From the Guidelines
Vasopressin should be used as a second-line vasopressor in septic shock, typically added to norepinephrine when it is insufficient to maintain adequate blood pressure, at a standard dosing of 0.01-0.04 units/minute as a continuous IV infusion, with 0.03 units/minute being the most common fixed dose. The use of vasopressin in septic shock is supported by the Surviving Sepsis Campaign guidelines, which suggest adding vasopressin (up to 0.03 U/min) to norepinephrine with the intent of raising mean arterial pressure to target, or adding vasopressin (up to 0.03 U/min) to decrease norepinephrine dosage 1. Vasopressin works through V1 receptors causing direct vasoconstriction, which is beneficial in septic shock where patients often develop catecholamine resistance. Some key points to consider when using vasopressin include:
- Monitoring for digital and splanchnic ischemia
- Potential hyponatremia with prolonged use
- Awareness that vasopressin has a longer half-life than norepinephrine, so it should be weaned after other vasopressors
- The physiological basis for its effectiveness lies in correcting relative vasopressin deficiency that develops in prolonged shock states and its ability to maintain vascular tone through a mechanism independent of adrenergic receptors 1. It is also important to note that vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension, and vasopressin doses higher than 0.03–0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) 1. Overall, the use of vasopressin in septic shock should be guided by the most recent and highest quality evidence, and should prioritize the single most recent and highest quality study, which in this case is the Surviving Sepsis Campaign guidelines 1.
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. In addition, vasopressin stimulates antidiuresis via stimulation of V2 receptors which are coupled to adenyl cyclase.
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.
Vasopressin Description and Usage:
- Mechanism of Action: Vasopressin causes vasoconstriction by binding to V1 receptors, and stimulates antidiuresis via V2 receptors.
- Clinical Usage: Vasopressin is used in clinical scenarios, particularly in septic shock, to increase systemic vascular resistance and mean arterial blood pressure, and to reduce the dose requirements for norepinephrine.
- Key Effects:
- Increases systemic vascular resistance
- Increases mean arterial blood pressure
- Reduces dose requirements for norepinephrine
- Decreases heart rate and cardiac output
- Administration: Vasopressin is administered intravenously, with a pressor effect that reaches its peak within 15 minutes and fades within 20 minutes after stopping the infusion 2.
- Clinical Studies: Increases in systolic and mean blood pressure following administration of vasopressin were observed in studies in septic shock 2.
From the Research
Description of Vasopressin
- Vasopressin is a hormone that plays a crucial role in regulating blood pressure and fluid balance in the body 3.
- It is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock 4.
- Vasopressin has marked vasopressor effects, even at doses that would not affect blood pressure in healthy individuals, making it a useful treatment option for septic shock 3.
Usage of Vasopressin in Clinical Scenarios
- In septic shock, vasopressin is used to increase blood pressure and improve tissue perfusion 4, 5.
- The timing of vasopressin initiation is crucial, with some studies suggesting that earlier initiation may be associated with better outcomes 5.
- Vasopressin can be used in combination with other vasoactive agents, such as norepinephrine, to achieve optimal blood pressure control 4, 6.
- The use of vasopressin in septic shock is supported by several studies, including the Vasopressin and Septic Shock Trial, which found that low-dose vasopressin was associated with decreased mortality in patients with less severe septic shock 4, 7.
Clinical Trials and Studies
- The Vasopressin and Septic Shock Trial compared the effects of low-dose vasopressin and norepinephrine on mortality in patients with septic shock, and found no significant difference in 28-day mortality between the two groups 4.
- 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.
- A narrative review of vasopressin use in septic shock discussed the rationale for vasopressin use, summarized the results of clinical trials evaluating vasopressin, and focused on the timing of vasopressin initiation to provide clinicians with guidance for optimal adjunctive vasopressin initiation in patients with septic shock 5.