What are the clinical uses and dosing recommendations for vasopressin?

Vasopressin: Clinical Uses and Dosing Recommendations

Vasopressin is indicated as a second-line vasopressor added to norepinephrine at a fixed dose of 0.03 units/minute in septic shock and vasodilatory shock, never as monotherapy, to either raise mean arterial pressure to target or reduce norepinephrine requirements. 1, 2

Primary Clinical Indications

Septic Shock

• Add vasopressin at 0.03 units/minute when norepinephrine requirements remain elevated or when you need to decrease norepinephrine dosage to achieve a MAP target of 65 mmHg. 1
• The FDA-approved dosing range for septic shock is 0.01 to 0.07 units/minute, but the standard recommended dose is 0.03 units/minute. 2
• Never use vasopressin as the sole initial vasopressor—it must be added to norepinephrine, not used as first-line monotherapy. 1, 3

Post-Cardiotomy Shock

• The FDA approves vasopressin at 0.03 to 0.1 units/minute for post-cardiotomy shock to either raise MAP or decrease norepinephrine dosage. 1, 2

Vasodilatory Shock (General)

• Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. 2

Dosing Protocol

Standard Dosing

• Start vasopressin at 0.03 units/minute as a continuous IV infusion when added to norepinephrine. 1, 3
• The dose range is 0.01-0.07 units/minute for septic shock, with 0.03 units/minute being the standard target dose. 1, 2
• Doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy only (when other vasopressors have failed to achieve target MAP). 1

Preparation and Administration

• Dilute the 20 units/mL multiple dose vial with normal saline (0.9% sodium chloride) or 5% dextrose in water (D5W) to either 0.1 units/mL or 1 unit/mL for intravenous administration. 2
• Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration. 2
• Administer through central venous access with continuous arterial blood pressure monitoring. 1, 3

When to Initiate Vasopressin

Timing Relative to Norepinephrine

• Start vasopressin when norepinephrine alone fails to maintain adequate MAP despite appropriate fluid resuscitation (minimum 30 mL/kg crystalloid). 1, 3
• Add vasopressin when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, rather than continuing to escalate norepinephrine alone. 4

Hemodynamic Targets

• Target MAP ≥65 mmHg with continuous arterial blood pressure monitoring. 1, 3
• Once vasopressin is added, you can either raise MAP to target OR decrease norepinephrine dosage while maintaining hemodynamic stability. 1, 3

Escalation Strategy for Refractory Shock

If Vasopressin Plus Norepinephrine Fails

• Add epinephrine as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute. 1, 3
• Consider dobutamine (up to 20 mcg/kg/min) for persistent hypoperfusion despite adequate vasopressor support, particularly with evidence of myocardial dysfunction. 1, 3

Critical Warnings and Adverse Effects

Contraindications

• Vasopressin is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol. 2

Major Adverse Effects

• The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia, and ischemia (coronary, mesenteric, skin, digital). 2
• Vasopressin can worsen cardiac function and may cause reversible diabetes insipidus. 2
• Doses above 0.03-0.04 units/minute are associated with cardiac, digital, and splanchnic ischemia. 1
• Above 0.04 U/min, vasopressin may lead to cardiac arrest. 5

Monitoring Requirements

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 3
• Watch for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 1, 3
• Assess perfusion markers beyond just MAP, including capillary refill, urine output, lactate clearance, and mental status. 3

Special Populations

Pregnancy

• Vasopressin may induce uterine contractions. 2

Pediatric Use

• Safety and effectiveness have not been established in pediatric patients. 2
• For pediatric vasodilatory shock, the initial dose is 0.0002-0.0005 units/kg/min, titrated up to a maximum of 0.002 units/kg/min based on hemodynamic response. 4

Geriatric Use

• No specific safety issues have been identified in older patients. 2

Drug Interactions

• Pressor effects of catecholamines and vasopressin are expected to be additive. 2
• Indomethacin may prolong the effects of vasopressin. 2
• Co-administration of ganglionic blockers or drugs causing SIADH may increase the pressor response. 2
• Co-administration of drugs causing diabetes insipidus may decrease the pressor response. 2

Common Pitfalls to Avoid

• Never use vasopressin as first-line monotherapy—it must always be added to norepinephrine. 1, 3
• Do not escalate vasopressin beyond 0.03-0.04 units/minute except as salvage therapy. 1
• Avoid starting vasopressin without adequate fluid resuscitation (minimum 30 mL/kg crystalloid). 1, 3
• Do not use dopamine for renal protection—this is strongly discouraged and has no benefit. 1, 3
• Avoid phenylephrine as first-line therapy—it may raise blood pressure while worsening tissue perfusion. 1