1167 WHICH ANTIDOTE FOR CYANIDE? IN most sorts of poisoning, treatment with antidotes is unnecessary. An exception is cyanide intoxication. In Britain the recommended treatment is emergency inhalation of amyl nitrite followed by intravenous cobalt edetate (’Kelocyanor’);1 where cobalt edetate is not available, the advice is for sodium nitrite followed by
sodium thiosulphate, both intravenous.2 Cyanide inhibits the cytochrome-oxidase system and thus blocks intracellular respiration.3 Inhalation of large amounts will kill in minutes, but if small amounts are swallowed, particularly on a full stomach, death may not ensue for hours. Poisoning may show itself in head-
ache, tachypnoea, excitement, vomiting, hypotension, convulsions, and coma. Lactic acidosis and pulmonary oedema were prominent features in a case lately reported.4 The antidotes work in different ways. Cobalt edetate is a chelating agent which forms a complex with cyanide.5 The nitrites convert haemoglobin to methaemoglobin which competes preferentially for cyanide with cytochrome. The cyanmethaemoglobin so formed slowly releases cyanide which is then converted by the liver rhodanase system to thiocyanate. Sulphur is
needed for this reaction, hence the thiosulphate. Both these treatments have disadvantages. Cobalt edetate induces vomiting, often, and anaphylactic reactions, occasionally. Nitrites may cause hypotension and there is a danger of anoxia if too much methaemoglobin is formed. An effective but completely safe antidote would be welcome, and Graham et al.4 suggest hydroxocobalamin, which combines with cyanide to form cyanocobalamin (vitamin B,2). The antidotal effect of hydroxocobalamin in laboratory animals has been known for many years6 and the substance is free from side-effects (at least in doses used for pernicious anaemia). However, existing preparations of hydroxocobalamin are unsuitable as a treatment for cyanide poisoning. Experiments suggest that at least fifty times more hydroxocobalamin than cyanide is needed;6 thus, to neutralise 200 mg of cyanide (around the fatal dose) about ten litres of the 1 mg/ml solution would be required. Some doctors working in industries where cyanide is used extensively have taken to using cobalt edetate only in unconscious patients. This is because most cases they see are only poisoning scares, and the early symptoms of cyanide poisoning, such as excitement and tachycardia, are similar to the effects of anxiety in workers who think they have been exposed. In hospital practice the situation is different. Most casualty officers will not have previously seen a case of cyanide poisoning and the amounts involved are generally much larger. In these circumstances cobalt edetate should be given to all patients with symptoms. If there is no recovery after injection of 600 mg then a further 300 mg may be given. The manufacturers recommend dextrose afterwards, but the reason for this is obscure. Sodium thiosulphate may be tried in patients who have not responded to cobalt
1. Mathew, H., Lawson, A.
A. H. Treatment of Common
Acute Poisonings.
Edinburgh, 1975. 2. Dreisbach, R. H. Handbook of Poisoning. Los Altos, 1974. 3. Gosselin, R. E., Hodge, H. C., Smith, R. P., Gleason, M. N. Clinical Toxicology of Commercial Products. Baltimore, 1976. 4. Graham D. L., et al. Archs intern. Med. 1977, 137, 1051. 5. Paulet, G. Path. Biol 1960, 8, 255. 6. Muskett, C. W., et al. Proc. Soc. exp Biol. Med. 1952, 81, 234.
edetate. Set against the lethality of cyanide the risk of adverse reaction to cobalt edetate is negligible and this drug remains the antidote of choice. 7,8
DANGERS AT WORK WHEN a Faculty of Occupational Medicine is established within the Royal College of Physicians of London, probably some time next year, there will be no shortage of topics of public interest which the Faculty can tackle. It will not be the duty of the College to lay down the law on matters concerning occupational medicine, but, since this area is one where there could easily be .conflict of interest between employer and employee, the College is likely to be seen as a source of unbiased assessments and recommendations. At a symposium on Nov. 23, organised by the College’s committee on occupational health, to which managers and trade-union leaders were invited, three areas were selected for discussion: the assessment and forecasting of risks at work (and the kind of decisions that have to be taken based on these assessments); the value of screening; and the risks at work from medication. The unresolved dilemma facing those who have to assess such risks and to make decisions were illustrated in The Lancet a fortnight ago by Dr Andre McLean in his discussion9 of the testing of industrial chemicals. At the symposium, an assessment of the value, or lack of value, of general health screening (not of special screening for specific hazards) was provided by Dr M. F. d’Souza, who described the findings of a 10-year follow-up of 3500 middle-aged men and women from two general practices in South London: those screened had no improvement in health compared with a similar number of unscreened controls. Many employees seem to have assumed that health screening is of value; this view is reflected not only in the proposal at the Trades Union Congress to press for screening for all employees but also in a finding from the Heart Disease Prevention Project (set up in 1971 and described at the symposium by Prof. Geoffrey Rose) that such screening is popular with middle-aged men in industry. This project covers nearly 20 000 men in Britain and it has been extended to include people from centres in Belgium, Poland, and
Italy. One aspect of occupational health that has received little attention is the risk at work to workers who have been prescribed such drugs as tranquillisers, sedatives, and antihistamines. These drugs have been shown to impair performance under experimental conditions, but there have been no surveys of how they affect people at work, Do they improve work performance in those who need the treatment; are they a danger for people working with machines; do their effects on performance depend on variables such as the amount of sleep; who (doctor, patient, or employer) is liable when accidents befall someone working under the influence of a prescribed drug? While such questions are being examined, the Post Office is planning to draw the attention of its employees to the possible effect of drugs, in order to encourage them to discuss it with their own doctors or with those in the Post Office health service. 7. Hillman, B., Bardhan, K. D., Bain, J. T. B. Postgrad. 8. Bain, J. T. B., Knowles, E. C. Br. med. J. 1967, ii, 763. 9. McLean, A. E. M. Lancet, Nov. 19, 1977, p. 1070.
med. J. 1974, 50, 171.
sodium thiosulphate, both intravenous.2 Cyanide inhibits the cytochrome-oxidase system and thus blocks intracellular respiration.3 Inhalation of large amounts will kill in minutes, but if small amounts are swallowed, particularly on a full stomach, death may not ensue for hours. Poisoning may show itself in head-
ache, tachypnoea, excitement, vomiting, hypotension, convulsions, and coma. Lactic acidosis and pulmonary oedema were prominent features in a case lately reported.4 The antidotes work in different ways. Cobalt edetate is a chelating agent which forms a complex with cyanide.5 The nitrites convert haemoglobin to methaemoglobin which competes preferentially for cyanide with cytochrome. The cyanmethaemoglobin so formed slowly releases cyanide which is then converted by the liver rhodanase system to thiocyanate. Sulphur is
needed for this reaction, hence the thiosulphate. Both these treatments have disadvantages. Cobalt edetate induces vomiting, often, and anaphylactic reactions, occasionally. Nitrites may cause hypotension and there is a danger of anoxia if too much methaemoglobin is formed. An effective but completely safe antidote would be welcome, and Graham et al.4 suggest hydroxocobalamin, which combines with cyanide to form cyanocobalamin (vitamin B,2). The antidotal effect of hydroxocobalamin in laboratory animals has been known for many years6 and the substance is free from side-effects (at least in doses used for pernicious anaemia). However, existing preparations of hydroxocobalamin are unsuitable as a treatment for cyanide poisoning. Experiments suggest that at least fifty times more hydroxocobalamin than cyanide is needed;6 thus, to neutralise 200 mg of cyanide (around the fatal dose) about ten litres of the 1 mg/ml solution would be required. Some doctors working in industries where cyanide is used extensively have taken to using cobalt edetate only in unconscious patients. This is because most cases they see are only poisoning scares, and the early symptoms of cyanide poisoning, such as excitement and tachycardia, are similar to the effects of anxiety in workers who think they have been exposed. In hospital practice the situation is different. Most casualty officers will not have previously seen a case of cyanide poisoning and the amounts involved are generally much larger. In these circumstances cobalt edetate should be given to all patients with symptoms. If there is no recovery after injection of 600 mg then a further 300 mg may be given. The manufacturers recommend dextrose afterwards, but the reason for this is obscure. Sodium thiosulphate may be tried in patients who have not responded to cobalt
1. Mathew, H., Lawson, A.
A. H. Treatment of Common
Acute Poisonings.
Edinburgh, 1975. 2. Dreisbach, R. H. Handbook of Poisoning. Los Altos, 1974. 3. Gosselin, R. E., Hodge, H. C., Smith, R. P., Gleason, M. N. Clinical Toxicology of Commercial Products. Baltimore, 1976. 4. Graham D. L., et al. Archs intern. Med. 1977, 137, 1051. 5. Paulet, G. Path. Biol 1960, 8, 255. 6. Muskett, C. W., et al. Proc. Soc. exp Biol. Med. 1952, 81, 234.
edetate. Set against the lethality of cyanide the risk of adverse reaction to cobalt edetate is negligible and this drug remains the antidote of choice. 7,8
DANGERS AT WORK WHEN a Faculty of Occupational Medicine is established within the Royal College of Physicians of London, probably some time next year, there will be no shortage of topics of public interest which the Faculty can tackle. It will not be the duty of the College to lay down the law on matters concerning occupational medicine, but, since this area is one where there could easily be .conflict of interest between employer and employee, the College is likely to be seen as a source of unbiased assessments and recommendations. At a symposium on Nov. 23, organised by the College’s committee on occupational health, to which managers and trade-union leaders were invited, three areas were selected for discussion: the assessment and forecasting of risks at work (and the kind of decisions that have to be taken based on these assessments); the value of screening; and the risks at work from medication. The unresolved dilemma facing those who have to assess such risks and to make decisions were illustrated in The Lancet a fortnight ago by Dr Andre McLean in his discussion9 of the testing of industrial chemicals. At the symposium, an assessment of the value, or lack of value, of general health screening (not of special screening for specific hazards) was provided by Dr M. F. d’Souza, who described the findings of a 10-year follow-up of 3500 middle-aged men and women from two general practices in South London: those screened had no improvement in health compared with a similar number of unscreened controls. Many employees seem to have assumed that health screening is of value; this view is reflected not only in the proposal at the Trades Union Congress to press for screening for all employees but also in a finding from the Heart Disease Prevention Project (set up in 1971 and described at the symposium by Prof. Geoffrey Rose) that such screening is popular with middle-aged men in industry. This project covers nearly 20 000 men in Britain and it has been extended to include people from centres in Belgium, Poland, and
Italy. One aspect of occupational health that has received little attention is the risk at work to workers who have been prescribed such drugs as tranquillisers, sedatives, and antihistamines. These drugs have been shown to impair performance under experimental conditions, but there have been no surveys of how they affect people at work, Do they improve work performance in those who need the treatment; are they a danger for people working with machines; do their effects on performance depend on variables such as the amount of sleep; who (doctor, patient, or employer) is liable when accidents befall someone working under the influence of a prescribed drug? While such questions are being examined, the Post Office is planning to draw the attention of its employees to the possible effect of drugs, in order to encourage them to discuss it with their own doctors or with those in the Post Office health service. 7. Hillman, B., Bardhan, K. D., Bain, J. T. B. Postgrad. 8. Bain, J. T. B., Knowles, E. C. Br. med. J. 1967, ii, 763. 9. McLean, A. E. M. Lancet, Nov. 19, 1977, p. 1070.
med. J. 1974, 50, 171.
