What are the clinical uses and dosing recommendations for vasopressin?

Vasopressin: Clinical Uses and Dosing Recommendations

Primary Indication

Vasopressin is indicated as a second-line vasopressor added to norepinephrine in adults with vasodilatory shock (septic shock or post-cardiotomy shock) who remain hypotensive despite adequate fluid resuscitation and first-line catecholamine therapy. 1, 2

FDA-Approved Dosing

Septic Shock

• Standard dose: 0.03 units/minute as a fixed-rate infusion 1, 2
• Acceptable dosing range: 0.01-0.07 units/minute 1
• Never use vasopressin as monotherapy—it must be added to norepinephrine, not used as the sole initial vasopressor 1, 3

Post-Cardiotomy Shock

• Dosing range: 0.03-0.1 units/minute 2

Preparation and Administration

• Dilute the 20 units/mL vial with normal saline or D5W to either 0.1 units/mL or 1 unit/mL 2
• Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration 2
• Requires central venous access for safe administration 1, 3
• Continuous arterial blood pressure monitoring via arterial catheter is mandatory 1, 3

Clinical Algorithm for Vasopressin Initiation

Step 1: Ensure Norepinephrine is First-Line

• Start norepinephrine as the mandatory first-choice vasopressor targeting MAP ≥65 mmHg 1, 4
• Ensure adequate fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours) 1, 4

Step 2: Add Vasopressin When Norepinephrine Requirements Remain Elevated

• Add vasopressin at 0.03 units/minute when norepinephrine alone fails to maintain MAP ≥65 mmHg despite appropriate fluid resuscitation 1, 3
• The goal is either to raise MAP to target OR decrease norepinephrine dosage while maintaining hemodynamic stability 1, 3

Step 3: Escalation for Refractory Hypotension

• If MAP targets remain unmet despite norepinephrine plus vasopressin at 0.03 units/minute, add epinephrine (0.05-2 mcg/kg/min) as a third agent rather than increasing vasopressin dose 1, 3, 4
• Consider dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressor support, particularly with evidence of myocardial dysfunction 1, 3, 4

Critical Dosing Warnings

Maximum Dose Limitations

• Doses above 0.03-0.04 units/minute should be reserved for salvage therapy only (when all other vasopressors have failed) 1, 5
• Higher doses are associated with cardiac, digital, and splanchnic ischemia 1, 4, 5
• Doses above 0.04 units/minute may lead to cardiac arrest 6

Mechanism of Action

• Vasopressin acts on V1 receptors causing vasoconstriction and V2 receptors mediating water reabsorption 7, 8
• Provides complementary vasoconstriction through different vascular receptors than alpha-1 adrenergic receptors, explaining its norepinephrine-sparing effect 4, 7
• At low plasma concentrations, vasopressin mediates vasodilation in coronary, cerebral, and pulmonary arterial circulations 8

Monitoring Requirements

Hemodynamic Monitoring

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 3
• Assess perfusion markers beyond MAP: capillary refill, urine output, lactate clearance, and mental status 3, 4

Watch for Adverse Effects

• Monitor for signs of excessive vasoconstriction: cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction 1, 3, 5
• Common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia, and ischemia (coronary, mesenteric, skin, digital) 2, 5
• May cause ischemia of mesenteric mucosa, skin, and myocardium; elevated hepatic transaminases; hyponatremia; and thrombocytopenia 5

Agents to Avoid in Vasodilatory Shock

Dopamine

• Strongly contraindicated for renal protection—offers no benefit and is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 3, 4
• Should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 3

Phenylephrine

• Not recommended except 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, 3, 4
• May raise blood pressure on the monitor while actually worsening tissue perfusion through excessive vasoconstriction 1

Special Considerations

Contraindications

• Known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol 2

Warnings

• Can worsen cardiac function—use cautiously in patients with cardiac dysfunction 2, 5
• May cause reversible diabetes insipidus 2
• May induce uterine contractions in pregnancy 2

Drug Interactions

• Pressor effects of catecholamines and vasopressin are additive 2
• Indomethacin may prolong vasopressin effects 2
• Ganglionic blockers or drugs causing SIADH may increase pressor response 2
• Drugs causing diabetes insipidus may decrease pressor response 2

Adjunctive Therapy for Refractory Shock

• Consider hydrocortisone 200 mg/day (50 mg IV every 6 hours) if hypotension remains refractory to vasopressors after 4 hours of norepinephrine or epinephrine at ≥0.25 mcg/kg/min 4