DESCRIPTION

Nitroprusside is a short-acting parenteral antihypertensive agent.

FORMS AND USES

Most commonly used to treat hypertension. Sodium nitroprusside is available in 50-mg vials.

MECHANISM OF ACTION

• Nitroprusside is a direct-acting vasodilator.
• The onset of hypotensive effect occurs within 1 minute of intravenous administration.
• Hypotensive effects may persist from 3 to 5 minutes following discontinuation of the infusion.
• Oral administration does not produce hypotension.
• Nitroprusside contains five cyanide groups.
  • Metabolism releases these groups slowly.
  • Under normal conditions, the enzyme rhodanese can easily detoxify cyanide. However, cyanide and thiocyanate may accumulate and produce toxicity if the rate of cyanide production overwhelms the activity of rhodanese or if thiocyanate elimination is impaired.

DRUG AND DISEASE INTERACTIONS

• Nitroprusside can potentiate hypotension caused by other drugs.
• Geriatric patients need close monitoring for the development of cyanide toxicity due to age-related renal and hepatic insufficiency.
• Older patients may be more sensitive to hypotensive effects.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Due to risk of cyanide toxicity, nitroglycerin is preferred in the treatment of life-threatening hypertension in pregnancy.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Persistent severe hypertension (diastolic pressure greater than 130 mm Hg and not responsive to sedation) or hypertension complicated by end-organ effects (CNS bleed, chronic heart failure, myocardial ischemia, congestive heart failure, aortic dissection).
• Induction of controlled hypotension in surgery.
• Treatment of peripheral ischemia secondary to ergot alkaloids and sympathomimetic agents.
• Treatment of myocardial ischemia (may cause coronary steal syndrome), aortic stenosis, or pulmonary hypertension.

CONTRAINDICATIONS

Treatment of hypertension that is compensatory (ventricular septal defect, arteriovenous shunting, coarctation of the aorta) precludes use of nitroprusside.

ADVERSE EFFECTS

• Hypotension is common and usually responds promptly to discontinuation of infusion.
• Nausea, vomiting, muscle twitching, headache, and lightheadedness may occur.
• Cyanide toxicity may result.
  • High-dose nitroprusside therapy (less than 2 µg/kg/min is not usually associated with toxicity) is a risk factor for cyanide toxicity, especially when treatment involves more than 3 to 4 µg/kg/min for 12 to 24 hours, more than 5 µg/kg/min for several hours, or more than 50 mg infused over 6 hours.
  • Prolonged infusion over days is a risk factor for cyanide toxicity.
  • Malnutrition may reduce endogenous levels of thiosulfate and thereby allow accumulation of cyanide.
  • Whole-blood cyanide levels correlate poorly with toxicity because they may not accurately reflect tissue cyanide concentrations.
  • Some clinicians recommend following cyanide levels as a general guide for toxicity:
    • Less than 0.2 µg/ml is unlikely to cause toxicity.
    • 0.5 to 1.0 µg/ml may cause mild symptoms.
    • 1.0 to 2.5 µg/ml is associated with change in mental status.
    • More than 2.5 µg/ml may produce life-threatening toxicity.
  • Thiocyanate levels should be monitored during high-dose nitroprusside therapy.
    • More than 5 to 10 µg/ml is considered an elevated level.
    • More than 60 µg/ml is associated with an increased incidence of thiocyanate toxicity.
• Methemoglobinemia has been reported, with increased incidence in patients with hemoglobin M, hereditary methemoglobinemia (NADH-methemoglobin reductase deficiency), or concomitant exposure to other agents capable of causing methemoglobinemia.
• Hypothyroidism. Thiocyanate inhibits iodide production by thyroid and may produce hypothyroidism if used for prolonged periods.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

PREPARATION

• Nitroprusside solution needs protection from photodegradation with an opaque covering such as aluminum foil.
  • Photodegradation will produce marked dark discoloration.
  • Intravenous tubing does not need to be protected from light.
• Nitroprusside powder is initially reconstituted using 2 to 3 ml of D5W or sterile water (without bacteriostatic agents) and then diluted to 250 ml or greater volume with D5W.
• Blood pressure must be continuously monitored; intraarterial blood pressure monitoring is recommended.
• Baseline renal and hepatic function should be checked.

ADMINISTRATION

• Nitroprusside is administered by continuous intravenous infusion with an infusion pump to regulate the infusion rate.
  • Direct intravenous push or gravity-driven infusion should not be used.
  • The initial dose for adults and children is 0.5 µg/kg/min by continuous intravenous infusion.
  • Infusion is increased by 0.25 to 0.50 µg/kg/min every 5 minutes, titrating dose to the desired effect.
• Cessation of nitroprusside therapy should be gradual in order to avoid rebound hypertension.
• Administration of large doses over prolonged periods carries the risk of cyanide toxicity.
  • The risk of cyanide toxicity is doserelated, especially in patients with either renal or hepatic insufficiency.
  • Concurrent administration of sodium thiosulfate may prevent cyanide toxicity.
    • For concurrent sodium thiosulfate therapy (see SECTION III, Cyanide Antidote Package chapter), each 100 mg of sodium nitroprusside should be mixed with 1 g of sodium thiosulfate (10 ml of 10% sodium thiosulfate).
    • Very high rates of nitroprusside infusion are possible by using this admixture.
    • The mixture is stable for 7 days if protected from light.

Section Outline:

• PREPARATION
• ADMINISTRATION

• Ambient light will degrade nitroprusside solution if not protected from light.
• It is difficult to recognize the development of cyanide toxicity, especially in patients with renal insufficiency and in patients treated for a prolonged period.
• Because sodium thiosulfate has a very low rate of adverse effects, the clinician should not wait for laboratory confirmation of cyanide toxicity before administering sodium thiosulfate to the patient when cyanide toxicity is suspected.
• Failure to infuse sodium thiosulfate concurrently and prophylactically when patients are receiving high doses for prolonged durations increases the risk of cyanide toxicity.
• Tachyphylaxis to nitroprusside hypotensive effect is rare, but has been reported.
  • If the hypotensive effect of nitroprusside diminishes, the clinician should ensure that the drug is actually infusing.
  • If tachyphylaxis is suspected, treatment with another antihypertensive agent should be considered.
• If the patient has renal insufficiency, the nitroprusside infusion is administered in the standard manner; however, the patient is at increased risk of developing toxicity.
  • The clinician must monitor closely for the development of cyanide toxicity because thiocyanate renal clearance is impaired.
  • Thiocyanate can be removed by either hemodialysis or peritoneal dialysis.
• If the patient has hepatic insufficiency, nitroprusside is administered in the standard manner; however, the clinician must monitor closely for the development of cyanide toxicity because cyanide conversion to thiocyanate by hepatic rhodanese may be impaired.

Poisoning by agents primarily acting in the smooth and skeletal muscles and respiratory system.

See Also: SECTION III, Cyanide Antidote Package chapter; and SECTION IV, Cyanide chapter.

RECOMMENDED READING

Curry SC, Arnold-Capell P. Nitroprusside, nitroglycerin, and angiotensin converting enzyme inhibitors. Crit Care Clin 1991;7:555-581.

Rindone JP, Sloane EP. Cyanide toxicity from sodium nitroprusside: risks and management. Ann Pharmacother 1992;26:515-519.

Author: Edwin K. Kuffner

Reviewer: Katherine M. Hurlbut