Vasopressin (Pitressin, Vasostrict)

Anesthesia Implications

Classification: Antidiuretic, Vasopressor
Therapeutic Effects: Vasoconstriction, Water Retention

Duration: Plasma half-life: 10-35 min.

Primary Considerations

Refractory Hypotension – Used as a first-line treatment for vasoplegia (another word for refractory hypotension). This drug is typically given when fluids and other vasopressors have failed to raise the SVR. The iconic use of this drug is its use in patients with refractory hypotension taking ACE inhibitors. However, the general indications for use specify any patient with vasodilatory shock that has not responded to fluids or catecholemines.

Baroreceptor reflex – anticipate this. The baroreceptor reflex may reduce cardiac output.

Pulmonary sparing – vasopressin-induced vasoconstriction is primarily in SVR and is relatively pulmonary sparing.

Beach chair position – administration of vasopressin to correct reduced blood pressure in the beach chair position was reported to cause reduced cerebral oxygenation.

Thrombosis risk – Vasopressin activates V2 receptors on endothelial cells. This results in the release of endothelial vWF, enhances platelet aggregation, and thereby increases the risk of thrombosis. Be especially cautious with patients that have coronary artery disease or occlusive artery disease.

Sensitive patients – Patients in refractory shock associated with severe sepsis, cardiogenic or vasodilatory shock, or cardiopulmonary bypass. These patients will have abnormally low ADH and will be VERY sensitive to vasopressin.

Neuraxial Anesthesia – epidurals (especially high thoracic epidurals) block sympathetic impulses to the vasculature and adrenal gland. This may cause the renin–angiotensin–aldosterone system to be severely limited in compensating for hypotension. Vasopressin has been shown to be effective in raising blood pressure in these patients.

Septic Shock – Vasopressin is considered the first-line adjunct to Norepinephrine. There are theories that levels of endogenous vasopressin (ADH) are altered during sepsis, which make it impossible for the body to meet fluid-balancing demands. Low-dose infusions (0.01 – 0.04 U/min) have been shown to be effective at reducing norepinephrine infusion rates with no difference in mortality rates or organ dysfunction in SEVERELY septic patients. In patients with low severity of shock (defined as receiving baseline norepinephrine 5–15 µg/min), a vasopressin infusion decreased mortality by almost 10%. Vasopressin should be considered an adjunct treatment with norepinephrine, but not as the first-choice vasopressor in severe sepsis and septic shock. Infusion doses should never exceed 0.04 U/min as higher doses may produce myocardial ischemia and cardiac arrest.

Constricts the EFFERENT arteriole of the nephron – This is a benefit over typical vasoconstrictors (which constrict the afferent arteriole – which lowers GFR and UOP).  This will help to maintain both GFR and UOP better than phenylephrine or ephedrine.

Acidic environments – In contrast to catecholamines, vasopressin is very effective in acidic environments.

Catecholamine sparing – this helps prevent desensitization of adrenergic receptors.

Refrigerated – If you think you may need this drug, make sure you know where it is! Most often, it will not be in the room as it needs to be refrigerated.

IV push dose

Vasoplegia: Most start with a 0.5 – 1.0 unit and titrate from there.

Anaphylaxis refractory hypotension: The successful uses ranged from 2 units to 8 units after the typical dose of epinephrine (0.5 – 1.0 mg) failed to restore hemodynamic stability.

Vials of vasopressin should be diluted to 0.1 units/mL OR 1.0 units/mL. In a typical 20 unit vial, you would draw the vasopressin and dilute with 19 mL of solution to achieve 1 unit/mL.

IV infusion dose

Vasoplegia: 0.5 – 1.0 unit LOADING dose IV, followed by 0.03 units/minute

Method of Action

This drug works primarily on the kidneys ability to increase reabsorption of water in the late distal tubule and collecting duct. When injected, Vasopressin causes profound vasoconstriction by binding to the V1 receptor of vascular smooth muscle.

In its natural state, ADH is released in states of hypernatremia and/or hypovolemia. ADH is the primary hormone that maintains tonicity homeostasis. Hyperosmolarity is the primary trigger for its release. It is released from the posterior pituitary gland and binds to the type-2 receptor in principle cells of the collecting duct. This results in an increase in water reabsorption. Conversely, ADH is reduced with reduced osmolality and/or hypervolemic states.

When sympathetic and renin-angiotensin systems are intact, ADH plays very little role in blood pressure and cardiovascular sympathetic regulation. Rather, ADH plays a ‘backup’ role when those two systems are compromised. In fact, the most potent trigger for ADH release is systemic hypotension.

Other factors that contribute to the release of ADH are angiotensin II, pain, nausea, hypoglycemia, nicotine, opiates, and ethanol. Ethanol has an inhibitory affect on ADH, which is responsible for increased diuresis during intoxicated states.

Metabolism

Hydrolyzed very rapidly by trypsin. This is the reason Vasopressin has to be given parenterally. Furthermore, rapid metabolism also occurs by liver and kidney vasopressinases.

Elimination

Renal

Cuzzo. Physiology, vasopressin. 2021. web link
Park. Role of vasopressin in current anesthetic practice. 2017. web link
Rhodes. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. 2017. web link
Schummer. The pivotal role of vasopressin in refractory anaphylactic shock. 2008. web link