Cyanide Toxicity

Introduction

• Cyanide toxicity is a potentially lethal condition that may cause rapid hemodynamic and neurological dysfunction.^1,2
• Cyanide toxicity is usually suspected in the following settings:¹
  • Inhalation of smoke from domestic fires
  • Industrial exposures within metal industries, plastics, and agriculture
  • Prolonged administration of sodium nitroprusside at high doses
• Cyanide can exist as a gas (hydrogen cyanide) or a salt (potassium cyanide).³
• Cyanide is rapidly absorbed through the respiratory tract and mucus membranes. It can also be absorbed through the gastrointestinal tract and skin.³
• Cyanide reversibly binds to the ferric ions of cytochrome oxidase a3 within the mitochondria and inhibits oxidative phosphorylation and aerobic respiration.
• Despite adequate oxygenation, adenosine triphosphate (ATP) synthesis will shift to anaerobic respiration to create ATP. This process leads to the buildup of lactic acid and metabolic acidosis with normal to increased oxygen saturation.²
• In vivo, cyanide metabolism is primarily via rhodanese, an enzyme found abundantly in many tissues, especially the liver and muscle.³

Clinical Presentation and Diagnosis

• Cyanide toxicity must be considered in all patients with smoke inhalation smoke injury.¹
• Many presenting signs and symptoms of cyanide toxicity are nonspecific. Despite normal oxygen saturation on pulse oximetry, patients with cyanide toxicity may have tachycardia and tachypnea.
• Additional symptoms include confusion, dizziness, headaches, nausea, vomiting, hypotension, respiratory failure, or loss of consciousness. Less common signs and symptoms in cyanide toxicity are cardiac arrest, seizures, and cyanosis.²
• Cherry-red skin color and an almond odor are characteristic findings in cyanide toxicity. However, these presenting signs are rarely reported.²

Differential Diagnosis

• In the setting of smoke exposure, carbon monoxide poisoning is high in the differential diagnosis given its similar exposure risk and presentation. Of note, seizures and pupillary dilation are more common in cyanide toxicity and less likely to occur with carbon monoxide toxicity.³
• Other ingestions with similar presentations causing anion gap metabolic acidosis include ingestion of methanol, ethylene glycol, salicylates, and isoniazid.³

Laboratory and Diagnostic Tests

• The initial evaluation should include complete blood cell counts, serum electrolytes, urine drug screen, and urinalysis. An anion gap metabolic acidosis due to elevated lactate would be expected in cyanide toxicity.³
• An arterial blood gas (ABG) should be collected to measure pH and assess serum lactic acid levels. ABG shows normal P_aO₂ and S_aO₂ and elevated serum lactic acid concentration.
• Plasma lactate levels greater than 8 mmol/L has a 94% sensitivity and 70% specificity of elevated serum cyanide levels in an analysis of a small series of acute cyanide poisonings.⁴
• A venous blood gas shows normal to increased venous oxygen saturations (S_vO₂) as no aerobic respiration is taking place.
• A co-oximetry can be performed to measure carboxyhemoglobin (COHb) levels and screen for carbon monoxide poisoning given the similar presentation to cyanide poisoning. This would also measure a methemoglobin (MetHb) level to screen for methemoglobinemia, which is important as previous cyanide antidotes, such as 4-dimethylaminophenol (4-DMAP) and amyl or sodium nitrite, function as methemoglobin inducers.
• A pretreatment serum cyanide level may be ordered to confirm the diagnosis; however, the result of this test may take too long to result in the acute setting. As such, empiric treatment of cyanide toxicity is often indicated based on presentation and overall clinical picture.⁴

Management

The empiric treatment of suspected cyanide toxicity includes:

• Administration of 100% oxygen
• Stabilization of the patient’s airway, breathing, and circulation
• Mouth-to-mouth resuscitation is contraindicated because of the risk to the provider.³
• Cessation of the offending agent, such as sodium nitroprusside
• Correction of the lactic acidosis
• Decontamination is essential. All clothing should be removed and a dose of activated charcoal (50g in adults and 1g/kg up to a maximum of 50g in children) may be administered in cases of oral ingestion.³
• Administration of an antidote (see below)

Antidotes for cyanide toxicity include:

Hydroxocobalamin: First Line Treatment

• Hydroxocobalamin’s effectiveness as a cyanide antidote was first recognized in 1952. It was licensed for use in France in 1996 and approved by the FDA in 2008.²
• Hydroxocobalamin binds directly to cyanide and forms cyanocobalamin (vitamin B12), which is then excreted in the urine.
• Hydroxocobalamin has been suggested as the first line of treatment in patients suffering from smoke inhalation injuries due to its quick onset of action.²
• In the setting of smoke inhalation, 100% oxygen should be administered, and if the patient’s Glasgow coma scale is less than 14 or cardiovascular instability is present, hydroxocobalamin 5g should be administered intravenously (IV).³
• If the patient is in cardiac arrest, 10 g IV hydroxocobalamin may be administered.
• In the setting of plasma lactate levels greater than 10 mmol/L, 5g hydroxocobalamin may be administered.

Sodium Nitrate

• It has a slower onset than hydroxocobalamin.
• Forms methemoglobin which has a high affinity for CN, therefore, more cytochrome oxidase is available for aerobic metabolism.
• Sodium nitrite 300mg ampule (10 ml) or 10mg/kg IV should be administered over 3-5 min in adults and 0.2mL/kg in children, not to exceed 10 mL.³
• It should not be used if inhalation injury is suspected, as it needs to be converted to methemoglobin, which could be unsafe in patients with carbon monoxide toxicity.

Sodium Thiosulfate

• It is no longer recommended as a single antidote for cyanide toxicity because of its slow onset of action and short half-life.
• It is used in conjunction with other agents, such as hydroxocobalamin.
• Cyanide is naturally excreted from the body by binding sulfur to cyanide and forming thiocyanate which is then excreted by the kidneys.¹
• Treatment with sodium thiosulfate upregulates the body’s excretion of cyanide and limits toxicity.
• Side effects include nausea, vomiting, and headache.¹