Vasopressin
Antidiuretic hormone in critical care and emergency medicine
Vasopressin, also known as arginine vasopressin or antidiuretic hormone (ADH), is an endogenous peptide hormone of nine amino acids. It is produced in the hypothalamus, stored in the posterior pituitary and released according to osmolarity or circulatory status. As a medicine it is available in Germany in recombinant synthetic form (argipressin, trade name Empressin) and as the long acting analogue terlipressin for intravenous use. Vasopressin and its analogues are among the standard vasopressors in critical care medicine.
The clinical role of vasopressin has changed over the past two decades. The VAAST study and the VANISH study investigated vasopressin as an alternative or adjunct to noradrenaline in septic shock. The current Surviving Sepsis Campaign guidelines recommend vasopressin as a second line vasopressor to reduce noradrenaline requirements in persistent shock. Terlipressin is also established in hepatorenal syndrome and in the treatment of acute oesophageal variceal bleeding.
Mechanism of Action
Vasopressin acts through three different G protein coupled receptors. At the V1a receptor of vascular smooth muscle it produces pronounced vasoconstriction, particularly of the skin, muscle, splanchnic bed and coronary arteries. At the V2 receptor of the renal collecting ducts it promotes insertion of aquaporin 2 channels and increases water reabsorption, concentrating the urine and reducing diuresis. At the V1b or V3 receptor of pituitary cells it stimulates ACTH release.
The vasoactive component is of particular interest in septic shock. During the course of sepsis vasopressin levels paradoxically fall despite severe circulatory shock (relative vasopressin deficit). Exogenously administered vasopressin can correct this deficit and stabilise the mean arterial pressure without a significant rise in heart rate. Unlike catecholamines vasopressin retains reliable activity even in pronounced acidosis.
In acute oesophageal variceal bleeding terlipressin acts through vasoconstriction of the splanchnic vessels; portal venous pressure falls and bleeding often stops. In hepatorenal syndrome it improves renal perfusion pressure and glomerular filtration via splanchnic constriction and volume redistribution.
Indications
- Septic shock as a second line vasopressor to reduce noradrenaline requirements, frequently as a continuous infusion up to 0.03 IU per minute
- Vasoplegic syndrome after cardiac surgery in catecholamine resistance
- Central diabetes insipidus in a relative vasopressin deficiency, usually as desmopressin (V2 agonist)
- Acute oesophageal variceal bleeding as intravenous terlipressin, combined with endoscopic ligation
- Hepatorenal syndrome type 1 as terlipressin plus albumin
- Cardiopulmonary resuscitation: discussed in older guidelines, no longer routinely recommended in the current ERC guidelines
Dosage and Administration
Argipressin in septic shock: continuous intravenous infusion of 0.01 to 0.03 IU per minute through a central venous catheter. Dose titration according to mean arterial pressure, with a target of 65 mmHg or more. If there is no response within a few hours or if severe tissue hypoperfusion persists the therapeutic decision must be individually reassessed.
Terlipressin: in acute oesophageal variceal bleeding an initial 2 mg intravenously, then 1 to 2 mg every 4 to 6 hours for 2 to 5 days. In hepatorenal syndrome 0.5 to 2 mg every 4 to 6 hours combined with human albumin. Diabetes insipidus: desmopressin (V2 selective) as nasal spray, tablets or subcutaneous injection.
Monitoring in the intensive care unit includes at least arterial blood pressure, heart rate, central venous pressure, urine output, lactate, sodium, creatinine, temperature and, where indicated, haemodynamic monitoring with pulse contour analysis or pulmonary artery catheter. The infusion must be administered through a central venous line; peripheral venous administration carries a risk of extravasation and necrosis.
Side Effects
Very common and common: pronounced vasoconstriction with skin pallor, hypoperfusion of the extremities, intestinal ischaemia, myocardial ischaemia, tachycardia or paradoxical bradycardia, hyponatraemia (V2 effect), headache.
Uncommon: bronchoconstriction, allergic reactions, thrombosis at the injection site, gastrointestinal spasms, uterine contractions, anxiety and restlessness.
Serious: ischaemic necrosis of fingers, toes, nose and abdominal wall on prolonged high dosing or peripheral infusion, mesenteric ischaemia with bowel necrosis, cerebral infarction, severe hypertension with myocardial infarction, hepatic dysfunction, severe hyponatraemia with seizures.
Extravasation: leakage from the venous access threatens local necrosis. Stop the infusion immediately, mark the affected area, infiltrate phentolamine for local α blockade and consult plastic surgery if there is soft tissue injury.
Interactions
- Catecholamines (noradrenaline, adrenaline, dobutamine): additive vasoactive effect, often deliberately combined with close monitoring
- SSRIs, SNRIs, tricyclic antidepressants: increased risk of hyponatraemia
- Carbamazepine, thiazides: additional fall in sodium through water retention
- Oxytocin, prostaglandins: increased uterine activity
- Ganglion blockers: intensified antidiuretic effect
- Halothane, other inhalational anaesthetics: cardiovascular reactions are unpredictable, careful titration required
Special Notes
Who may prescribe vasopressin? Administration is restricted to intensive care units or emergency departments by physicians with appropriate experience. Dose titration is closely tied to invasive monitoring, and the substance does not belong in ambulatory or office based practice.
Contraindications: severe coronary artery disease with acute instability, untreated hypertension, bronchial asthma with marked bronchoconstriction, peripheral arterial occlusive disease with critical ischaemia, hypertrophic cardiomyopathy, septic shock without adequate volume optimisation. Use in pregnancy should be restrained because of the risk of premature contractions.
Monitoring of sodium homeostasis: during continuous therapy and with V2 agonists (desmopressin) the risk of water intoxication with hyponatraemia is relevant. Sodium levels at least once per shift, more closely in elderly patients on diuretics or psychotropic drugs.
Desmopressin specific notes: desmopressin is a synthetic analogue with reduced V1 activity and pronounced V2 activity. It is used in diabetes insipidus, in haemophilia A and von Willebrand syndrome (mild forms) and in nocturnal enuresis of children. The nocturnal enuresis indication requires strict restriction of fluid intake in the evening to avoid water intoxication.
Pregnancy: terlipressin and vasopressin are relatively contraindicated in pregnancy because labour and uterine contractions may be triggered. Breastfeeding: data are limited, use only on a vital indication.
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Frequently Asked Questions
Why is vasopressin used in septic shock?
In septic shock there is a relative vasopressin deficit, and exogenous vasopressin supplements the body's own hormone production. It stabilises blood pressure complementary to noradrenaline, reduces catecholamine requirements and continues to work reliably even in severe acidosis. The Surviving Sepsis Campaign guidelines recommend it as second line.
What is the difference between vasopressin and desmopressin?
Vasopressin acts on all receptor subtypes (V1a, V2, V1b), is strongly vasoconstrictive and antidiuretic. Desmopressin is a synthetic analogue with largely V2 selectivity, acting predominantly antidiuretically and only minimally vasoactive. It is therefore used in diabetes insipidus and bleeding disorders, not in shock.
What is terlipressin used for in liver cirrhosis?
Terlipressin, a vasopressin analogue with slower release of active metabolites, is standard therapy in acute oesophageal variceal bleeding and in hepatorenal syndrome type 1. Splanchnic constriction reduces portal pressure, stops bleeding and improves renal perfusion. The combination with endoscopic ligation and albumin is standard.
Why must vasopressin be given centrally?
If extravasation occurs from peripheral accesses, the intense local vasoconstriction can cause tissue necrosis. For this reason vasopressin, like noradrenaline and other potent vasopressors, is administered only through a central venous catheter. In case of accidental extravasation phentolamine is the local countermeasure.
Sources
- EMA, European Medicines Agency
- Surviving Sepsis Campaign Guidelines
- Gelbe Liste, Vasopressin and Terlipressin active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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