Sodium Nitroprusside

Sodium Nitroprusside is a rapid acting antihypertensive agent. Sodium Nitroprusside is a complex of iron, cyanide group and a nitroso moiety. Chemically Sodium Nitroprusside is disodium pentacyanonitrosylferrate (2-) dihydrate. Sodium Nitroprusside is a powerful vasodilator acts by direct dilatation of blood vessels. Given parenterally for severe and acute hypertensive emergencies or for control of blood pressure during surgical procedures. Duration of action is short as metabolized to cyanide and then thiocyanate. Excessive dosage may lead to cyanide poisoning.

Sodium Nitroprusside is primarily indicated in conditions like Analgesia especially during short operative procedure, Congestive heart failure, Heart failure, Hypertension, Hypertensive crisis, Hypertensive emergencies, Hypotensive anaesthesia, Maintenance of BP at 30-40% lower than pretreatment diastolic BP, Myocardial infarction, Prophylaxis of NSAID-induced duodenal ulcer, Severe or recurrent duodenal and gastric ulceration, and can also be given in adjunctive therapy as an alternative drug of choice in Arteriovenous shunt, Pre-eclampsia.

Sodium Nitroprusside is contraindicated in conditions like Tobacco amblyopia, Arteriovenous shunt, Coarctation of aorta, Vitamin B12 deficiency, Leber's optic atrophy.

The severe or irreversible adverse effects of Sodium Nitroprusside, which give rise to further complications include Hypothyroidism. Sodium Nitroprusside produces potentially life-threatening effects which include Increased anaerobic metabolism. which are responsible for the discontinuation of Sodium Nitroprusside therapy. The symptomatic adverse reactions produced by Sodium Nitroprusside are more or less tolerable and if they become severe, they can be treated symptomatically, these include Dizziness, Headache, Nausea, Restlessness, Palpitation, Diaphoresis, Muscle twitching, Retrosternal discomfort, Abdominal discomfort.

Injection concentrate must be further diluted with sterile 5% dextrose injection prior to infusion. (See Boxed Warning.) Slightly excessive infusion rates can result in profound hypotension; subsequent hemodynamic changes can result in various associated symptoms or BP may decrease to the point where perfusion of vital organs may be compromised. (See Boxed Warning.) This reaction is self-limiting within 1–10 minutes following discontinuance of the infusion; place patient in Trendelenburg’s position during this time to maximize venous return. If BP does not normalize within a few minutes, sodium nitroprusside may not be the cause of the hypotension and another cause should be sought. Infusion at rates >2 mcg/kg per minute generate cyanide ion (CN - ) in amounts greater than can be effectively buffered by the methemoglobin normally present in the body. (See Boxed Warning.) The capacity of the buffering system is exhausted by the CN - produced by 500 mcg/kg of sodium nitroprusside; this amount is administered in <1 hour when the drug is administered at 10 mcg/kg per minute. The actual frequency of clinically important cyanide toxicity not established. Most cases occurred with prolonged use or high dosages; however, elevated cyanide levels, metabolic acidosis, and marked clinical deterioration reported occasionally in patients receiving recommended rates of infusion for only a few hours, and in 1 case, for only 35 minutes. Toxic effects of cyanide may be rapid, serious, and fatal; toxicity may manifest as venous hyperoxemia (secondary to the inability of tissues to extract oxygen from erythrocytes, with resultant bright red venous blood), lactic acidosis, air hunger, confusion, and death. Monitor acid-base balance and venous oxygen concentrations; these tests may indicate cyanide toxicity, but do not rely on these tests alone to guide therapy. Hypertensive patients and those receiving other antihypertensive agents may be more sensitive to the effects of sodium nitroprusside than healthy individuals. Sodium thiosulfate has been administered with sodium nitroprusside at infusion rates 5–10 times that of the sodium nitroprusside to accelerate the metabolism of cyanide; coadministration of these agents has not been extensively researched and further study is needed. Caution advised; avoid prolonged or excessive dosages of sodium nitroprusside with sodium thiosulfate, since thiocyanate toxicity and/or hypovolemia may result. The same precautions and contraindications apply to this method of administration as to the administration of sodium nitroprusside alone. Reasonable suspicion of cyanide toxicity adequate to initiate treatment. First, discontinue sodium nitroprusside and administer 3% sodium nitrite solution IV at a dosage of 4–6 mg/kg (approximately 0.2 mL/kg of the 3% solution) injected over 2–4 minutes. This dose 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. Following these steps, administer a 10 or 25% solution of sodium thiosulfate IV in a dose of 150–200 mg/kg; a typical adult dose is 50 mL of the 25% solution. May repeat injections of sodium nitrite and sodium thiosulfate at one-half the initial recommended doses after 2 hours. Accumulation of thiocyanate can occur, especially in those with impaired renal function, those receiving prolonged infusions at infusion rates exceeding 3 mcg/kg per minute, or those receiving sodium thiosulfate concomitantly with sodium nitroprusside to accelerate the metabolism of cyanide to thiocyanate. Mild neurotoxic effects (e.g., tinnitus, miosis, hyperreflexia) possible at serum concentrations of 60 mcg/mL; may be life-threatening at concentrations of 200 mcg/mL. To maintain thiocyanate levels below 60 mcg/mL, one manufacturer recommends maintaining infusion rates of sodium nitroprusside below 3 mcg/kg per minute in patients with normal renal function or 1 mcg/kg per minute in anuric patients. Daily monitoring of serum thiocyanate levels recommended with more rapid infusions. Another manufacturer recommends maintaining infusion rates of sodium nitroprusside below 3 mcg/kg per minute in patients with eGFR of <30 mL/minute per 1.73 m 2 . Infusions of sodium nitroprusside result in the conversion of hemoglobin to methemoglobin in a dose-dependent manner. Can suspect methemoglobinemia 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 PaO 2 . In patients with symptomatic methemoglobinemia (i.e., ≥10%), infuse 1–2 mg/kg of methylene blue IV slowly over several minutes. Sodium nitroprusside can increase intracranial pressure. Use with caution in patients with increased intracranial pressure. Capacity to compensate for anemia and hypovolemia may be reduced when used for controlled hypotension during surgery. If possible, correct preexisting anemia and hypovolemia prior to use. Use with extreme caution in patients who are especially poor surgical risks. Based on animal findings and its mechanism of action, sodium nitroprusside may lead to cyanide exposure and adverse effects on the fetus. Available postmarketing data are insufficient to establish a drug-associated risk. Animal data has shown sodium nitroprusside crosses the placenta and exhibits maternal dose-related effects. Prolonged use and higher dosages of sodium nitroprusside during pregnancy can result in cyanide toxicity, which can be fatal to a developing fetus. In the unusual situation that there is no alternative therapy to sodium nitroprusside, inform pregnant women of the potential fetal risk. Not known whether sodium nitroprusside distributes into human milk; however, thiocyanate, a metabolite, is present in milk. It is unclear if and for how long thiocyanate levels in milk are clinically relevant. Efficacy established in pediatric patients based on adult trials and supported by 2 studies in pediatric patients <17 years of age, including neonates, for reduction of BP. In 2 pediatric studies, the drug produced similar effects on mean arterial pressure (MAP) in all age groups, and no novel safety issues were noted. Caution in geriatric patients; may exhibit greater sensitivity. Caution in patients with hepatic impairment; more susceptible to cyanide toxicity. Thiocyanate may accumulate in patients with renal impairment; monitor for thiocyanate toxicity (e.g., neurotoxic effects). Half-life may be doubled or tripled in renal failure. Thiocyanate may be removed with hemodialysis in cases of serious toxicity.

Injection concentrate must be further diluted with sterile 5% dextrose injection prior to infusion. (See Boxed Warning.) Slightly excessive infusion rates can result in profound hypotension; subsequent hemodynamic changes can result in various associated symptoms or BP may decrease to the point where perfusion of vital organs may be compromised. (See Boxed Warning.) This reaction is self-limiting within 1–10 minutes following discontinuance of the infusion; place patient in Trendelenburg’s position during this time to maximize venous return. If BP does not normalize within a few minutes, sodium nitroprusside may not be the cause of the hypotension and another cause should be sought. Infusion at rates >2 mcg/kg per minute generate cyanide ion (CN - ) in amounts greater than can be effectively buffered by the methemoglobin normally present in the body. (See Boxed Warning.) The capacity of the buffering system is exhausted by the CN - produced by 500 mcg/kg of sodium nitroprusside; this amount is administered in <1 hour when the drug is administered at 10 mcg/kg per minute. The actual frequency of clinically important cyanide toxicity not established. Most cases occurred with prolonged use or high dosages; however, elevated cyanide levels, metabolic acidosis, and marked clinical deterioration reported occasionally in patients receiving recommended rates of infusion for only a few hours, and in 1 case, for only 35 minutes. Toxic effects of cyanide may be rapid, serious, and fatal; toxicity may manifest as venous hyperoxemia (secondary to the inability of tissues to extract oxygen from erythrocytes, with resultant bright red venous blood), lactic acidosis, air hunger, confusion, and death. Monitor acid-base balance and venous oxygen concentrations; these tests may indicate cyanide toxicity, but do not rely on these tests alone to guide therapy. Hypertensive patients and those receiving other antihypertensive agents may be more sensitive to the effects of sodium nitroprusside than healthy individuals. Sodium thiosulfate has been administered with sodium nitroprusside at infusion rates 5–10 times that of the sodium nitroprusside to accelerate the metabolism of cyanide; coadministration of these agents has not been extensively researched and further study is needed. Caution advised; avoid prolonged or excessive dosages of sodium nitroprusside with sodium thiosulfate, since thiocyanate toxicity and/or hypovolemia may result. The same precautions and contraindications apply to this method of administration as to the administration of sodium nitroprusside alone. Reasonable suspicion of cyanide toxicity adequate to initiate treatment. First, discontinue sodium nitroprusside and administer 3% sodium nitrite solution IV at a dosage of 4–6 mg/kg (approximately 0.2 mL/kg of the 3% solution) injected over 2–4 minutes. This dose 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. Following these steps, administer a 10 or 25% solution of sodium thiosulfate IV in a dose of 150–200 mg/kg; a typical adult dose is 50 mL of the 25% solution. May repeat injections of sodium nitrite and sodium thiosulfate at one-half the initial recommended doses after 2 hours. Accumulation of thiocyanate can occur, especially in those with impaired renal function, those receiving prolonged infusions at infusion rates exceeding 3 mcg/kg per minute, or those receiving sodium thiosulfate concomitantly with sodium nitroprusside to accelerate the metabolism of cyanide to thiocyanate. Mild neurotoxic effects (e.g., tinnitus, miosis, hyperreflexia) possible at serum concentrations of 60 mcg/mL; may be life-threatening at concentrations of 200 mcg/mL. To maintain thiocyanate levels below 60 mcg/mL, one manufacturer recommends maintaining infusion rates of sodium nitroprusside below 3 mcg/kg per minute in patients with normal renal function or 1 mcg/kg per minute in anuric patients. Daily monitoring of serum thiocyanate levels recommended with more rapid infusions. Another manufacturer recommends maintaining infusion rates of sodium nitroprusside below 3 mcg/kg per minute in patients with eGFR of <30 mL/minute per 1.73 m 2 . Infusions of sodium nitroprusside result in the conversion of hemoglobin to methemoglobin in a dose-dependent manner. Can suspect methemoglobinemia 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 PaO 2 . In patients with symptomatic methemoglobinemia (i.e., ≥10%), infuse 1–2 mg/kg of methylene blue IV slowly over several minutes. Sodium nitroprusside can increase intracranial pressure. Use with caution in patients with increased intracranial pressure. Capacity to compensate for anemia and hypovolemia may be reduced when used for controlled hypotension during surgery. If possible, correct preexisting anemia and hypovolemia prior to use. Use with extreme caution in patients who are especially poor surgical risks. Based on animal findings and its mechanism of action, sodium nitroprusside may lead to cyanide exposure and adverse effects on the fetus. Available postmarketing data are insufficient to establish a drug-associated risk. Animal data has shown sodium nitroprusside crosses the placenta and exhibits maternal dose-related effects. Prolonged use and higher dosages of sodium nitroprusside during pregnancy can result in cyanide toxicity, which can be fatal to a developing fetus. In the unusual situation that there is no alternative therapy to sodium nitroprusside, inform pregnant women of the potential fetal risk. Not known whether sodium nitroprusside distributes into human milk; however, thiocyanate, a metabolite, is present in milk. It is unclear if and for how long thiocyanate levels in milk are clinically relevant. Efficacy established in pediatric patients based on adult trials and supported by 2 studies in pediatric patients <17 years of age, including neonates, for reduction of BP. In 2 pediatric studies, the drug produced similar effects on mean arterial pressure (MAP) in all age groups, and no novel safety issues were noted. Caution in geriatric patients; may exhibit greater sensitivity. Caution in patients with hepatic impairment; more susceptible to cyanide toxicity. Thiocyanate may accumulate in patients with renal impairment; monitor for thiocyanate toxicity (e.g., neurotoxic effects). Half-life may be doubled or tripled in renal failure. Thiocyanate may be removed with hemodialysis in cases of serious toxicity.

20 to 400 ug/min (210 (210)) As recommended. IV Inf — As Required

0.3 to 1.4 ug/kg.min (0.85 (0.85)) As recommended. IV Infusion — As required

( ) — Not recommended in this age group

Sodium Nitroprusside is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAlteplaseDigoxinDobutamine (HCl)Dopamine (HCl) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Inj (reconsitututed soln) Store at room temperature. Protect from Sunlight, Moisture and Heat. Use within 24 hrs if kept at room temperature.