Nitroprusside toxicity Treatment


Mechanism of Action of Sodium Nitroprusside:

After parenteral injection, sodium nitroprusside enters red blood cells, where it receives an electron from the iron (Fe2+) of oxyhemoglobin. This nonenzymatic electron transfer results in an unstable nitroprusside radical and methemoglobin (Hgb Fe3+). The former moiety spontaneously decomposes into five cyanide ions and the active nitroso (NO) group.

The cyanide ions can be involved in one of three possible reactions: 1) binding to methemoglobin to form cyanmethemoglobin; 2) undergoing a reaction in the liver and kidney catalyzed by the enzyme rhodanase (thiosulfate + cyanide thiocyanate); 3) or binding to tissue cytochrome oxidase, which interferes with normal oxygen utilization.

Sodium nitroprusside causes toxicity by three primary mechanisms: 1) the most common adverse effect is direct vasodilation resulting in hypotension and dysrhythmias; 2) thiocyanate toxicity occurs infrequently, resulting in tinnitus, altered mental status changes, nausea, and abdominal pain; 3) in rare cases, cyanide toxicity can occur, resulting in coma, metabolic acidosis, or respiratory arrest. In very rare cases, and in susceptible patients, methemoglobinemia can occur, which, if levels reach greater than 15 percent, can result in symptomatic cellular hypoxia.

Toxicity associated with sodium nitroprusside is usually related to prolonged administration or occurs in patients with renal or hepatic failure.

Cyanide toxicity

Acute cyanide toxicity occurs when the cyanide ions bind to tissue cytochrome oxidase and interfere with normal oxygen utilization. This as a result leads to metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (as a result of the inability to utilize oxygen). Another early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis). (It should be noted that tachyphylaxis implies acute tolerance to the drug following multiple rapid injections, as opposed to tolerance, which is caused by more chronic exposure). Cyanide toxicity can usually be avoided if the cumulative dose of sodium nitroprusside is less than 0.5 mg/kg/h.

Symptoms: Cyanide toxicity is often associated with the odor of almonds on breath and can result in acidosis, tachycardia, mental status changes, and death.

How to intervene: Patients with cyanide toxicity should be mechanically ventilated with 100% oxygen to maximize oxygen availability.

Pharmacological treatment: Treatment of cyanide toxicity depends on increasing the kinetics of the two reactions by administeringsodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrate (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin, or by limiting the administration of nitroprusside.


Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrate can be treated with methylene blue (1–2 mg/kg of a 1% solution over 5 min), which reduces methemoglobin to hemoglobin.

Thiocyanate toxicity

Symptoms: Thiocyanate toxicity causes anorexia, fatigue, and mental status changes, including psychosis, weakness, seizures, tinnitus, and hyperreflexia. Thiocyanate is usually excreted in the urine. Toxicity can be minimized by avoiding prolonged administration of nitroprusside and by limiting drug use in patients with renal insufficiency. If necessary, thiocyanate can be removed by dialysis.


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