Toxicity
Contained in some insecticides and smoke from burning plastic
Cyanide is a metabolite of sodium nitroprusside – prolonged high-dose use may lead to cyanide toxicity
Cyanide reversibly binds to, and inhibits, cytochrome oxidase within the mitochondria
Cytochrome oxidase is last enzyme (complex 4) in the respiratory electron transport chain. It generates a transmembrane electrochemical potential which ATP synthase uses to synthesise ATP
As such, in cyanide toxicity, ATP is produced only by anaerobic means and cytotoxic hypoxia ensues.
Features
- Clinical features are vague
- Confusion
- Dyspnoea
- Coma
- Seizures
- Classic biochemical picture is of unexplained lactic acidosis and high ScvO2 (anaerobic metabolism despite adequate oxygen delivery)
Management
Cyanide can be absorbed through the skin – avoid contamination!
Consider gastric lavage
The following antidotes are available:
Amyl nitrate
- Converts haemoglobin to methaemoglobin
- Cyanide has a higher affinity for methaemoglobin than for cytochrome oxidase so preferably binds to the former
- High methaemoglobin levels may however result in reduced O2 delivery
- Titrate therapy to achieve methaemoglobin levels of 20-30%
Hydroxocobalamin
- Binds to cyanide to form cyanocobalamin (excreted in urine)
- Used on a routine basis for smoke inhalation victims regardless of evidence of cyanide toxicity
Sodium thiosulphate
- Binds to cyanide to form thiocyanate (excreted in urine)
- This reaction is however slow so sodium thiosulphate cannot be used as monotherapy
Dicobalt edetate (EDTA)
- Cobalt ions bind to cyanide
- Limited to severe cases as ocbalt-containing compounds are toxic (mitigated by co-administration of glucose)
