Vasopressin (antidiuretic hormone) is a polypeptide hormone secreted by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary (neurohypophysis) in mammals; the primary physiologic role of vasopressin is to maintain serum osmolality within a normal range, but the hormone also causes vasoconstriction.152, 157, 167, 170
Vasopressin is used for its vasoconstrictive effects to increase blood pressure in patients with vasodilatory shock (e.g., postcardiotomy shock, septic shock); the drug is considered a second-line therapy in patients who remain hypotensive despite adequate fluid resuscitation and treatment with catecholamines (e.g., norepinephrine).151, 157, 167, 168, 169, 172
Evidence supporting the use of vasopressin in the management of vasodilatory shock is based principally on studies from the published literature, including 7 studies in adults with septic shock and 8 studies in adults with vasodilatory shock after cardiac surgery (i.e., postcardiotomy shock).167, 168, 172, 173 While these studies had some limitations, vasopressin (administered in doses of 0.01 to 0.1 units/minute by continuous IV infusion) was shown to consistently increase mean arterial pressure (MAP) in patients with these hypotensive states.167, 168, 169, 172 Although vasopressin appears to have a catecholamine-sparing effect, the effect of the drug on mortality remains unclear.167, 169, 173 In a randomized double-blind study comparing the effects of vasopressin (0.01-0.03 units/minute) and norepinephrine (5-10 mcg/minute) in patients with septic shock, no substantial difference in 28-day mortality was observed between the vasopressors.173 Large studies comparing vasopressin to other vasopressors for the treatment of septic shock generally are lacking.169
The Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock recommend norepinephrine as the first-line vasopressor of choice in adults with septic shock.169 Vasopressin may be added if further increase in MAP is required or to reduce dosage requirements of norepinephrine.169 The guidelines recommend that vasopressin be used with caution in patients who are not euvolemic.169 Because of the risk of ischemic complications, use of vasopressin dosages greater than 0.03 units/minute should be reserved for situations in which alternative vasopressors have failed.168, 169
Advanced Cardiovascular Life Support
Vasopressin has been used for its vasopressor effects as a nonadrenergic peripheral vasoconstrictor in patients with cardiac arrest†.152, 153, 157, 400, 401
High-quality cardiopulmonary resuscitation (CPR) and defibrillation are integral components of advanced cardiovascular life support (ACLS) and the only proven interventions to increase survival to hospital discharge.400, 401 Other resuscitative efforts, including drug therapy, are considered secondary and should be performed without compromising the quality and timely delivery of chest compressions and defibrillation.400, 401 The principal goal of pharmacologic therapy during cardiac arrest is to facilitate return of spontaneous circulation (ROSC), and epinephrine is considered the drug of choice for this use.400, 401 In previous ACLS guidelines, vasopressin was recommended as a substitute for epinephrine, with one dose of vasopressin (40 units by IV or intraosseous [IO] injection) replacing either the first or second dose of epinephrine, in the treatment of adult cardiac arrest.157, 401 While some clinicians have suggested that vasopressin may be more effective than epinephrine in asystolic arrest because of underlying differences in the mechanism of action and cardiovascular effects of the drugs (e.g., epinephrine consumes oxygen whereas vasopressin increases coronary blood flow),152, 153, 158, 160, 161, 164, 166 current evidence indicates that vasopressin offers no advantage compared with epinephrine in patients with cardiac arrest.152, 153, 157, 160, 161, 163, 166, 400, 401 Results of several randomized controlled studies demonstrated no difference in outcomes (ROSC, survival to discharge or neurologic outcome) when vasopressin (used alone or in combination with epinephrine) was compared with epinephrine alone.400, 401 In one of these studies in patients with out-of-hospital ventricular fibrillation, a larger proportion of patients initially treated with vasopressin (40 units IV) were successfully resuscitated and survived 24 hours compared with those treated with epinephrine (1 mg IV); however, there was no difference in survival to hospital discharge.160, 400 In another large (1186 patients), multinational, European study in adults with out-of-hospital cardiac arrest, vasopressin (up to 2 initial 40-unit IV doses) and epinephrine (up to 2 initial 1-mg IV doses) were comparably effective in the primary end point of survival to hospital admission as well as the secondary end point of survival to hospital discharge in patients with ventricular fibrillation (patients who responded successfully to electrical defibrillation were excluded) or pulseless electrical activity.152, 153, 157 Although a post-hoc analysis found that vasopressin was more effective than epinephrine for survival to hospital admission as well as hospital discharge in patients with asystolic cardiac arrest, vasopressin did not improve neurologically intact survival.152, 153, 157 Because of the equivalence of effect of vasopressin and epinephrine and efforts to simplify the management approach when therapies are found to be equivalent, vasopressin has been removed from the current ACLS treatment algorithm for adult cardiac arrest.400, 405 There is insufficient evidence to recommend for or against routine use of vasopressin during cardiac arrest in pediatric patients.403
Vasopressin has been used in the treatment of drug-induced distributive shock† associated with drug-induced cardiovascular emergencies or altered vital signs.157
Vasopressin also has been used in severely hypotensive patients with anaphylaxis† as a potential therapy to prevent cardiopulmonary arrest.157
Vasopressin has been used in the management of central diabetes insipidus†, a disorder caused by a deficiency of endogenous vasopressin, to control symptoms of polydypsia, polyuria, and dehydration.170, 171, 176 However, desmopressin, a synthetic analog of vasopressin that has a longer duration of action and lower incidence of adverse effects, is considered the drug of choice for this use.171, 176, 177 Although vasopressin injection may be used in the initial or emergency treatment of the disease, chronic therapy with the drug is impractical because of its short duration of action. Vasopressin is not effective in controlling polyuria caused by renal disease, nephrogenic diabetes insipidus, hypokalemia or hypercalcemia, or polyuria secondary to the administration of demeclocycline or lithium carbonate.
Abdominal Distention and Abdominal Radiographic Procedures
Vasopressin injection has been used to stimulate peristalsis in the prevention or treatment of intestinal paresis†, postoperative abdominal distention†, and distention complicating pneumonias or toxemias†. In addition, the drug has been used prior to abdominal radiographic procedures† including IV urography, cholecystography, and kidney biopsy to dispel interfering gas shadows and/or to concentrate the contrast media.
Vasopressin injection has been used in the past as a provocative test for pituitary release of growth hormone and corticotropin†; however, other diagnostic tests (e.g., insulin tolerance test) are considered more reliable diagnostic indicators of growth hormone reserve.
Vasopressin has been administered IV or intra-arterially† into the superior mesenteric artery as an adjunct in the treatment of acute, massive GI hemorrhage† caused by various conditions including esophageal varices, inflammatory bowel disease,178 peptic ulcer disease, esophagogastritis, esophageal laceration, acute gastritis, colitis associated with Behcet's disease, colonic diverticulosis, Mallory-Weiss syndrome, and intestinal perforation. The drug also has been infused into the mesenteric artery prior to and during portosystemic shunt surgery for esophageal varices. Use of vasopressin in such situations is a temporary measure, intended to decrease portal venous pressure and increase clotting and hemostasis. There is no evidence that the drug substantially improves overall survival. Although vasopressin is a potent splanchnic vasoconstrictor that may provide effective control of bleeding, the clinical usefulness of the drug is limited because of its adverse effects.178, 179, 180, 182, 183 In addition, there is a high recurrence of bleeding when the drug is discontinued.182 Current management of acute GI hemorrhage usually includes endoscopic therapy or a combination of endoscopy and pharmacologic therapy with a splanchnic vasoconstrictor (e.g., most commonly octreotide because of its longer duration of action and favorable adverse effect profile).178, 179, 180, 181, 183
Vasopressin is administered by IV infusion for the management of vasodilatory shock.167 The drug also has been administered by IM† or subcutaneous† injection for other uses (e.g., postoperative abdominal distention, diabetes insipidus).170, 172
Vasopressin also has been applied topically† to the nasal mucosa (e.g., with a cotton pledget, nasal spray, or dropper) in the treatment of diabetes insipidus.170
Vasopressin has been administered by intraosseous (IO)† injection for advanced cardiovascular life support (ACLS)†, generally when IV access is not readily available; onset of action and systemic concentrations of the drug are comparable to those achieved with venous administration.400, 401, 403 Vasopressin also has been administered endotracheally† when vascular (IV or IO) access cannot be established during cardiac arrest; however, IV or IO administration is preferred whenever possible because of more predictable drug delivery and pharmacologic effect.401
In addition, the drug has been administered by intra-arterial infusion† in the management of GI hemorrhage†. Intra-arterial infusion of the drug requires specialized techniques, including angiographic placement of the catheter, and should only be performed by clinicians familiar with this method of administration and the management of potential complications.
For IV administration, vasopressin is commercially available as a 20-units/mL injection that should be further diluted with 0.9% sodium chloride or 5% dextrose injection prior to administration.167 The manufacturer recommends dilution to a final concentration of 0.1 or 1 unit/mL depending on the patient's fluid status.167 In patients who are not fluid restricted, a concentration of 0.1 units/mL may be prepared by mixing 50 units (2.5 mL) of vasopressin injection with 500 mL of diluent.167 In patients who are fluid restricted, a more concentrated solution of 1 unit/mL may be prepared by mixing 100 units (5 mL) of vasopressin injection with 100 mL of diluent.167
Unused portions of the diluted solution should be discarded after 18 hours at room temperature or 24 hours under refrigeration.167 Vasopressin solutions should be inspected visually for particulate matter and discoloration prior to administration.167
Standardized concentrations for vasopressin have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 249, 250Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249, 250Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249, 250 For additional information on S4S (including updates that may be available), see[Web].249, 250
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Adults | 0.2 units/mL | units/min or units/kg/min a |
0.4 units/mL | ||
1 unit/mL | ||
Pediatric patients (<50 kg) | 0.05 units/mL | milliunits/kg/min for vasoconstriction/GI bleed or milliunits/kg/hr for diabetes insipidusb |
0.2 units/mL | ||
1 unit/mL |
aThe S4S panel recommends trying to standardize dosing units but understands that some protocols may use “flat” dosing while others may require weight-based dosing.
Vasopressin dosage requirements are variable and must be adjusted according to patient response. In order to avoid adverse effects, it is desirable to give doses that are just sufficient to elicit the desired response.
The manufacturer states that dosage of vasopressin is empiric for the management of vasodilatory shock; in general, dosage should be titrated to the lowest dose compatible with a clinically acceptable response.167 The goal of therapy is to optimize and maintain perfusion to critical organs without causing ischemic complications.167
The manufacturer recommends an initial vasopressin dosage of 0.03 units/minute in adults with postcardiotomy shock and 0.01 units/minute in adults with septic shock.167 If target blood pressure response is not achieved, the infusion rate may be increased by 0.005 units/minute at intervals of 10-15 minutes to a maximum dosage of 0.1 units/minute for postcardiotomy shock or 0.07 units/minute for septic shock.167 Some experts recommend that infusion rates higher than 0.03 units/minute be used with caution because of the risk of cardiac and peripheral ischemia.169 After target blood pressure has been maintained for 8 hours without the use of catecholamines, the vasopressin infusion rate should be tapered by 0.005 units/minute every hour as tolerated to maintain target blood pressure.167
Advanced Cardiovascular Life Support
For advanced cardiovascular life support (ACLS) in patients with cardiac arrest†, vasopressin has been given in a single dose of 40 units by IV or IO† injection as a replacement for the first or second dose of epinephrine.157, 400, 401
For the treatment of central diabetes insipidus† , vasopressin has been given in an adult dosage of 5-10 units 2-3 times daily as needed by IM or subcutaneous injection.170 Dosage has ranged from 5-60 units daily. In children, vasopressin has been given in proportionately reduced doses of 2.5-10 units by IM or subcutaneous injection 2-4 times daily. For the treatment of diabetes insipidus, vasopressin also has been administered intranasally at individualized dosages.
Abdominal Distention and Abdominal Radiographic Procedures
For the management of postoperative abdominal distention† in adults, vasopressin has been administered at an initial dose of 5 units by IM injection.170 Subsequent injections have been given every 3-4 hours with doses increased to 10 units if necessary.170 In children, proportionately reduced doses have been used.170
For use in abdominal roentgenography†, it has been suggested that two 10-unit IM or subcutaneous injections of vasopressin be administered, the first injection at 2 hours and the second injection at 30 minutes, prior to exposure of the radiograph; many clinicians recommend giving an enema prior to the first dose of vasopressin.170
When used as a provocative test for growth hormone and corticotropin release†, vasopressin injection has been given IM in a dose of 10 units for adults and 0.3 units/kg for children.
For the management of GI hemorrhage†, vasopressin has been administered by continuous IV or intra-arterial infusion after dilution with 0.9% sodium chloride or 5% dextrose injection to a concentration of 0.1-1 unit/mL. Continuous IV rather than intra-arterial infusion of the drug is preferred.
For IV infusion in patients with GI hemorrhage, vasopressin has been infused into a peripheral vein via a controlled infusion device. For continuous intra-arterial infusion in patients with esophageal varices or upper GI bleeding, the drug has been infused into the superior or inferior mesenteric artery via a controlled infusion device.
For the management of GI bleeding†, dosage of vasopressin is empiric and must be individualized according to the response and tolerance of the patient. Because many of the adverse effects of vasopressin are dose related, the lowest possible effective dosage should be used. Some experts recommend continuous use of vasopressin for no longer than 24 hours.180 IV dosage generally has been initiated at 0.2-0.4 units/minute and progressively increased to a maximum of 0.6-0.9 units/minute if necessary based on individual patient response.180, 183 To minimize adverse effects, some experts recommend concomitant use of IV nitroglycerin (initiated at 40 mcg/minute, increased to a maximum of 400 mcg/minute).180, 183 When vasopressin is administered by intra-arterial infusion, a dosage of 0.1-0.5 units/minute has been used.
Dosage in Hepatic and Renal Impairment
There is limited information regarding exposure of vasopressin in patients with hepatic impairment and no specific dosage recommendations are available for such patients; dosage should be titrated to effect.168
There is limited information regarding exposure of vasopressin in patients with renal impairment and no specific dosage recommendations are available for such patients; dosage should be titrated to effect.168
Adverse effects associated with low doses of vasopressin are infrequent and mild, but increase in frequency and severity with high doses. Reported adverse effects include circumoral pallor, sweating, tremor, pounding in the head, abdominal cramps, passage of gas, vertigo, nausea, vomiting, and eructation. In addition, diarrhea, intestinal hyperactivity, and uterine cramps may occur. Some manufacturers state that blanching of the skin, abdominal cramps, and nausea that may occur following subcutaneous or IM injection of the drug can be minimized by drinking 1 or 2 glasses of water at the time of vasopressin administration. Vasopressin may also increase plasma cortisol concentrations and serum concentrations of growth hormone.
In large doses, vasopressin may produce increased blood pressure, bradycardia, minor arrhythmias, premature atrial contraction, heart block, peripheral vascular constriction or collapse, coronary insufficiency, decreased cardiac output, myocardial ischemia, or myocardial infarction. In patients with vascular disease (especially of the coronary arteries), even small doses of the drug can precipitate angina. Coronary vasodilators (e.g., nitroglycerin) may be used to treat angina if it occurs. An ECG should be used to monitor the hormone's cardiac effects during IV or intra-arterial therapy.
Adverse effects reported in the published literature with IV vasopressin in patients with vasodilatory shock include hemorrhagic shock, decreased platelets, intractable bleeding, right heart failure, atrial fibrillation, bradycardia, myocardial ischemia, mesenteric ischemia, increased bilirubin levels, acute renal insufficiency, distal limb ischemia, hyponatremia, and ischemic lesions.167
When fluid intake is not excessive, there is little danger involved in the use of small antidiuretic doses of vasopressin to control diabetes insipidus. Overhydration was more likely to occur with the long-acting suspension of vasopressin tannate (no longer commercially available in the US) than with vasopressin injection; infants and children are often much more susceptible to such volume disturbances than are adults. If water intoxication occurs, some experts have recommended that vasopressin be discontinued and fluid intake restricted until the specific gravity of the urine decreases to less than 1.015 and polyuria occurs. In severe overhydration, osmotic diuresis with mannitol, hypertonic dextrose, or urea, alone or in conjunction with furosemide, is often effective in rapidly decreasing fluid overload. Hypertonic saline solutions are not indicated unless immediate correction of hyponatremia is required.
Hypersensitivity reactions characterized by urticaria, angioedema, bronchoconstriction, fever, rash, wheezing, dyspnea, circulatory collapse, cardiac arrest, and anaphylaxis have been reported with vasopressin administration. Appropriate agents for the treatment of hypersensitivity reactions should be readily available.
Coronary thrombosis, mesenteric infarction, venous thrombosis, infarction and necrosis of the small bowel, and peripheral emboli resulting from intra-arterial catheterization have been reported following infusion of vasopressin injection into the superior mesenteric artery. In one patient, intra-arterial injection of vasopressin produced mottling and cyanosis of the left foot. Several patients reportedly developed signs of cutaneous gangrene proximal to the site of IV infusion of the drug. Bilateral nipple necrosis, which gradually resolved over 10-14 days after discontinuance of the drug, has occurred in at least 2 patients during IV infusion of the drug. Reversible ischemic colitis has been reported in a patient receiving IV infusion of the drug for the management of variceal hemorrhage.
Precautions and Contraindications
Vasopressin should be used cautiously in preoperative and postoperative polyuric patients, since hormone requirements in these patients may be considerably less than normal. Fluid intake and output should be monitored closely, especially in comatose or semicomatose patients. Electrolyte balance also should be monitored periodically. Patients receiving vasopressin should be observed for early signs of water intoxication such as drowsiness, listlessness, headache, confusion, anuria, and weight gain in order to prevent ensuing seizures, coma, and death.
Vasopressin should be used cautiously in patients with seizure disorders, migraine, asthma, heart failure, vascular disease (especially of the coronary arteries), angina pectoris, coronary thrombosis, renal disease, goiter with cardiac complications, arteriosclerosis, or any other disease in which rapid addition to extracellular fluids may be hazardous. ECG monitoring should be performed periodically during therapy with the drug. Patients with impaired cardiac response may experience worsening cardiac output.167
Aggressive treatment with vasopressin in patients with vasodilatory shock can compromise perfusion of organs, including those of the GI tract, whose function is difficult to monitor.167 Dosage should be titrated to the lowest dose compatible with a clinically acceptable response.167
Geriatric patients and children are particularly sensitive to the effects of vasopressin; therefore, the drug should be used cautiously in these patients.
Vasopressin is contraindicated in patients with known allergy or hypersensitivity (e.g., anaphylaxis) to synthetic vasopressin (8-L-arginine vasopressin) or chlorobutanol (a preservative in the formulation).167, 170 Some manufacturers have stated that the drug is also contraindicated in patients with chronic nephritis accompanied by nitrogen retention and should not be used until reasonable nitrogen concentrations are attained.170
The manufacturer states that safety and efficacy of vasopressin in pediatric patients with vasodilatory shock have not been established.167 Although the drug has been evaluated in several studies for the treatment of pediatric vasodilatory shock, inconclusive results were reported and a wide range of doses were employed.168, 174, 175
Clinical studies of vasopressin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.167 Clinical experience to date has not identified any differences in response between geriatric and younger patients.167 In general, dosage selection in geriatric patients should be cautious, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group.167
There are no adequate or well-controlled studies of vasopressin in pregnant women, and animal reproduction studies with the drug have not been conducted.167, 170 It is not known whether vasopressin can cause fetal harm when administered to pregnant women or can affect reproduction capacity; the drug should be used during pregnancy only if the potential benefits justify the potential risks to a fetus.167, 170
Vasopressin may produce tonic uterine contractions that could threaten the continuation of pregnancy.167
Clearance of vasopressin is increased in the second and third trimester of pregnancy; dosages exceeding 0.1 units/minute may be required in patients with postcardiotomy shock and dosages exceeding 0.07 units/minute may be required in patients with septic shock.167
It is not known whether vasopressin is distributed into human milk.167 Some manufacturers recommend that the drug be used with caution in nursing women.170
Oral absorption of vasopressin in a nursing infant is considered unlikely since the drug is rapidly destroyed in the GI tract.167 Consideration may be given to advising a lactating woman to pump and discard her breast milk for 1.5 hours after receiving vasopressin to minimize potential exposure to the infant.167
Alcohol may decrease the antidiuretic effects of vasopressin.170
Concomitant use of catecholamines and vasopressin is expected to result in additive effects on mean arterial blood pressure and other hemodynamic parameters.167
Drugs Causing Diabetes Insipidus
Drugs suspected of causing diabetes insipidus (e.g., demeclocycline, lithium, foscarnet, clozapine) may decrease the pressor effect and antidiuretic activity of vasopressin.167
Drugs Causing Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Drugs suspected of causing syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (e.g., selective serotonin-reuptake inhibitors [SSRIs], tricyclic antidepressants, haloperidol, chlorpropamide, enalapril, methyldopa, pentamidine, vincristine, cyclophosphamide, ifosfamide, felbamate) may increase the pressor effect and antidiuretic activity of vasopressin.167
Furosemide increases the effect of vasopressin on osmolar clearance and urine flow.167 Furosemide increased osmolar clearance and urine flow by 4 and 9 times, respectively, in healthy subjects receiving vasopressin.167
Ganglionic blocking agents may markedly increase sensitivity to the pressor effects of vasopressin.167 In healthy individuals, administration of tetra-ethylammonium (a ganglionic blocking agent) increased the pressor effect of vasopressin by 20%.167
Heparin may decrease the antidiuretic effects of vasopressin.170
Indomethacin may prolong the effects of vasopressin on peripheral vascular resistance and cardiac output.167
Norepinephrine may decrease the antidiuretic effects of vasopressin.170
Exogenous vasopressin elicits all the pharmacologic responses usually produced by endogenous vasopressin (antidiuretic hormone). The primary physiologic role of vasopressin is to maintain serum osmolality within a normal range. The hormone produces relatively concentrated urine by increasing reabsorption of water by the renal tubules. Its action in regulating body fluid balance is mediated by renal vasopressin V2 receptors, which are coupled to adenyl cyclase and the generation of cyclic AMP.151 At the tubular level, vasopressin stimulates adenyl cyclase activity, leading to increases in cyclic adenosine monophosphate (AMP). Cyclic AMP increases water permeability at the luminal surface of the distal convoluted tubule and collecting duct, resulting in increased urine osmolality and decreased urinary flow rate. The antidiuretic activity of vasopressin conserves up to 90% of the water that might otherwise be excreted in the urine. Vasopressin also increases reabsorption of urea by the collecting ducts. Although solute diuresis does not generally occur, increased sodium and decreased potassium reabsorption have been induced by vasopressin. Vasopressin, however, plays no etiologic role in edema formation.
In doses greater than those required for antidiuretic effects, vasopressin directly stimulates contraction of smooth muscle V1 receptors.167 The vasoconstrictive action of vasopressin is mediated by vascular V1 receptors;151, 167 the vascular receptors are coupled to phospholipase C, resulting in release of calcium from sarcoplasmic reticulum in smooth muscle cells, leading to vasoconstriction.151, 167 The hormone exhibits relatively little vasoconstrictor effect in hemodynamically normal individuals, but is an important endogenous vasopressor when arterial pressure is threatened.151 Vasopressin causes vasoconstriction,157, 167 particularly of capillaries and of small arterioles, resulting in decreased blood flow to the splanchnic, coronary, GI, pancreatic, skin, and muscular systems. At therapeutic doses, vasopressin elicits a vasoconstrictive effect in most vascular beds, including the splanchnic, renal, and cutaneous circulation.167 When administered into the celiac or superior mesenteric arteries, vasopressin constricts gastroduodenal, left gastric, superior mesenteric, and splenic arteries; however, hepatic arteries are not constricted and, instead, hepatic blood flow often increases. When used to produce antidiuresis, vasopressin has little effect on blood pressure. The drug indirectly decreases coronary blood flow and may precipitate myocardial infarction. In addition, the hormone can decrease heart rate and cardiac output and increase pulmonary arterial pressure and blood pressure.
Patients with septic shock or postcardiotomy shock appear to have a relative deficiency of endogenous vasopressin, which can contribute to the vasodilatory hypotension observed in these shock states.169, 172, 173 When administered in therapeutic doses to patients with vasodilatory shock, vasopressin increases systemic vascular resistance and mean arterial blood pressure.167, 169 In addition, the drug tends to decrease heart rate and cardiac output.167 The pressor effect of vasopressin is proportional to the infusion rate of the drug.167 No evidence of tachyphylaxis or tolerance to the pressor effect of vasopressin has been observed.167
Endogenous vasopressin concentrations in patients undergoing cardiopulmonary resuscitation (CPR) are higher in those who survive than in those who do not have return to spontaneous circulation (ROSC).150, 152, 153 This finding suggested that exogenous vasopressin might be beneficial during cardiac arrest.150, 152, 153 After ventricular fibrillation of short duration, administration of vasopressin during CPR has increased coronary perfusion pressure, vital organ blood flow, ventricular fibrillation median frequency, and cerebral oxygen delivery.150 Similar findings have been reported with prolonged cardiac arrest and pulseless electrical activity.150 The hormone did not result in bradycardia after ROSC.150 Interaction of vasopressin with V1 receptors during CPR causes intense peripheral vasoconstriction of skin, skeletal muscle, intestine, and fat with relatively less vasoconstriction of coronary and renal vascular beds and vasodilatation of cerebral vasculature.150 Vasopressin does not exhibit β-adrenergic activity and therefore does not produce skeletal muscle vasodilatation or increased myocardial oxygen consumption during CPR.150
At pressor doses, vasopressin triggers contraction of smooth muscles in the GI tract mediated by muscular V1 receptors and release of prolactin and ACTH via V3 receptors.167 In the intestinal tract, vasopressin increases peristaltic activity, particularly of the large bowel. Vasopressin also causes an increase in GI sphincter pressure and a decrease in gastric secretion but has no effect on gastric acid concentration.
The oxytocic properties of vasopressin are minimal, but in large doses the drug may stimulate uterine contraction. The hormone also possesses slight milk ejecting properties but its role during lactation is negligible.
In addition to its peripheral effects, vasopressin causes release of corticotropin, growth hormone, and follicle-stimulating hormone.
Vasopressin is destroyed by trypsin, which is found in the GI tract, and, therefore, must be administered parenterally or intranasally. Absorption of vasopressin through the nasal mucosa is relatively poor. Following subcutaneous or IM administration of vasopressin injection, the duration of antidiuretic activity is variable but effects are usually maintained for 2-8 hours.170 Urine isotonicity is maintained when plasma concentrations of vasopressin are approximately 1 microunit/mL, while plasma concentrations of 4.5-6 microunits/mL produce maximum concentration of urine. Following IV infusion of vasopressin in patients with vasodilatory shock, onset of the pressor effect is rapid, with peak effects occurring within 15 minutes.167 Pressor effects fade within 20 minutes following discontinuance of infusion.167
Vasopressin is distributed throughout the extracellular fluid; there is no evidence of plasma protein binding.
It is not known whether vasopressin is distributed into human milk.167
Vasopressin is predominantly metabolized by the liver and kidneys.167 The drug is cleaved by serine protease, carboxipeptidase, and disulfide oxidoreductase at relevant sites for its pharmacologic activity; resulting metabolites are not expected to be pharmacologically active.167 Vasopressin has a plasma half-life of about 10-20 minutes.170 When administered by IV infusion at usual rates for vasodilatory shock (e.g., 0.1-1 units/minute), the apparent half-life is 10 minutes or less.167 Oxytocinase, a circulating enzyme produced early in pregnancy, is capable of cleaving the polypeptide; otherwise, plasma inactivation of vasopressin is negligible. Approximately 5% of a subcutaneous dose of vasopressin is excreted in urine unchanged after 4 hours, and following IV administration, 5-15% of the total vasopressin dosage appears in urine.167, 170
Vasopressin is a polypeptide hormone secreted by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary (neurohypophysis) in mammals. In humans and most other mammals, the natural hormone is arginine vasopressin. Commercially available vasopressin injection is an aqueous solution of synthetic arginine vasopressin.167 The potency of vasopressin (arginine) is standardized according to its pressor activity in rats and is expressed in USP Posterior Pituitary (pressor) Units. Antidiuretic activity of the commercially available preparations may be variable.
Vasopressin is soluble in water.167 Vasopressin injection for IV infusion contains a sodium acetate buffer to adjust the pH to 3.8.167 Vasopressin injection solution contains chlorobutanol (anhydrous) as a preservative; glacial acetic acid and/or sodium hydroxide may be added during manufacture to adjust the pH to 2.5-4.5.170
Vasopressin injection for IV infusion should be stored at 2-8°C and should not be frozen.167 Unopened vials may be stored at room temperature (20-25°C) for up to 12 months or up to the manufacturer's labeled expiration date (whichever comes first); once removed from the refrigerator, the vials should be marked to indicate the revised 12-month expiration date (if it occurs before the manufacturer's labeled expiration date).167 Unused diluted solutions should be discarded after 18 hours at room temperature or after 24 hours under refrigeration.167, 168
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV infusion | 20 units/mL |
Only references cited for selected revisions after 1984 are available electronically.
150. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation . 2000; 102(Suppl I) I-87,I-130-1, I-143, I-145-8, I-150, I-307, I-309, I-319.
151. Rozenfeld V, Cheng WM. The role of vasopressin in the treatment of vasodilation in shock states. Ann Pharmacother . 2000; 34:250-. [PubMed 10676834]
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