Sodium nitroprusside is a vasodilating and hypotensive agent.600, 1201
Immediate Reduction of Blood Pressure
Intravenous sodium nitroprusside is used for immediate reduction in blood pressure in adult and pediatric patients in hypertensive emergency and asymptomatic markedly elevated blood pressure.600, 1201, 1202
Baseline-controlled clinical trials have shown that sodium nitroprusside exerts a rapid hypotensive effect upon therapy initiation across all patient populations.600, 1201 It has been found to lower blood pressure with increasing infusion rates, without an observed limit of this effect.600, 1201 An open-label trial enrolled 63 pediatric patients (<17 years of age) who required a reduction in mean arterial pressure (MAP) of at least 20 mmHg (at least 15 mmHg if <2 years of age).600, 1201, 1205 Sodium nitroprusside was administered for 12 to 24 hours with dose titrated by response.600, 1201, 1205 Patients were then randomized to sodium nitroprusside or placebo during a subsequent double-blind phase.600, 1201, 1205 Sodium nitroprusside was associated with a lower MAP compared to placebo for each timepoint measured, demonstrating its effectiveness for a period of ≥12 hours.600, 1201
The most recent guidelines on treatment of hypertension from the American College of Cardiology (ACC)/American Heart Association (AHA) Task force and updated guidelines from the AHA on elevated blood pressure define hypertensive emergencies as severely elevated blood pressure (>180/120 mmHg) with evidence of new or worsening target organ damage.1200, 1202 Immediate reduction of blood pressure (not necessarily to normal range) is needed to prevent further target organ damage.1200
Such emergencies may be associated with hypertensive encephalopathy, acute myocardial infarction (MI), unstable angina pectoris, acute left ventricular failure with pulmonary edema, acute renal failure, acute ischemic stroke, eclampsia, or aortic dissection.1200
Patients with hypertensive emergencies require hospitalization and are treated initially with an appropriate parenteral agent.1200 Several antihypertensive drugs from various pharmacologic classes are available for the treatment of hypertensive emergencies, including vasodilators such as sodium nitroprusside.1200, 1202 Because of the lack of evidence to support the use of one antihypertensive drug over another, experts state that selection of an appropriate agent should be individualized based on the underlying cause of hypertension, degree of target organ damage, desired rate of blood pressure reduction, specific drug characteristics, and patient comorbidities.1200 Excessive falls in blood pressure should be avoided in any hypertensive crisis since they may precipitate renal, cerebral, or coronary ischemia.1200 No more than a 25% reduction in systolic blood pressure within the first hour is recommended.1200 However, under certain conditions (e.g., aortic dissection, pheochromocytoma crisis), a more rapid reduction in blood pressure may be required.1200
Controlled Hypotension during Surgery
Sodium nitroprusside is used for induction and maintenance of controlled hypotension in adults and pediatric patients during surgery, to reduce bleeding.600, 1201 Clinical trials have shown sodium nitroprusside-induced hypotension to be associated with reduced blood loss during surgery.600, 1201
The efficacy of sodium nitroprusside to induce hypotension during surgery in pediatric patients (<17 years of age) was evaluated in a double-blind trial.600, 1201, 1204 One study enrolled 203 pediatric patients, randomized to 1 of 4 doses of nitroprusside.600, 1201, 1204 The primary outcome was change in MAP after 30 minutes of infusion.600, 1201, 1204 For all dosage groups, MAP decreased by a mean of 11 to 20 mmHg from baseline.600, 1201, 1204
Sodium nitroprusside is used in the management of acute heart failure to reduce left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, peripheral vascular resistance, and MAP.600, 1201
Current guidelines from the AHA/ACC/Heart Failure Society of America (HFSA) for the management of acute decompensated heart failure in adults recommend addressing reversible factors, achieving optimal volume status, and advanced medical therapy as needed.700 For patients hospitalized for acute decompensated heart failure, IV vasodilators (nitroglycerin or sodium nitroprusside) can be considered to relieve symptoms of pulmonary congestion in some patients.700 Sodium nitroprusside has been reported to be useful in the management of patients with severe congestion and hypertension or severe mitral valve regurgitation complicating left ventricular dysfunction.700
Available guidelines have included sodium nitroprusside as one of several options for treatment of “no-reflow” phenomenon, a complication of primary percutaneous coronary intervention (PCI) for reperfusion after ST-segment elevated MI†.527 A systematic review on the use of sodium nitroprusside for preventing “no-reflow” during PCI evaluated 4 studies using intracoronary† sodium nitroprusside.1207 In a meta-analysis of the 3 studies that reported applicable data, intracoronary sodium nitroprusside was associated with a significant reduction in “no-reflow” or “slow-flow” following PCI.1207
For patients with acute ST-segment elevated MI and left ventricular dysfunction†, nitroprusside has been used to treat hypertension in severe cases not responding to standard of care (including an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist and IV nitrates).1211
Sodium nitroprusside has been used as adjunctive therapy to control blood pressure in patients with acute aortic syndrome†.1209 Acute aortic syndrome is a syndrome that encompasses 4 acute aortic conditions: classic aortic dissection, intramural hematoma, penetrating aortic ulcer, and incomplete dissection.1208 Initial treatment during the acute phase of acute aortic syndrome includes blood pressure control (target 100-120 mmHg), pulse rate control (target ≤60 beats/minute), and pain relief.1208 Depending on the type of dissection, immediate surgery may also be needed.1209 For acute medical management, IV beta-blockers are the initial recommended treatment.1209 If beta-blockers cannot be used, IV nondihydropyridine calcium channel blockers are typically used.1209 Intravenous vasodilators, including sodium nitroprusside, can be used as an adjunct to IV beta-blockers to help reduce blood pressure and heart rate; these agents are not recommended as initial therapy.1209
Sodium nitroprusside has been used for blood pressure reduction in patients with acute ischemic stroke† who would otherwise be eligible for fibrinolytic therapy.1210 For patients with acute ischemic stroke, use of a fibrinolytic (i.e., IV alteplase) is generally recommended, with administration initiated as quickly as possible.1210 Patients eligible for fibrinolytic therapy, but with elevated blood pressure, should receive treatment to achieve a blood pressure of <185 mmHg systolic and <110 mmHg diastolic prior to administration of the fibrinolytic.1210 Guidelines from the AHA/American Stroke Association on early management of acute ischemic stroke recommend use of IV labetalol, nicardipine, or clevidipine to achieve target blood pressure.1210 If target blood pressure is not achieved, these agents can be titrated to effect.1210 Intravenous sodium nitroprusside can be considered if blood pressure is not controlled or if diastolic pressure is >140 mmHg.1210
Dispensing and Administration Precautions
Sodium nitroprusside is administered by IV infusion only using a controlled-infusion device (i.e., infusion pump); IV infusion devices regulated only by gravity or mechanical clamps should not be used.600 The rate of administration should be adjusted to maintain the desired hypotensive effect, as determined by continuous monitoring of blood pressure, using either a continually reinflated sphygmomanometer or, preferably, an intra-arterial pressure sensor.600 The drug should be administered for no longer than 10 minutes at the maximum infusion rate (i.e., 10 mcg/kg per minute).600 When titrating sodium nitroprusside infusion, blood pressure should be assessed for at least 5 minutes before further titrating the infusion rate.600, 1201
Sodium nitroprusside is commercially available prediluted in 0.9% sodium chloride injection (0.5 mg/mL and 0.2 mg/mL concentrations) and as an injection concentrate (25 mg/mL).600, 1201 Commercially available sodium nitroprusside injection concentrate (25 mg/mL) must be further diluted prior to IV infusion.600 The contents of one vial of injection concentrate containing 50 mg of the drug should be diluted in 250-1000 mL of 5% dextrose injection.600 Vials of the drug are for single use only.600, 1201 Nitroprusside solutions prepared using the injection concentrate should be protected from light by promptly wrapping the containers in the supplied opaque sleeve, aluminum foil, or other opaque material; it is not necessary to cover the infusion drip chamber or IV tubing.600 If properly protected from light, diluted solutions of the drug are stable for 24 hours.600 The infusion solution has a clear colorless to red/brown color; if it is blue, green, or bright red, it should not be used.600, 1201 No other drug should be added to the infusion fluid for simultaneous administration with sodium nitroprusside.600, 1201
Sodium nitroprusside vials should be stored protected from light in their carton until use at 20-25°C.600, 1201
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. 249, 250Multidisciplinary expert panels were convened to determine recommended standard concentrations .249, 250Because 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 .249, 250 For additional information on S4S (including updates that may be available), see [Web].249, 250
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Adults | 200 mcg/mL | mcg/kg/min |
500 mcg/mL | ||
Pediatric patients (<50 kg) | 200 mcg/mL | mcg/kg/min |
500 mcg/mL |
Immediate Reduction of Blood Pressure
In adults receiving sodium nitroprusside for hypertensive crises, the manufacturer states that the average effective IV dosage is about 3 mcg/kg per minute, with a range of 0.5-10 mcg/kg per minute; however, some patients will experience profound hypotension when receiving the drug at this rate.600 Therefore, the infusion should be started at a very low rate (e.g., 0.3 mcg/kg per minute) and gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 If an adequate reduction in blood pressure is not obtained within 10 minutes at this maximum infusion rate, the infusion should be immediately discontinued.600 Because of the rapidity of sodium nitroprusside's hypotensive onset and dissipation of effect, small changes in infusion rate can lead to large, undesirable fluctuations in blood pressure.600 The manufacturer states that prior to increasing the dosage, the drug's effects should be confirmed by measuring blood pressure 5 minutes after any change in infusion rate to achieve the desired blood pressure response.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
Longer-acting hypotensive agents should be administered concomitantly with sodium nitroprusside to minimize the duration of sodium nitroprusside therapy.600
Controlled Hypotension during Surgery
In adults receiving sodium nitroprusside for hypertensive crises or for controlled hypotension during surgery, the manufacturer states that the average effective IV dosage is about 3 mcg/kg per minute, with a range of 0.5-10 mcg/kg per minute; however, some patients will experience profound hypotension when receiving the drug at this rate.600 Therefore, the infusion should be started at a very low rate (e.g., 0.3 mcg/kg per minute) and gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 If an adequate reduction in blood pressure is not obtained within 10 minutes at this maximum infusion rate, the infusion should be immediately discontinued.600 Because of the rapidity of sodium nitroprusside's hypotensive onset and dissipation of effect, small changes in infusion rate can lead to large, undesirable fluctuations in blood pressure.600 The manufacturer states that prior to increasing the dosage, the drug's effects should be confirmed by measuring blood pressure 5 minutes after any change in infusion rate to achieve the desired blood pressure response.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
When sodium nitroprusside is used in adults with acute congestive heart failure, the manufacturer recommends that the infusion be initiated at a rate of 0.3 mcg/kg per minute.600 The dosage should be gradually titrated upward every few minutes until the desired effect is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 The manufacturer states that the average effective dosage is about 3 mcg/kg (range: 0.5-10 mcg/kg) per minute.600 Adjustment of the infusion rate must be guided by the results of invasive hemodynamic monitoring and monitoring of urine output.600 Titration of sodium nitroprusside dosage can be accomplished by increasing the infusion rate until cardiac output is no longer increasing, systemic blood pressure cannot be further reduced without compromising vital organ perfusion, or the maximum recommended infusion rate is reached, whichever occurs first.600 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.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
Immediate Reduction of Blood Pressure
In pediatric patients receiving sodium nitroprusside for immediate blood pressure reduction, the manufacturer states that the average effective IV dosage is about 3 mcg/kg per minute, with a range of 0.5-10 mcg/kg per minute; however, some patients will experience profound hypotension when receiving the drug at this rate.600 Therefore, the infusion should be started at a very low rate (e.g., 0.3 mcg/kg per minute) and gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 If an adequate reduction in blood pressure is not obtained within 10 minutes at this maximum infusion rate, the infusion should be immediately discontinued.600 Because of the rapidity of sodium nitroprusside's hypotensive onset and dissipation of effect, small changes in infusion rate can lead to large, undesirable fluctuations in blood pressure.600 The manufacturer states that prior to increasing the dosage, the drug's effects should be confirmed by measuring blood pressure 5 minutes after any change in infusion rate to achieve the desired blood pressure response.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
Longer-acting hypotensive agents should be administered concomitantly with sodium nitroprusside to minimize the duration of sodium nitroprusside therapy.600
Controlled Hypotension During Surgery
In pediatric patients receiving sodium nitroprusside for controlled hypotension during surgery, the manufacturer states that the average effective IV dosage is about 3 mcg/kg per minute, with a range of 0.5-10 mcg/kg per minute; however, some patients will experience profound hypotension when receiving the drug at this rate.600 Therefore, the infusion should be started at a very low rate (e.g., 0.3 mcg/kg per minute) and gradually titrated upward every few minutes until adequate blood pressure control is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 If an adequate reduction in blood pressure is not obtained within 10 minutes at this maximum infusion rate, the infusion should be immediately discontinued.600 Because of the rapidity of sodium nitroprusside's hypotensive onset and dissipation of effect, small changes in infusion rate can lead to large, undesirable fluctuations in blood pressure.600 The manufacturer states that prior to increasing the dosage, the drug's effects should be confirmed by measuring blood pressure 5 minutes after any change in infusion rate to achieve the desired blood pressure response.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
When sodium nitroprusside is used in pediatric patients with acute congestive heart failure, the manufacturer recommends that the infusion be initiated at a rate of 0.3 mcg/kg per minute.600 The dosage should be gradually titrated upward every few minutes until the desired effect is achieved or the maximum recommended infusion rate of 10 mcg/kg per minute has been reached.600 The manufacturer states that the average effective dosage is about 3 mcg/kg (range: 0.5-10 mcg/kg) per minute.600 Adjustment of the infusion rate must be guided by the results of invasive hemodynamic monitoring and monitoring of urine output.600 Titration of sodium nitroprusside dosage can be accomplished by increasing the infusion rate until cardiac output is no longer increasing, systemic blood pressure cannot be further reduced without compromising vital organ perfusion, or the maximum recommended infusion rate is reached, whichever occurs first.600 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.600
Prolonged infusions should not exceed 3 mcg/kg per minute to prevent concentrations of thiocyanate (a byproduct of sodium nitroprusside metabolism) from reaching neurotoxic levels; monitor thiocyanate concentrations daily if this rate is exceeded.600
Although dosage adjustments are not specified for patients with hepatic impairment, the manufacturer states that such patients are more susceptible to developing cyanide toxicity.1201
Thiocyanate may accumulate in patients with renal impairment or in patients receiving prolonged infusions of sodium nitroprusside at rates exceeding 3 mcg/kg per minute.600 To maintain the steady-state concentration of thiocyanate below 60 mcg/mL (the level at which mild neurotoxic effects have been observed), one manufacturer states that infusion rates of sodium nitroprusside should be maintained below 3 mcg/kg per minute in patients with normal renal function or 1 mcg/kg per minute in anuric patients.600 It is also recommended to maintain the infusion rate below 3 mcg/kg per minute in patients with an estimated glomerular filtration rate (eGFR) of <30 mL/minute per 1.73 m2.1201 When prolonged infusions are more rapid than this, serum thiocyanate concentrations should be monitored daily.600
Hemodialysis may be required to remove excess thiocyanate in cases of severe toxicity.600, 1201
The manufacturer states that special caution should be used with sodium nitroprusside in geriatric patients, as they may be more sensitive to the hypotensive effects of the drug.600
Direct Injection of Injection Concentrate
A boxed warning about the need for dilution of sodium nitroprusside injection concentrate prior to IV infusion is included in the drug's prescribing information.600 Sodium nitroprusside injection concentrate must be further diluted with sterile 5% dextrose injection prior to infusion.600
A boxed warning about the possibility of excessive hypotension with sodium nitroprusside and the potential hypoperfusion of vital organs is included in the drug's prescribing information.600, 1201 The hypotensive effect of sodium nitroprusside occurs rapidly and the possible sequelae of hypotension (e.g., irreversible ischemic injury, death) are serious.600, 1201 Because sodium nitroprusside can produce precipitous decreases in blood pressure, the drug should be administered only when adequate facilities, equipment, and personnel are available for close monitoring of blood pressure.600, 1201
Hypotension generally is self-limiting within 1-10 minutes following the discontinuance of the infusion; during this time, patients may benefit from being placed in Trendelenburg's position to maximize venous return.600, 1201 If blood pressure does not normalize within a few minutes, sodium nitroprusside may not be the principal cause of the hypotension and another cause should be sought.600, 1201
A boxed warning about the risk of developing cyanide toxicity is included in the prescribing information for sodium nitroprusside.600, 1201 The toxic effects of cyanide may be rapid, serious, and possibly fatal and 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 An early sign of cyanide toxicity is an increase in dosage requirements to maintain blood pressure control.1201 While 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 Cyanide toxicity resulting from causes other than sodium nitroprusside has been associated with angina and myocardial infarction, ataxia, seizures, stroke, and other diffuse ischemic damage.600
Sodium nitroprusside infusions at rates exceeding 2 mcg/kg per minute generate cyanogen (cyanide radical) in amounts greater than can be effectively buffered by the methemoglobin normally present in the body; cyanide toxicity can result when this buffering system is exhausted.600 The capacity of this system is exceeded when more than 500 mcg/kg of sodium nitroprusside is given; this amount is produced in under 1 hour when the drug is administered at a rate of 10 mcg/kg per minute.600 Most cases of cyanide toxicity have occurred when sodium nitroprusside is used for prolonged periods or at high dosages; however, elevated cyanide levels, metabolic acidosis, and marked clinical deterioration have been reported occasionally in patients receiving the drug at recommended rates of infusion for only a few hours, and in one case, for only 35 minutes.600 Infusions of sodium nitroprusside at the maximum recommended rate of 10 mcg/kg per minute should never last longer than 10 minutes; if blood pressure is not adequately controlled after 10 minutes, the infusion should be discontinued immediately.600
Sodium thiosulfate has been administered concomitantly with sodium nitroprusside at infusion rates 5-10 times that of the sodium nitroprusside infusion to accelerate the metabolism of cyanide; however, coadministration of these agents has not been extensively researched and further study is necessary.600 Caution must be exercised to 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
The manufacturer states that reasonable suspicion of cyanide toxicity is adequate to start treatment for cyanide toxicity.600, 1201 This first involves the discontinuation of sodium nitroprusside.600, 1201 A 3% sodium nitrite solution should then be administered IV at a dosage of 4-6 mg/kg (approximately 0.2 mL/kg of the 3% solution) injected over 2-4 minutes.600, 1201 This dose can be expected to convert about 10% of the patient's hemoglobin to methemoglobin; however, this degree of methemoglobinemia alone is not associated with any important hazard.600, 1201 Following these steps, a 10 or 25% solution of sodium thiosulfate is administered IV in a dose of 150-200 mg/kg; a typical adult dose is 50 mL of the 25% solution.600, 1201 Injections of sodium nitrite and sodium thiosulfate may be repeated at one-half the initial recommended doses after 2 hours.600, 1201 Hemodialysis is ineffective for removing cyanide, but will remove most thiocyanate.600, 1201
Thiocyanate may accumulate in the blood of patients receiving sodium nitroprusside therapy, especially in those with impaired renal function, or in patients receiving prolonged infusions of sodium nitroprusside at infusion rates exceeding 3 mcg/kg per minute or receiving sodium thiosulfate concomitantly with sodium nitroprusside to accelerate the metabolism of cyanide to thiocyanate.600, 1201 Thiocyanate can cause mild neurotoxic effects (e.g., tinnitus, miosis, hyperreflexia) at serum concentrations of 60 mcg/mL and may be life-threatening at concentrations of 200 mcg/mL.600, 1201
To maintain the steady-state concentration of thiocyanate below 60 mcg/mL (the level at which mild neurotoxic effects have been observed), one manufacturer states that infusion rates of sodium nitroprusside should be maintained below 3 mcg/kg per minute in patients with normal renal function or 1 mcg/kg per minute in anuric patients.600 It is also recommended to maintain the infusion rate below 3 mcg/kg per minute in patients with an estimated glomerular filtration rate (eGFR) of <30 mL/minute per 1.73 m2.1201 When prolonged infusions are more rapid than this, serum thiocyanate concentrations should be monitored daily.600
Infusions of sodium nitroprusside result in the conversion of hemoglobin to methemoglobin in a dose-dependent manner.600, 1201 Because methemoglobin binds to oxygen more strongly than hemoglobin, oxygen release from capillaries may be impaired when there are increased methemoglobin serum levels.600, 1201 Although the conversion of methemoglobin back to hemoglobin is normally rapid, clinically important methemoglobinemia (>10%) rarely may occur.600, 1201 Methemoglobinemia should be suspected in patients who have received >10 mg/kg of sodium nitroprusside and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and arterial partial pressure of oxygen (PaO2).600, 1201
In patients with symptomatic methemoglobinemia (i.e., ≥10%), 1-2 mg/kg of methylene blue should be infused IV slowly over several minutes.600, 1201
Increased Intracranial Pressure
Sodium nitroprusside, like other vasodilating agents, can produce increases in intracranial pressure; therefore, the drug should be used only with extreme caution in patients with preexisting increased intracranial pressure.600
Anemia and Hypovolemia with Anesthesia
When IV sodium nitroprusside is used for controlled hypotension during anesthesia, a patient's capacity to compensate for anemia and hypovolemia may be reduced.600, 1201 If possible, preexisting anemia and hypovolemia should be corrected prior to use of the drug.600, 1201 Hypotensive anesthetic techniques also may affect pulmonary ventilation/perfusion ratio.600 In patients who cannot tolerate additional dead air space at normal oxygen partial pressure, higher oxygen partial pressure may be beneficial.600 Sodium nitroprusside IV infusion should be used with extreme caution in patients who are especially poor surgical risks.600
Based on animal findings and its mechanism of action, sodium nitroprusside may lead to cyanide exposure and adverse effects on the fetus.1201 Available postmarketing data in pregnant women are insufficient to establish a drug-associated risk of adverse pregnancy outcomes with sodium nitroprusside.1201 Studies in pregnant sheep have shown sodium nitroprusside crosses the placenta and effects were maternal dose-related.600, 1201
Prolonged use and higher dosages of sodium nitroprusside during pregnancy can result in cyanide toxicity, which may be fatal to a developing fetus.1201 In the unusual situation that there is no alternative therapy to sodium nitroprusside, pregnant women should be informed of the potential fetal risk.1201
There are no data on the presence of sodium nitroprusside in human milk, the effects on the breast-fed infant, or the effects on milk production; however, thiocyanate, a metabolite of sodium nitroprusside, is present in human milk.1201 It is unclear if and for how long thiocyanate levels in milk are clinically relevant.1201
Efficacy of sodium nitroprusside in pediatric patients has been established based on adult trials and supported by 2 studies in pediatric patients: a parallel, dose-ranging study and a long-term infusion study in which sodium nitroprusside dosage was titrated according to blood pressure.600, 1201 The primary efficacy variable in these studies was mean arterial pressure (MAP).600, 1201 The patients were <17 years of a at least 50% of the patients were prepubertal, and about 50% of prepubertal patients were <2 years of age, including 4 neonates.600, 1201 Both studies demonstrated the blood pressure-lowering effect of sodium nitroprusside.600, 1201 In the latter study, sodium nitroprusside reduced MAP below that of placebo control for at least 12 hours.600, 1201 Similar effects on MAP were observed in all age groups in these studies, and no novel safety issues were noted.600, 1201
Geriatric patients may be more sensitive to the hypotensive effects of sodium nitroprusside, therefore caution should be exerted with use in this patient population.600
Caution should be exerted when sodium nitroprusside is used in patients with hepatic dysfunction,600 as they are more susceptible to developing cyanide toxicity.1201
Thiocyanate, a product of cyanide metabolism, primarily undergoes renal clearance, and may accumulate in renal impairment.600, 1201 The half-life of thiocyanate may be doubled or tripled in renal failure.600, 1201 In cases of serious toxicity, hemodialysis may be used to remove thiocyanate.600, 1201
Adverse effects resulting from IV administration of sodium nitroprusside are uncommon and are usually associated with a too-rapid reduction in blood pressure.600 Excessive hypotension and cyanide toxicity are the most common.600, 1201
The hypotensive effects of sodium nitroprusside are additive when used concomitantly with ganglionic blocking agents, negative inotropic agents, general anesthetics (e.g., enflurane), and most other circulatory depressants.600
Concomitant use of phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) is contraindicated.1201
Soluble Guanylate Cyclase Stimulators
Concomitant use of soluble guanylate cyclase stimulators (e.g., riociguat) is contraindicated.1201
Sodium nitroprusside is a potent direct arterial and venous dilator.600, 1201 Sodium nitroprusside exhibits more venous than arterial activity, although it has less selectivity than nitroglycerin.600, 1201 When sodium nitroprusside is administered by IV infusion to hypertensive or normotensive patients, slight increases in heart rate and a variable effect on cardiac output are observed with decreased blood pressure.600, 1201 Moderate doses of sodium nitroprusside in hypertensive patients produce renal vasodilation without an appreciable increase in renal blood flow or a decrease in glomerular filtration.600, 1201
The hypotensive action of sodium nitroprusside results from peripheral vasodilation caused by a direct action on vascular smooth muscle.600, 1201 No relaxation of other smooth muscle tissue, such as the uterus or duodenum, has been demonstrated.600, 1201 The drug's venous dilatory effect promotes peripheral pooling of the blood and reduced venous cardiac return, which decreases left ventricular end diastolic pressure and pulmonary capillary wedge pressure (preload).600, 1201 Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, mean arterial pressure (afterload), and dilates the coronary arteries.600, 1201
IV infusion of sodium nitroprusside produces hypotensive effects within 1-2 minutes of initiation.600, 1201 Blood pressure begins to rise immediately when the infusion is slowed or stopped and returns to pretreatment levels within 1-10 minutes.600, 1201 Sodium nitroprusside is rapidly distributed into the extracellular fluid compartment.600, 1201 Animal studies have shown that nitroprusside passes the placental barrier.600, 1201 Thiocyanate, a metabolite of sodium nitroprusside, has also been shown to distribute into human milk.1201
Sodium nitroprusside is cleared by a reaction with hemoglobin in erythrocytes to form cyanmethemoglobin and cyanide.600, 1201 Cyanogen (cyanide radical) is produced, which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase (rhodanase).600 This mitochondrial enzyme normally is present in excess quantities such that the rate-limiting factor in the conversion of cyanogen to thiocyanate usually is the availability of sulfur donors (e.g., thiosulfate, cystine, cysteine).600 Physiologic thiocyanate serum levels normally range from 3<15 mcg/mL.600 Physiologic conversion of cyanide to thiocyanate at steady-state generally occurs at about 1 mcg/kg per minute; conversion capacity is exceeded with sodium nitroprusside infusions of slightly above 2 mcg/kg per minute, resulting in the accumulation of cyanide.600, 1201 Mild neurotoxicity (tinnitus, miosis, hyperreflexia) begins to appear at serum thiocyanate concentrations of 60 mcg/mL; fatalities have been reported at concentrations of 200 mcg/mL.600, 1201 The circulatory half-life of sodium nitroprusside is approximately 2 minutes.600, 1201
Most of the cyanide produced during sodium nitroprusside metabolism is excreted in the form of thiocyanate.600 Cyanide not otherwise removed binds to cytochromes.600 Thiocyanate excretion is primarily renal.600 The elimination half-life of thiocyanate is 3 days when renal function is normal, but is doubled or tripled in patients with renal failure.600
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion only | 25 mg/mL* | Sodium Nitroprusside Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV infusion | 10 mg/50 mL (0.2 mg/mL) of sodium nitroprusside | Nipride® RTU | |
20 mg/100 mL (0.2 mg/mL) of sodium nitroprusside* | Nipride® RTU | |||
Sodium Nitroprusside in Sodium Chloride Injection | ||||
50 mg/100 mL (0.5 mg/mL) of sodium nitroprusside* | Nipride® RTU | |||
Sodium Nitroprusside in Sodium Chloride Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2025 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
250. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2025 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
300. Institute for Safe Medication Practices (ISMP). ISMP list of high-alert medications in acute care settings. ISMP; 2024.
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