Prevention or control of polydypsia, polyuria, and dehydration in diabetes insipidus caused by a deficiency of endogenous posterior pituitary ADH (neurohypophyseal diabetes insipidus), but desmopressin usually considered drug of choice.
May be used in the initial or emergency treatment of the disease, but, because of its short duration of action, its use is impractical for chronic therapy.
Intranasal aqueous vasopressin may be effective for daily maintenance therapy and the degree of absorption is usually adequate to control mild diabetes insipidus; other drugs are preferred (e.g., chlorpropamide).
Polyuria
May correct fluid imbalance associated with transient polyuria due to ADH deficiency accompanying neurosurgery or head injury.
Used for its vasopressor effects; may give 1 dose to replace first or second dose of epinephrine in ACLS during CPR.
Comparably effective to epinephrine in patients with cardiac arrest (presented with VF or pulseless electrical activity); however, conflicting evidence exists whether vasopressin is more effective than epinephrine in patients with asystolic cardiac arrest.
May enhance the probability of return of spontaneous circulation (ROSC), survival to hospital admission, as well as hospital discharge.
Combination of vasopressin and epinephrine (if refractory) has been reported to be more effective than repeated epinephrine alone for refractory cardiac arrest; however, optimal timing of vasopressin administration in relation to epinephrine use during cardiac arrest not fully established (i.e., replacement of first versus second epinephrine dose).
Abdominal Distention
To stimulate peristalsis in the prevention or relief of intestinal paresis, postoperative abdominal distention, and distention complicating pneumonias or toxemias.
Abdominal Radiographic Procedures
To dispel interfering gas shadows and/or to concentrate the contrast media prior to abdominal radiographic procedures including IV urography, cholecystography, and kidney biopsy.
Diagnostic Uses
Although vasopressin injection has been used as a provocative test for pituitary release of growth hormone and corticotropin†, arginine hydrochloride and insulin generally are considered the most reliable diagnostic indicators of growth hormone reserve.
GI Hemorrhage
Administered IV† or intra-arterially† into the superior mesenteric artery as an adjunct in the treatment of acute and life-threatening, massive GI hemorrhage† caused by ruptured esophageal varices (e.g., in alcoholic cirrhotics), peptic ulcer disease, esophagogastritis, esophageal laceration, acute gastritis, colitis associated with Behcet’s disease, colonic diverticulosis, small intestinal typhoid infection, Mallory-Weiss syndrome, or intestinal perforation.
Infused into the mesenteric artery† prior to and during portosystemic shunt surgery for esophageal varices†.
May provide effective control of bleeding, but there is no evidence that the drug substantially improves overall survival.
May consider for hemodynamic support as a continuous infusion† in vasodilatory shock† such as septic shock and sepsis syndrome, if conventional adrenergic vasopressor drugs are ineffective.
Dosage and Administration
General
May administer 1–2 glasses of water with vasopressin to reduce occurrence of adverse effects (e.g., skin blanching, abdominal cramps, nausea) and improve therapeutic response.
Administration
Administer IM or sub-Q.
May administer topically to nasal mucosa for antidiuresis; do not inhale.
May administer IV† (e.g., for ACLS during CPR, GI hemorrhage), by intraosseous injection† (e.g., for ACLS during CPR) or intra-arterially (e.g., for GI hemorrhage). Although vasopressin may be administered via an endotracheal tube† for ACLS during CPR, a specific dose is not established and IV† or intraosseous† administration is preferred because of more predictable drug delivery and pharmacologic effect.
IM or Sub-Q Administration
Usually, administer IM or sub-Q at 3- to 4-hour intervals as needed.
Intranasally
May be applied topically to the nasal mucosa as a spray, drops, or via a saturated pledget; the drug should not be inhaled.
IV or Intra-arterial Administration
May administer by IV injection† for ACLS during CPR.
May administer by continuous IV† or intra-arterial† infusion (e.g., for GI hemorrhage†).
GI hemorrhage, particularly alcoholic cirrhotics: Preferably, administer initially by continuous IV infusion, since intra-arterial infusion is not more effective but is technically more difficult; patients who fail to respond adequately to initial IV infusion therapy may respond to intra-arterial infusion therapy.
GI hemorrhage: Perform intra-arterial† or IV† administration only under the supervision of a clinician familiar with the pharmacologic effects of vasopressin and with all acceptable treatment modalities for GI bleeding.
GI hemorrhage: Intra-arterial† infusion requires specialized techniques, including angiographic placement of the catheter; limit to clinicians familiar with this method of administration and the management of potential complications.
Dilution
GI hemorrhage, intra-arterial or continuous IV infusion: Generally dilute with 0.9% sodium chloride or 5% dextrose injection to a concentration of 0.1–1 unit/mL.
Rate of Administration
GI hemorrhage: Adjust rate to response and tolerance.
GI hemorrhage, IV infusion: Into a peripheral vein via controlled-infusion device; usually, 0.2–0.9 units/minute.
GI hemorrhage, intra-arterial infusion: Usually, into the superior mesenteric artery via controlled-infusion device; usually, 0.1–0.5 units/minute.
GI hemorrhage, intra-arterial infusion: Also into the splenic or celiac axis usually, 0.1–0.5 units/minute.
Diverticular hemorrhage, intra-arterial infusion: Into the inferior mesenteric artery.
Intraosseous Administration
For ACLS during CPR in adults, may administer by intraosseous injection†; onset of action and systemic concentrations are comparable to those achieved with central venous administration.
Dosage
Potency of vasopressin (arginine and lysine) is standardized according to pressor activity in rats and is expressed in USP posterior pituitary (pressor) units.
Antidiuretic activity of commercially available preparations may be variable.
Antidiuretic dosages are variable and must be adjusted according to response; to avoid adverse effects, it is desirable to give doses that are just sufficient to elicit the desired response.
Adults: 10 units elicit full physiologic response; 5 units adequate in many cases.
Pediatric Patients
Diabetes Insipidus
Neurohypophyseal
IM or Sub-Q
2.5–10 units 2–4 times daily.
Intranasal
Individualize dosage and dosing interval according to response.
Abdominal Distention and Abdominal Radiographic Procedures
IM
Give doses proportionately reduced from adult dose.
Diagnostic Uses
Provocative Testing for Growth Hormone and Corticotropin Release
IM
0.3 units/kg; then obtain blood specimens and assay for hormones.
Adults
Diabetes Insipidus
Neurohypophyseal
IM or Subcutaneous
5–10 units 2–4 times daily as needed; range 5–60 units daily.
Intranasal
Individualize dosage and dosing interval according to response.
CPR (Cardiac Arrest)
VF, Pulseless VT, Pulseless Electrical Activity, and Asystole in ACLS
IV
40 units, given as a single dose, may replace first or second dose of epinephrine.
Intraosseous
40 units, given as a single dose, may replace first or second dose of epinephrine.†
Abdominal Distention and Abdominal Radiographic Procedures
Abdominal Distention
IM
Usually, 5 units; may give subsequent doses every 3–4 hours, increasing to 10 units if necessary.
Dosage applies to prevention and relief of postoperative distention and other causes.
Abdominal Radiographic Procedures
Sub-Q
5–15 units given 2 hours and repeated 30 minutes prior to abdominal radiographs and kidney biopsy (before films are exposed); usually give an enema prior to the first dose.
Diagnostic Uses
Provocative Testing for Growth Hormone and Corticotropin Release
IM
10 units; then obtain blood specimens and assay for hormones.
GI Hemorrhage
Esophageal Varices and GI Bleeding
IV Infusion
Dosage is empiric and must be individualized according to response and tolerance.
Because many of the adverse effects are dose related, the lowest possible effective dosage should be used.
Usually initiate at 0.2–0.4 units/minute and progressively increase to 0.9 units/minute if necessary. Additional benefit at higher rates unlikely.
After 24 hours, the infusion rate should be tapered according to patient response, but administration of vasopressin has been continued for 3 days to 2 weeks.
Intra-arterial Infusion
Dosage is empiric and must be individualized according to the response and tolerance.
Because many of the adverse effects are dose related, the lowest possible effective dosage should be used.
Usually, 0.1–0.5 units/minute; after 20–30 minutes, the vasoconstrictive and clotting responses to intra-arterial vasopressin can be assessed by angiography.
Response also can be monitored with portal pressures or hepatic wedge pressures.
After 24 hours, the infusion rate should be tapered according to patient response, but administration of vasopressin has been continued for 3 days to 2 weeks.
Vasodilatory Shock
IV Infusion
Optimum dosage and duration remain to be established; usually, 0.02–0.1 units/minute.
Special Populations
Hepatic Impairment
Hepatic Impairment
No specific dosage recommendations for patients with hepatic impairment.
Renal Impairment
Renal Impairment
No specific dosage recommendations for patients with renal impairment.
Geriatric Patients
No specific dosage recommendations compared to younger adults.
Cautions
Contraindications
Chronic nephritis accompanied by nitrogen retention, until reasonable nitrogen concentrations are attained.
Diseases in Which Rapid Addition to Extracellular Fluids May Be Hazardous
Use 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.
Little danger with small antidiuretic doses of vasopressin to control diabetes insipidus when fluid intake is not excessive.
Hypertonic saline solutions are not indicated unless immediate correction of hyponatremia is required.
Cardiac Effects
In large doses, 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, and myocardial infarction.
Extreme caution, if at all, in patients with vascular disease (especially of the coronary arteries), since even small doses can precipitate angina; AMI risk with large doses.
An ECG should be used to monitor the hormone’s cardiac effects during IV or intra-arterial therapy.
General Precautions
Polyuria
Caution in preoperative and postoperative polyuric patients, since vasopressin requirements may be considerably less than normal.
Monitoring
Monitor fluid intake and output closely, especially in comatose or semicomatose patients.
Monitor electrolyte balance periodically.
Perform ECGs periodically during therapy.
Observe for early signs of water intoxication (e.g., drowsiness, listlessness, headache, confusion, anuria, weight gain) in order to prevent ensuing seizures, coma, and death).
Risks of Intra-arterial Administration
Risk of coronary thrombosis, mesenteric infarction, venous thrombosis, infarction and necrosis of the small bowel, and peripheral emboli resulting from intra-arterial catheterization and infusion into the superior mesenteric artery.
Specific Populations
Pregnancy
Category C.
Although doses sufficient for an antidiuretic effect are not likely to produce tonic uterine contractions that could be deleterious to the fetus or threaten the continuation of the pregnancy, use in pregnant women only when clearly needed.
When administered in ACLS, may decrease blood flow to the uterus; however, the woman must be resuscitated for survival of the fetus.
Lactation
Caution if used in nursing women.
Pediatric Use
Children are particularly sensitive to vasopressin’s effects (e.g., volume/hydration disturbances); exercise caution.
Safety and efficacy as vasopressor therapy for pediatricadvanced life support (PALS) not established; insufficient evidence to make a recommendation for or against routine use during cardiac arrest in pediatric patients.
Geriatric Use
Geriatric patients are particularly sensitive to vasopressin’s effects; exercise caution.
Common Adverse Effects
Adverse effects associated with low doses are infrequent and mild, but increase in frequency and severity with high doses.
Common 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.
Patients can be advised that some of these effects (e.g., blanching of the skin, abdominal cramps, nausea) may be minimized by taking 1 or 2 glasses of water at the time of vasopressin administration.
Interactions
Specific Drugs
Drug
Interaction
Comments
Alcohol
May block the antidiuretic activity of vasopressin in varying degrees
May block the antidiuretic activity of vasopressin in varying degrees
Norepinephrine
May block the antidiuretic activity of vasopressin in varying degrees
Drugs blocking antidiuretic effect
May block the antidiuretic activity of vasopressin in varying degrees
Drugs potentiating antidiuretic effect
May potentiate the antidiuretic response to vasopressin
Ganglionic blocking agents
Ganglionic blocking agents may produce a marked increase in sensitivity to the hormone’s pressor effects
Phenformin
May potentiate the antidiuretic response to vasopressin
Urea
May potentiate the antidiuretic response to vasopressin
Pharmacokinetics
Absorption
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.
Duration
Sub-Q or IM, antidiuretic activity: Variable but effects are usually maintained for 2–8 hours.
Plasma Concentrations
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.
Distribution
Extent
Distributed throughout the extracellular fluid.
Plasma Protein Binding
No evidence of plasma protein binding.
Elimination
Metabolism
The majority of a dose is rapidly destroyed in the liver and kidneys.
Elimination Route
Sub-Q: Approximately 5% of a dose is excreted in urine unchanged after 4 hours.
IV: 5–15% of the total dosage appears in urine.
Half-life
About 10–20 minutes.
Special Populations
Oxytocinase, a circulating enzyme produced early in pregnancy, is capable of cleaving the polypeptide; otherwise, plasma inactivation of vasopressin is negligible.
Stability
Storage
Parenteral
Injection
Store between 15–25°C (59° and 77°F); do not freeze.
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Evaluated by pushing vasopressin through a Y-site over 5 seconds
Actions
Exogenous vasopressin elicits all the pharmacologic responses usually produced by endogenous vasopressin (antidiuretic hormone); primary physiologic role of vasopressin is to maintain serum osmolality within a normal range.
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. 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.
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.
Increases coronary blood flow and the availability of oxygen to the myocardium. A preferred approach in patients with asystoliccardiac arrest would be to administer vasopressin rather than epinephrine initially, reserving epinephrine for patients who do not experience ROSC with the initial vasopressin doses.
In doses greater than those required for antidiuretic effects, vasopressin directly stimulates contraction of smooth muscle V1 receptors.
The vasoconstrictive action of vasopressin is mediated by vascular V1 receptors; the vascular receptors are coupled to phospholipase C, resulting in release of calcium from sarcoplasmic reticulum in smooth muscle cells, leading to vasoconstriction.
Causes vasoconstriction, particularly of capillaries and of small arterioles, resulting in decreased blood flow to the splanchnic, coronary, GI, pancreatic, skin, and muscular systems.
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.
In the intestinal tract, increases peristaltic activity, particularly of the large bowel; also causes an increase in GI sphincter pressure and a decrease in gastric secretion but has no effect on gastric acid concentration. Contraction of smooth muscle of the gallbladder and of the urinary bladder also occurs.
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.
Importance of alerting patients that ceratin adverse effects (e.g., blanching of skin, abdominal cramps, nausea) may be reduced by taking 1 or 2 glasses of water at the time of administration. These side effects are usually not serious and probably will disappear within a few minutes.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Vasopressin
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Parenteral
Injection
20 units/mL*
Pitressin®
Monarch
Vasopressin Injection
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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