When is vasopressin recommended as a vasopressor?

Vasopressin as a Vasopressor: Recommendations for Use

Vasopressin is indicated as an adjunct vasopressor in adults with vasodilatory shock who remain hypotensive despite fluid resuscitation and catecholamine vasopressors (typically norepinephrine). 1, 2

Mechanism and Pharmacology

Vasopressin functions as a vasopressor through:

• Binding to V1 receptors on vascular smooth muscle, causing vasoconstriction 2
• Increasing systemic vascular resistance and mean arterial blood pressure
• Reducing the dose requirements for norepinephrine in shock states 2
• Typically decreasing heart rate and cardiac output 2

Primary Indications for Vasopressin

1. Septic Shock

• Recommended as an adjunct to norepinephrine at 0.03 units/minute to:
  • Raise mean arterial pressure (MAP) to target (≥65 mmHg)
  • Decrease norepinephrine dosage requirements 1
  • May be particularly beneficial in less severe septic shock 3

2. Vasodilatory Shock

• FDA-approved for increasing blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines 2
• Addresses the relative vasopressin deficiency that occurs in septic and other vasodilatory shock states 4, 5

3. Refractory Hypotension

• When high doses of norepinephrine (≥1 μg/kg/min) fail to achieve target MAP 6
• Combining vasopressin with norepinephrine may help achieve target MAP or reduce norepinephrine requirements 1, 6

Dosing Guidelines

• Standard dose: 0.03 units/minute (fixed dose) 1
• Therapeutic range: 0.01-0.04 units/minute 4, 5
• Warning: Doses >0.04 units/minute may lead to adverse vasoconstriction-mediated events 4
• No titration is typically needed as it is used as an adjunct at a fixed dose

Clinical Considerations

Benefits

• May reduce requirements for renal replacement therapy compared to norepinephrine alone 7
• Maintains blood pressure with potentially less tachycardia than with increasing doses of catecholamines 5
• May be beneficial in patients with less severe septic shock 3

Timing of Initiation

• Current guidelines recommend adding vasopressin after norepinephrine has been initiated 1
• Consider adding when norepinephrine requirements are increasing or sustained at moderate-to-high doses

Monitoring

• Continuous arterial blood pressure monitoring is essential
• Monitor for:
  • Changes in heart rate and cardiac output
  • Tissue perfusion markers (lactate, skin perfusion, mental status, urine output)
  • Signs of peripheral ischemia

Potential Adverse Effects

• Digital and splanchnic ischemia due to vasoconstriction
• Cardiac dysfunction at higher doses
• Drug interactions: Indomethacin more than doubles the time to offset vasopressin's effect on peripheral vascular resistance 2
• Tetra-ethylammonium (ganglionic blocking agent) increases vasopressin's pressor effect by 20% 2

Clinical Pearls

• Vasopressin should not replace norepinephrine as first-line therapy but serves as a valuable adjunct 7
• The pharmacokinetics of vasopressin include a short half-life (≤10 minutes) and rapid onset of action (peak effect within 15 minutes) 2
• Vasopressin levels are often inappropriately low in septic shock, creating a state of "relative vasopressin deficiency" 4
• In pregnancy, clearance of vasopressin increases progressively (up to 5-fold by term) due to placental vasopressinase 2