Vasopressin
Cardiovascular / Critical CareAlso known as: ADH, Antidiuretic Hormone, Vasostrict, Pitressin
Mechanism
A natural hormone made in the brain that has two main jobs: it raises blood pressure by constricting blood vessels, and it tells the kidneys to hold onto water. In hospitals, synthetic vasopressin is used in the ICU to treat life-threatening low blood pressure (septic shock) when other vasopressors aren't enough, and to treat diabetes insipidus (a condition where the kidneys can't concentrate urine).
Technical detail
Endogenous cyclic nonapeptide (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, disulfide bridge Cys1-Cys6) synthesized in supraoptic and paraventricular nuclei of hypothalamus, released from posterior pituitary. Three receptor subtypes: V1a (Gq/PLC/Ca2+ — vascular smooth muscle vasoconstriction, hepatic glycogenolysis), V1b/V3 (Gq — anterior pituitary ACTH release), V2 (Gs/cAMP — renal collecting duct aquaporin-2 insertion, water reabsorption, vWF/Factor VIII release). In septic shock: 0.01-0.04 units/min IV infusion (Vasostrict) — acts on V1a receptors to restore vascular tone in catecholamine-resistant vasodilation. VASST trial: vasopressin + norepinephrine reduced mortality in less severe septic shock subgroup. For diabetes insipidus: replaces deficient ADH. Half-life ~10-20 min (rapid hepatic/renal clearance). Also used in cardiac arrest (ACLS) and variceal bleeding.
Effects
## Detailed Effects — Vasopressin ### Cardiovascular System — Vasopressor [Tier 1] - Endogenous nonapeptide (9 amino acids, cyclic disulfide). Also called antidiuretic hormone (ADH) or arginine vasopressin (AVP). - V1aR (vascular smooth muscle): vasoconstriction independent of catecholamine pathways. This is why vasopressin works in catecholamine-resistant shock. - V1bR (anterior pituitary): stimulates ACTH release. - V2R (renal collecting duct): antidiuretic effect — inserts aquaporin-2 channels. - **VASST Trial (Russell et al., NEJM 2008, n=778)**: Low-dose vasopressin (0.03 U/min) + norepinephrine vs norepinephrine alone in septic shock. No overall mortality difference, but post-hoc analysis: vasopressin reduced mortality in patients with less severe septic shock (norepinephrine 5-14 mcg/min at randomization). - **VANISH Trial (Gordon et al., JAMA 2016, n=409)**: Early vasopressin vs norepinephrine in septic shock — no mortality difference but vasopressin group had less need for renal replacement therapy (25.4% vs 35.3%). - Surviving Sepsis Campaign: recommends vasopressin as second-line vasopressor added to norepinephrine (not replacing it) to reach MAP target or to reduce norepinephrine dose. ### Renal System [Tier 1] - V2R activation: increases water reabsorption in collecting duct via AQP2 insertion → concentrated urine, reduced urine output. - Treats central diabetes insipidus (CDI) — replaces deficient ADH. - In sepsis: low-dose vasopressin may preserve renal function better than escalating catecholamines (VANISH trial data). ### Hemostasis [Tier 1] - V2R activation on endothelial cells releases von Willebrand factor (vWF) and Factor VIII from Weibel-Palade bodies. - Desmopressin (DDAVP, a V2-selective analog) exploits this mechanism for hemophilia A and von Willebrand disease treatment. ### GI System [Tier 1-2] - V1aR activation constricts splanchnic arterioles → reduces portal pressure. - Used (as terlipressin or vasopressin + nitroglycerin) for acute variceal hemorrhage. - Can cause mesenteric ischemia at high doses — nitroglycerin co-administration mitigates this risk.
Practitioner Guide
## Practitioner Guide — Vasopressin ### FDA-Approved Indications 1. **Vasodilatory shock** (including septic shock) in adults who remain hypotensive despite fluids and catecholamines. 2. **Diabetes insipidus** (central) — diagnostic and therapeutic. 3. **Post-operative abdominal radiograph distension** (historical, rarely used). ### Septic Shock Protocol (Current Standard) - **Dose**: 0.03-0.04 U/min IV infusion (FIXED dose — do NOT titrate like catecholamines). - **When to add**: When norepinephrine requirements reach 0.25-0.5 mcg/kg/min and MAP remains <65 mmHg. - **Administration**: Via central line. Can use peripheral line briefly if central access not yet available. - **Weaning**: Wean vasopressin LAST (after catecholamines are at low doses). Taper gradually — abrupt discontinuation can cause rebound hypotension. - **Key principle**: Vasopressin is a FIXED-DOSE adjunct, not a titrated first-line vasopressor. ### Diabetes Insipidus (Central) - **Diagnosis**: Urine osmolality <300 mOsm/kg with serum osmolality >290 mOsm/kg and polyuria (>3 L/day). - **Treatment**: Desmopressin (DDAVP) is preferred over vasopressin for DI due to selective V2 action (no V1a vasoconstrictive effects). - Vasopressin itself is used in the water deprivation test for diagnostic purposes. ### Cardiac Arrest (ACLS) - **Dose**: 40 units IV push (single dose) — can substitute for the first or second dose of epinephrine in cardiac arrest (ACLS guidelines). - Evidence for benefit over epinephrine is not strong; both are acceptable per AHA guidelines. ### GI Variceal Bleeding - **Dose**: 0.2-0.4 U/min IV infusion. Max 0.8 U/min. - **Always co-administer nitroglycerin** (IV or transdermal) to reduce mesenteric ischemia and cardiac afterload. - Largely replaced by terlipressin and octreotide in modern practice. ### Storage - Vasopressin injection (Vasostrict): Store at room temperature (20-25°C). Do not freeze. - Dilute in D5W or NS. Stable for 18 hours at room temperature or 24 hours refrigerated once diluted. ### Monitoring - Continuous arterial BP monitoring in shock. - Urine output (goal >0.5 mL/kg/hr in sepsis). - Serum sodium and osmolality (risk of hyponatremia with V2 effects). - Monitor for digital/mesenteric ischemia (V1a-mediated).
Research Summary
## Research Summary — Vasopressin ### Tier 1: Randomized Controlled Trials - **VASST (Russell et al., NEJM 2008, n=778)**: Low-dose vasopressin + norepinephrine vs norepinephrine alone in septic shock. No overall 28-day mortality difference. Post-hoc: mortality benefit in less severe shock and trend toward benefit with concomitant corticosteroids. - **VANISH (Gordon et al., JAMA 2016, n=409)**: Early vasopressin vs norepinephrine as initial vasopressor in septic shock. No mortality difference. Less renal replacement therapy with vasopressin (25.4% vs 35.3%, p=0.03). - **VASPA (Hajjar et al., JAMA 2017, n=300)**: Vasopressin vs norepinephrine for post-cardiac surgery vasoplegia. No mortality difference. Less atrial fibrillation with vasopressin. ### Tier 2: Systematic Reviews & Meta-Analyses - **Surviving Sepsis Campaign (2021)**: Vasopressin recommended as second-line vasopressor in septic shock to reduce catecholamine exposure (conditional recommendation, moderate evidence). - Meta-analyses of vasopressin in septic shock: no clear mortality benefit vs catecholamines alone, but consistent catecholamine-sparing effect and possible renal protection. - Cochrane Review: insufficient evidence to recommend vasopressin over catecholamines as first-line, but useful as adjunct. ### Tier 3: Case Reports & Practitioner Protocols - Intensivists widely use 0.03-0.04 U/min vasopressin as second-line in septic shock — this is standard ICU practice worldwide. - Some centers use vasopressin first-line in patients with tachyarrhythmias (avoids catecholamine-induced tachycardia). - Emerging interest in copeptin (vasopressin surrogate biomarker) for guiding vasopressin therapy. ### Gaps - Optimal vasopressin dose in septic shock (0.03 vs 0.04 vs 0.06 U/min) not compared in RCTs. - Whether vasopressin should be combined with corticosteroids routinely is unclear (synergy suggested in VASST subgroup). - Biomarker-guided vasopressin dosing (using copeptin levels) not validated. ### Active Trials - Vasopressin in pediatric septic shock. - Copeptin-guided vasopressor therapy trials. - Studies of vasopressin receptor-specific analogs with improved safety profiles.