Vasopressin and Its Analogs
Aqueous Vasopressin
Aqueous vasopressin (arginine vasopressin, AVP) is a synthetic form of the endogenous antidiuretic hormone used in critical care settings for vasopressor support and specific endocrine conditions.
Key Points
- Generic Name: Vasopressin Injection, USP
- Available Forms: 20 units/mL
- Route: Intravenous only
- Half-life: 10-20 minutes
- Onset: 15-20 minutes
- Duration: 2-8 hours
Clinical Pharmacology
Receptor Activity:
- V1 (Vasopressor) Effects:
- Vascular smooth muscle contraction
- Increased systemic vascular resistance
- Increased mean arterial pressure
- Selective splanchnic vasoconstriction
- V2 (Antidiuretic) Effects:
- Increased water reabsorption in collecting ducts
- Decreased urine output
- Increased urine osmolality
- Release of von Willebrand factor
- V3 (Pituitary) Effects:
- ACTH release
- Endocrine modulation
Pharmacokinetics:
- Distribution: Minimal protein binding
- Metabolism: Hepatic and renal vasopressinases
- Elimination: Renal excretion
- Bioavailability: 100% (IV administration)
Clinical Indications
Primary Indications:
- Shock States:
- Vasodilatory shock
- Septic shock
- Post-cardiotomy shock
- Neurogenic shock
- Cardiac Arrest:
- As alternative to epinephrine
- Post-resuscitation support
- Vasoplegic Syndrome:
- Post-cardiopulmonary bypass
- Post-transplant
Secondary Indications:
- Portal Hypertension
- Gastrointestinal Bleeding
- Diabetes Insipidus (acute management)
- Catecholamine-resistant shock
Dosing & Administration
Standard Dosing Protocols:
- Shock States:
- Initial: 0.0003-0.002 units/kg/min
- Maximum: 0.008 units/kg/min
- Typical range: 0.0003-0.005 units/kg/min
- Cardiac Arrest:
- Bolus: 0.4-1 units/kg
- Maximum single dose: 40 units
- Diabetes Insipidus:
- Initial: 0.0003 units/kg/hour
- Titrate based on urine output
Administration Guidelines:
- Preparation:
- Central line preferred
- Compatible with normal saline or D5W
- Avoid mixing with other medications
- Titration:
- Based on MAP targets
- Monitor response every 15-30 minutes
- Adjust by 0.0001-0.0002 units/kg/min
Monitoring & Safety
Clinical Monitoring:
- Hemodynamic Parameters:
- Blood pressure (continuous)
- Heart rate and rhythm
- Central venous pressure
- Cardiac output (if available)
- End-organ Perfusion:
- Urine output
- Mental status
- Skin perfusion
- Lactate levels
- Laboratory Monitoring:
- Serum electrolytes
- Blood glucose
- Cardiac markers
- Coagulation profile
Adverse Effects:
- Common:
- Digital/peripheral ischemia
- Cardiac arrhythmias
- Splanchnic vasoconstriction
- Hyponatremia
- Serious:
- Myocardial ischemia
- Mesenteric ischemia
- Skin necrosis
- Thrombotic events
Clinical Protocols
Shock Management:
- First-line Vasopressor:
- Norepinephrine preferred
- Add vasopressin at 0.0003 units/kg/min
- Consider earlier in catecholamine-resistant shock
- Weaning Protocol:
- Maintain MAP >65 mmHg
- Wean norepinephrine first
- Gradual vasopressin taper
Special Circumstances:
- Cardiac Arrest:
- Consider after first epinephrine dose
- May improve ROSC
- Post-operative Care:
- Early initiation for vasoplegia
- Monitor cardiac function closely
Precautions & Considerations
Contraindications:
- Absolute:
- Chronic renal failure
- Severe coronary artery disease
- Known vasopressin hypersensitivity
- Relative:
- Peripheral vascular disease
- Seizure disorders
- Asthma
Special Populations:
- Neonates:
- Limited data available
- Close monitoring required
- Consider lower starting doses
- Cardiac Surgery:
- May be beneficial in vasoplegia
- Monitor coronary perfusion
Vasopressin Analogs
Vasopressin analogs are synthetic derivatives of the natural antidiuretic hormone (ADH) that regulate water homeostasis and vascular tone.
Key Points
- Major Classes:
- Desmopressin (DDAVP)
- Terlipressin
- Vasopressin
- Available Forms:
- Intranasal spray
- Oral tablets
- Sublingual formulation
- Injectable solution
Types & Formulations
1. Desmopressin (DDAVP)
- Formulations:
- Nasal spray (10 mcg/spray)
- Oral tablets (0.1, 0.2 mg)
- Sublingual lyophilisate (60, 120, 240 mcg)
- Injectable (4 mcg/mL)
- Duration: 8-24 hours
- Selectivity: V2 receptor selective
2. Terlipressin
- Formulations:
- Injectable solution
- Powder for reconstitution
- Duration: 4-6 hours
- Selectivity: V1/V2 receptor activity
3. Vasopressin
- Formulations:
- Injectable solution
- Duration: 30-60 minutes
- Selectivity: V1/V2 receptor activity
Mechanism of Action
- V1 Receptor Effects:
- Vasoconstriction
- Platelet aggregation
- Glycogenolysis
- Uterine contraction
- V2 Receptor Effects:
- Increased water reabsorption
- Insertion of aquaporin-2 channels
- von Willebrand factor release
- Factor VIII release
- V3 Receptor Effects:
- ACTH release
- Prolactin secretion
Clinical Indications
Primary Indications:
- Central Diabetes Insipidus:
- Congenital
- Acquired (post-surgical, trauma)
- Idiopathic
- Nocturnal Enuresis:
- Primary bedwetting
- Age ≥5 years
- After behavioral interventions
- Bleeding Disorders:
- Mild von Willebrand disease
- Mild hemophilia A
- Platelet function defects
Other Uses:
- Shock States:
- Vasodilatory shock
- Septic shock
- Post-cardiotomy shock
- Gastrointestinal Bleeding
- Hepatorenal Syndrome
Dosing & Administration
Desmopressin Dosing:
- Central Diabetes Insipidus:
- Oral: 0.05-0.4 mg twice daily
- Intranasal: 5-20 mcg once or twice daily
- Sublingual: 60-240 mcg daily
- Nocturnal Enuresis:
- Oral: 0.2-0.4 mg at bedtime
- Intranasal: 10-40 mcg at bedtime
- Sublingual: 120-240 mcg at bedtime
- Coagulation Disorders:
- 0.3 mcg/kg IV/SC
- Maximum: 20 mcg
Terlipressin Dosing:
- Variceal Bleeding:
- 2 mg IV every 4 hours
- Reduce to 1 mg after bleeding control
Vasopressin Dosing:
- Shock:
- 0.0003-0.002 units/kg/min
- Titrate to effect
Monitoring & Safety
Required Monitoring:
- Clinical Parameters:
- Fluid balance
- Urine output
- Vital signs
- Mental status
- Weight changes
- Laboratory Monitoring:
- Serum sodium
- Serum osmolality
- Urine osmolality
- Electrolytes
Adverse Effects:
- Common:
- Hyponatremia
- Fluid retention
- Headache
- Nausea
- Abdominal pain
- Serious:
- Water intoxication
- Seizures
- Thrombotic events
- Hypertension
Contraindications & Precautions
Absolute Contraindications:
- Hyponatremia
- SIADH
- Severe renal insufficiency
- Von Willebrand Type IIB
- Unstable coronary artery disease
Relative Contraindications:
- Cardiac insufficiency
- Hypertension
- History of thrombosis
- Fluid overload states
Special Precautions:
- Risk Management:
- Fluid restriction during treatment
- Regular electrolyte monitoring
- Avoid evening fluids in enuresis
- Dose adjustment in renal impairment
