What is the most effective dose of vasopressin (Vasopressin) for treatment?

From the Guidelines

The most effective dose of vasopressin for septic shock is 0.03 units/minute, as it can be added to norepinephrine to raise mean arterial pressure or decrease norepinephrine dosage, as recommended by the Surviving Sepsis Campaign guidelines 1. When considering the use of vasopressin, it's essential to understand its mechanism of action and potential side effects. Vasopressin works by binding to V1 receptors on vascular smooth muscle, causing vasoconstriction, and V2 receptors in the kidneys to increase water reabsorption. Some key points to consider when using vasopressin include:

• The dose of 0.03 units/minute is recommended as an addition to norepinephrine, with the intent of raising mean arterial pressure to target or decreasing norepinephrine dosage 1.
• Vasopressin doses higher than 0.03–0.04 units/minute should be reserved for salvage therapy, as recommended by the Surviving Sepsis Campaign guidelines 1.
• The use of vasopressin in septic shock is supported by its ability to increase blood pressure and decrease norepinephrine requirements, as well as its potential to mitigate cardiac depression and vascular leak 1. It's crucial to carefully titrate and monitor vasopressin administration, as side effects can include hyponatremia, vasoconstriction leading to tissue ischemia, and cardiac complications. In terms of specific clinical indications, the dose of vasopressin may vary:
• For cardiac arrest, a one-time intravenous (IV) dose of 40 units is recommended as an alternative to epinephrine or after epinephrine has failed.
• For vasodilatory shock, a continuous IV infusion of 0.01-0.07 units/minute is typically used, often starting at 0.03 units/minute and titrating based on blood pressure response.
• For diabetes insipidus, desmopressin (DDAVP) is preferred, with doses of 1-2 mcg IV/subcutaneously every 12 hours or 10-40 mcg intranasally daily in divided doses.
• For gastrointestinal bleeding, terlipressin 2 mg IV every 4-6 hours is commonly used in countries where available.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action Vasopressin causes vasoconstriction by binding to V1 receptors on vascular smooth muscle coupled to the Gq/11-phospholipase C-phosphatidyl-inositol-triphosphate pathway, resulting in the release of intracellular calcium. 12. 2 Pharmacodynamics At therapeutic doses exogenous vasopressin elicits a vasoconstrictive effect in most vascular beds including the splanchnic, renal and cutaneous circulation. In patients with vasodilatory shock vasopressin in therapeutic doses increases systemic vascular resistance and mean arterial blood pressure and reduces the dose requirements for norepinephrine. The pressor effect is proportional to the infusion rate of exogenous vasopressin. The pressor effect reaches its peak within 15 minutes After stopping the infusion the pressor effect fades within 20 minutes. There is no evidence for tachyphylaxis or tolerance to the pressor effect of vasopressin in patients.

The most effective dose of vasopressin is not explicitly stated in the provided drug label. However, it is mentioned that therapeutic doses of vasopressin elicit a vasoconstrictive effect and increase systemic vascular resistance and mean arterial blood pressure in patients with vasodilatory shock.

• The pressor effect is proportional to the infusion rate of exogenous vasopressin.
• The pressor effect reaches its peak within 15 minutes.
• After stopping the infusion, the pressor effect fades within 20 minutes. 2

From the Research

Effective Dose of Vasopressin

• The most effective dose of vasopressin is still a topic of debate, with various studies suggesting different dosages 3, 4, 5, 6, 7.
• A study published in 2004 found that starting vasopressin in patients with septic shock at a dose of 0.03 U/minute or less may minimize the development of adverse effects 3.
• Another study published in 2011 found that low-dose vasopressin infusion (0.03 U/minute or less) may be effective in patients with less severe septic shock already receiving norepinephrine 4.
• A retrospective cohort study published in 2019 found that early initiation of vasopressin to norepinephrine resulted in a reduced time to target mean arterial pressure (MAP) compared to norepinephrine monotherapy, with a dose of vasopressin not specified 7.
• A case report published in 2020 described the use of push-dose vasopressin (1 unit intravenous bolus) to improve hemodynamics in a patient with vasodilatory septic shock 6.

Adverse Effects

• Vasopressin has been associated with adverse effects such as ischemia of the mesenteric mucosa, skin, and myocardium, elevated hepatic transaminase and bilirubin concentrations, hyponatremia, and thrombocytopenia 3.
• Higher doses of vasopressin (0.06 units/minute) have been found to have greater hemodynamic effects, but also unique adverse effects such as elevated liver enzymes and serum bilirubin 4.

Comparison with Other Vasopressors

• A study published in 2019 found that shock-free survival durations were similar between epinephrine- and vasopressin-exposed patients in a matched cohort 5.
• Another study published in 2011 found that low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine 4.