Cyanide Poisoning

Overview

Definition

Cyanide is a highly lethal mitochondrial toxin causing death within minutes to hours of exposure.

Epidemiology

• Human exposures to cyanide 1993–2002: 3165 exposures (2.5% fatal)
• Annual incidence in the United States: 5,000–10,000 smoke inhalation deaths
• Industrial exposure and suicide by cyanide poisoning occur mostly in men.

Etiology

• Domestic fires: 
  • Most common cause of cyanide poisoning
  • Byproduct of synthetic product combustion (plastic, paints)
• Diet: ingestion of amygdalin (cyanogenic glucoside in apricot seeds)
• Medical: 
  • Side effect of nitroprusside use (either a high dose or long-term use) 
  • Short-acting medication for hypertensive emergency results in cyanide release
• Suicide or homicide: potassium cyanide, sodium cyanide
• Industrial: manufacturing workplace exposure

Pathophysiology and Clinical Presentation

Pathophysiology

• Absorbed through the skin, lungs, mucous membranes, or GI tract
• Quickly distributed throughout the body
• Major mechanism of action:
  • Inhibits the mitochondrial electron transport chain by the inhibition of complex IV (cytochrome c oxidase, a3 subunit) as it binds to ferric iron (Fe³⁺)
  • Result: blockage of oxidative phosphorylation and inhibition of aerobic ATP production
  • ATP is then produced primarily by the anaerobic pathway, resulting in lactic acid production and metabolic acidosis.
  • Result: functional histotoxic hypoxia:
    • Inability to use O₂ due to poisoned electron chain
    • Especially deleterious to the cardiovascular and central nervous systems
• Additional contributing mechanisms of cyanide:
  • Inhibition of antioxidants
  • Induction of apoptotic cell death
  • Inhibition of gamma-aminobutyric acid (GABA) formation → risk of seizures
  • Binds to hemoglobin → cyanohemoglobin (unable to transport O₂)
• Cyanide metabolism:
  • Detoxified by the rhodanese enzyme
  • Converts cyanide to water-soluble thiocyanate (needs sulfur), which is excreted in urine

Clinical presentation

Symptoms develop within seconds to minutes.

• Breath may have a bitter or almond odor.
• Skin:
  • Flushed or cherry red
  • Cyanosis (more common)
  • Irritant dermatitis
• Cardiovascular:
  • Tachycardia/hypertension
  • Progression to bradycardia/hypotension
  • Dysrhythmia, cardiac arrest
• Respiratory:
  • Tachypnea/hyperventilation (reduced PaCO₂)
  • Progression to respiratory depression/failure 
  • Pulmonary edema
• Neurologic:
  • Headache
  • Vertigo
  • Dizziness
  • Seizures
  • Coma
  • Anoxic brain injury and permanent brain damage
• Nausea and vomiting 
• Rhabdomyolysis
• Renal failure
• Hepatic necrosis

Diagnosis and Management

Diagnosis

History and physical exam:

• History of exposure
• Bitter/almond smell
• Color change of skin (flushed/cyanotic)
• Characteristic symptoms

Laboratory tests:

• Severe metabolic acidosis with anion gap
• ↑ Lactic acid
• Narrowed venous-arterial PO₂ gradient (venous hyperoxia)
• Blood cyanide level (not very reliable test)
• Glucose (to evaluate for hypoglycemia)
• Other tests to obtain:
  • Carboxyhemoglobin and methemoglobin: Rule out concomitant carbon monoxide (CO) exposure and ingestion of other drugs.
  • Acetaminophen and salicylate levels: Rule out coingestion of other drugs.

Management

General considerations:

• Address any suspected cyanide poisoning quickly because of high mortality.
• Can be hard to diagnose/recognize
• Suspect in any smoke inhalation victim.

Decontamination:

• Remove patient from the source.
• Remove clothes.
• Cleanse wounds.
• Administer activated charcoal in the case of oral ingestion.

Resuscitation:

• Assess airway, breathing, circulation (ABC).
• Secure airway and provide high flow O₂ (use of hyperbaric oxygenation is controversial).
• IV fluids and pressors if needed
• Glucose administration if hypoglycemic
• Benzodiazepines for seizures 

Antidotes:

• Hydroxocobalamin (vitamin B₁₂) directly binds cyanide molecules and is the preferred treatment. 
• Sodium thiosulfate acts as a sulfur donor for the enzyme rhodanese to convert cyanide to excretable thiocyanate.
• Nitrites (sodium nitrite or amyl nitrite) induce methemoglobinemia:
  • Converts ferrous iron (Fe²⁺) to Fe³⁺
  • Fe³⁺ binds cyanide and avidly forms cyanmethemoglobin.
  • Do not use for concomitant CO poisoning as induction of methemoglobinemia can be lethal.

Differential Diagnosis

• Methemoglobinemia: a condition of elevated methemoglobin containing oxidized Fe³⁺ instead of Fe²⁺. Methemoglobin does not bind O₂. Methemoglobinemia can be caused by nitrates, dapsone, and local anesthetics and causes tissue hypoxia. Presentation includes cyanosis, headache, dizziness, nausea, seizures, shortness of breath, and/or arrhythmias. Methemoglobinemia is diagnosed with blood gas and treated with methylene blue and vitamin C administration. 
• Carbon monoxide poisoning: an odorless, tasteless, colorless, nonirritating gas formed by hydrocarbon combustion (fires, car exhaust, gas heaters). Carbon monoxide has a higher affinity to hemoglobin than O₂ and forms carboxyhemoglobin, which results in impaired O₂ transport and utilization. Features include confusion, headache, dizziness, rosy cheeks, coma, and death. Diagnosis is established clinically and confirmed by blood gas. Management is 100% O₂ and, if failed, hyperbaric oxygenation. 
• Drug ingestion: various drugs can produce symptoms of poisoning similar to cyanide. The drugs include tricyclic antidepressants, salicylates, organophosphates, isoniazid, and strychnine. Detailed history and a high index of clinical suspicion are essential for correct diagnosis. Management depends on the offending agent.