- Email: [email protected]
EMERGENCY TREATMENT OF CYANIDE POISONING
86
lactating breast, the expression of such an effect in breast might indeed be important in determining the behaviour of these tumours, especially in bone metastases.
the
cancer
Department of Medicine, University of Melbourne, Repatriation General Hospital, West Heidelberg, Victoria 3077, Australia
T.
Endocrine Unit, Royal Postgraduate Medical School, Hammersmith Hosptial, London W12 0HS
I. MACINTYRE
J. MARTIN
EMERGENCY TREATMENT OF CYANIDE POISONING
SiR,—You’ and others2-4 have argued that cobalt edetate (’Kelocyanor’) remains the drug of choice in the emergency treatment of cyanide poisoning, the risk of adverse reactions to this drug being negligible in comparison with the lethality of cyanide.2-4 Recent experience has led us to question this view. A skilled workman with 30 years’ experience of handling cyanide salts (used for hardening metals) suffered 8% bodysurface burns from splashes of molten potassium cyanide accidentally ejected from the cyanide pot with which he was workRoutine emergency treatment was immediately carried out, including removal of contaminated clothing and decontamination of the skin. Although distressed and in some pain, he was fully conscious some 5 min after the incident. Despite this and because of the possible risk of further absorption of cyanide from the burnt encrusted surfaces of the skin, 20 ml of kelocyanor was slowly injected intravenously, after withdrawal of blood for baseline cyanide levels. At once the patient became more distressed and on the way to hospital vomited several times in the ambulance. His immediate progress as an inpatient in the local burns unit was very stormy as a result of gross laryngeal and facial oedema. His baseline bloodcyanide level was not abnormal. He made an excellent recovery and was discharged from hospital 3 days later. Clearly this man suffered substantial cyanide burns with no evidence of raised blood-cyanide level or loss of consciousness, but he had a severe and potentially extremely dangerous anaphylactic reaction to cobalt edetate. It is known that this drug can induce vomiting, but anaphylactic reactions are said to be rare.’ As far as we can ascertain, this man had no previous contact with the drug and no history of allergy. We urge colleagues to follow Bryson’s advice6not to administer kelocyanor where poisoning is in doubt but to take a carful history, give reassurance, and observe. Drowsiness is the best clinical indicator of the severity of poisoning and hence the need for administration of the antidote.
ing.
Girling Ltd, Tyseley, Birmingham B11 2AH Lucas
M.
J. MCKIERNAN
known. I know of two patients with propranolol poisoning who died (in March, 1979, and March, 1980) while being treated unsuccessfully with atropine and catecholamines. These patients might have survived if they had been given large amounts of glucagon. I have successfully treated with glucagon two patients with no recordable blood pressure due to beta-blocker poisoning (one patient had taken slow-release oxprenololand the other propranolol) and I agree with Dr Robson (June 21) that glucagon is the treatment of choice for this condition. Your brief review of the features of beta-blocker poisoning does not mention hypoglyctmia, which has been reported after propranolol poisoning in children8 and which should be excluded in an unconscious patient. However, in the few cases reported in adults the blood glucose has been normal or raised?’Glucagon raises the blood glucose, but this effect is reduced by beta-blockade with propranolol and hyperglycæmia has not been a problem in the treatment of beta-blocker poisoning with glucagon. Most reports of beta-blocker overdosage concern propranolol or oxprenolol, and it would be interesting to know the effects of glucagon on the circulation and blood glucose after overdosage of the "cardioselective" beta-
blocking drugs. Your editorial referred to my Practitioner article2 but readers of this paper may have been confused by some printers’ errors and editorial changes made after I had corrected the proofs. A few corrected copies are
available on request.
Accident and
Emergency Department, General Infirmary, Leeds LS1 3EX
DRUG SAFETY IN PORPHYRIA
SIR,-The dangers of extrapolating data obtained from animal experiments to the treatment of human disease is well illustrated by the letter from Dr Blekkenhorst and colleagues (June 21, p. 1367) on drug safety in porphyria. They report that rifampicin does not increase hepatic 8-aminolxvulinic acid synthase (ALA-S) activity in the livers of rats treated with 3,5-diethoxycarbonyl-l, 4-dihydrocollidine and would "probably not elicit an acute attack in susceptible porphyric individuals." Hepatic microsomal enzyme inducers such as the barbiturates increase de novo synthesis of cytochrome P-450 apoproteins which are believed to regulate ALA-S synthesis at a translational level and thus may precipitate a porphyric attack.’ Rifampicin is a potent enzyme inducer in manbut not in the rat. Rifampicin should, therefore, be regarded as contraindicated for the porphyric patient. Department of Clinical Pharmacology, Hammersmith Hospital, London W12 0HS
GLUCAGON FOR BETA-BLOCKER POISONING
SiR,—Your editorial (April 12) and subsequent correspondence (May 10 and June 21) have drawn attention to the value of glucagon in the treatment of beta-blocker poisoning. This was described in 1971,6 but until recently it was not widely
1. Editorial. Which antidote for cyanide? Lancet 1977; ii: 1167. 2. Hillman B, Bardhan KD, Bain JTB. The use of dicobalt edetate
(Kelo-
cyanor) in cyanide poisoning. Postgrad Med J 1974; 50: 171-740. 3. Bain JTB,Knowles EC. Successful treatment of cyanide poisoning. Br Med J 1967; ii: 763. 4. Mathew H, Lawson AAH. Treatment of common acute poisonings. Edin-
burgh: Churchill-Livingstone, 1975; 66. 5. Bryson DD. Cyanide poisoning. Lancet 1978; i: 92. 6. Kosinski EJ, Stein N, Malindzak GS, Boone E. Glucagon and
(Inderal) toxicity. N Engl J Med 1971,
285: 1325.
propranolol
ROBIN N. ILLINGWORTH
7.
Illingworth
RN.
Glucagon
M.
J.
BRODIE
for beta-blocker poisoning. Practitioner 1979;
223: 683-85. 8. Hesse B, Pedersen JT. Hypoglycæmia after propranolol in children. Acta Med Scand 1973; 193: 551-52. 9. Frishman W, Jacob H, Eisenberg E, Ribner H. Self-poisoning with betaadrenoceptor blocking agents: Recognition and management. Am Heart J
1979; 98: 798-811. 10. Messerli FH, Kuchel O, Tolis G, Hamet P, Fraysse J, Genest J. Effects of beta-adrenergic blockade on plasma cyclic AMP and blood sugar responses to glucagon and isoproterenol in man. Int J Clin Pharmacol 1976; 14: 189-94. 1. De Matteis F. The effect of drugs on 5-aminolævulinate synthetase and other enzymes in the pathway of liver haem biosynthesis. In: Park DV, ed. Enzyme induction. London: Plenum Press, 1975: 185-205. 2. Ohnhaus EE, Park BK. Measurement of urinary 6-&bgr;-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol 1979; 15: 139-45. 3 Heubel F, Netter KJ. Atypical inductive properties of rifamipicin. Biochem Pharmacol 1979; 28: 3373-78.
lactating breast, the expression of such an effect in breast might indeed be important in determining the behaviour of these tumours, especially in bone metastases.
the
cancer
Department of Medicine, University of Melbourne, Repatriation General Hospital, West Heidelberg, Victoria 3077, Australia
T.
Endocrine Unit, Royal Postgraduate Medical School, Hammersmith Hosptial, London W12 0HS
I. MACINTYRE
J. MARTIN
EMERGENCY TREATMENT OF CYANIDE POISONING
SiR,—You’ and others2-4 have argued that cobalt edetate (’Kelocyanor’) remains the drug of choice in the emergency treatment of cyanide poisoning, the risk of adverse reactions to this drug being negligible in comparison with the lethality of cyanide.2-4 Recent experience has led us to question this view. A skilled workman with 30 years’ experience of handling cyanide salts (used for hardening metals) suffered 8% bodysurface burns from splashes of molten potassium cyanide accidentally ejected from the cyanide pot with which he was workRoutine emergency treatment was immediately carried out, including removal of contaminated clothing and decontamination of the skin. Although distressed and in some pain, he was fully conscious some 5 min after the incident. Despite this and because of the possible risk of further absorption of cyanide from the burnt encrusted surfaces of the skin, 20 ml of kelocyanor was slowly injected intravenously, after withdrawal of blood for baseline cyanide levels. At once the patient became more distressed and on the way to hospital vomited several times in the ambulance. His immediate progress as an inpatient in the local burns unit was very stormy as a result of gross laryngeal and facial oedema. His baseline bloodcyanide level was not abnormal. He made an excellent recovery and was discharged from hospital 3 days later. Clearly this man suffered substantial cyanide burns with no evidence of raised blood-cyanide level or loss of consciousness, but he had a severe and potentially extremely dangerous anaphylactic reaction to cobalt edetate. It is known that this drug can induce vomiting, but anaphylactic reactions are said to be rare.’ As far as we can ascertain, this man had no previous contact with the drug and no history of allergy. We urge colleagues to follow Bryson’s advice6not to administer kelocyanor where poisoning is in doubt but to take a carful history, give reassurance, and observe. Drowsiness is the best clinical indicator of the severity of poisoning and hence the need for administration of the antidote.
ing.
Girling Ltd, Tyseley, Birmingham B11 2AH Lucas
M.
J. MCKIERNAN
known. I know of two patients with propranolol poisoning who died (in March, 1979, and March, 1980) while being treated unsuccessfully with atropine and catecholamines. These patients might have survived if they had been given large amounts of glucagon. I have successfully treated with glucagon two patients with no recordable blood pressure due to beta-blocker poisoning (one patient had taken slow-release oxprenololand the other propranolol) and I agree with Dr Robson (June 21) that glucagon is the treatment of choice for this condition. Your brief review of the features of beta-blocker poisoning does not mention hypoglyctmia, which has been reported after propranolol poisoning in children8 and which should be excluded in an unconscious patient. However, in the few cases reported in adults the blood glucose has been normal or raised?’Glucagon raises the blood glucose, but this effect is reduced by beta-blockade with propranolol and hyperglycæmia has not been a problem in the treatment of beta-blocker poisoning with glucagon. Most reports of beta-blocker overdosage concern propranolol or oxprenolol, and it would be interesting to know the effects of glucagon on the circulation and blood glucose after overdosage of the "cardioselective" beta-
blocking drugs. Your editorial referred to my Practitioner article2 but readers of this paper may have been confused by some printers’ errors and editorial changes made after I had corrected the proofs. A few corrected copies are
available on request.
Accident and
Emergency Department, General Infirmary, Leeds LS1 3EX
DRUG SAFETY IN PORPHYRIA
SIR,-The dangers of extrapolating data obtained from animal experiments to the treatment of human disease is well illustrated by the letter from Dr Blekkenhorst and colleagues (June 21, p. 1367) on drug safety in porphyria. They report that rifampicin does not increase hepatic 8-aminolxvulinic acid synthase (ALA-S) activity in the livers of rats treated with 3,5-diethoxycarbonyl-l, 4-dihydrocollidine and would "probably not elicit an acute attack in susceptible porphyric individuals." Hepatic microsomal enzyme inducers such as the barbiturates increase de novo synthesis of cytochrome P-450 apoproteins which are believed to regulate ALA-S synthesis at a translational level and thus may precipitate a porphyric attack.’ Rifampicin is a potent enzyme inducer in manbut not in the rat. Rifampicin should, therefore, be regarded as contraindicated for the porphyric patient. Department of Clinical Pharmacology, Hammersmith Hospital, London W12 0HS
GLUCAGON FOR BETA-BLOCKER POISONING
SiR,—Your editorial (April 12) and subsequent correspondence (May 10 and June 21) have drawn attention to the value of glucagon in the treatment of beta-blocker poisoning. This was described in 1971,6 but until recently it was not widely
1. Editorial. Which antidote for cyanide? Lancet 1977; ii: 1167. 2. Hillman B, Bardhan KD, Bain JTB. The use of dicobalt edetate
(Kelo-
cyanor) in cyanide poisoning. Postgrad Med J 1974; 50: 171-740. 3. Bain JTB,Knowles EC. Successful treatment of cyanide poisoning. Br Med J 1967; ii: 763. 4. Mathew H, Lawson AAH. Treatment of common acute poisonings. Edin-
burgh: Churchill-Livingstone, 1975; 66. 5. Bryson DD. Cyanide poisoning. Lancet 1978; i: 92. 6. Kosinski EJ, Stein N, Malindzak GS, Boone E. Glucagon and
(Inderal) toxicity. N Engl J Med 1971,
285: 1325.
propranolol
ROBIN N. ILLINGWORTH
7.
Illingworth
RN.
Glucagon
M.
J.
BRODIE
for beta-blocker poisoning. Practitioner 1979;
223: 683-85. 8. Hesse B, Pedersen JT. Hypoglycæmia after propranolol in children. Acta Med Scand 1973; 193: 551-52. 9. Frishman W, Jacob H, Eisenberg E, Ribner H. Self-poisoning with betaadrenoceptor blocking agents: Recognition and management. Am Heart J
1979; 98: 798-811. 10. Messerli FH, Kuchel O, Tolis G, Hamet P, Fraysse J, Genest J. Effects of beta-adrenergic blockade on plasma cyclic AMP and blood sugar responses to glucagon and isoproterenol in man. Int J Clin Pharmacol 1976; 14: 189-94. 1. De Matteis F. The effect of drugs on 5-aminolævulinate synthetase and other enzymes in the pathway of liver haem biosynthesis. In: Park DV, ed. Enzyme induction. London: Plenum Press, 1975: 185-205. 2. Ohnhaus EE, Park BK. Measurement of urinary 6-&bgr;-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol 1979; 15: 139-45. 3 Heubel F, Netter KJ. Atypical inductive properties of rifamipicin. Biochem Pharmacol 1979; 28: 3373-78.