What is the recommended dose of vasopressin for various indications?

Vasopressin Dosing Recommendations

For septic shock, initiate vasopressin at 0.01 units/minute as a second-line agent after norepinephrine, titrating to a maximum of 0.03-0.04 units/minute, never as monotherapy. 1, 2, 3

Septic Shock Dosing Protocol

Starting Dose and Titration

• Begin at 0.01 units/minute when norepinephrine alone fails to maintain MAP ≥65 mmHg despite adequate fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours) 1, 2, 3
• Titrate upward by 0.005 units/minute every 10-15 minutes until target MAP is achieved 1
• Maximum routine dose: 0.03-0.04 units/minute - doses above this threshold are reserved exclusively for salvage therapy when all other vasopressors have failed 1, 2, 3
• Standard maintenance dose: 0.03 units/minute when added to norepinephrine 1, 2

Critical Prerequisites Before Initiation

• Norepinephrine must be the first-line vasopressor already running - vasopressin is never used as initial monotherapy 1, 2, 3
• Central venous access is required for safe administration 1, 3
• Arterial catheter must be placed for continuous blood pressure monitoring 1, 3
• Adequate volume resuscitation must be completed or ongoing 1, 3

When to Add Vasopressin

• Add when norepinephrine requirements remain elevated (typically ≥15 mcg/min, though guidelines suggest adding earlier) 1, 4
• Add to either raise MAP to target of 65 mmHg OR to decrease norepinephrine dosage while maintaining hemodynamic stability 1, 2
• The 2020 study by Fitch et al. demonstrated safety with initiating vasopressin at higher norepinephrine thresholds (median 40 mcg/min vs 25 mcg/min), which decreased vasoactive costs without increasing mortality 4

Dosing for Other Indications

Variceal Hemorrhage

• Initial dose: 0.2-0.4 units/minute as continuous IV infusion 2
• Maximum dose: 0.8 units/minute 2
• Mandatory co-administration: IV nitroglycerin to mitigate cardiac and splanchnic ischemia 2

Post-Cardiotomy Shock

• Standard dose: 0.03 units/minute when added to norepinephrine 1
• Similar titration principles as septic shock apply 1

Cardiac Arrest/CPR

• Bolus dose: 40 units IV as single dose to replace first or second epinephrine bolus, regardless of initial rhythm 5, 6
• This is fundamentally different from the continuous infusion used in shock states 5, 6
• Evidence from randomized trials showed potential benefit in asystole but raised concerns about neurologic outcomes 5, 7

Pharmacokinetic Considerations

Onset and Duration

• Onset of pressor effect: rapid, with peak effect within 15 minutes 8
• Duration after stopping infusion: pressor effect fades within 20 minutes 8
• Half-life: ≤10 minutes at infusion rates of 0.01-0.1 units/minute 8
• Clearance: 9-25 mL/min/kg in vasodilatory shock 8

Special Population: Pregnancy

• Clearance increases 4-fold by third trimester and up to 5-fold at term 8
• Doses may need to be up-titrated beyond 0.1 units/minute in post-cardiotomy shock and 0.07 units/minute in septic shock during pregnancy 8
• Vasopressin may produce tonic uterine contractions threatening pregnancy continuation 8
• Clearance returns to baseline within 2 weeks postpartum 8

Critical Safety Thresholds and Adverse Effects

Dose-Related Toxicity

• Doses >0.04 units/minute are associated with cardiac, digital, and splanchnic ischemia 1
• At higher doses, vasopressin causes gastrointestinal hypoperfusion and ischemic skin lesions 7
• The FDA label confirms that infusions >0.04 units/minute lead to adverse vasoconstriction-mediated events 8, 9

Monitoring Requirements

• Continuous arterial blood pressure via arterial catheter (mandatory) 1, 3
• Hourly urine output (target ≥0.5 mL/kg/h) 1
• Lactate levels every 2-4 hours 3
• Mental status and peripheral perfusion assessment 3
• Watch specifically for: digital ischemia, decreased urine output, rising lactate, worsening organ dysfunction despite adequate MAP 1

Escalation Algorithm for Refractory Shock

When vasopressin at 0.03-0.04 units/minute plus norepinephrine fails to achieve target MAP:

1. Add epinephrine 0.05-2 mcg/kg/min as third vasopressor agent rather than increasing vasopressin dose 1, 3
2. Consider dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP, particularly with myocardial dysfunction 1, 3
3. Add hydrocortisone 200 mg/day IV for refractory shock 1

Common Pitfalls to Avoid

• Never use vasopressin as first-line monotherapy - it must always be added to norepinephrine 1, 2, 3
• Never titrate vasopressin like a traditional vasopressor - it should be used at fixed low doses (0.01-0.04 units/minute), not escalated indefinitely 7, 9
• Do not delay adequate fluid resuscitation - vasopressin requires appropriate volume status to work effectively 1, 3
• Avoid exceeding 0.03-0.04 units/minute for routine use - higher doses dramatically increase ischemic complications without proven benefit 1, 2, 9
• Do not use dopamine for renal protection when managing shock - this is strongly discouraged and provides no benefit 1

Drug Interactions Affecting Dosing

• Indomethacin more than doubles the time to offset for vasopressin's vascular effects 8
• Furosemide increases osmolar clearance 4-fold and urine flow 9-fold when co-administered 8
• Ganglionic blockers increase pressor effect by 20% 8