|Trade names||Vasostrict, Reverpleg, Empressin, others|
|Other names||Arginine vasopressin; argipressin|
|Main uses||Shock, cardiac arrest, diabetes insipidus, paralytic ileus, gastrointestinal bleeding|
|Side effects||Stomach ache, world spinning, flatulence, headache, tremor|
|Breastfeeding||No evidence of harm|
|Intravenous (IV), intramuscular (IM), subcutaneous (SC)|
|Onset of action||Rapid|
|Duration of action||20 min (after IV stopped)|
|Source tissues||Supraoptic nucleus; Paraventricular nucleus of hypothalamus|
|Receptors||V1A, V1B, V2, OXTR|
|Metabolism||Predominantly in the liver and kidneys|
|Metabolism||Predominantly in the liver and kidneys|
|Elimination half-life||10-20 minutes|
|Chemical and physical data|
|Molar mass||1084.24 g·mol−1|
|3D model (JSmol)|
Vasopressin, sold under the brand name Argipressin among others, is a medication used for shock not responding to fluid resuscitation or norepinephrine. Other uses include cardiac arrest, diabetes insipidus, paralytic ileus, and gastrointestinal bleeding. It may also be used as part of a number of medical tests. It is given by injection. Onset of effects is rapid with the maximum effect at 15 min.
Common side effects include stomach ache, world spinning, flatulence, headache, or tremor. Other side effects may include a slow heart rate, mesenteric ischemia, water intoxication, and coronary ischemia. During the later part of pregnancy it may result in contraction of the uterus. It works by activating the vasopressin receptor resulting in contraction of blood vessels. In the kidneys in results in concentration of the urine.
Vasopressin was first isolated by Vincent du Vigneaud in 1953 and manufactured in 1958. It is available as a generic medication. In the United Kingdom a vial of 20 units costs the NHS about £80 as of 2020. This amount in the United States costs about 60 USD.
Vasopressin is used to manage anti-diuretic hormone deficiency. It has off-label uses and is used in the treatment of gastrointestinal bleeding, ventricular tachycardia and ventricular defibrillation. Vasopressin is used to treat diabetes insipidus related to low levels of antidiuretic hormone. It is available as Pressyn.
Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of von Willebrand disease and in mild haemophilia A) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasoconstrictors in certain conditions. Use of vasopressin analogues for esophageal varices commenced in 1970.
Catecholamine refractory shock
Efficacy of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock have been studied and published first in 2001 Later, the group concluded the ischemic skin lesions (ISL) developed in patients with catecholamine-resistant vasodilatory shock have multi-factorial cause and shall not necessarily been seen a side effect of AVP solely. The presence of septic shock and a history of peripheral arterial occlusive disease are independent risk factors for the development of ISL. In the last decade, in early hyperdynamic septic shock, the administration of high-dose AVP as a single agent proved to fail to increase mean arterial pressure in the first hour but maintains it above 70mmHg in two-thirds of patients at 48h. AVP decreases NE exposure, has no effect on the PrCO(2) - PaCO(2 )difference, and improves renal function and SOFA score. This led to development of a large trial to see theeffect of arginin vasopressin as add-on to norepinephrine in septic shock. It could be shown, if giving vasopressin in early stage of septic shock (norepinephrin < 15 microgramm/min and lactate < 1.4 mmol/L) there is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased 28 and 90 days mortality and organ dysfunction compared with norepinephrine and corticosteroids.
2018 Surviving Sepsis Campaign
The Surviving Sepsis Campaign guidelines recommend the very early management of the sepsis focusing on the hour-1 bundle. This includes use of Vasopressin 0.03 units/minute as add-on to norepinephrine (NE) with intent of either raising the mean arterial pressure or decreasing the norepinephrine dosage (i.e. de-catecholaminization).
Modern interest in vasopressors as a treatment for cardiac arrest stem mostly from canine studies performed in the 1960s by anesthesiologists Dr. John W. Pearson and Dr. Joseph Stafford Redding in which they demonstrated improved outcomes with the use of adjunct intracardiac epinephrine injection during resuscitation attempts after induced cardiac arrest. Also contributing to the idea that vasopressors may be useful treatments in cardiac arrest are studies performed in the early to mid 1990s that found significantly higher levels of endogenous serum vasopressin in adults after successful resuscitation from out-of-hospital cardiac arrest compared to those who did not live. Results of animal models have supported the use of either vasopressin or epinephrine in cardiac arrest resuscitation attempts, showing improved coronary perfusion pressure and overall improvement in short-term survival as well as neurological outcomes.
Vasopressin vs. epinephrine
Although both vasopressors, vasopressin and epinephrine differ in that vasopressin does not have direct effects on cardiac contractility as epinephrine does. Thus, vasopressin is theorized to be of increased benefit over epinephrine in cardiac arrest due to its properties of not increasing myocardial and cerebral oxygen demands. This idea has led to the advent of several studies searching for the presence of a clinical difference in benefit of these two treatment choices. Initial small studies demonstrated improved outcomes with vasopressin in comparison to epinephrine. However, subsequent studies have not all been in agreement. Several randomized controlled trials have been unable to reproduce positive results with vasopressin treatment in both return of spontaneous circulation (ROSC) and survival to hospital discharge, including a systematic review and meta-analysis completed in 2005 that found no evidence of a significant difference with vasopressin in five studied outcomes.
Vasopressin and epinephrine vs. epinephrine alone
There is no current evidence of significant survival benefit with improved neurological outcomes in patients given combinations of both epinephrine and vasopressin during cardiac arrest. A systematic review from 2008 did, however, find one study that showed a statistically significant improvement in ROSC and survival to hospital discharge with this combination treatment; unfortunately, those patients that survived to hospital discharge had overall poor outcomes and many suffered permanent, severe neurological damage. A more recently published clinical trial out of Singapore has shown similar results, finding combination treatment to only improve the rate of survival to hospital admission, especially in the subgroup analysis of patients with longer "collapse to emergency department" arrival times of 15 to 45 minutes.
Congenital heart disease
Vasopressin is used in managing hemodynamic instability in newborns and older children recovering from cardiac surgery. There is evidence that some children recovering from cardiac surgery have relative vasopressin deficiency, such that their endogenous plasma concentrations of arginine vasopressin are lower than what would be expected in this clinical setting. Though low endogenous vasopressin concentrations in and of themselves do not cause hemodynamic instability, neonates and children recovering from cardiac surgery who develop hemodynamic instability and have low endogenous vasopressin concentrations are optimal candidates for this surgery. Unfortunately, measurement of endogenous vasopressin concentration is time consuming and cumbersome, and not practical for bedside application. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying patients with low endogenous vasopressin concentrations. Further research is needed. Also, systemic corticosteroids have been shown to suppress endogenous vasopressin production and release. Neonates and children recovering from cardiac surgery who are receiving systemic corticosteroid therapy may also be optimal candidates for vasopressin therapy should hemodynamic instability be present.
Vasopressin receptor inhibition
For low blood pressure, generally 2.5 ml of 20 unit per mL solution is mixed in 500 mL of normal saline to give a solution of 0.1 units per mL. This is than given at a rate of 0.015 to 0.1 units per minute (0.15 to 1 mL per min). In cardiac arrest a single dose of 40 units iv may be used.
For diabetes insipidus 5 to 20 units either IM or SC every four hours may be used.
The most common side effects during treatment with vasopressin are dizziness, angina, chest pain, abdominal cramps, heartburn, nausea, vomiting, trembling, fever, water intoxication, pounding sensation in the head, diarrhoea, sweating, paleness, and flatulence. The most severe adverse reactions are myocardial infarction and hypersensitivity.
The use of lysine vasopressin is contraindicated in the presence of hypersensitivity to beef or pork proteins, increased BUN and chronic kidney failure. It is recommended that it be cautiously used in instances of perioperative polyuria, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.
- alcohol - may lower the antidiuretic effect
- carbamazepine, chloropropamide, clofibrate, tricyclic antidepressants and fludrocortisone may raise the diuretic effect
- lithium, demeclocycline, heparin or norepinephrine may lower the antidiuretic effect
- vasopressor effect may be higher with the concurrent use of ganglionic blocking medications
Vasopressin is administered through an intravenous device, intramuscular injection or a subcutaneous injection. The duration of action depends on the mode of administration and ranges from thirty minutes to two hours. It has a half life of ten to twenty minutes. It is widely distributed throughout the body and remains in the extracellular fluid. It is degraded by the liver and excreted through the kidneys. Arginin vasopressins for use in septic shock are intended for intravenous use only.
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