Nitrates: Nitroprusside
Indication
Nitroprusside (also known as sodium nitroprusside) is used in adults to treat hypertensive crises, congestive heart failure, and to reduce systemic vascular resistance to generate controlled hypotension during anesthesia. In pediatric patients, it is used to treat hypertension in inpatient settings (e.g., the intensive care unit), in which minute-to-minute control of blood pressure is desired. It is also used to reduce systemic vascular resistance (afterload) after cardiopulmonary bypass surgery.
Mechanism of Action
Like nitroglycerin, nitroprusside is an nitric oxide donor that induces vascular smooth muscle relaxation and, thus, vasodilation. Nitroprusside seems to cause more systemic arterial (at the arteriolar level) dilation than systemic venous dilation. Therefore, it causes more reduction of afterload than preload. Cardiac output increases and aortic and left ventricular impedance are decreased.
Dosing
Neonates (premature and full term) and infants: insufficient data on dosing exist for neonates and infants. In clinical practice, dosing guidelines developed for children are typically followed for infants
Children:
I.V. continuous infusion: initial, 0.5 to l µg/kg/min by continuous I.V. infusion. The dose is titrated to achieve the desired reduction in blood pressure by increasing in increments of 1 µg/kg/min every 20 to 60 minutes. Usual dose is 3 µg/kg/min; maximum dose is 5µg/kg/min Adults:
I.V. continuous infusion: initial, 0.3 to 0.5 µg/kg/min by continuous I.V. infusion. The dose is titrated to achieve the desired effect or until headache or nausea appear by increasing in increments of 0.5 µg/kg/ min. Usual dose is 3 µg/kg/min; maximum dose, 10µg/kg/min
Pharmacokinetics
Onset of action: less than 2 minutes (hypotensive effect)
Half-life: parent drug, less than 10 minutes; thiocyanate, 2.7 to 7 days
Duration: effects cease within 10 minutes of discontinuation of administration
Metabolism: converted by erythrocytes and tissue sulfhydryl group interactions to cyanide, which is then converted to thiocyanate in the liver by the enzyme rhodanase
Elimination: thiocyanate is excreted in the urine
Monitoring Parameters
Blood pressure and heart rate (reflex tachycardia with hypotension) should be monitored continuously. Monitor closely for signs of cyanide and thiocyanate oxicity, including acid-base status, blood cyanide level (especially patients with hepatic dysfunction), and blood thiocyanate level.
Contraindications
Hypersensitivity to nitroprusside or any component, decreased cerebral per-fusion, arteriovenous shunt, unrepaired coarctation of the aorta, high-output congestive heart failure, and congenital optic atrophy.
Adverse Effects
Cardiovascular: excessive hypotensive response, palpitations, reflex tachycardia, substernal chest pain
Respiratory: tachypnea or respiratory distress (from metabolic acidosis caused by cyanide toxicity), hypoxemia
Central nervous system: disorientation, restlessness, headache, psychosis, elevated intracranial pressure
Gastrointestinal: nausea, vomiting
Neuromuscular and skeletal: weakness, muscle spasm
Endocrine/metabolic: thyroid suppression
Hematological: thiocyanate toxicity
Other: diaphoresis, tinnitus
Precautions
Because both the liver and kidney contribute to removal of nitroprusside’s breakdown products, use with caution in patients with either hepatic or renal dysfunction. Patients with renal dysfunction are at increased risk of thiocyanate toxicity, and patients with hepatic dysfunction are at increased risk of cyanide toxicity.
Drug-Drug Interactions
The addition of nitroprusside to treatment regimens that include other agents that reduce blood pressure can lead to excessive hypotension.
Poisoning Information
Toxicity from nitroprusside can occur either by cyanide toxicity or thiocyanate toxicity. Signs and symptoms of excessive cyanide levels include metabolic acidosis (with increased blood lactate), increased mixed venous oxygen saturation, tachycardia, altered consciousness, coma, convulsions, and an almond-like smell on the breath. Thiocyanate toxicity is manifested by psychosis, hyperreflexia, confusion, weakness, tinnitus, dilated pupils, seizures, and coma. Patients with hepatic dysfunction or anemia should have blood cyanide levels measured. Patients receiving nitroprusside doses of at least 4 µg/kg/min I.V. lasting longer than 3 days, or with renal dysfunction, should have blood thiocyanate levels measured.
If toxicity develops, in addition to discontinuing nitroprusside administration, therapies include:
Table. Reference ranges for blood thiocyanate and cyanide levels
| Thiocyanate | Cyanide |
| Therapeutic: 6-29 µg/mL | Normal: < 0.2 µg/mL |
| Toxic:35-100 µg/mL | Normal (smoker): <0.4µg/mL |
| Fatal: > 200 µg/mL | Toxic: 2 µg/mL |
| Potentially lethal: 3 g/mL |
1. Support respiration and supply oxygen.
2. Antidotal therapy with sodium nitrate 300 mg I.V. and sodium thiosulfate 12.5 grams I.V. (adult doses), and, if needed:
3. Dialysis (thiocyanate is removed by dialysis).
Compatible Diluents/Administration
Nitroprusside should be prepared for I.V. administration by dilution in D5W. Because light causes nitroprusside to break down to form cyanide, it must be protected from light (e.g., by wrapping mixture in aluminum foil). Use only if the mixed solution remains clear; slight discoloration (e.g., brownish, light orange) is common, but blue discoloration suggests break down to cyanide. Discard any solution suspected of degradation and prepare a fresh mixture. The solution is stable at room temperature for up to 24 hours if protected from light.
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