From the Guidelines
Vasopressin should be administered as an adjunctive vasopressor at a fixed dose of 0.03 units/minute in patients with septic shock who remain hypotensive despite adequate fluid resuscitation and norepinephrine therapy, as recommended by the Surviving Sepsis Campaign guidelines 1.
Pathophysiology of Vasopressin Depletion
Vasopressin depletion is a significant pathophysiological feature of sepsis that contributes to hemodynamic instability. In septic shock, patients initially experience high vasopressin levels, but these levels decline as shock progresses, leading to relative vasopressin deficiency. This depletion contributes to refractory hypotension.
Use of Vasopressin in Septic Shock
Exogenous vasopressin can be administered to improve hemodynamics or reduce norepinephrine requirements. The physiological basis for this approach is that vasopressin works through V1 receptors to cause vasoconstriction via a different mechanism than catecholamines, making it effective even when catecholamine receptors are downregulated in sepsis. Additionally, vasopressin helps preserve renal blood flow despite its vasoconstrictive effects.
Monitoring and Weaning
Monitoring for potential adverse effects including digital and splanchnic ischemia, hyponatremia, and cardiac dysfunction is essential during vasopressin administration. Vasopressin should be weaned after hemodynamic stability is achieved, typically after norepinephrine requirements have decreased significantly.
Key Considerations
- Vasopressin should not be used as the first-line vasopressor but added to norepinephrine to either improve hemodynamics or reduce norepinephrine requirements 1.
- The dose of vasopressin should be limited to 0.03 units/minute, as higher doses are not recommended for initial therapy 1.
- The use of vasopressin in septic shock is supported by the Surviving Sepsis Campaign guidelines, which recommend its use as an adjunctive therapy in patients with septic shock who remain hypotensive despite adequate fluid resuscitation and norepinephrine therapy 1.
- Recent studies have also highlighted the potential benefits of highly selective V1a agonists, which may have better effects in septic shock than vasopressin due to their narrow focus on the V1a receptor 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Vasopressin Depletion in Sepsis
- Vasopressin is an important stress hormone that has both vasoactive and antidiuretic properties 2
- In septic shock, there is a deficiency of vasopressin, and infusion of relatively low doses of vasopressin improves responsiveness to infused catecholamines such as norepinephrine 2
- The use of vasopressin as a first-line vasopressor in septic shock has been studied, with some studies showing a significant reduction in the requirement for renal replacement therapy (RRT) 3
Comparison of Vasopressin with Other Vasopressors
- A systematic review and meta-analysis compared vasopressin with norepinephrine as the first-line vasopressor in septic shock, and found no significant differences in 28-day mortality rates or intensive care unit (ICU) mortality between the two groups 3
- Another study compared norepinephrine and vasopressin with norepinephrine and epinephrine in adults with septic shock, and found similar shock-free survival durations and mortality rates between the two groups 4
- A review of the literature on vasopressors in sepsis found that norepinephrine is the first-line vasopressor in shock, and that epinephrine and vasopressin are appropriate second-line vasopressors 5
Clinical Studies of Vasopressin in Septic Shock
- At least 16 clinical studies have investigated the infusion of vasopressin in patients with septic shock, with the majority finding that vasopressin infusion increased blood pressure and urine output, and decreased the dose requirement of norepinephrine 2
- A systematic review and meta-analysis of vasopressors for the treatment of septic shock found that norepinephrine was associated with decreased all-cause mortality compared to dopamine, but found no other mortality benefit for the comparisons of norepinephrine to epinephrine, phenylephrine, and vasopressin/terlipressin 6