation Options

If target MAP is still not achieved after adding vasopressin:

• Consider adding epinephrine as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute. 1, 3

• Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressor support, particularly with evidence of myocardial dysfunction. 1, 2

• Phenylephrine is not recommended except when norepinephrine causes serious arrhythmias, cardiac output is known to be high with persistently low blood pressure, or as salvage therapy. 1, 3

Monitoring Requirements

• Maintain continuous arterial blood pressure monitoring for all patients on vasopressors. 1, 2, 3

• Supplement MAP targets with assessment of regional and global perfusion: lactate clearance, urine output, mental status, and skin perfusion. 1, 2

• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 3