Nitroprusside Side Effects
For the Consumer
Applies to nitroprusside: intravenous powder for injection, intravenous solution
Get emergency medical help if you have any of these signs of an allergic reaction while taking nitroprusside: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Tell your caregivers at once if you have a serious side effect such as:
feeling like you might pass out, even while lying down;
gasping, struggling to breathe, or shallow breathing;
confusion, ringing in your ears;
dizziness with nausea and vomiting, rapid breathing, seizure (convulsions);
fast, slow, or uneven heart rate;
numb or cold feeling in your arms and legs; or
chills, sweating, tremors, twitching, overactive reflexes.
Less serious side effects of nitroprusside may include:
mild skin rash;
mild stomach pain or nausea;
warmth, redness, or tingly feeling under your skin;
darkening or deeper color of veins through your skin; or
irritation around the IV needle.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
For Healthcare Professionals
Applies to nitroprusside: intravenous powder for injection, intravenous solution
Nitroprusside toxicity may present as hypotension, cyanide toxicity, or thiocyanate toxicity.[Ref]
Metabolic side effects are potentially life-threatening. Nitroprusside metabolism involves the production of cyanide (CN), which may be extremely toxic. Cyanide is normally immediately converted by rhodanase to thiocyanate, which has 1% the toxicity of cyanide and is normally readily eliminated by the kidney.
Cyanide may irreversibly block electron transport in mitochondrial cytochromes, which may result in metabolic acidosis and/or ischemia injury or death. Acidosis may not appear until more than one hour after the appearance of dangerous CN levels, and prompt countermeasures are recommended without further tests.
Cyanide accumulation is more likely in patients who are receiving nitroprusside at rates of 2 mcg/kg/min or more, but has been reported in rare cases after lesser dosages within 0.5 to 3.0 hours of infusion time. The risk of thiocyanate toxicity is increased in patients with underlying renal insufficiency.
Cardiopulmonary bypass is a risk factor in the development of cyanide toxicity associated with nitroprusside. Hemoglobin is a biologically active substance capable of catalyzing the release of cyanide from nitroprusside. Hemolysis occurs as a consequence of cell injury during CPB which may make a greater amount of hemoglobin available to react with nitroprusside and this ultimately increases the risk of cyanide toxicity.
Thiocyanate may cause mild tinnitus, miosis, and hyperreflexia at serum levels of 60 mcg/L, but may be life-threatening at serum levels of 200 mcg/L. Thiocyanate may interfere with iodine uptake by the thyroid.[Ref]
Cytochrome toxicity is more likely when serum cyanide levels exceed 200 mcmol/L, and is expected with serum CN levels between 300 and 3,000 mcmol/L in patients with normal red blood cell concentrations and mass.
Nitroprusside should be stopped if toxicity is suspected or documented. Amyl nitrite inhalant can be administered if intravenous access is not immediately available.
Cyanide toxicity can be prevented and treated by infusing sodium nitrite 3% solution 4 to 6 mg/kg (approximately 0.2 mL/kg) over 2 to 4 minutes, then sodium thiosulfate 25% solution 150 to 200 mg/kg (approximately 50 mL). This regimen may be repeated at half doses in 2 hours, if needed.[Ref]
Cardiovascular side effects have included profound and potentially reversible hypotension and myocardial ischemia. Nitroprusside-induced precipitous decreases in blood pressure can result in irreversible ischemic injuries or death. Tachycardia, bradycardia, flushing, palpitations, ECG changes, venous streaking, and retrosternal discomfort have also been reported.[Ref]
Myocardial ischemia is thought to be due to a "coronary artery steal phenomenon" due to nitroprusside-induced decreased coronary vascular resistance.[Ref]
Nervous system side effects usually associated with excessively rapid decreases in blood pressure have included headache, restlessness, apprehension, muscle twitching, and dizziness. Cyanide toxicity has been associated with ataxia, seizures, stroke, confusion, drowsiness, coma, increased intracranial pressure, bilateral globus pallidum necrosis, and death.[Ref]
Patients who require mechanical ventilation, who are anesthetized, or who are sedated or immobilized are at higher risk of hypoxemia because areas of their lungs may be hypoventilated due to ventilation-perfusion mismatch. Nitroglycerin also may cause this phenomenon.
A 32-year-old female who had received nitroprusside to provide controlled hypotension during surgery developed acute pulmonary edema postoperatively. The patient was thought to be normovolemic with increased pulmonary capillary permeability due to an unknown mechanism. The patient had also received general anesthesia and propranolol.
A 29-year-old female developed fatal Adult Respiratory Distress Syndrome (ARDS) five days after beginning nitroprusside for postpartum hypertension. Her syndrome was complicated by disseminated intravascular coagulopathy (DIC), microangiopathic anemia, anuria, and acute renal failure. The patient had previously recovered from postpartum shock and DIC before developing ARDS.[Ref]
Respiratory side effects are related to the vasodilatory properties of nitroprusside. Significant increases in ventilation-perfusion mismatch have been documented due to an inhibition of the normal hypoxic vasoconstrictive reflex that occurs in hypoventilated areas of the lung. This may result in significant hypoxemia. A case of acute pulmonary edema and Adult Respiratory Distress Syndrome (ARDS) has been associated with the use of this drug. Nasal stuffiness has also been reported.[Ref]
Methemoglobinemia should be promptly treated with methylene blue 1 to 2 mg/kg intravenously over several minutes. Caution is recommended when antidotal methylene blue is administered since it may cause release of hemoglobin-bound cyanide, which is potentially toxic.[Ref]
Hematologic side effects have included methemoglobinemia, thrombocytopenia, and platelet dysfunction. Methemoglobinemia has been more likely in patients who have received total doses of 10 mg/kg or more. Thrombocytopenia and platelet dysfunction have been more likely with infusion rates of 3 mcg/kg/min or more.[Ref]
Renal side effects have included increases in serum creatinine and rarely, renal insufficiency and acute azotemia.[Ref]
A 65-year-old male with coronary artery disease, diabetes mellitus, and new congestive heart failure associated with complete AV heart block developed progressive oliguric prerenal azotemia (despite improved cardiac output) and hypervolemia associated with nitroprusside. The oliguria and azotemia resolved after nitroprusside withdrawal. The patient was also receiving dobutamine. The authors believe the mechanism is possibly related to a "steal phenomenon" due to preferential dilation of nonrenal vascular beds. Alternatively, nitroprusside may have resulted in activation of the sympathetic nervous and renin-angiotensin systems, with secondary renal vasoconstriction and salt and water retention.
Implication of nitroprusside is difficult in many of the case reports because the patients had underlying cardiac or renal disease, as well as hemodynamic instability.[Ref]
A 65-year-old woman developed acute phlebitis at the intravenous site within 30 minutes after beginning nitroprusside therapy. The raised erythema along the vein disappeared within 30 minutes of drug discontinuation, and was reproducible on rechallenge. The authors of the case report believe the phlebitis was due to a local vasodilatory phenomenon rather than an allergic reaction.[Ref]
Local reactions have included acute phlebitis and injection site irritation.[Ref]
Gastrointestinal side effects have included abdominal pain (associated with rapid reduction of blood pressure), nausea, retching, vomiting, and rare reports of ileus.[Ref]
Endocrine side effects have included hypothyroidism due to thiocyanate-induced inhibition of iodine uptake by the thyroid. Diaphoresis has also been reported.[Ref]
Psychiatric side effects have rarely included delirium.[Ref]
Dermatologic side effects have included rash.[Ref]
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It is possible that some side effects of nitroprusside may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.
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