Cyanide
GENERAL PRINCIPLES
• The most common source of cyanide poisoning in the US and other western countries is combustion of plastics and other synthetic materials in house fires.
• Patients may also be exposed to cyanide in laboratory or industrial settings, during therapy with sodium nitroprusside, or by ingestion of compounds that liberate cyanide during metabolism (such as acetonitrile, the pits of stone fruits, and inappropriately processed cassava).
Pathophysiology
• Cyanide is a chemical asphyxiant. It induces cellular hypoxia by inhibiting complex IV (also known as cytochrome c oxidase or cytochrome oxidase aa3) in the electron transport chain and thus preventing the formation of adenosine triphosphate which results in anaerobic metabolism and metabolic acidosis.
• Cyanide is also an excitotoxin in the central nervous system.
DIAGNOSIS
Clinical Presentation
• Poisoning by cyanide is typically rapid in onset and not subtle: patients are either critically ill or not poisoned.
Patients who have ingested cyanogenic substances may have a more delayed onset of toxicity and initial complain of more mild symptoms.
• Cyanide poisoning causes cardiovascular instability (initial tachycardia and hypertension followed by cardiovascular collapse) and neurotoxicity (mental status depression, seizures, and coma).
• “Classic” textbook signs of cyanide poisoning such as the bitter almond odor and cherry red skin discoloration are unreliable and should not be used to make or exclude the diagnosis of cyanide poisoning.
Diagnostic Testing
LABORATORIES
• Blood cyanide concentrations are not available in a timely fashion and have no role in clinical decision making.
• A profoundly elevated lactate (8-10 mmol/L or higher) in the correct clinical context is suggestive of cyanide toxicity.
• “Arterialization” of venous blood (i.e., equilibration of the venous and arterial pO2) may suggest cyanide toxicity, as cyanide poisoning effectively halts extraction of oxygen from arterial blood by the tissue.
TREATMENT
• The treatment of choice for cyanide poisoning is hydroxocobalamin.
î Hydroxocobalamin directly binds to cyanide, forming cyanocobalamin (vitamin B12).
î Hydroxocobalamin is safe—the adverse effects are usually minor and transient hypertension and tachycardia and discoloration of the skin and body fluids (which may briefly interfere with pulse oximetry and colorimetric laboratory tests).
î The dose of hydroxocobalamin is 5 g IV over 15 minutes.
#9632; This dose may be repeated once if necessary based on clinical response.
#9632; Usually, repeated dosing is not necessary, except in patients who have ingested cyanogenic substances.
• If hydroxocobalamin is not available, the older cyanide antidote kit may be used.
î First, sodium nitrite is used to induce methemoglobinemia; cyanide binds more avidly to methemoglobin than to complex IV, so methemoglobin formation encourages the dissociation of cyanide from the mitochondria.
î Second, sodium thiosulfate is administered to accelerate the endogenous detoxification of cyanide, which relies on the presence of sulfur donors.
î The antidote kit is not preferred as first-line therapy because the induction of methemoglobinemia can be dangerous in critically ill patients, nitrites cause hypotension, and the dosing of nitrites is challenging.
• The rest of care is supportive, including adequate volume resuscitation, airway support, and vasopressor and inotropic support as needed.