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Sodium Nitroprusside

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

Warning(s)

  • Thoroughly review the prescribing information before administration.600

  • Dilution
  • Injection concentrate must be diluted further with 5% dextrose injection before infusion.600

  • Hypotension
  • Can produce precipitous decreases in BP; profound hypotension can lead to irreversible ischemic injury or death.600

  • Administer in a setting with equipment and personnel available to continuously monitor BP.600

  • Cyanide Intoxication
  • Administration (except when used for short periods of time or at low infusion rates [e.g., <2 mcg/kg per minute]) can result in the production of clinically important levels of cyanide ion, which can reach toxic or potentially lethal concentrations.600

  • Infusions at the maximum recommended rate of 10 mcg/kg per minute should never last longer than 10 minutes; if BP is not adequately controlled after 10 minutes, immediately discontinue the infusion.600

  • 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.600

Introduction

Vasodilating and hypotensive agent.207 600

Uses for Sodium Nitroprusside

Hypertensive Crises

For immediate reduction of BP in hypertensive emergencies.207 500 502 542 600 Administer with other longer-acting hypotensive agents to minimize the duration of nitroprusside therapy.600 Use in carefully selected patients because of potential for serious toxicity (see Cautions).542

Can be used for most hypertensive emergencies (e.g., hypertensive encephalopathy, MI, unstable angina pectoris, acute left ventricular failure with pulmonary edema, eclampsia, aortic dissection).207 500

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

Use caution if high intracranial pressure or azotemia is present.500

Other antihypertensive agents (e.g., hydralazine, labetalol, nifedipine) preferred for management of acute severe hypertension in preeclampsia; reserve sodium nitroprusside for treatment failures.208 209 500 540

Contraindicated in compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta).600 (See Contraindications under Cautions.)

Heart Failure and Low-Output Syndromes

Management of acute decompensated (e.g, congestive) heart failure.207 524 600

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.524

Particularly useful in severe heart failure caused by regurgitant valvular lesions of aortic insufficiency and mitral regurgitation.206 Also useful in management of heart failure in patients with severe congestion and hypertension.524

Also useful for afterload reduction when left ventricular dysfunction is accompanied by right ventricular ischemia.202 600 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 heart failure, nitroglycerin is the preferred vasodilator.202

Not indicated for the treatment of heart failure associated with reduced peripheral vascular resistance.600 (See Contraindications under Cautions.)

Controlled Hypotension

Used to produce controlled hypotension to reduce bleeding during surgery.600

Sodium Nitroprusside Dosage and Administration

Administration

Administer by IV infusion only.600

Administer in a setting with equipment and personnel available to continuously monitor blood pressure.600

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.600

Dilution

Injection concentrate (25 mg/mL) must be further diluted prior to IV infusion.600 Dilute contents of one vial (50 mg) in 250–1000 mL of 5% dextrose injection.600 Vials are for single use only.600

Protect from light by promptly wrapping the container in aluminum foil or other opaque material;600 it is not necessary to cover the infusion drip chamber or tubing.600

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.600

When sodium nitroprusside is used in heart failure, titrate rate based on results of invasive hemodynamic monitoring and urine output.600

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 BP control is achieved or the maximum infusion rate of 10 mcg/kg per minute is reached.600 Usual dosage is 3 mcg/kg (range of 0.1–10 mcg/kg) per minute.205 207 600

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.600

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 BP control is achieved or the maximum rate of infusion of 10 mcg/kg per minute is reached.600 Usual dosage is 3 mcg/kg (range of 0.1–10 mcg/kg) per minute.207 600

Management of hypertensive emergency: Goal is to reduce mean arterial BP 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.500 If this BP is well tolerated and the patient is clinically stable, further gradual reductions toward normal can be implemented in the next 24–48 hours.500

Patients with aortic dissection: Goal is to reduce systolic pressure to <100 mm Hg if tolerated.500

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.600

Prescribing Limits

Pediatric Patients

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

Maximum 10 mcg/kg per minute.205 207 600

Prolonged infusions should not exceed rate of 3 mcg/kg per minute; monitor thiocyanate concentrations if this rate is exceeded for prolonged periods.600

Adults

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

Maximum 10 mcg/kg per minute.207 600

Prolonged infusions should not exceed rate of 3 mcg/kg per minute; monitor thiocyanate concentrations if this rate is exceeded for prolonged periods.600

Special Populations

Renal Impairment

Anuric patients: Prolonged infusions should not exceed rate of 1 mcg/kg per minute (to maintain thiocyanate concentrations <60 mcg/mL).600

Cautions for Sodium Nitroprusside

Contraindications

  • Treatment of compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta).600

  • Controlled hypotension during surgery in patients with inadequate cerebral circulation.600

  • Use during emergency surgery in patients near death.600

  • Congenital (Leber’s) optic atrophy or tobacco amblyopia (associated with absent or deficient thiosulfate sulfurtransferase; patients have unusually high cyanide to thiocyanate ratios).600 (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).600

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.600

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.600

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.600

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.600

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.600

The actual frequency of clinically important cyanide toxicity has not been established.600

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.600

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.600

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.600 (See Boxed Warning.)

Hypertensive patients and those receiving other antihypertensive agents may be more sensitive to the effects of sodium nitroprusside than healthy individuals.600

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.600

Caution advised; avoid prolonged or excessive dosages of sodium nitroprusside with sodium thiosulfate, since thiocyanate toxicity and/or hypovolemia may result.600 The same precautions and contraindications apply to this method of administration as to the administration of sodium nitroprusside alone.600

Major Toxicities

Methemoglobinemia

Administration of sodium nitroprusside can result in the sequestration of hemoglobin as methemoglobin.600 The conversion of methemoglobin back to hemoglobin is normally rapid; clinically important methemoglobinemia (>10%) occurs rarely.600

Suspect methemoglobinemia in patients who have received >10 mg/kg and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and arterial PaO2.600

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.600

Thiocyanate Accumulation

Thiocyanate may accumulate in the blood, especially in patients with impaired hepatic or renal function or hyponatremia207 600 or in patients receiving prolonged sodium nitroprusside infusions at rates >3 mcg/kg per minute or receiving prolonged sodium thiosulfate.207 600 These patients should be monitored for thiocyanate intoxication (e.g., metabolic acidosis).207 600

Thiocyanate is mildly neurotoxic at serum concentrations of 60 mcg/mL and may be life-threatening at concentrations of 200 mcg/mL.600 Toxicity is manifested as confusion, hyperreflexia, and seizures.207 600

General Precautions

Effects on Intracranial Pressure

Sodium nitroprusside can increase intracranial pressure.600

Use with caution in patients with increased intracranial pressure.600

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.600

If possible, correct preexisting anemia and hypovolemia prior to use.600

Use with extreme caution in patients who are especially poor surgical risks.600

Specific Populations

Pregnancy

Category C.543 600

Lactation

Not known whether sodium nitroprusside or its metabolites are distributed into milk; discontinue nursing or the drug.600

Hepatic Impairment

Caution in patients with hepatic impairment.600

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

Renal Impairment

Caution in patients with renal impairment.600 (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.207 600 (See Cyanide Toxicity and also Thiocyanate Accumulation under Cautions.)

Common Adverse Effects

Excessive hypotension, cyanide toxicity.600

Interactions for Sodium Nitroprusside

The hypotensive effects are additive when used with ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics.600

Sodium Nitroprusside Pharmacokinetics

Absorption

Onset

Immediate reduction in BP.600

Duration

BP begins to rise immediately when infusion is slowed or stopped; BP returns to pretreatment levels within 1–10 minutes.600

Distribution

Extent

Rapidly distributed.600

Elimination

Metabolism

Sodium nitroprusside is metabolized by combination with hemoglobin to form cyanmethemoglobin and cyanide.600

Essentially all cyanide in the blood is bound to methemoglobin until intraerythrocytic methemoglobin is saturated.600

Cyanide is enzymatically converted to thiocyanate by thiosulfate sulfurtransferase (a mitochondrial enzyme).207 600 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).600

Cyanide not otherwise removed binds to cytochromes.600

Elimination Route

Eliminated principally in urine as thiocyanate.600 Some cyanide is expired as hydrogen cyanide.600

Half-life

Sodium nitroprusside: Circulation half-life: 2 minutes.600

Thiocyanate: 3 days.600

Special Populations

Half-life of thiocyanate is increased in patients with renal failure.600

Stability

Storage

Parenteral

Injection

20–25°C; protect from light by storing in the carton.600

If properly protected from light, diluted solutions are stable for 24 hours.600

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.600 Discard discolored solutions or solutions with visible particulate matter.600

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.600

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 bitartrate

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.600

  • Direct vasodilation causes decreases in right and left ventricular filling (preload) resulting in relief of pulmonary congestion and reduced left ventricular volume and pressure.207 600 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.207 600

  • May exert a direct coronary vasodilator effect.600

  • Induces renal vasodilation generally proportional to decreases in systemic BP with no appreciable changes in renal blood flow or GFR.600

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.600

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.600

  • Importance of informing patients of other important precautionary information.600 (See Cautions).

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.

Sodium Nitroprusside

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, concentrate, for IV infusion only

25 mg/mL

Nitropress

Hospira

AHFS DI Essentials. © Copyright 2017, Selected Revisions February 6, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

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.

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.

208. Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013; 7:CD001449. [PubMed 23857334]

209. ACOG task force on hypertension in pregnancy: hypertension in pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013.

500. 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 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. [PubMed 23817082]

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

540. Magee LA, Pels A, Helewa M et al., for the Canadian Hypertensive Disorders of Pregnancy (HDP) Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014; 4:105-45. [PubMed 26104418]

542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007; 131:1949-62. [PubMed 17565029]

543. 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.

600. Hospira Inc. Nitropress (sodium nitroprusside) injection prescribing information. Lake Forest, IL; 2014 Jan.

700. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :.

701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; :.

703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther. 2016; 41:119-27. [PubMed 26992459]

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

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