Cyanide

Introduction and epidemiology

Cyanide refers to any substance that contains the cyano (CN) group. It is used in a variety of commercial processes including metal extraction (especially gold) and recovery, metal hardening and in the production of agricultural and horticultural pest control compounds. A list of potential sources of cyanide exposure is found in Box 25.13.1 .

Organic salts such as hydrogen cyanide (HCN) are highly toxic and can occur in a liquid or gaseous form. HCN has a distinctive odour of bitter almonds; however, 20% to 40% of people are genetically unable to detect this. Cyanide gas production from house fires is well documented. In one study, blood cyanide concentrations greater than 40 μmol/L (toxic level) were measured in 74% of victims found dead at the scenes of fires. In another study 11 of 138 patients with fire-related deaths had potentially fatal blood cyanide levels (greater than 100 μmol/L). It is suggested that in patients with severe burns, elevated lactate and/or carboxyhaemoglobin greater than 10%, the use of a safe cyanide antidote should be considered. It should be noted, however, although blood cyanide concentration can be measured, it is not of use for diagnosis in the acute setting as few laboratories perform the assay and results cannot be obtained rapidly. Diagnosis is therefore clinical.

Death from cyanide poisoning is one of the most rapid and dramatic seen in medicine and appropriate resuscitation with antidotal therapy must be given early to alter outcome. A dose of 200 mg of ingested cyanide, or a 3-minute exposure to HCN gas, is potentially lethal. Historically cyanide has been used in mass homicides (Zyklon B gas used by the Nazis during the Second World War) and suicide. Cyanide is considered a likely agent of terrorism because it possesses attributes of the ideal chemical weapon. It is readily available and, because of its use in industry and research laboratories, is widely distributed making it susceptible to theft, hijacking attempts and other terrorist acts and is capable of causing mass incapacitation and casualties. It can be released in the atmosphere as a gaseous weapon or introduced into pharmaceuticals, the food supply and is considered a primary threat to water supplies.

Toxicokinetics and pathophysiology

The uptake of cyanide into cells is rapid and follows a first-order kinetic simple diffusion process. The half-life of cyanide is from 2 to 3 hours.

While the precise in vivo action of cyanide is yet to be determined, it is believed that its major effect is due to binding with the ferric ion (Fe ³⁺ ) of cytochrome oxidase, the last cytochrome in the respiratory chain ( Fig 25.13.1 ). This results in inhibition of oxidative phosphorylation, halting electron transport, oxygen consumption and adenosine triphosphate (ATP) formation. This leads to a net accumulation of hydrogen ions, a change in the NAD:NADH ratio and greatly increased lactic acid production. Other enzymatic processes, involving antioxidant enzymes, catalase, superoxide dismutase and glutathione, may contribute to toxicity. Cyanide is also a potent stimulator of neurotransmitter release in both the central and the peripheral nervous systems. Humans detoxify cyanide by sulphur transfer to form thiocyanate (SCN). The availability of the enzymes that sequester cyanide as thiocyanate, rhodanase and 3-mercaptopyruvate sulphurtransferase is the rate-limiting step.

Clinical features ( Fig. 25.13.2 )

Any acute cyanide exposure is potentially lethal. Onset of symptoms is usually rapid and can be within seconds to minutes for inhalation and within an hour for oral exposure. The ‘classical’ presentation is rapid onset of coma, seizures, shock and profound lactic acidosis.

Cyanide toxicity is characterized by effects on the central nervous system (CNS), respiratory and cardiovascular systems and by a marked metabolic acidosis.

CNS manifestations, in order of increasing severity of cyanide exposure, are headache, anxiety, disorientation, lethargy, seizures, respiratory depression, CNS depression and cerebral death. An initial tachypnoea gives way to respiratory depression as CNS depression develops.

Cardiovascular manifestations include hypertension followed by hypotension, tachycardia followed by bradycardia, arrhythmias, atrioventricular block and increased cardiac output followed by myocardial depression and cardiovascular collapse. Cyanide poisoning can shorten the QT interval to the point of ‘T on R’ phenomenon. The classic finding of bright red skin due to poor tissue oxygen usage (secondary to a decreased arteriovenous oxygen gradient) is not observed if significant myocardial, respiratory or CNS depression has already occurred, in which case the patient may appear cyanotic.

Clinical investigations

There is no reliable commercially available cyanide diagnostic that will provide a cyanide level in a clinically significant time frame. Arterial blood gas analysis and serum lactate measurements reveal metabolic acidosis with a raised lactate. Concentration decay curves suggest that serum lactate concentration is closely correlated to blood cyanide concentration. In smoke-inhalation victims without severe burns, plasma lactate concentrations above 10 mmol/L correlate with blood cyanide concentrations above 40 μmol/L, with a sensitivity of 87%, a specificity of 94% and a positive predictive value of 95%.

Cyanide is concentrated 10-fold by erythrocytes and whole-blood cyanide concentrations are used as the benchmark when comparing levels. Symptomatic intoxication starts at levels of 20 μmol/L, toxicity at 40 μmol/L, and 100 μmol/L is considered potentially lethal. Environmental detectors that detect airborne toxic industrial chemicals such as cyanide are available to some first responder organizations and may provide the clinician with useful prehospital information.