Vasopressin Weaning Strategy in Shock
Vasopressin should be discontinued LAST, after norepinephrine has been completely stopped, to avoid hemodynamic instability and rebound hypotension.
Evidence-Based Weaning Protocol
FDA-Approved Tapering Sequence
The FDA label provides explicit guidance on vasopressin withdrawal: after target blood pressure has been maintained for 8 hours without the use of catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated to maintain target blood pressure 1. This clearly indicates vasopressin should only be weaned after catecholamines (including norepinephrine) are discontinued.
Clinical Evidence Supporting This Approach
Discontinuing vasopressin before norepinephrine results in a 74% incidence of hemodynamic instability compared to only 16.7% when vasopressin is stopped last (P < 0.01) 2
When vasopressin is withdrawn first, hemodynamic instability occurs significantly faster (median 5 hours vs 15 hours, P < 0.01) 2
Rebound hypotension is a well-documented complication of premature vasopressin cessation, often requiring the drug to be administered for several days to avoid this phenomenon 3
Physiologic Rationale
Vasopressin deficiency is a known consequence of septic shock, with endogenous levels decreasing to normal range within 24-48 hours despite ongoing shock 4
Vasopressin acts through V1 receptors on vascular smooth muscle, providing a complementary mechanism to α1-adrenergic stimulation by norepinephrine 5
The non-adrenergic mechanism of vasopressin makes it particularly valuable as catecholamine requirements decrease, preventing the hemodynamic collapse that occurs when both pathways are simultaneously withdrawn 2
Practical Weaning Algorithm
Maintain both agents until hemodynamic stability is achieved for at least 8 hours 1
Wean norepinephrine first by decreasing the dose gradually (typically by 0.05 μg/kg/min decrements) while maintaining vasopressin at a fixed dose of 0.01-0.03 units/minute 6, 5
Discontinue norepinephrine completely once the dose reaches approximately 0.2 μg/kg/min and blood pressure remains stable 5
Begin vasopressin taper only after norepinephrine is stopped and 8 hours of stability without catecholamines has been achieved 1
Taper vasopressin slowly by 0.005 units/minute every hour, monitoring for hypotension 1
Critical Pitfalls to Avoid
Never discontinue vasopressin first - this is associated with a 4-fold increase in hemodynamic instability requiring fluid boluses, increased norepinephrine requirements, or addition of alternative vasopressors 2
Do not use vasopressin as monotherapy - it must never be the sole vasopressor agent and should always be used in conjunction with norepinephrine 5, 6
Avoid doses above 0.04 units/minute except as salvage therapy, as higher doses are associated with cardiac, digital, and splanchnic ischemia 4
Monitor closely during the first 5-15 hours after vasopressin discontinuation as this is when hemodynamic instability most commonly occurs 2