J R Army Med Corps 2002; 148: 383-386 J R Army Med Corps: first published as 10.1136/jramc-148-04-08 on 1 December 2002. Downloaded from

Cyanogen Agents

GENERAL HCN + Na2S2O3 ‘HSCN + Na2SO3 This reaction with thiosulphate Introduction forms the basis of a therapy of agents produce their effects by poisoning. Metal ions easily form complexes interfering with utilization at the with cyanide ions for example: cellular level. Their toxicity is primarily derived from the liberation of the CN-group. - 2- - Inhalation is the usual route of entry. The CoCl2 + 4CN ‘Co(CN) 4+ 2Cl . term "blood agents" has, in the past been These types of reaction are employed in used to describe cyanogen agents and is still reactive where the charcoal is in widespread use. It should be noted, impregnated with metal ions in order to however, that not all "blood agents" are increase the absorptive capacity of charcoal. (e.g. monoxide). Similar reactions with complexed metal ions The commodity industrial chemical are also utilised in some forms of therapy. cyanide (HCN (AC)) was used during WWI and is still attractive as an Detection improvised weapons fill because of its Automatic detectors are available which availability. is released detect attack concentrations of cyanide when (e.g. cyanohydrine, vapour. DraegerTM tubes are also available, as , ) are are testing kits. spilled in water or subjected to . The cyanogen halides, (ClCN Protection (CK)) and (BrCN), were Hydrogen cyanide, because of its used during WWI. The toxicity of cyanogen and low molecular weight, is poorly absorbed halides is due to the CN-group and the by the charcoal in the canister of the irritant properties of the halogen moiety.The respirator. This charcoal is made more http://militaryhealth.bmj.com/ commodity chemical hydrogen sulphide reactive by impregnating it with metal salts.

(H25) has a toxicity comparable to hydrogen In field conditions the respirator gives good cyanide and appears to act by a similar protection against gas. Modern NBC filters mechanism. are effective against attack with hydrogen cyanide, but should be changed immediately HYDROGEN CYANIDE afterwards. Properties Decontamination Because of its physical properties the agent Physical Properties will not remain for long in its liquid state; Under most field conditions, hydrogen decontamination should not be necessary. on September 26, 2021 by guest. Protected copyright. cyanide is a colourless gas and represents a non-persistent hazard. The vapour is less Mechanism of Action dense than air and has a faint odour, The cyanide ion forms a reversible complex somewhat like bitter , although with the respiratory cytochrome oxidase, an about up to 40 % of people are unable to enzyme system essential for oxidative smell this. It is highly soluble and stable in processes within cells. This results in water. impairment of cellular oxygen utilisation. The central nervous system, particularly the Chemical Properties. respiratory centre, is especially susceptible to The CN compounds hydrolyse slowly in this effect and respiratory failure is the usual water with subsequent gradual loss of cause of death. toxicity. They are readily oxidised by strong oxidants; e.g. potassium permanganate. Signs and Symptoms Hydrogen cyanide has an affinity for oxygen As a result of the high rate of detoxification and is flammable; hence it is less efficient in the body, high concentrations of cyanide when dispersed by artillery shells. for short periods produce greater toxicity. Compounds which contain labile sulphur - High concentrations: At high concentrations atoms (R-S=S2-) react with HCN even in there is an increase in the depth of vivo, for example: respiration within a few seconds. This 384 J R Army Med Corps: first published as 10.1136/jramc-148-04-08 on 1 December 2002. Downloaded from

stimulation may be so powerful that a DMAP). Methaemoglobin-forming casualty cannot voluntarily hold his or her compounds should be used cautiously in breath. Loss of consciousness with possible patients suffering from concurrent carbon convulsions occur after 20 to 30 sec with monoxide poisoning or hypoxia. cessation of respiration within 1 min. 2. Cyanide is detoxified at a rate that is of prac- Cardiac failure follows within a few tical importance, about 17 µg.kg-1.min-1. minutes. Sudden loss of consciousness in Provision of additional sulphur groups to the absence of other characteristic features enhance the detoxification of cyanide to of intoxication is a key by endogenous rhodanese is indicator of potentially lethal cyanide accomplished by giving sodium thio- poisoning. sulphate. - Low Concentrations: At low concentrations, It is generally agreed that binding the the early symptoms are weakness of the cyanide ions is the main priority of treatment legs, vertigo, nausea and headache. but that thiosulphate should be provided Convulsions may follow with which with most treatment regimen to promote may last for hours or days depending on conversion of cyanide to non-toxic the duration of exposure to the agent. thiocyanate ions. Recovery from prolonged coma may disclose residual damage to the central nervous system manifested by irrationality, Drugs That Induce The Binding altered reflexes and unsteady gait which Of Cyanide Ions may last for several weeks or longer; temporary or permanent nerve deafness Sodium has also been described. In mild cases Sodium nitrite must be administered there may be headache, vertigo and nausea intravenously.Ten millilitres of a 3% for several hours before complete recovery. (300 mg) of sodium nitrite should be injected intravenously over a period of 3 min. Casualty Management The sodium nitrite is administered in order First Aid Measures. The casualty should be to produce methaemoglobin, thus removed from the source of hydrogen sequestering the cyanide on the cyanide. Rescue workers should wear methaemoglobin. Subsequent intravenous adequate individual protective equipment administration of sodium thiosulphate is (IPE). required to promote the conversion of Therapy. The key to treatment of patients cyanide to thiocyanate ion which is then poisoned with hydrogen cyanide is speed. excreted from the body. Although there is disagreement regarding the The decrease in blood pressure following ideal drugs for use in the treatment there is sodium nitrite injections is negligible unless http://militaryhealth.bmj.com/ no doubt that urgent action is necessary. the patient is allowed to get into an upright position. The development of a slight degree Treatment of cyanosis may be associated with the production of methaemoglobin (methaemo- Any casualty who is fully conscious and globinaemia) and does not in itself call for breathing normally more than 5 min after artificial ventilation. It is not anticipated that presumed exposure to cyanide agents has an extreme or injurious degree of ceased will recover spontaneously and does methaemoglobinaemia will develop at the not require treatment (cyanide is detoxified dosages stated above. If it does occur, very rapidly in the body). Successful treatment is oxygen administration. If treatment for acute on September 26, 2021 by guest. Protected copyright. methaemoglobin formation is severely depends upon rapid fixation of the cyanide symptomatic, blue may be given ion, either by methaemoglobin formation or to convert methaemoglobin to haemoglobin. by fixation with cobalt compounds. Artificial Methylene Blue is given 1-2 mg.kg-1 by slow ventilation is not likely to be helpful in the IV injection over 5 - 10 min; repeated once absence of administration of antidote. after 1 h if there is no response.

Treatment Approaches 4-Dimethylaminophenol-hydrochloride (4- Two major approaches are involved in the DMAP) treatment by antidote of cyanide poisoning: 4-DMAP induces the rapid formation of 1. By providing alternative binding sites for methaemoglobin and must be injected the cyanide ions, the cytochrome oxidase intravenously at a dose of 250 mg over 3 - 5 enzyme activity is restored. Binding sites min. Muscular necrosis may follow may be provided by drugs such as dicobalt intramuscular injection and this route edetate and hydroxocobalamin or by the should be avoided. Subsequent intravenous production of methaemoglobin in the administration of sodium thiosulphate is blood. Methaemoglobin avidly binds required to promote the conversion of cyanide ions and may be produced by cyanide to thiocyanate ion which is then compounds such as sodium nitrite, amyl excreted from the body. If sodium nitrite and dimethylaminophenol (4- thiosulphate is not immediately available, 385 J R Army Med Corps: first published as 10.1136/jramc-148-04-08 on 1 December 2002. Downloaded from

250 mg of 4-DMAP should be given every require antidotal treatment and will be hour until thiosulphate can be given; the expected to make a full recovery. latter completes the treatment. Occasionally, when tissue hypoxia has been prolonged, residual injury of the CNS may Amyl Nitrite persist for weeks and some damage may be Amyl nitrite may be of benefit when used as permanent. a first aid measure, prior to the use of intravenous antidotes. Crushing the CYANOGEN HALIDES ampoule around the face or even inside the facepiece of the respirator is worthless unless Introduction the casualty is breathing. It should not be Cyanogen chloride and cyanogen bromide used with concurrent oxygen administration were used during WWI (usually in mixtures due to the risk of explosion. Treatment with with other warfare agents - hydrogen amyl nitrite should be followed by sodium cyanide, ).Their effects on the thiosulphate. body are similar to those of hydrogen cyanide but they also have irritant effects on the eyes Hydroxocobalamin and upper respiratory passages. The Hydroxocobalamin (vitamin B12a) is a fast threshold concentration for cyanogen acting antidote that binds cyanide to form chloride is approximately 2.5 mg.m-3. non-toxic (vitamin B12). Both are excreted by the kidneys. It must Physical and Chemical only be given intravenously. The initial dose of 5g (ca.70 mg.kg-1) has to be infused over Properties Under most field conditions, cyanogen 30 min. One or 2 further injections may be administered depending on the severity of chloride is a colourless, strongly irritant gas. poisoning. In practice, there are no known Although only slightly soluble in water, it side effects. Association with thiosulphate is dissolves readily in organic solvents. Its usually not necessary however, if performed, vapour, heavier than air, is very irritating to care should be taken not to mix both drugs the eyes and mucus membranes. Cyanogen in the same infusion. chloride has pungent, biting odour. Normally cyanogen chloride is non Dicobalt Edetate persistent. Dicobalt edetate releases cobalt ions that react with cyanide ions. Highly stable Detection cyanide-cobalt complexes are excreted by the Automatic detectors are available which kidneys. It must be given intravenously in detect attack concentrations of vapour. DraegerTM tubes are also available, as are

doses of 600 mg followed immediately by 50 http://militaryhealth.bmj.com/ ml of a glucose hypertonic solution. The water testing kits. injection should be followed by an intravenous injection of sodium thiosulphate. Protection Another 300 mg dose may be injected. It Cyanogen halides are rather poorly absorbed should be noted that cobalt edetate is toxic to onto charcoal, especially if the charcoal is the kidney and causes hypotension, damp. The cyanide group (which is not hypoglycaemia, vomiting, diarrhoea and ionised) does not react well with the metal headaches.These effects are more prominent salts found in respirator charcoals. in non-intoxicated casualties. Decontamination Provision of Sulphur Groups As with hydrogen cyanide, because of its on September 26, 2021 by guest. Protected copyright. Sodium thiosulphate provides additional physical properties the agent will not remain thiosulphate ions and these combine with for long in its liquid state. Decontamination cyanide ions in a reaction catalysed by should not, therefore, be necessary. rhodanase to produce thiocyanate. With most treatment regimen it should be given to Mechanism of Action supplement other forms of treatment for Cyanogen chloride acts in two ways. Its cyanide poisoning. The dose is 12.5 - 25 g systemic effects are similar to those of diluted for intravenous administration over a hydrogen cyanide but it also has local irritant 10 minute period. effects on the eyes, upper respiratory tract and lungs as a result of the formation of Additional Therapy . If available, 100% oxygen should be given, with or without positive pressure ventilation. Pathology Cyanogen chloride injures the respiratory Course and Prognosis tract, resulting in severe inflammatory Death may occur within minutes without changes in the bronchioles and congestion treatment, but a casualty who is fully and oedema in the lungs. Very low conscious and breathing normally 5 min concentrations (e.g. 10-20 mg.min.m-3) after presumed exposure has ceased does not produce eye irritation and lachrymation. 386 J R Army Med Corps: first published as 10.1136/jramc-148-04-08 on 1 December 2002. Downloaded from

Signs and Symptoms Course and Prognosis The signs and symptoms caused by Recovery from the systemic effects of cyanogen chloride are a combination of cyanogen halide poisoning is usually as those produced by hydrogen cyanide and a prompt as in hydrogen cyanide poisoning. lung irritant such as . Initially, However, a higher incidence of residual cyanogen chloride stimulates the respiratory damage to the central nervous system is centre and then rapidly paralyses it. In high likely. Depending on the concentration of concentrations however, its local irritant cyanogen halide, the pulmonary effects may action may be so great that dyspnoea is develop immediately or may be delayed until produced. Exposure is followed by an the systemic effects have subsided. Early immediate intense irritation of the nose, prognosis must therefore be guarded. throat and eyes, with coughing, tightness in the chest and lachrymation. Subsequently, Further Reading the exposed person may become dizzy and Ballantine B. Clinical and Experimental Toxicology of increasingly dyspnoeic. Unconsciousness is Cyanides. Wright, 1987. Brewer TG. Therapy for Cyanide Poisoning. followed by failing respiration and death Pharmacology Division of USAMRICD/Experimental within a few minutes. Convulsions, retching Therapeutics Division WRAXR. and involuntary defecation may occur. If Chen KK. "Amyl Nitrite and Cyanide Poisoning." these effects are not fatal, the signs and JAMA, 17 June 1993. Cyanide Antidote Package. Eli Lilly and Company, PA symptoms of pulmonary oedema may 0705 AMP. develop. There may be persistent cough with Evans CL. "Cobalt Compounds as Antidotes for much frothy sputum, rales in the chest, Hydrocyanic Acid." British Journal of Pharmacology, severe dyspnoea and marked cyanosis. Feb 1964. Graham DL. "Acute Cyanide Poisoning Complicated by Lactic Acidosis and Pulmonary Oedema." Archives Treatment of Internal Medicine, Vol 137, Aug 1977. Cyanogen halide poisoning should be treated Marrs TC. "Antidotal Treatment of Acute Cyanide in the same way as hydrogen cyanide Poisoning." Adverse Drug Reactions Acute Poisoning poisoning in respect of its cyanide-like Revue. 1988; 4:179-206. Treatment of Chemical Agent Casualties and Conventional effects. Pulmonary irritation should be Military Chemical Injuries. FM 8--285, Washington, treated in the same way as phosgene DC, HQ, Dept of the Army, Feb 1990. poisoning. http://militaryhealth.bmj.com/ on September 26, 2021 by guest. Protected copyright.