Vasopressin CRI

Non-catecholamine vasopressor. Acts at V1 receptors on vascular smooth muscle to cause peripheral vasoconstriction independent of adrenergic receptors, which preserves activity even in catecholamine-refractory vasoplegia. V2 receptors at the renal collecting duct mediate free-water retention (this is the ADH effect). Onset 1–2 min IV; duration ~10–20 min after stop. Metabolized by hepatic and renal vasopressinase.

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Clinical background

Vasopressin (arginine vasopressin, AVP; also called antidiuretic hormone) is an endogenous neurohypophyseal nonapeptide. In the ICU it is used as an adjunct vasopressor in vasodilatory shock that is not responding adequately to norepinephrine, and as an alternative or supplement to epinephrine during cardiopulmonary arrest. The clinical pivot is that vasopressin produces vasoconstriction through a pathway entirely independent of α-adrenergic receptors, so it retains efficacy when those receptors have downregulated (after prolonged catecholamine exposure) or stopped responding (severe acidosis, septic vasoplegia, advanced shock).

Pharmacology

Vasopressin acts through three receptor families with different downstream effects:

• V1a receptors on vascular smooth muscle. Receptor occupancy triggers a Gq-coupled cascade, intracellular calcium release, and vasoconstriction. This is the target action for ICU vasopressor use.
• V1b (V3) receptors on the anterior pituitary, stimulating ACTH release. Clinically minor at vasopressor doses.
• V2 receptors on renal collecting duct principal cells, inserting aquaporin-2 channels and producing water retention. This is the antidiuretic hormone role, dominant at low endogenous concentrations.

At the doses used as a vasopressor, V1a is the principal mediator. The vasoconstriction profile differs from catecholamines in a few clinically relevant ways. There is essentially no inotropic or chronotropic effect (no β-adrenergic activity), so heart rate does not rise the way it does with epinephrine or dopamine, and there is no direct support for cardiac output. The pulmonary vascular bed is much less constricted by vasopressin than by α-adrenergic pressors, which can be useful in patients with pulmonary hypertension. Splanchnic and renal beds are constricted at high doses, so the often-cited “splanchnic-sparing” effect is dose-dependent and disappears above ~3 mU/kg/min.

Onset is within 1–2 minutes after starting an IV infusion. The plasma half-life is short (4–20 minutes), but the clinical effect outlasts plasma levels because of receptor-binding kinetics. Cleared by liver and kidney peptidases.

Indications

Primary use cases:

• Catecholamine-refractory vasodilatory shock as an add-on to norepinephrine. The most common vet ICU indication. Adding vasopressin frequently allows the norepinephrine dose to be reduced, which can ease catecholamine-driven tachyarrhythmia and tissue-ischemia burden.
• Septic shock with persistent hypotension despite adequate volume resuscitation and norepinephrine. Human sepsis guidelines (Surviving Sepsis Campaign) position vasopressin as the second pressor when MAP targets are not met on norepinephrine alone; veterinary practice has converged on the same approach.
• Cardiopulmonary arrest. RECOVER 2024 lists vasopressin (0.8 U/kg IV) as an alternative to or adjunct to epinephrine, particularly for asystole or pulseless electrical activity, with some evidence in human medicine that vasopressin may be advantageous when the rhythm is non-shockable and acidosis is severe.
• Anaphylactic shock refractory to epinephrine. Less common but reported. The α-receptor downregulation that can accompany severe anaphylaxis is exactly the setting where the non-adrenergic pathway is useful.

Vasopressin is not a substitute for fluid resuscitation. Like every pressor, it raises pressure by reducing vascular compliance; perfusion does not improve if volume is not corrected first.

Dosing

• Dogs and cats, vasodilatory shock CRI: 0.5–4 mU/kg/min, titrated against MAP. Most patients respond at 0.5–2 mU/kg/min.
• Initial rate: 0.5–1 mU/kg/min.
• Caution above: 3 mU/kg/min. Higher doses progressively erode the splanchnic-sparing effect and raise the risk of bowel and digital ischemia. If MAP is not at target on norepinephrine plus vasopressin above 3 mU/kg/min, reassess fluid status, source control, and whether a third pressor or inotrope is needed before continuing to escalate vasopressin.
• Cardiac arrest, single dose: 0.8 U/kg IV, may repeat once after 3–5 minutes (RECOVER 2024). Note the unit change: arrest dose is in units, CRI maintenance is in milliunits. This is the most common transcription error around vasopressin and is worth a second read at every order.

Cat dosing uses the same range as dogs. Published feline data are thinner than canine but the receptor biology is the same and the published vet dose ranges do not differ between species.

Start at 0.5–1 mU/kg/min and titrate in 0.5 mU/kg/min steps every 5–15 minutes against MAP. Vasopressin is often added when norepinephrine is at or above 0.5–1 µg/kg/min and a second pressor is being considered; the goal in that setting is usually to allow norepinephrine to be reduced, not to chase a higher MAP on top of an already-maximal catecholamine load.

Administration

Stock concentration in the US is 20 U/mL (Pitressin and equivalents), typically a 1 mL ampule. For CRI delivery the stock is diluted into 0.9% sodium chloride or 5% dextrose. The InfusionFox calculator preselects three weight-banded preparations (200, 80, or 40 mU/mL) so the pump rate stays in its accurate range across the typical patient-size span.

Vasopressin is compatible with most IV fluids and can be co-administered through a peripheral line. Extravasation risk is real but lower than with norepinephrine because the local vasoconstriction takes longer to develop. Central venous access is still preferred for sustained CRIs, particularly when running concurrent norepinephrine; the same line works for both.

Stability is good at refrigerator temperature and at room temperature for the typical 24-hour hang time. Discard if any color change or precipitate appears.

Drug interactions

• Ganglionic blockers and α-adrenergic antagonists do not blunt vasopressin’s effect because the pathway is independent. This is why vasopressin works when norepinephrine no longer does in advanced shock.
• Carbamazepine, chlorpropamide, fludrocortisone, urea, fluorinated anesthetics potentiate the antidiuretic effect at higher doses (clinically minor at vasopressor doses).
• Lithium, demeclocycline, heparin, norepinephrine reduce the antidiuretic response.
• Concurrent norepinephrine is the standard combination in refractory shock, not a contraindication. The two work through complementary pathways and the dose of each can usually be reduced when both are running.

Adverse effects

• Tissue ischemia and digital necrosis at higher doses. Mostly reported in human ICU at vasopressin doses exceeding 0.04 U/min in adults (roughly equivalent to 4–5 mU/kg/min in small-animal scaling) and with prolonged duration. In dogs and cats the risk is presumed similar; tail, ear, and paw extremities deserve specific inspection.
• Splanchnic ischemia at high doses. Bowel hypoperfusion can manifest as elevated lactate that does not correct with volume, or as ileus and rising creatinine. Reassess dose before assuming this is progression of the underlying shock.
• Bradycardia at high doses. Likely vagal reflex from MAP rise rather than direct cardiac depression. Usually not problematic unless rate becomes hemodynamically limiting.
• Hyponatremia with prolonged infusion. The V2-mediated antidiuretic effect causes free-water retention; monitor sodium every 12–24 hours in patients on multi-day infusions.
• Coronary vasoconstriction in humans has been reported as a cause of myocardial ischemia; clinical significance in dogs and cats is not well established but is worth keeping in mind in patients with known myocardial disease.

Monitoring

• Continuous or frequent blood pressure, ideally MAP (arterial line) for ICU use. Set a MAP target before starting (commonly 65–80 mmHg in dogs, 60–75 mmHg in cats) and titrate to it. The endpoint is the target, not “as much vasopressin as possible.”
• Continuous ECG for rhythm and rate.
• Lactate trend, particularly looking for divergence between MAP improvement and lactate stagnation, which can flag splanchnic hypoperfusion.
• Urine output as a perfusion marker. Note that vasopressin itself promotes water retention through V2; falling output can be either antidiuresis or true hypoperfusion. Trend together with body weight and BUN/creatinine.
• Sodium every 12–24 hours during prolonged infusion.
• Distal extremities at every assessment, particularly in patients on combined vasopressin and norepinephrine. Cold or mottled paws, tail tip, or pinnae should prompt a dose reassessment.

Weaning

Once MAP is sustained on lower catecholamine doses, vasopressin is usually weaned before norepinephrine. The rationale is that the longer plasma half-life of vasopressin masks rebound vasodilation more than the brief norepinephrine half-life does; weaning vasopressin first reveals whether the catecholamine alone is now sufficient.

Reduce by 0.5 mU/kg/min increments every 30–60 minutes. Abrupt discontinuation can produce rebound hypotension, especially after infusions running longer than 24 hours, and is best avoided.

Sources

• Plumb’s Veterinary Drugs, vasopressin monograph (current edition).
• Hart S, Silverstein DC. Catecholamines. In: Silverstein DC, Hopper K, eds. Small Animal Critical Care Medicine. 3rd ed. Elsevier; 2023:855–859. Chapter 147; Table 147.1.
• Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: clinical guidelines. J Vet Emerg Crit Care. 2024 (updated). (Vasopressin dose 0.8 U/kg for asystole/PEA.)
• Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care. 2011;15(4):226. (Human sepsis evidence base that informed veterinary adoption.)
• Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. (Vasopressin as second-line pressor.)