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Introduction

  1. Pharmacology. Nitroprusside is an ultra-short-acting, titratable parenteral hypotensive agent that acts by directly relaxing vascular smooth muscle as a nitric oxide donor leading to arterial and venous dilation. The effect is more marked in patients with hypertension. A small increase in heart rate may be observed in hypertensive patients. Intravenous administration produces a nearly immediate onset of action, with a duration of effect of 1-10 minutes. Resistance may occur with high renin activity. Nitroprusside is metabolized rapidly, with a serum half-life of about 1-2 minutes. Cyanide is produced during metabolism and is converted to the less toxic thiocyanate. Thiocyanate has a half-life of 2-3 days and accumulates in patients with renal insufficiency.
  2. Indications
    1. Rapid control of severe hypertension (eg, in patients with stimulant intoxication or monoamine oxidase inhibitor toxicity).
    2. Arterial vasodilation in patients with ergot-induced peripheral arterial spasm.
  3. Contraindications
    1. Compensatory hypertension—for example, in patients with increased intracranial pressure (eg, hemorrhage or mass lesion) or patients with coarctation of the aorta. If nitroprusside is required in such patients, use with extreme caution.
    2. Use with caution in patients with hepatic insufficiency because cyanide metabolism may be impaired.
  4. Adverse effects
    1. Nausea, vomiting, headache, and sweating may be caused by excessively rapid lowering of blood pressure.
    2. Cyanide toxicity, manifested by altered mental status and metabolic (lactic) acidosis, may occur with rapid high-dose infusion (10-15 mcg/kg/min) for periods of 1 hour or longer. Patients with depleted thiosulfate stores (eg, malnourished) may have elevated cyanide levels at lower infusion rates. Continuous intravenous infusion of hydroxocobalamin, 25 mg/h, or thiosulfate has been used to limit cyanide toxicity. If severe cyanide toxicity occurs, discontinue the nitroprusside infusion and consider antidotal doses of thiosulfate and sodium nitrite or high-dose hydroxocobalamin.
    3. Thiocyanate intoxication, manifested by disorientation, delirium, muscle twitching, and psychosis, may occur with prolonged high-dose nitroprusside infusions (usually ≥3 mcg/kg/min for ≥48 hours), particularly in patients with renal insufficiency (may occur at rates as low as 1 mcg/kg/min). Thiocyanate production is also enhanced by coadministration of sodium thiosulfate. Monitor thiocyanate levels if the nitroprusside infusion lasts more than 1-2 days; toxicity is associated with thiocyanate levels of 50 mg/L or greater. Usually treat by lowering the infusion rate or discontinuing the use of nitroprusside. Thiocyanate is removed effectively by hemodialysis.
    4. Rebound hypertension may be observed after sudden discontinuance.
    5. Methemoglobinemia may be observed in patients receiving more than 10 mg/kg but is typically not severe.
    6. Use in pregnancy. FDA Category C (indeterminate Introduction). It may cross the placenta and may affect uterine blood flow; however, it has been used successfully in pregnant women.
  5. Drug or laboratory interactions. A hypotensive effect is potentiated by other antihypertensive agents and inhalational anesthetics.
  6. Dosage and method of administration
    1. Use only in an emergency or intensive care setting with the capability of frequent or continuous blood pressure monitoring.
    2. Dilute the 50-mg vial (2 mL, 25 mg/mL) of sodium nitroprusside with 5% dextrose to a volume of 250, 500, or 1,000 mL to achieve a concentration of 200, 100, or 50 mcg/mL, respectively. Protect the solution from light to avoid photodegradation (as evidenced by a color change) by covering the bottle and tubing with paper or aluminum foil.
    3. Start with an intravenous infusion rate of 0.3 mcg/kg/min; use a controlled infusion device and titrate to desired effect. The average dose is 3 mcg/kg/min in children and adults (range, 0.5-10 mcg/kg/min).
      1. The maximum rate should not exceed 10 mcg/kg/min to avoid the risk for acute cyanide toxicity. If there is no response after 10 minutes at the maximum rate, discontinue the infusion and use an alternative vasodilator (eg, phentolamine).
      2. Sodium thiosulfate has been added in a ratio of 10-mg thiosulfate to 1-mg nitroprusside to reduce or prevent cyanide toxicity.