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Sodium Nitroprusside

Class: Direct Vasodilators
VA Class: CV490
CAS Number: 13755-38-9
Brands: Nitropress

Warning(s)

  • Thoroughly review the package insert before administration.b

  • Dilution
  • After reconstitution, sodium nitroprusside is not suitable for direct injection; must be diluted further with 5% dextrose injection before infusion.b

  • Acid-base balance and venous oxygen concentrations should be monitored and may indicate cyanide toxicity; these tests alone should not be relied upon to guide therapy.b

  • Hypotension
  • Can produce precipitous decreases in blood pressure; profound hypotension can lead to irreversible ischemic injury or death.b

  • Administer in a setting with equipment and personnel available to continuously monitor blood pressure.b

  • Cyanide Intoxication
  • Administration (except when used for short periods of time or at low infusion rates [e.g., ≤2 mcg/kg per minute or slower]) can result in the production of clinically important levels of cyanide ion, which can reach toxic or potentially lethal concentrations.b

  • Infusions at the maximum recommended rate of 10 mcg/kg per minute should never last longer than 10 minutes; if after 10 minutes the blood pressure has not been adequately controlled, the infusion should be immediately discontinued.b

Introduction

Vasodilating and hypotensive agent.a b 207

Uses for Sodium Nitroprusside

Hypertensive Crises

For immediate reduction of blood pressure in hypertensive crises (hypertensive emergencies).b 204 207 Administer with other longer-acting hypotensive agents to minimize the duration of nitroprusside therapy.b

Can be used for most hypertensive emergencies (e.g., hypertensive encephalopathy, MI, unstable angina pectoris, pulmonary edema, preeclampsia, stroke, head trauma, life-threatening arterial bleeding, aortic dissection).204 207

May be considered in the treatment of hypertensive emergencies associated with stimulant (e.g., amphetamines, methamphetamines, cocaine, phencyclidine, ephedrine) toxicity.207

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Caution if high intracranial pressure or azotemia is present.204

Acute severe hypertension in preeclampsia (e.g., persistent diastolic blood pressures of ≥105–110 mm Hg): Other antihypertensives (e.g., hydralazine) preferred; sodium nitroprusside reserved for treatment failures.204

Ischemic stroke: Clinical trials do not support immediate antihypertensive therapy in these patients.204

Contraindicated in compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta).b (See Contraindications under Cautions.)

Heart Failure and Low-Output Syndromes

Management of acute CHF.b 207

Particularly useful in severe heart failure caused by regurgitant valvular lesions of aortic insufficiency and mitral regurgitation.206

Also particularly useful for afterload reduction to unload the left and subsequently right ventricle when left ventricular dysfunction is accompanied by right ventricular ischemia.b 202 Monitoring intra-arterial pressure is useful.202

Management of low-output syndromes associated with acute MI; in many cases, other drugs (e.g., nitroglycerin, norepinephrine, dopamine, dobutamine) are preferred.202

In acute MI complicated by CHF, nitroglycerin is the preferred vasodilator.202

Not indicated for the treatment of CHF associated with reduced peripheral vascular resistance.b (See Contraindications under Cautions.)

Controlled Hypotension

Used to produce controlled hypotension to reduce bleeding during surgery.b

Sodium Nitroprusside Dosage and Administration

Administration

Administer by IV infusion only.b

Administer in a setting with equipment and personnel available to continuously monitor blood pressure.b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using a controlled-infusion device to allow precise measurement of flow rate.b

When used for the management of acute severe hypertension in preeclampsia, administer before induction of labor.204

Reconstitution

Dissolve 50 mg of sodium nitroprusside in 2–3 mL of 5% dextrose injection or sterile water for injection (without preservative).a HID Bacteriostatic water for injection should not be used because preservatives increase the rate of nitroprusside decomposition.a

Alternatively, reconstitute ADD-Vantage vials containing 50 mg according to the manufacturer’s directions.a

Dilution

Add the initially reconstituted solution or the commercially available solution containing 50 mg to 250, 500, or 1000 mL of 5% dextrose injection to provide solutions containing 200, 100, or 50 mcg/mL, respectively.b HID 207

Protect from light by promptly wrapping the container in aluminum foil or other opaque material;207 it is not necessary to cover the infusion drip chamber or tubing.b

Rate of Administration

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

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

Dosage

Pediatric Patients

Hypertensive Crises, Heart Failure and Low-output Syndromes, Controlled Hypotension
IV

Initially, 0.3 mcg/kg per minute; gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum infusion rate of 10 mcg/kg per minute is reached.b Usual dosage is 3 mcg/kg (range of 0.1–10 mcg/kg) per minute.a 205 207

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

Adults

Hypertensive Crises, Heart Failure and Low-output Syndromes, Controlled Hypotension
IV

Initially, 0.3 mcg/kg per minute; gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum rate of infusion of 10 mcg/kg per minute is reached.b Usual dosage is 3 mcg/kg (range of 0.1–10 mcg/kg) per minute.a 207

Management of a hypertensive emergency: Goal is to reduce mean arterial blood pressure by no more than 25% within minutes to 1 hour, followed by further reduction if stable toward 160/100 to 110 mm Hg within the next 2–6 hours; avoid excessive declines in pressure.201 If this blood pressure is well tolerated and the patient is clinically stable, further gradual reductions toward normal can be implemented in the next 24–48 hours.204

Patients with aortic dissection: Goal is to reduce systolic pressure to <100 mm Hg if tolerated.204

Management of acute severe hypertension in preeclampsia: Goal is to reduce diastolic blood pressure to 95–105 mm Hg.204

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

Prescribing Limits

Pediatric Patients

Hypertensive Crises, Heart Failure and Low-output Syndromes, Controlled Hypotension
IV

Maximum 10 mcg/kg per minute.b 205 207

Prolonged infusions should not exceed 3 mcg/kg per minute; monitor thiocyanate concentrations if this rate is exceeded for prolonged periods.b

Adults

Hypertensive Crises, Heart Failure and Low-output Syndromes, Controlled Hypotension
IV

Maximum 10 mcg/kg per minute.b 207

Prolonged infusions should not exceed 3 mcg/kg per minute; monitor thiocyanate concentrations if this rate is exceeded for prolonged periods.b

Special Populations

Renal Impairment

Anuric patients: Prolonged infusions should not exceed 1 mcg/kg per minute (to maintain thiocyanate concentrations <60 mcg/mL).b

Cautions for Sodium Nitroprusside

Contraindications

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

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

  • Use during emergency surgery in patients near death.b

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

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

Warnings/Precautions

Warnings

Excessive Hypotension

Slightly excessive infusion rates can result in profound hypotension; subsequent hemodynamic changes can result in various associated symptoms or blood pressure may decrease to the point where perfusion of vital organs may be compromised.b

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.b

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.b

May cause hypotension with reflex tachycardia in the presence of hypovolemia. 207

Invasive hemodynamic monitoring may be useful during therapy.207

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.b

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.b

The actual frequency of clinically important cyanide toxicity has not been established.b

The only patients whose deaths have been unequivocally attributed to cyanide toxicity received the drug at rates (e.g., 30–120 mcg/kg per minute) exceeding the recommended maximum rate.b Elevated cyanide levels, metabolic acidosis, and marked clinical deterioration have been reported in patients receiving sodium nitroprusside at the recommended rates of infusion for only a few hours, and in 1 case, for only 35 minutes.b

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.b

Cyanide may accumulate in patients with hepatic or renal disease or those receiving infusions at rates >3 mcg/kg per minute for >72 hours; monitor for cyanide toxicity (e.g., metabolic acidosis).207

Monitor acid-base balance and venous oxygen concentrations; these tests may indicate cyanide toxicity.b (See Boxed Warning.)

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

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.b

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

Major Toxicities

Methemoglobinemia

Administration of sodium nitroprusside can result in the sequestration of hemoglobulin as methemoglobin.b The conversion of methemoglobin back to hemoglobin is normally rapid; clinically important methemoglobinemia (>10%) occurs rarely.b

Suspect methemoglobinemia in patients who have received >10 mg/kg and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and arterial PaO2.b

Methylene blue 1–2 mg/kg administered IV over several minutes may be used to treat methemoglobinemia; use with extreme caution in patients who are likely to have substantial amounts of cyanide bound to methemoglobin.b

Thiocyanate Accumulation

Thiocyanate may accumulate in the blood, especially in patients with impaired hepatic or renal function or hyponatremiab 207 or in patients receiving sodium nitroprusside infusions at rates >3 mcg/kg per minute for >72 hours or receiving sodium thiosulfate.a 207 These patients should be monitored for thiocyanate intoxication (e.g., metabolic acidosis).207

Thiocyanate is mildly neurotoxic at serum concentrations of 60 mcg/mL and may be life-threatening at concentrations of 200 mcg/mL.b Toxicity is manifested as confusion, hyperreflexia, and seizures.207

General Precautions

Effects on Intracranial Pressure

Sodium nitroprusside can increase intracranial pressure.b

Use with caution in patients with increased intracranial pressure.b

Use in Pulmonary Disease

May reverse hypoxic pulmonary vasoconstriction in patients with pulmonary disease (e.g., pneumonia, adult respiratory distress syndrome), which may exacerbate intrapulmonary shunting resulting in worsened hypoxemia.207

Use in Anesthesia

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

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

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

Specific Populations

Pregnancy

Category C.b d

Lactation

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

Hepatic Impairment

Caution in patients with hepatic impairment.b

Cyanide and thiocyanate may accumulate in patients with hepatic disease; monitor for cyanide and thiocyanate toxicity.b 207 (See Cyanide Toxicity and also Thiocyanate Accumulation under Cautions.)

Renal Impairment

Caution in patients with severe renal impairment.a (See Renal Impairment under Dosage and Administration and Thiocyanate Accumulation under Cautions.)

Cyanide and thiocyanate may accumulate in patients with renal disease; monitor for cyanide and thiocyanate toxicity.b 207 (See Cyanide Toxicity and also Thiocyanate Accumulation under Cautions.)

Common Adverse Effects

Excessive hypotension, cyanide toxicity.b

Interactions for Sodium Nitroprusside

The hypotensive effects are additive when used with ganglionic blocking agents, negative inotropic agents, general anesthetics (e.g., halothane, enflurane), and most other circulatory depressants.a

Sodium Nitroprusside Pharmacokinetics

Absorption

Onset

Immediate reduction in blood pressure.b

Duration

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

Distribution

Extent

Rapidly distributed.b

Elimination

Metabolism

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

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

Cyanide is enzymatically converted to thiocyanate by thiosulfate sulfurtransferase (a mitochondrial enzyme).b 207 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).b

Cyanide not otherwise removed binds to cytochromes.b

Elimination Route

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

Half-life

Sodium nitroprusside: Circulation half-life: 2 minutes.b

Thiocyanate: 3 days.b

Special Populations

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

Stability

Storage

Parenteral

Injection

15–30°C; protect from light by storing in the carton.b

If properly protected from light, reconstituted solutions and solutions for infusion are stable for 24 hours.b

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.b Discard discolored solutions or solutions with visible particulate matter.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

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

Parenteral

Solution CompatibilityHID

Compatible

Ringer’s injection, lactated (when protected from light)

Variable

Dextrose 4% in sodium chloride 0.18% (compatible when protected from light)

Dextrose 5% in water (compatible when protected from light)

Sodium chloride 0.9% (compatible when protected from light)

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Alcohol 10% in dextrose 5%

Alprostadil

Atracurium besylate

Bivalirudin

Calcium chloride

Dexmedetomidine HCl

Diltiazem HCl

Dopamine HCl

Dopamine HCl with dobutamine HCl

Dopamine HCl with lidocaine HCl

Dopamine HCl with nitroglycerin

Enalaprilat

Epinephrine HCl

Esmolol HCl

Famotidine

Furosemide

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Inamrinone lactate

Indomethacin sodium trihydrate

Isoproterenol HCl

Labetalol HCl

Lidocaine HCl

Lidocaine HCl with dobutamine HCl

Lidocaine HCl with dopamine HCl

Lidocaine HCl with nitroglycerin

Magnesium sulfate

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Nitroglycerin

Nitroglycerin with dobutamine HCl

Nitroglycerin with dopamine HCl

Nitroglycerin with lidocaine HCl

Norepinephrine bitrate

Pancuronium bromide

Potassium chloride

Potassium phosphates

Procainamide HCl

Propofol

Tacrolimus

Theophylline

Vecuronium bromide

Incompatible

Drotrecogin alfa (activated)

Levofloxacin

Variable

Amiodarone HCl

Dobutamine HCl

Haloperidol lactate

Propafenone

Actions

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

  • Direct vasodilation causes decreases in right and left ventricular filling (preload) resulting in relief of pulmonary congestion and reduced left ventricular volume and pressure.b 207 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.b 207

  • No direct effect on the myocardium,a but may exert a direct coronary vasodilator effect.b

  • Induces renal vasodilation generally proportional to decreases in systemic blood pressure with no appreciable changes in renal blood flow or glomerular filtration rate.b

Advice to Patients

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

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

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

Preparations

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

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

Sodium Nitroprusside

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion only

25 mg/mL*

Nitropress

Hospira

Sodium Nitroprusside Injection

For injection, for IV infusion only

50 mg

Nitropress ADD-Vantage

Hospira

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

200. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

201. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

202. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.

203. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

204. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Complete Version. Bethesda, MD: 2003 Nov 5. Hypertension. 2003; 42:1206-52. [PubMed 14656957]

205. National high blood pressure education program working group on hypertension control in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76.

206. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2000; 102(Suppl I): I-133.

207. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1493-1501.

a. AHFS drug information 2007. McEvoy GK, ed. Sodium Nitroprusside. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1743-6.

b. Abbott Laboratories. Nitropress (Sodium Nitroprusside) injection prescribing information. North Chicago, Il; 2000 Jan.

d. Nitroprusside. In: Briggs GG, Freeman RK, Yaffe SJ. Drug in pregnancy and lactation: a reference guide to fetal and neonatal risk. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002:1008.

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