Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity (see WARNINGS) or as thiocyanate toxicity (see ADVERSE REACTIONS).
The acute intravenous mean lethal doses (LD50) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.
Treatment of cyanide toxicity: Cyanide levels can be measured by many laboratories, and blood-gas studies that can detect venous hyperoxemia or acidosis are widely available. Acidosis may not appear until more than an hour after the appearance of dangerous cyanide levels, and laboratory tests should not be awaited. Reasonable suspicion of cyanide toxicity is adequate grounds for initiation of treatment.
Treatment of cyanide toxicity consists of
discontinuing the administration of sodium nitroprusside;
providing a buffer for cyanide by using sodium nitrite to convert as much hemoglobin into methemoglobin as the patient can safely tolerate; and then
infusing sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate.
The necessary medications for this treatment are contained in commercially available Cyanide Antidote Kits. Alternatively, discrete stocks of medications can be used.
Hemodialysis is ineffective in removal of cyanide, but it will eliminate most thiocyanate.
Cyanide Antidote Kits contain both amyl nitrite and sodium nitrite for induction of methemoglobinemia. The amyl nitrite is supplied in the form of inhalant ampoules, for administration in environments where intravenous administration of sodium nitrite may be delayed. In a patient who already has a patent intravenous line, use of amyl nitrite confers no benefit that is not provided by infusion of sodium nitrite.
Sodium nitrite is available in a 3% solution, and 4-6 mg/kg (about 0.2 mL/kg) should be injected over 2-4 minutes. This dose can be expected to convert about 10% of the patient’s hemoglobin into methemoglobin; this level of methemoglobinemia is not associated with any important hazard of its own. The nitrite infusion may cause transient vasodilatation and hypotension, and this hypotension must, if it occurs, be routinely managed.
Immediately after infusion of the sodium nitrite, sodium thiosulfate should be infused. This agent is available in 10% and 25% solutions, and the recommended dose is 150-200 mg/kg; a typical adult dose is 50 mL of the 25% solution. Thiosulfate treatment of an acutely cyanide-toxic patient will raise thiocyanate levels, but not to a dangerous degree.
The nitrite/thiosulfate regimen may be repeated, at half the original doses, after two hours.