Sodium nitroprusside is a vasodilating and hypotensive agent.600
IV sodium nitroprusside is used in hypertensive crises for immediate reduction of blood pressure in patients in whom such reduction is considered an emergency (hypertensive emergencies).502, 542, 600, 1200 The drug is consistently effective in the management of hypertensive emergencies, irrespective of etiology; however, sodium nitroprusside is contraindicated in compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta). Because of the potential for serious toxicity (see Cautions), sodium nitroprusside should be used for treatment of hypertensive emergencies in carefully selected patients.542
Hypertensive emergencies are those rare situations requiring immediate blood pressure reduction (not necessarily to normal ranges) to prevent or limit 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 Some experts state that the use of sodium nitroprusside is contraindicated for the treatment of eclampsia or preeclampsia.1200 (For additional information on the use of antihypertensive drugs in women with preeclampsia, see Uses: Hypertension, Severe Hypertension during Pregnancy, in Hydralazine 24:08.20.)Patients with hypertensive emergencies require hospitalization and are treated initially with an appropriate parenteral agent.542, 1200 Several antihypertensive drugs from various pharmacologic classes are available for the treatment of hypertensive emergencies; 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.542, 1200 Hypertensive urgencies (i.e., situations in which there is severe elevation in blood pressure without acute or impending target organ damage) generally can be managed with intensification or reinstitution (e.g., following noncompliance) of the current antihypertensive regimen; there is no indication that hospitalization and immediate reduction of blood pressure is required in these situations.1200
Almost any desired blood pressure can be maintained by varying the rate of IV sodium nitroprusside infusion. Blood pressure reduction by sodium nitroprusside is a temporary measure. Administration of other longer-acting hypotensive agents should be started as soon as possible while the blood pressure is being controlled by sodium nitroprusside to minimize the duration of sodium nitroprusside therapy. The IV infusion should be slowed or stopped as the other medication takes effect.
Sodium nitroprusside is used in the management of acute decompensated (e.g., congestive) heart failure.524, 600 The precipitating cause of acute heart failure decompensation should be carefully assessed to inform appropriate treatment, optimize outcomes, and prevent future acute events in patients with heart failure.524 Current guidelines for the management of heart failure in adults generally recommend inhibition of the renin-angiotensin-aldosterone system with a combination of drug therapies, including neurohormonal antagonists (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-adrenergic blocking agents [β-blockers], aldosterone receptor antagonists), to inhibit the detrimental compensatory mechanisms in heart failure and reduce morbidity and mortality.524, 700, 701, 703 (See Uses: Heart Failure in Carvedilol 24:24 and in Sacubitril and Valsartan 24:32.92.) IV vasodilators have not been shown to improve outcomes in patients hospitalized for heart failure; however, in the absence of symptomatic hypotension, sodium nitroprusside may be considered as an adjunct to diuretic therapy for relief of dyspnea in patients hospitalized for acutely decompensated heart failure.524 Administration of the drug produces rapid hemodynamic and clinical improvement by inducing arteriolar dilatation with subsequent reduction in systemic vascular resistance, thereby increasing cardiac output; by producing vasodilation and thus decreasing left ventricular filling, ventricular filling pressures are reduced. In addition, sodium nitroprusside has been reported to be particularly useful in the management of severe heart failure caused by the regurgitant valvular lesions of aortic insufficiency and mitral regurgitation.26, 524 Some experts state that sodium nitroprusside may also be potentially useful in the management of heart failure in patients with severe pulmonary congestion and hypertension.524
Controlled Hypotension during Surgery
Sodium nitroprusside also is used to produce controlled hypotension during anesthesia in order to reduce bleeding during surgical procedures when appropriate. Use of the drug is contraindicated in patients with inadequate cerebral circulation or in patients requiring emergency surgery who are near death.600
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†.100, 101, 102, 202, 527 An inotropic agent (e.g., dobutamine) should be used initially to improve myocardial contractility and cardiac output; if blood pressure permits, afterload-reducing agents may be added to decrease cardiac work and pulmonary congestion.202 Use of sodium nitroprusside may be limited by coronary steal, a phenomenon whereby altered myocardial blood flow distribution causes diversion of blood away from ischemic areas.202, 602 Nitroglycerin is the preferred vasodilator in patients with acute MI because of its ability to relieve ischemia by reducing left ventricular preload and increasing coronary blood flow.202, 527
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 Because of the potential for toxicity, the drug should be administered for the shortest possible duration.600, 1200 Prolonged infusions should not exceed a rate of 3 mcg/kg per minute to prevent thiocyanate (byproduct of sodium nitroprusside metabolism) concentrations from reaching neurotoxic levels; thiocyanate concentrations should be monitored daily if this rate is exceeded.600
Commercially available sodium nitroprusside injection concentrate (25 mg/mL) must be further diluted prior to IV infusion.600 The contents of one vial 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 Nitroprusside solutions 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 (See Chemistry and Stability: Stability.) Parenteral solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration.600 The freshly prepared infusion solution has a very faint brownish tint; if it is highly colored (e.g., blue, green, red) or contains particulate matter, it should be discarded.600 No other drug should be added to the infusion fluid for simultaneous administration with sodium nitroprusside.600
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 |
Hypertensive Crises or Controlled Hypotension during Surgery
In adults and pediatric patients 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;600 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 Some experts state that for management of severe hypertension with life-threatening symptoms in children and adolescents, an initial infusion rate of 0-3 mcg/kg per minute should be used.1150 These experts suggest that blood pressure be reduced by no more than 25% of the planned reduction over the first 8 hours, with the remainder of the planned reduction over the next 12-24 hours.1150 For the management of a hypertensive emergency in adults, some experts recommend an initial dosage of 0.3-0.5 mcg/kg per minute, with increases in increments of 0.5 mcg/kg per minute, up to a maximum rate of 10 mcg/kg per minute, to achieve desired blood pressure control.1200 The infusion duration should be as short as possible;1200 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 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
Diastolic blood pressure usually is decreased and maintained about 30-40% below pretreatment levels with sodium nitroprusside dosages of 3 mcg/kg per minute. Smaller dosages of sodium nitroprusside are adequate in patients receiving other hypotensive agents and in geriatric patients.
In adults who have a hypertensive emergency with a compelling indication (i.e., aortic dissection, pheochromocytoma crisis), some experts recommend that systolic blood pressure be reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes.1200 In adults who have a hypertensive emergency without a compelling indication, systolic blood pressure should be reduced by no more than 25% over the first hour, followed by further blood pressure reduction if stable to 160/110 or 160/100 mm Hg within the next 2-6 hours; excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia should be avoided.1200 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.1200
Longer-acting hypotensive agents should be administered concomitantly with sodium nitroprusside to minimize the duration of sodium nitroprusside therapy.600
When sodium nitroprusside is used in adults and 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 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
The most clinically important adverse effects of sodium nitroprusside are profound hypotension and cyanide toxicity.600 Other adverse effects are less common and develop less rapidly.600
Sodium nitroprusside can produce precipitous decreases in blood pressure and profound hypotension when administered at transient, slightly excessive infusion rates; the subsequent hemodynamic changes can result in a variety of associated symptoms, or blood pressure may decrease to the point where perfusion of vital organs may be compromised.600 The hypotensive effect of the drug occurs rapidly and the possible sequelae of hypotension (e.g., irreversible ischemic injury, death) are serious.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. The capacity of this system is exceeded when more than 500 mcg/kg of sodium nitroprusside is given; this amount is produced in less than 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
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 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 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
Infusions of sodium nitroprusside can result in the sequestration of hemoglobin as methemoglobin; cyanide combines with methemoglobin to form cyanmethemoglobin. Although the conversion of methemoglobin back to hemoglobin is normally rapid, clinically important methemoglobinemia (greater than 10%) rarely may occur.600 Even patients who are congenitally incapable of converting methemoglobin back to hemoglobin should demonstrate 10% methemoglobinemia only following a total sodium nitroprusside dose of 10 mg/kg (i.e., infusion at the maximum recommended rate of 10 mcg/kg per minute for greater than 16 hours).600 Methemoglobinemia should be suspected in patients who have received greater than 10 mg/kg of sodium nitroprusside and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and arterial PaO2.600
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.600 (See Cautions: Precautions and Contraindications, and Chronic Toxicity.) Thiocyanate is mildly neurotoxic (e.g., tinnitus, miosis, hyperreflexia) at serum concentrations of 60 mcg/mL and may be life-threatening at concentrations of 200 mcg/mL.600 (See Cautions: Precautions and Contraindications
Since thiocyanate inhibits both uptake and binding of iodine, symptoms of hypothyroidism may occur. Thiocyanate retention and hypothyroidism have been reported in one patient with severe hypertension and uremia who had received 3.9 g of sodium nitroprusside IV over a period of 21 days. Elevated plasma thiocyanate concentrations and signs of hypothyroidism diminished after peritoneal dialysis.
Cyanogen (cyanide radical) as well as thiocyanate may interfere with vitamin B12 distribution and metabolism. A fall in total plasma cobalamins has been reported during administration of sodium nitroprusside; however, a rise in plasma cyanocobalamin has been noted in patients receiving the drug for prolonged periods.
Increases in serum creatinine concentrations, which returned to normal after the infusion was stopped, have also occurred during sodium nitroprusside use.
Other adverse effects resulting from IV administration of sodium nitroprusside are uncommon and are usually associated with a too-rapid reduction in blood pressure. Nausea, retching, diaphoresis, apprehension, headache, restlessness, muscle twitching, retrosternal discomfort, palpitation, dizziness, and abdominal pain or cramps have been reported during use of the drug.600 These symptoms may be relieved by slowing the rate of infusion or temporarily discontinuing the drug, or minimized by keeping the patient supine. In addition, bradycardia, tachycardia, ECG changes, rash, decreased platelet aggregation, ileus, increased intracranial pressure, flushing, venous streaking, and irritation at the site of injection have been reported.
Precautions and Contraindications
Sodium nitroprusside injection concentrate is not suitable for direct injection; the drug must be further diluted in 5% dextrose injection before IV infusion.600 (See Dosage and Administration: Administration.)
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 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 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.
Except when used for short periods of time or at low infusion rates (e.g., 2 mcg/kg per minute or slower), therapy with sodium nitroprusside can result in the production of clinically important levels of cyanide, which can reach toxic or potentially lethal concentrations.600 If excessive dosages of sodium nitroprusside are used and/or sulfur (usually thiosulfate) stores become depleted, cyanogen toxicity may occur. (See Cautions: Cyanogenic Effects and see Chronic Toxicity.) Sodium nitroprusside infusions at the maximum recommended infusion 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.600
Sodium nitroprusside should be used with caution in patients with hepatic insufficiency, hypothyroidism, or hyponatremia. 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), 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 When prolonged infusions are more rapid than these, serum thiocyanate concentrations should be monitored daily.600 Some clinicians recommend that plasma cyanogen concentrations be monitored daily after 1 or 2 days in patients with impaired hepatic function. Peritoneal dialysis or hemodialysis may be required to remove excess thiocyanate and relieve the symptoms. (See Chronic Toxicity: Treatment.)
Because sodium nitroprusside may interfere with vitamin B12 distribution and metabolism, the drug should be used with caution in patients with low plasma vitamin B12 concentrations. Because hydroxocobalamin is an antidote for cyanogen (combining to form cyanocobalamin), its use may be advisable before and during sodium nitroprusside administration in these patients.
Frequent monitoring of acid-base balance is necessary in all patients, particularly if tolerance to the pharmacologic effects of sodium nitroprusside develops during therapy (manifested as the need for higher infusion rates to control blood pressure), since metabolic acidosis is one of the earliest and most reliable signs of cyanogen toxicity; however, laboratory tests alone should not be relied upon to guide therapy since acidosis may not be evident until more than 1 hour after the development of toxic cyanogen concentrations. If signs of metabolic acidosis or increased tolerance to the hypotensive effect of the drug occurs during sodium nitroprusside therapy, the drug should be discontinued and alternative treatment should be administered.
In patients with symptomatic methemoglobinemia (i.e., 10% or greater), 1-2 mg/kg of methylene blue should be administered IV slowly over several minutes.600 However, treatment of methemoglobinemia should be undertaken with extreme caution in patients who are likely to have substantial amounts of cyanide bound to methemoglobin as cyanmethemoglobin.600
Young, healthy males may require higher than recommended dosages of sodium nitroprusside for hypotensive anesthetic procedures; however, the maximum infusion rate of 10 mcg/kg per minute should not be exceeded. (See Dosage and Administration: Dosage.) Deepening of anesthesia in these patients may produce adequate hypotension with administration of sodium nitroprusside in the recommended dosage range.
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
When IV sodium nitroprusside is used for controlled hypotension during anesthesia, tolerance to loss of blood, anemia, and hypovolemia may be decreased. If possible, preexisting anemia and hypovolemia should be corrected prior to use of the drug. Hypotensive anesthetic techniques also may affect pulmonary ventilation perfusion ratio. In patients who cannot tolerate additional dead air space at normal oxygen partial pressure, higher oxygen partial pressure may be beneficial. Sodium nitroprusside IV infusion should be used with extreme caution in patients who are especially poor surgical risks.
The use of sodium nitroprusside to produce controlled hypotension during surgery is contraindicated in patients with inadequate cerebral circulation and is not intended for use during emergency surgery in patients near death.600 Sodium nitroprusside should not be used in the treatment of compensatory hypertension (e.g., arteriovenous shunt or coarctation of the aorta).600 Use of the drug also should be avoided in patients with congenital (Leber's) optic atrophy or tobacco amblyopia; these conditions, although rare, are associated with absent or deficient thiosulfate sulfurtransferase (rhodanase), and these patients have unusually high cyanogen to thiocyanate ratios. The manufacturer states that sodium nitroprusside should not be used in patients with acute heart failure associated with reduced peripheral vascular resistance, such as high-output heart failure that may accompany endotoxic sepsis.600 Concomitant use of sodium nitroprusside and phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil) or soluble guanylate cyclase stimulators (e.g., riociguat) is contraindicated because of the potential for additive hypotensive effects.600
Sodium nitroprusside has been used to induce hypotension in a limited number of patients younger than 17 years of a at least 50% of such patients were prepubertal, and about 50% of prepubertal patients were younger than 2 years of age, including 4 neonates.600 Efficacy of the drug in pediatric patients has been established in a parallel, dose-ranging study and a long-term infusion study in which sodium nitroprusside dosage was titrated according to blood pressure; the primary efficacy variable in these studies was mean arterial pressure (MAP).600, 601 Both studies demonstrated the blood pressure-lowering effect of sodium nitroprusside.601 In the latter study, sodium nitroprusside reduced MAP below that of placebo control for at least 12 hours.600 Similar effects on MAP were observed in all age groups in these studies, and no novel safety issues were noted.600
Pregnancy, Fertility, and Lactation
Animal reproduction studies have not been performed with sodium nitroprusside. It is also not known whether the drug can cause fetal harm when administered to pregnant women. The manufacturer states that sodium nitroprusside should be used during pregnancy only when clearly needed; some experts state that the drug is contraindicated in women with preeclampsia or eclampsia.1200
The effects of sodium thiosulfate administration during pregnancy, either alone or in conjunction with sodium nitroprusside, are unknown.
It is not known whether sodium nitroprusside affects fertility in humans.
It is not known if sodium nitroprusside and its metabolites are distributed into human milk.600 Because many drugs are distributed into milk and because of the potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.600
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.
Additive hypotensive effects can occur if sodium nitroprusside is used concomitantly with phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil).600 Concomitant use of these drugs is contraindicated.600
Soluble Guanylate Cyclase Stimulators
Additive hypotensive effects can occur if sodium nitroprusside is used concomitantly with soluble guanylate cyclase stimulators (e.g., riociguat).600 Concomitant use of these drugs is contraindicated.600
Following IV administration, sodium nitroprusside is rapidly metabolized to cyanogen (cyanide radical) and subsequently converted to thiocyanate by the enzyme rhodanase. The rate of conversion from cyanogen to thiocyanate depends on the availability of sulfur, usually thiosulfate; however, cyanide toxicity can occur if excessive dosages of sodium nitroprusside are used and/or sulfur stores become depleted.
The toxicity of sodium nitroprusside has been attributed to cyanogen; however, the role of cyanogen in sodium nitroprusside poisoning has been questioned and it has been postulated that some toxic effects may be caused by profound hypotension.
The first signs of overdosage with sodium nitroprusside are those related to severe hypotension. Increasing tolerance to the hypotensive effects of the drug and metabolic acidosis are also early indications of overdosage with sodium nitroprusside and may be associated with or followed by dyspnea, headache, vomiting, dizziness, ataxia, or loss of consciousness. Frequent monitoring of acid-base balance is necessary in all patients receiving sodium nitroprusside, particularly in patients who develop tolerance to the drug's pharmacologic effects, since metabolic acidosis is the most reliable sign of cyanogen toxicity; however, laboratory tests alone should not be relied upon to guide therapy since acidosis may not be evident until more than 1 hour after the development of toxic cyanogen concentrations. Reasonable suspicion of cyanogen toxicity is adequate basis for initiation of treatment. If signs of metabolic acidosis or tolerance to the hypotensive effect of the drug occurs during sodium nitroprusside therapy, the drug should be discontinued and alternative treatment should be administered. Signs or symptoms of cyanogen toxicity may include coma, imperceptible pulse, absent reflexes, dilated pupils, pink coloration of the skin, distant heart sounds, or shallow breathing.
Deaths clearly caused by sodium nitroprusside are limited to cases in which large oral doses were taken in suicides. Autopsy showed all organs to be congested and some evidence of cyanogen poisoning was observed.
In the event of overdosage with sodium nitroprusside, nitrites should be administered to induce methemoglobin formation. Oxygen administration alone will not provide relief. Methemoglobin combines with cyanogen bound to cytochrome-c oxidase to yield cytochrome-c oxidase and cyanmethemoglobin, a nontoxic complex. Cyanogen gradually dissociates from cyanmethemoglobin and is converted to sodium thiocyanate by administration of thiosulfate in the presence of thiosulfate sulfurtransferase (rhodanase).
When overdosage with sodium nitroprusside occurs with signs of cyanogen toxicity, sodium nitroprusside should be discontinued; amyl nitrite inhalations may be administered until IV access can be established for sodium nitrite administration.600 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 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 Blood pressure should be carefully monitored during sodium nitrite administration since vasodilation and hypotension may occur; hypotension should be managed routinely. 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. Injections of sodium nitrite and sodium thiosulfate may be repeated at one-half the initial recommended doses after 2 hours.600
Thiosulfate treatment of acute cyanide toxicity will increase the serum concentration of thiocyanate; however, the increase should not pose any risk to the patient. Physiologic methods (e.g., altering urinary pH) have not been demonstrated to increase the elimination of thiocyanate.600 Although hemodialysis is ineffective for the removal of cyanide from circulation, most thiocyanate will be removed by this procedure; the clearance rate of thiocyanate can approach the blood flow rate of the dialyzer.600
Sodium nitroprusside is a potent direct arterial and venous dilator.600, 602 When sodium nitroprusside is administered by IV infusion to hypertensive or normotensive patients, a marked lowering of arterial blood pressure is produced. Venous pressure is also lowered and a moderate reduction in total peripheral resistance occurs. The effects of the drug on blood pressure are more pronounced in hypertensive than in normotensive patients.
The hypotensive action of sodium nitroprusside results from peripheral vasodilation caused by a direct action on vascular smooth muscle. Animal tests performed in situ have demonstrated no relaxation of other smooth muscle tissue, such as the uterus or duodenum, by sodium nitroprusside. The drug has no direct effect on vasomotor centers, sympathetic nerves, or adrenergic receptors. The hypotensive effect of sodium nitroprusside is augmented by concomitant use of other hypotensive agents and is not blocked by adrenergic blocking agents or vagotomy. Pressor agents such as epinephrine which stimulate the myocardium directly are the only drugs that cause an increase in blood pressure during sodium nitroprusside therapy. Resistance to the drug's hypotensive effects is very rare.
The effects of sodium nitroprusside on cardiac performance appear to depend on preexisting performance. Changes in cardiac performance are attributed mainly to a reduction in left ventricular afterload resulting from vasodilation but may also be related to reduction in venous return to the heart resulting from peripheral vascular pooling of blood, decreased arteriolar resistance, and increased diastolic compliance. The drug may exert a direct coronary vasodilator effect. When sodium nitroprusside is administered to hypertensive patients, a slight increase in heart rate usually occurs and cardiac output is usually decreased slightly. Decreases in cardiac index and stroke index are common; however, these decreases do not occur consistently and increases have occurred in some patients. When sodium nitroprusside is administered to patients with refractory heart failure and/or acute myocardial infarction, substantial improvement in left ventricular performance results with cardiac output, cardiac index, and stroke volume being increased and left ventricular filling pressure being decreased. In patients with congestive heart failure, a slight but clinically important slowing of the heart rate results, as well as reduction or cessation of arrhythmias. A reduction in myocardial oxygen consumption during sodium nitroprusside use has been noted which could prove beneficial when infarcted areas of the heart are already short of oxygen. In patients with congestive heart failure, improvement in cardiac performance is accompanied by prompt diuresis, with urine volume and sodium excretion both being increased.
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. Mean renal arterial pressure and renal vascular resistance are slightly decreased. The acute reduction in mean arterial pressure is accompanied by an increase in renin activity of renal venous plasma.
IV infusion of sodium nitroprusside produces an almost immediate reduction in blood pressure. Blood pressure begins to rise immediately when the infusion is slowed or stopped and returns to pretreatment levels within 1-10 minutes.
Distribution of nitroprusside in the body as well as passage across the placenta, into milk, or across the blood-brain barrier has not been studied.
Sodium nitroprusside is rapidly metabolized, probably by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase (rhodanase). This mitochondrial enzyme normally is present in excess quantities such that the rate-limiting step in the conversion of cyanogen to thiocyanate usually is the availability of sulfur donors (e.g., thiosulfate, cystine, cysteine). A thiocyanate oxidase present in the erythrocytes may oxidize small quantities of thiocyanate back to cyanogen. Toxic symptoms begin to appear at plasma thiocyanate concentrations of 50-100 mcg/mL; fatalities have been reported at concentrations of 200 mcg/mL.
Sodium nitroprusside is excreted entirely as metabolites, principally thiocyanate. In animals, sodium nitroprusside metabolites are excreted mainly in urine, exhaled air, and probably in feces. The elimination half-life of thiocyanate is 2.7-7 days when renal function is normal but is longer in patients with impaired renal function or hyponatremia.
Sodium nitroprusside is a hypotensive agent which is structurally unrelated to other available hypotensive agents. Sodium nitroprusside is commercially available as the dihydrate, and potency is expressed in terms of the hydrated drug. The drug occurs as reddish-brown, practically odorless, crystals or powder and is freely soluble in water and slightly soluble in alcohol.
Sodium nitroprusside is sensitive to, and must be protected from, light, heat, and moisture. Sodium nitroprusside injection concentrate should be protected from light and stored at 20-25°C.600
Exposure of sodium nitroprusside solutions to light causes deterioration which may be evidenced by a change from a brown to a blue color caused by reduction of the ferric ion to the ferrous ion. It has been reported that approximately 20% of sodium nitroprusside in solution in glass bottles undergoes degradation within 4 hours when exposed to fluorescent light. Solutions in Viaflex® bags exposed to fluorescent light are degraded even more rapidly. Specialized references should be consulted for specific stability information. Sodium nitroprusside solutions should be protected from light by wrapping the container with aluminum foil or other opaque material.600 If properly protected from light, diluted solutions of the drug are stable for 24 hours.600 Sodium nitroprusside solution is rapidly degraded by trace contaminants often forming highly colored products, usually blue, green, or red.600 If this occurs, the solution should be discarded.600 No other drug or preservative should be added to sodium nitroprusside infusions.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
26. Chatterjee K, Parmley WW, Swan HJ et al. Beneficial effects of vasodilator agents in severe mitral regurgitation due to dysfunction of subvalvar apparatus. Circulation . 1973; 48:684-90. [PubMed 4744778]
100. Franciosa JA, Limas CJ, Guiha NH et al. Improved left ventricular function during nitroprusside infusion in acute myocardial infarction. Lancet . 1972; 1:650-4. [PubMed 4125161]
101. Chatterjee K, Parmley WW, Ganz W et al. Hemodynamic and metabolic responses to vasodilator therapy in acute myocardial infarction. Circulation . 1973; 48:1183-93. [PubMed 4762476]
102. Armstrong PW, Walker DC, Burton JR et al. Vasodilator therapy in acute myocardial infarction. A comparison of sodium nitroprusside and nitroglycerin. Circulation . 1975; 52:1118-22. [PubMed 810265]
202. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation . 2004; 110:e82-292. [PubMed 15339869]
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.
249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
250. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
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.
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013; 127:e362-425. [PubMed 23247304]
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]
550. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2017; [PubMed 29133354]
600. Hospira Inc. Nitropress® (sodium nitroprusside) injection prescribing information. Lake Forest, IL; 2017 Oct.
601. Food and Drug Administration. Pediatric studies of sodium nitroprusside conducted in accordance with the public health service act; availability of summary report and requested labeling changes. [Docket No. FDA-2012-N-02848]. Fed Regist. 2014; 79:4167-8.
602. Hottinger DG, Beebe DS, Kozhimannil T et al. Sodium nitroprusside in 2014: A clinical concepts review. J Anaesthesiol Clin Pharmacol . 2014; 30:462-71. [PubMed 25425768]
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]
1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics . 2017; 140 [PubMed 28827377]
1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension . 2018; 71:el13-e115. [PubMed 29133356]