Sodium Nitroprusside (Monograph)

Brand name: Nitropress
Drug class: Direct Vasodilators

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Vasodilating and hypotensive agent.

Uses for Sodium Nitroprusside

Hypertensive Crises

For immediate reduction of BP in hypertensive emergencies. Administer with other longer-acting hypotensive agents to minimize the duration of nitroprusside therapy. Use in carefully selected patients because of potential for serious toxicity (see Cautions).

Hypertensive emergencies may be associated with hypertensive encephalopathy, MI, unstable angina pectoris, acute left ventricular failure with pulmonary edema, acute renal failure, acute ischemic stroke, eclampsia, or aortic dissection.

Do not use in patients with compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta). (See Contraindications under Cautions.)

Congestive Heart Failure

Management of acute decompensated (e.g, congestive) heart failure.

May be considered an adjunct to diuretic therapy for relief of dyspnea in patients hospitalized for acutely decompensated heart failure who do not have symptomatic hypotension.

Particularly useful in severe heart failure caused by regurgitant valvular lesions of aortic insufficiency and mitral regurgitation; also may be useful in management of heart failure in patients with severe pulmonary congestion and hypertension.

Do not use in patients with acute congestive heart failure associated with reduced peripheral vascular resistance. (See Contraindications under Cautions.)

Controlled Hypotension during Surgery

Used to produce controlled hypotension to reduce bleeding during surgery. Do not use in patients with inadequate cerebral circulation or in patients requiring emergency surgery who are near death. (See Contraindications under Cautions.)

Acute MI

Vasodilators such as sodium nitroprusside also have been used to improve cardiac output in patients with left ventricular failure and low cardiac output after acute MI^{† [off-label]}.

An inotropic agent (e.g., dobutamine) is used initially to improve myocardial contractility and cardiac output; if BP permits, afterload-reducing agents may be added to decrease cardiac work and pulmonary congestion.

Nitroglycerin is the preferred vasodilator in patients with acute MI because of its ability to reduce ischemia by reducing left ventricular preload and increasing coronary blood flow.

Related/similar drugs

lisinopril, metoprolol, furosemide, carvedilol, spironolactone, diltiazem, hydralazine

Sodium Nitroprusside Dosage and Administration

General

Hypertensive Crisis

• Adults with a hypertensive emergency and a compelling indication—pheochromocytoma crisis: Reduce SBP to <140 mm Hg during the first hour.

• Adults with a hypertensive emergency and a compelling indication—acute aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.

• Initial goal of IV therapy in adults who have a hypertensive emergency without a compelling indication is to reduce SBP by ≤25% within the first hour, followed by further reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours, avoiding excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia. If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.

• Children and adolescents: Some experts suggest reducing BP by ≤25% of the planned reduction over the first 8 hours, with remainder of planned reduction over next 12–24 hours.

Administration

Administer by IV infusion only.

Administer in a setting with equipment and personnel available to continuously monitor BP.

Because of potential for toxicity, administer for the shortest possible duration.

IV Administration

Administer by IV infusion using a controlled-infusion device (i.e., infusion pump), not an IV infusion device regulated only by gravity and mechanical clamp, to allow precise measurement of flow rate.

The manufacturer states that no other drug should be admixed in the sodium nitroprusside solution.

Dilution

Injection concentrate (25 mg/mL) must be further diluted prior to IV infusion. Dilute contents of one vial (50 mg) in 250–1000 mL of 5% dextrose injection. Vials are for single use only.

Protect from light by promptly wrapping the container in aluminum foil or other opaque material; it is not necessary to cover the infusion drip chamber or tubing.

Rate of Administration

Adjust rate to maintain the desired hypotensive effect, determined by continuous monitoring of BP, using a continually reinflated sphygmomanometer or, preferably, an intra-arterial pressure sensor.

When sodium nitroprusside is used in heart failure, titrate rate based on results of invasive hemodynamic monitoring and urine output.

Standardize 4 Safety

Standardized concentrations for sodium nitroprusside have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web] .

Dosage

Pediatric Patients

Hypertensive Crises, Controlled Hypotension during Surgery

IV

Manufacturer recommends initial dosage of 0.3 mcg/kg per minute; gradually titrate upward every few minutes until adequate BP control is achieved or maximum recommended infusion rate of 10 mcg/kg per minute is reached. Some experts recommend initial infusion rate of 0–3 mcg/kg per minute in children and adolescents with severe hypertension and life-threatening symptoms. Manufacturer states that average effective IV dosage is about 3 mcg/kg (range of 0.5–10 mcg/kg) per minute.

Infusion duration should be as short as possible; discontinue infusion immediately if adequate reduction in BP is not achieved within 10 minutes in patients receiving maximum recommended dosage of 10 mcg/kg per minute.

Prolonged infusions should not exceed 3 mcg/kg per minute to prevent thiocyanate (byproduct of sodium nitroprusside metabolism) concentrations from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.

Adults

Hypertensive Crises, Controlled Hypotension during Surgery

IV

Manufacturer recommends initial dosage of 0.3 mcg/kg per minute; gradually titrate upward every few minutes until adequate BP control is achieved or maximum recommended infusion rate of 10 mcg/kg per minute is reached. Alternatively, some experts recommend initial dosage of 0.3–0.5 mcg/kg per minute; increase infusion rate in increments of 0.5 mcg/kg per minute to achieve BP control, up to a maximum of 10 mcg/kg per minute. Manufacturer states that average effective IV dosage is about 3 mcg/kg (range of 0.5–10 mcg/kg) per minute.

Discontinue immediately if adequate reduction in BP is not achieved within 10 minutes in patients receiving the maximum recommended infusion rate of 10 mcg/kg per minute.

Prolonged infusions should not exceed 3 mcg/kg per minute to prevent thiocyanate (byproduct of sodium nitroprusside metabolism) concentrations from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.

Congestive Heart Failure

IV

Initially, 0.3 mcg/kg per minute; titrate every few minutes and until desired effect is achieved or maximum recommended infusion rate of 10 mcg/kg per minute is reached. Average effective dosage is about 3 mcg/kg (range of 0.5–10 mcg/kg) per minute.

Adjust infusion rate based on results of invasive hemodynamic monitoring and urine output. Increase infusion rate until cardiac output is no longer increasing, systemic BP cannot be further reduced without compromising vital organ perfusion, or maximum recommended infusion rate is reached, whichever occurs first.

While specific hemodynamic goals must be tailored to the clinical situation, improvements in cardiac output and left ventricular filling pressure must not be achieved at the expense of undue hypotension and consequent hypoperfusion.

Prolonged infusions should not exceed 3 mcg/kg per minute to prevent thiocyanate (byproduct of sodium nitroprusside metabolism) concentrations from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.

Prescribing Limits

Pediatric Patients

Hypertensive Crises, Controlled Hypotension during Surgery

IV

Maximum 10 mcg/kg per minute.

Adults

Hypertensive Crises, Congestive Heart Failure, Controlled Hypotension during Surgery

IV

Maximum 10 mcg/kg per minute.

Special Populations

Renal Impairment

Clearance of thiocyanate may be decreased in patients with renal failure. Prolonged infusions should not exceed 1 mcg/kg per minute to prevent accumulation of thiocyanate to neurotoxic levels.

Cautions for Sodium Nitroprusside

Contraindications

• Treatment of compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta).

• Controlled hypotension during surgery in patients with inadequate cerebral circulation.

• Use during emergency surgery in patients near death.

• Congenital (Leber’s) optic atrophy or tobacco amblyopia (associated with absent or deficient thiosulfate sulfurtransferase; patients have unusually high cyanide to thiocyanate ratios). (See Cyanide Toxicity under Cautions.)

• Treatment of acute heart failure associated with reduced peripheral vascular resistance (e.g., high-output heart failure as seen in endotoxic sepsis).

• Concomitant use with PDE type 5 inhibitors (e.g., sildenafil) or soluble guanylate cyclase stimulators (e.g., riociguat). (See Interactions.)

Warnings/Precautions

Warnings

Excessive Hypotension

Slightly excessive infusion rates can result in profound hypotension; subsequent hemodynamic changes can result in various associated symptoms or BP may decrease to the point where perfusion of vital organs may be compromised. (See Boxed Warning.)

This reaction is self-limiting within 1–10 minutes following discontinuance of the infusion; place patient in Trendelenburg’s position during this time to maximize venous return.

If BP does not normalize within a few minutes, sodium nitroprusside may not be the cause of the hypotension and another cause should be sought.

Cyanide Toxicity

Infusion at rates >2 mcg/kg per minute generate cyanide ion (CN^-) in amounts greater than can be effectively buffered by the methemoglobin normally present in the body. (See Boxed Warning.)

The capacity of the buffering system is exhausted by the CN^- produced by 500 mcg/kg of sodium nitroprusside; this amount is administered in <1 hour when the drug is administered at 10 mcg/kg per minute.

The actual frequency of clinically important cyanide toxicity not established.

Most cases occurred with prolonged use or high dosages; however, elevated cyanide levels, metabolic acidosis, and marked clinical deterioration reported occasionally in patients receiving recommended rates of infusion for only a few hours, and in 1 case, for only 35 minutes.

Toxic effects of cyanide may be rapid, serious, and fatal; toxicity may manifest as venous hyperoxemia (secondary to the inability of tissues to extract oxygen from erythrocytes, with resultant bright red venous blood), lactic acidosis, air hunger, confusion, and death.

Monitor acid-base balance and venous oxygen concentrations; these tests may indicate cyanide toxicity.

Hypertensive patients and those receiving other antihypertensive agents may be more sensitive to the effects of sodium nitroprusside than healthy individuals.

Sodium thiosulfate has been administered with sodium nitroprusside at infusion rates 5–10 times that of the sodium nitroprusside to accelerate the metabolism of cyanide; coadministration of these agents has not been extensively researched and further study is needed.

Caution advised; avoid prolonged or excessive dosages of sodium nitroprusside with sodium thiosulfate, since thiocyanate toxicity and/or hypovolemia may result. The same precautions and contraindications apply to this method of administration as to the administration of sodium nitroprusside alone.

General Precautions

Effects on Intracranial Pressure

Sodium nitroprusside can increase intracranial pressure.

Use with caution in patients with increased intracranial pressure.

Use during Surgery

Tolerance to loss of blood, anemia, and hypovolemia may be decreased when used for controlled hypotension during surgery.

If possible, correct preexisting anemia and hypovolemia prior to use.

Use with extreme caution in patients who are especially poor surgical risks.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women; not known whether sodium nitroprusside can cause fetal harm when administered during pregnancy. Use during pregnancy only when clearly needed. Some experts state that the drug is contraindicated in women with preeclampsia or eclampsia.

Lactation

Not known whether sodium nitroprusside or its metabolites are distributed into milk; discontinue nursing or the drug.

Pediatric Use

Has been used in pediatric patients <17 years of age, including neonates, for reduction of BP. In 2 pediatric studies, the drug produced similar effects on mean arterial pressure (MAP) in all age groups, and no novel safety issues were noted.

Hepatic Impairment

Caution in patients with hepatic impairment.

Renal Impairment

Thiocyanate may accumulate in patients with renal impairment; monitor for thiocyanate toxicity (e.g., neurotoxic effects). (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Excessive hypotension, cyanide toxicity.

Other adverse effects include methemoglobinemia (usually observed only in patients who have received >10 mg/kg of sodium nitroprusside) and thiocyanate toxicity (mildly neurotoxic at serum concentrations of 60 mcg/mL and life-threatening at concentrations of 200 mcg/mL).

Drug Interactions

Specific Drugs

Sodium Nitroprusside Pharmacokinetics

Absorption

Onset

Immediate reduction in BP.

Duration

BP begins to rise immediately when infusion is slowed or stopped; BP returns to pretreatment levels within 1–10 minutes.

Distribution

Extent

Rapidly distributed.

Elimination

Metabolism

Sodium nitroprusside is metabolized by combination with hemoglobin to form cyanmethemoglobin and cyanide.

Essentially all cyanide in the blood is bound to methemoglobin until intraerythrocytic methemoglobin is saturated.

Cyanide is enzymatically converted to thiocyanate by thiosulfate sulfurtransferase (a mitochondrial enzyme). This enzyme normally is present in excess quantities; the rate-limiting step in the conversion to thiocyanate is the availability of sulfur donors (e.g., thiosulfate, cystine, cysteine).

Cyanide not otherwise removed binds to cytochromes.

Elimination Route

Eliminated principally in urine as thiocyanate. Some cyanide is expired as hydrogen cyanide.

Half-life

Sodium nitroprusside: Circulation half-life: 2 minutes.

Thiocyanate: 3 days.

Special Populations

Half-life of thiocyanate is increased in patients with renal failure.

Stability

Storage

Parenteral

Injection

20–25°C; protect from light by storing in the carton.

If properly protected from light, diluted solutions are stable for 24 hours.

Sodium nitroprusside solution can be inactivated by reactions with trace contaminants; products of these reactions are often blue, green, or red and are much brighter than the very faint brownish tint of freshly prepared unreacted sodium nitroprusside solutions. Discard discolored solutions or solutions with visible particulate matter.

Actions

• Potent direct arterial and venous dilator.

• The hypotensive action results from peripheral vasodilation caused by a direct action on vascular smooth muscle.

• Direct vasodilation causes decreases in right and left ventricular filling (preload) resulting in relief of pulmonary congestion and reduced left ventricular volume and pressure. Arteriolar relaxation causes decreases in peripheral arterial resistance (afterload) resulting in enhanced systolic emptying with reduced left ventricular volume and wall stress and reduced myocardial oxygen consumption.

• May exert a direct coronary vasodilator effect.

• Induces renal vasodilation generally proportional to decreases in systemic BP with no appreciable changes in renal blood flow or GFR.

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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