What trial examines the initiation of vasopressin (Vasoconstrictor)

From the Guidelines

The VASST (Vasopressin and Septic Shock Trial) is the key trial examining the initiation of vasopressin in septic shock. This multicenter randomized controlled trial compared low-dose vasopressin (0.01-0.03 units/minute) to norepinephrine in patients with septic shock.

Key Findings

• Vasopressin should be considered as a second-line vasopressor in septic shock patients who remain hypotensive despite adequate fluid resuscitation and norepinephrine doses exceeding 0.1-0.2 mcg/kg/min.
• The typical dosing is 0.01-0.04 units/minute as a continuous infusion, without titration based on response.
• While VASST did not show an overall mortality benefit for vasopressin compared to norepinephrine alone, a subgroup analysis suggested potential benefit in patients with less severe shock.

Mechanism of Action

• Vasopressin works by binding to V1 receptors on vascular smooth muscle, causing vasoconstriction through a mechanism different from catecholamines, which may help restore vascular tone in septic shock when catecholamine receptors are downregulated.
• It also has effects on V2 receptors in the kidneys, potentially improving urine output.

Clinical Guidelines

• According to the Surviving Sepsis Campaign guidelines 1, norepinephrine is recommended as the first-choice vasopressor, and vasopressin can be added to norepinephrine to raise mean arterial pressure or decrease norepinephrine dosage.
• The guidelines also suggest that vasopressin can be used as a second-line vasopressor in septic shock patients who remain hypotensive despite adequate fluid resuscitation and norepinephrine doses exceeding 0.1-0.2 mcg/kg/min.

Additional Considerations

• Other studies have investigated the use of vasopressin in septic shock, including a study published in 2018 1 that discussed the potential benefits and limitations of vasopressin in this context.
• Another study published in 2009 1 provided guidance on the use of vasopressin in pediatric and neonatal septic shock.
• A study published in 2011 1 discussed the management of sepsis in neutropenic patients, including the use of vasopressin in septic shock.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Vasopressin Initiation Trials

• The Vasopressin and Septic Shock Trial (VASST) 2 was a randomized trial that compared vasopressin with norepinephrine in septic shock patients.
• The VASST trial found that low-dose vasopressin may decrease mortality in patients with less severe septic shock.
• The Optimal Vasopressin Initiation in Septic Shock: The OVISS Reinforcement Learning Study 3 used reinforcement learning to derive and validate a model for optimal vasopressin initiation in adult patients with septic shock.
• The OVISS study found that the model-recommended vasopressin initiation was associated with reduced mortality compared to clinician actions.

Key Findings

• The VASST trial suggested that vasopressin may be beneficial in patients with less severe septic shock, defined by a lower norepinephrine dose or lower arterial lactate level 2.
• The OVISS study found that the model-recommended vasopressin initiation was earlier and at lower norepinephrine doses compared to clinician actions 3.
• A network meta-analysis found that norepinephrine plus dobutamine was associated with a lower risk of 28-day mortality in septic shock patients, while dopamine was associated with a higher risk of 28-day mortality 4.

Study Comparisons

• The VASST trial compared vasopressin with norepinephrine, while the OVISS study compared model-recommended vasopressin initiation with clinician actions 2, 3.
• The network meta-analysis compared the effects of different types of vasoactive medications, including norepinephrine, epinephrine, vasopressin, and dopamine 4.