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4.2 Hydrogen cyanide may be absorbed by inha lation, ingestion, and through the eye and skin. Cyanides inhibit cellular respiration by blocking electron transport at the cytochrome a3 complex. This impairs mitochondrial oxidative metabolism. The clinical effects are primarily due to an inability to utilise oxygen, rather than tissue hypoxia. In massive cyanide poisoning other mechanisms may contribute to clinical effects such as pulmonary and coronary arterial vasoconstriction and impaired ventilation with decreased cardiac output. Cyanides act extremely quickly once absorbed. HCN inhalation can be lethal within seconds; ingestion of inorganic cyanide salts such as potassium or sodium cyanide may produce clinical effects within minutes and fatalities within hours. Dermal exposures to cyanides have resulted in fatalities.

Review of treatments

4.3 The treatment of hydrogen cyanide and cyanide salt poisoning is primarily supportive. It includes removal of the casualty from exposure, decontaminating where necessary and administration of high concentration oxygen. Support of ventilation and administration of oxygen are considered to be important aspects of treatment for severe poisoning.

4.4 There are, in addition, currently four cyanide antidotes available within the United Kingdom, though not all have licence authorisation for this specific use.

All these drugs have been recognised, and used as cyanide antidotes, for more than 40 years. A number of case reports testify to their clinical effectiveness with at times rapid and spectacular reversal of the cardiovascular and nervous system abnormalities induced by cyanide, even hours after poisoning has occurred. However, there are differences in the efficacy and side effects of these antidotes.

Methaemoglobin Formers

4.5 Methaemoglobin formers include sodium nitrite, amyl nitrite and 4-dimethylaminophenol (DMAP). Concerns exist about the safety of sodium nitrite because of the potential to form excess methaemoglobin, which reduces the oxygen carrying capacity of the blood, causing possible further harm. Further uncertainty concerns the recommended concentrations of methaemoglobin that need to be generated (ranging from <10% to 40%), the difficulty in predicting methaemoglobin levels for any one individual, and the difficulties in measuring methaemoglobin in the pre-hospital setting and the Accident and Emergency department. There is individual variation in susceptibility to methaemoglobin-inducing agents. The optimum concentration of methaemoglobin required is likely to depend upon the severity of the cyanide poisoning .

4.6 Nitrites may also be inhaled in the form of amyl nitrite and this used to be part of a cyanide antidote kit. Amyl nitrite is now a controlled drug and pharmacies are no longer incorporating it into cyanide antidote kits. It does, however, have the advantage of ease of administration. Nitrites may cause hypotension, particularly if given too quickly Dicobalt edetate

4.7 Commercial preparations of dicobalt edetate contain free cobalt ions. Cobalt ions are themselves toxic and thus administration of commercial preparations of dicobalt edetate in the absence of cyanide poisoning may lead to severe adverse effects. If cyanide ions are present these bind to the free cobalt ions and thus the toxic effects of both the cyanide ions and the free cobalt ions are mutually antagonised (i.e. the cobalticyanide complex is much less toxic than its components). Both dicobaltedetate and free cobalt ions bind covalently to cyanide ions. The adverse effects seen when commercial preparations of dicobalt edetate are given in the absence of cyanide poisoning include hypotension, cardiac arrhythmias and facial and laryngeal oedema. These effects can be reduced by the administration of glucose. Glucose is often given with the commercial preparations of dicobalt edetate as a precautionary measure. Equipment for emergency endotracheal intubation should be immediately available if dicobalt edetate is given.

Sodium thiosulphate

4.8 This is an additional antidote that aids cyanide elimination but acts too slowly to be used alone. It is often given with the other cyanide antidotes as 50 ml of a 25% solution over 10 minutes. Sodium thiosulphate is recommended after methaemoglobin-producing cyanide antidotes.

Hydroxocobalamin

4.9 Hydroxocobalamin binds cyanide and high doses have been studied in both healthy volunteers and in fire victims. These studies suggest that hydroxocobalamin, in doses up to 15 grams, is tolerated well though data on efficacy are less clear. The need for the rapid intravenous administration of large volumes of this antidote makes its use difficult in a pre-hospital setting.

Discussion

4.10 Table 4.1 summarises antidotes for cyanide poisoning by agent, mechanism of action, route of treatment, dose required, concurrent treatment recommendations, administration time recommended, response time, potential antidote toxicity, and the shelf life of the antidote.

4.11 In the absence of clear information concerning the nature of exposure it is often difficult to diagnose cyanide poisoning. The absence of specific diagnostic features, together with, for example, many people presenting with decreased consciousness is suggestive, but not diagnostic of cyanide poisoning. Rapid clinical diagnosis may rely in part upon the response to a therapeutic challenge with an antidote. An antidote that is both safe and effective is therefore clearly preferable.

4.12 Due to its rapid action, inhalation of hydrogen cyanide may result in patients who are severely poisoned and may not survive to receive any antidote. Patients who are fully conscious and breathing spontaneously probably do not require any life saving antidote, as they will ultimately detoxify any cyanide themselves.

4.13 In the presence of a clear history of cyanide exposure, for example in an industrial setting, or the event of multiple deliberate releases where the agent has been identified from a previous release, use of a cyanide antidote in addition to oxygen may be justified. Unless ambulances routinely carry antidotes it is difficult to foresee circumstances where pre-hospital administration is likely to occur unless prior knowledge of an intent to release is available.

4.14 By relying upon clinical criteria to diagnose HCN toxicity some patients may be treated unnecessarily. Although effective, the toxicity of dicobalt edetate in the absence of cyanide poisoning limits its use in the pre-hospital setting and potentially even in an Accident and Emergency Department. In circumstances of clear, severe cyanide poisoning its inherent toxicity is less of an issue. Concerns for the safety of methaemoglobin formers such as nitrites and DMAP complicate their use where mass casualties are being managed and in cases of cyanide poisoning where carbon monoxide poisoning coexists. Evidence exists for the safety of hydroxocobalamin in non-poisoned patients and in the management of HCN exposures, though large doses must be administered IV where poisoning is severe.

Recommendations

4.15 In cases of hydrogen cyanide inhalation the most important action fundamental to survival is removing the casualty from exposure and prevention of further absorption with decontamination. As long as the patient does not have severe clinical signs such as loss of consciousness or convulsions and the clinical condition is not deteriorating then supportive care with oxygen therapy may be sufficient. Issues surrounding the timely provision of all antidotes exist.

4.16 Any patient who is fully alert when they reach hospital (i.e. A on the AVPU scale) following hydrogen cyanide inhalation and who has been suitably decontaminated will only require observation and reassurance. However, those who arrive with an altered conscious level (i.e. VPU on the AVPU scale) may well require oxygen, ventilatory support and an antidote. Inevitably, decisions on specific treatment remain the responsibility of the clinician treating the patient.

• Download Table 4.1: Summary of Antidotes for Cyanide Poisoning (PDF, 21K)

References

International Programme on Chemical Safety Poisons Information Monograph. Cyanides. IPCS/INTOX/PIMGOO3. Author: Van Heijst ANP, Editor: M.Ruse (August, 1997).

• International Programme on Chemical Safety Poisons Information Monograph (opens new window)

Meredith TJ, Jacobsen D, Haines JA, Berger JC, Van Heijst ANP (editors).IPCS/CEC Evaluation of Antidote Series. Vol 2. Antidotes for Poisoning by Cyanide. Cambridge, UK: Cambridge University Press, 1993.()

• Evaluation of Antidote Series (opens new window)

Ballantyne B, Marrs TC (editors). Clinical and Experimental Toxicology of Cyanides. Bristol: John Wright & Sons, 1987.

Marrs TC. Antidotal treatment of acute cyanide poisoning. Adverse Drug React Acute Poisoning Rev 1988; 4: 179-206.

Beasley DMG, Glass WI. Cyanide poisoning: Pathophysiology and treatment recommendations. Occup Med 1998; 48: 427-431.

Salkowski AA, Penney DG. Cyanide poisoning in animals and humans: a review. Vet Human Toxicol 1994; 36: 455-66

Baskin SI, Horowitz AM, Nealley EW. The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning. J Clin Pharmacol 1992; 32: 368-375.

Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med 1986; 1 15: 1067-1074.