What is the recommended dose of vasopressin (antidiuretic hormone) for various clinical conditions?

Vasopressin Dosing for Clinical Conditions

Standard Dosing for Septic Shock

Add vasopressin at 0.03 units/minute when norepinephrine alone fails to maintain a mean arterial pressure (MAP) of 65 mmHg despite adequate fluid resuscitation. 1, 2

Key Dosing Parameters

• Standard dose: 0.03 units/minute (range 0.01-0.03 units/minute for septic shock) 2, 3
• FDA-approved range: 0.01-0.07 units/minute for septic shock 3
• Maximum safe dose: 0.03-0.04 units/minute for routine use 1, 2
• Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor 1, 2

Post-Cardiotomy Shock Dosing

• FDA-approved range: 0.03-0.1 units/minute for post-cardiotomy shock 3
• This represents a higher dosing range than septic shock, reflecting the different pathophysiology 3

When to Initiate Vasopressin

Start vasopressin when norepinephrine requirements remain elevated or when you need to decrease norepinephrine dosage to achieve target MAP. 1, 2

Practical Initiation Threshold

• Add vasopressin when norepinephrine alone cannot maintain MAP ≥65 mmHg despite appropriate fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours) 1, 4
• Some evidence suggests initiating when norepinephrine reaches ≥50 µg/min, though earlier initiation at lower norepinephrine doses is also reasonable 5
• Critical warning: Patients requiring ≥15 µg/min norepinephrine already have severe septic shock and should receive vasopressin to spare norepinephrine 1

Critical Dosing Warnings

Doses Above 0.04 Units/Minute Are Dangerous

• Doses exceeding 0.03-0.04 units/minute should be reserved only for salvage therapy when all other vasopressors have failed 1, 2
• Doses above 0.04 units/minute are associated with cardiac arrest, digital ischemia, splanchnic ischemia, and cardiac complications 1, 6
• In one case series, 6 cardiac arrests occurred, with all but one happening at vasopressin doses ≥0.05 units/minute 6

What to Do Instead of Escalating Vasopressin

• If hemodynamic targets remain unmet despite norepinephrine plus vasopressin at 0.03 units/minute, add epinephrine as a third agent rather than increasing vasopressin dose 1, 2
• Consider dobutamine (up to 20 mcg/kg/min) for persistent hypoperfusion despite adequate vasopressor support, particularly with evidence of myocardial dysfunction 1, 2, 4

Administration Requirements

Preparation and Delivery

• Dilute the 20 units/mL vial with normal saline or 5% dextrose to either 0.1 units/mL or 1 unit/mL 3
• Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration 3
• Requires central venous access for safe administration 1, 2
• Arterial catheter placement is recommended for continuous blood pressure monitoring as soon as practical 1, 2

Monitoring During Infusion

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2
• Assess perfusion markers beyond MAP: capillary refill, urine output, lactate clearance, and mental status 2, 4
• Watch for signs of excessive vasoconstriction: cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction 1, 2

Pharmacokinetics and Timing

• Steady-state plasma concentrations are achieved after 30 minutes of continuous infusion 3
• The pressor effect reaches its peak within 15 minutes 3
• After stopping the infusion, the pressor effect fades within 20 minutes 3
• The apparent half-life is ≤10 minutes at therapeutic infusion rates 3

Expected Hemodynamic Effects

• MAP increases by approximately 18% within 4 hours of initiation 6
• Vasopressin tends to decrease heart rate and cardiac output (mean cardiac index decreased by 11% at 4 hours in one series) 6
• Catecholamine requirements decrease by 33% at 4 hours and by 53% at 24 hours 6
• Urine output typically increases by 79% at 4 hours 6
• Systolic pulmonary artery pressure remains unchanged 6

Special Considerations

Drug Interactions

• Indomethacin more than doubles the duration of vasopressin's effect on peripheral vascular resistance and cardiac output 3
• Ganglionic blocking agents (e.g., tetra-ethylammonium) increase the pressor effect of vasopressin by 20% 3
• Pressor effects of catecholamines and vasopressin are additive 3

Pregnancy Considerations

• Vasopressin clearance increases 4-fold by the third trimester and up to 5-fold at term due to placental vasopressinase 3
• May induce uterine contractions 3
• Clearance returns to baseline within two weeks after delivery 3

Contraindications

• Known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol 3