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SUDDEN DEATH AFTER INTRAMUSCULAR FRUSEMIDE
1301 heart-rate when this is less than 60 per minute. Bradycardia is most usual in inferior myocardial infarction, where the area of muscle destruction may not be great; and there is no evidence that a rate of 50 to 60 beats per minute is a great hazard. Atropine has its place in the treatment of acute myocardial infarction, but, as with other drugs, its over-enthusiastic use may lead to more harm than good. B. L. PENTECOST M. A. BENNETT General Hospital, C. F. GEORGE. Birmingham 4.
CONTROLLING CLIOQUINOL SIR,-Since continuous ingestion of substantial amounts of iodine may impair thyroid function, besides causing much inconvenience in judging the usual tests for thyroid disease,! we should consider whether marketing and promoting the sale of clioquinol and other iodoquinolines is unethical, and whether it endangers the health of large groups of the population. Although these substances are of little or no value in " tourists’ diarrhoea", they seem to be recommended by every guide in every chartered flight to the Mediterranean countries, where most tourists live in a milieu well protected against amoebic dysentery. On the contrary these drugs may cause diarrhoea in many tourists.2 Is it impossible for travel agencies to stop this propaganda, and to have it suppressed in guide-books for tourists, for publichealth authorities to require that these drugs shall be sold only on medical prescription, and for the pharmaceutical houses to renounce the profit gained from misunderstood medical evidence ? Aker Sykehus, Oslo 5.
J. H. VOGT.
SUDDEN DEATH AFTER INTRAMUSCULAR FRUSEMIDE now SIR,-The widely used sulphamylanthranilic-acid derivative, frusemide, is a highly effective oral and parenteral diuretic. Its untoward effects, generally mild, infrequent, and transitory, include pruritus, rash, nausea, vomiting, diarrhoea, and postural hypotension. I here describe two patients who died almost immediately after a single intramuscular injection of frusemide. Case 1.-This 94-year-old man had been having digoxin, methyldopa, and chlorpropamide for hypertensive heartdisease and mild diabetes. His last admission to hospital had been for pulmonary oedema. On admission: striking dyspnoea, both lungs congested, liver enlarged. The electrocardiogram (E.C.G.) showed left bundle-branch block, and ST depression in leads V and Vg. The many laboratory tests, including serumelectrolytes, were normal, except for blood-urea (61 mg. per 100 ml.), and blood-sugar (171 mg. per 100 ml.). The patient improved on digoxin, aminophylline, morphine, and oxygen inhalation. Next day many rales again appeared over both lungs. The E.c.G. now showed auricular tachycardia with varying rates of atrioventricular conduction. After the rales were found he was given an intramuscular injection of 20 mg. frusemide. Within one minute after the injection, the patient suddenly died. The final E.C.G. showed ventricular tachycardia. Permission for necropsy was not obtained. Case 2.-This 62-year-old man had mild diabetes and arteriosclerotic heart-disease. Latterly he had complained of shortness of breath. A few months before his last admission (which was for severe dyspnoea), he had had a transurethral resection of an enlarged prostate. At that time his blood-urea Vogt, J. H. Tidsskr. norske Lœgeforen, 1966, 10, 807. Zondek, H., Leszynsky, H. G. Lancet, 1968, i, 671. ibid. p. 679. Sönksen, P. H., Ekins, R. P., Stevens, H. G., Williams, E. S., Nabarro, J. D. N. ibid. Aug. 24, 1968, p. 425. 2. Walters, J. H. Wld Med. 1965, 12, 184. 1.
was 119 mg. per 100 ml., and creatinine-clearance only 25 ml. per minute. Most recently he had complained of pain in the
left hypochondrium. On admission: tachycardia, many rales over the right lung, tenderness on percussion over the left lower ribs, hepatosplenomegaly. E.C.G. showed left ventricular strain. His blood-urea was 114 mg. per 100 ml., and non-fasting bloodsugar 306 mg. per 100 ml. A few hours after admission the patient developed pulmonary oedema. Initially he was given digoxin and oxygen, and finally an intramuscular injection of 20 mg. frusemide. Within one minute after the injection, the patient suddenly died. The final E.C.G. showed cardiac arrest. Necropsy showed: pulmonary oedema; hepatosplenomegaly; nephrosclerosis; a benign, large, retroperitoneal tumour; enlarged heart, with sclerosis, but no thrombosis of coronary arteries, and a small area of discoloration on the posterior wall of the myocardium. To the best of my knowledge, these are the first two reported cases of sudden death after a single, parenteral, administration of frusemide-i.e., before it could have caused any electrolyte imbalance. Since the death in both these cases may have been fortuitous and unrelated to this fairly new drug, further observations on this subiect are needed. Beilinson Hospital, Petah Tikva, Israel.
I. MACHTEY.
PURPURA WITH HYPOGAMMAGLOBULINÆMIA SIR,-Cases of purpura with hypogammaglobulinxniia have been reported by Dr. Pouggouras and his colleagues,! and by Professor Cordeiro and Dr. Abecasis,2 and I report another here. A boy, aged 1 year 3 months, was first admitted here with a history of pyrexia, cough, and anorexia for 1 week, after having had chloramphenicol for a few days from the family doctor without improvement. He was the second child in the family, and had no history of previous diseases. His brother, a 3-yearold boy, and both parents were normal. The boy looked very ill, and his temperature was 103°F (39-5°C), but he showed no abnormalities apart from a very sore throat and small ulcers on the buccal mucosa. His blood showed: Hb 8-6 g. per 100 ml., white blood-cells 9300 per c.mm (granulocytes 0%, lymphocytes 95%, monocytes 5%), adequate platelets. Bone-marrow aspirate showed hyperplasia of the red series with a shift to the left, and a preponderance of eosinophils and reticulum cells; the polymorphs were maturing up to the stage of promyelocytes and myelocytes. Granulocytopenia due to chloramphenicol was diagnosed, and treatment was started with oxytetracycline, and with prednisone which the patient took for only 3 days (a total of 30 mg.). The temperature dropped very soon, and he was improving clinically, but his parents removed him before his blood-picture became normal. The patient was readmitted at 3 years 8 months, because of frequent respiratory infections and pyodermia of his face. A year before he had had pleurisy which had cleared with antibiotics. His blood showed Hb 85 g. per 100 ml., white bloodcells 8500 per c.mm (granulocytes 7%, lymphocytes 87%, eosinophils 6%), and adequate platelets; bone-marrow aspirate was normal. Electrophoresis of Hb showed the trait of p-thalasssemia, and that of proteins showed considerable decrease of y-globulins. Immunoelectrophoresis of y-globulins revealed complete lack of IgA and IgM and very small amounts of IgG. Chest X-ray and bronchography disclosed bronchiectasis of the left lower lobe. The patient was started on y-globulins, antibiotics (according to sensitivity cultures), and postural drainage. During a physiotherapy session he suddenly developed petechix all over his face and trunk. The mother then remembered that these punctate haemorrhages had appeared spontaneously many times in the past, lasting a few days on each occasion. Full hsematological investigation was normal, except for a positive Rumpel-Leede test. 1. 2.
Pouggouras, P., Simos, A., Papazacharias, A. Lancet, 1968, i, 141. Cordeiro, M., Abecasis, M. ibid. p. 534.
CONTROLLING CLIOQUINOL SIR,-Since continuous ingestion of substantial amounts of iodine may impair thyroid function, besides causing much inconvenience in judging the usual tests for thyroid disease,! we should consider whether marketing and promoting the sale of clioquinol and other iodoquinolines is unethical, and whether it endangers the health of large groups of the population. Although these substances are of little or no value in " tourists’ diarrhoea", they seem to be recommended by every guide in every chartered flight to the Mediterranean countries, where most tourists live in a milieu well protected against amoebic dysentery. On the contrary these drugs may cause diarrhoea in many tourists.2 Is it impossible for travel agencies to stop this propaganda, and to have it suppressed in guide-books for tourists, for publichealth authorities to require that these drugs shall be sold only on medical prescription, and for the pharmaceutical houses to renounce the profit gained from misunderstood medical evidence ? Aker Sykehus, Oslo 5.
J. H. VOGT.
SUDDEN DEATH AFTER INTRAMUSCULAR FRUSEMIDE now SIR,-The widely used sulphamylanthranilic-acid derivative, frusemide, is a highly effective oral and parenteral diuretic. Its untoward effects, generally mild, infrequent, and transitory, include pruritus, rash, nausea, vomiting, diarrhoea, and postural hypotension. I here describe two patients who died almost immediately after a single intramuscular injection of frusemide. Case 1.-This 94-year-old man had been having digoxin, methyldopa, and chlorpropamide for hypertensive heartdisease and mild diabetes. His last admission to hospital had been for pulmonary oedema. On admission: striking dyspnoea, both lungs congested, liver enlarged. The electrocardiogram (E.C.G.) showed left bundle-branch block, and ST depression in leads V and Vg. The many laboratory tests, including serumelectrolytes, were normal, except for blood-urea (61 mg. per 100 ml.), and blood-sugar (171 mg. per 100 ml.). The patient improved on digoxin, aminophylline, morphine, and oxygen inhalation. Next day many rales again appeared over both lungs. The E.c.G. now showed auricular tachycardia with varying rates of atrioventricular conduction. After the rales were found he was given an intramuscular injection of 20 mg. frusemide. Within one minute after the injection, the patient suddenly died. The final E.C.G. showed ventricular tachycardia. Permission for necropsy was not obtained. Case 2.-This 62-year-old man had mild diabetes and arteriosclerotic heart-disease. Latterly he had complained of shortness of breath. A few months before his last admission (which was for severe dyspnoea), he had had a transurethral resection of an enlarged prostate. At that time his blood-urea Vogt, J. H. Tidsskr. norske Lœgeforen, 1966, 10, 807. Zondek, H., Leszynsky, H. G. Lancet, 1968, i, 671. ibid. p. 679. Sönksen, P. H., Ekins, R. P., Stevens, H. G., Williams, E. S., Nabarro, J. D. N. ibid. Aug. 24, 1968, p. 425. 2. Walters, J. H. Wld Med. 1965, 12, 184. 1.
was 119 mg. per 100 ml., and creatinine-clearance only 25 ml. per minute. Most recently he had complained of pain in the
left hypochondrium. On admission: tachycardia, many rales over the right lung, tenderness on percussion over the left lower ribs, hepatosplenomegaly. E.C.G. showed left ventricular strain. His blood-urea was 114 mg. per 100 ml., and non-fasting bloodsugar 306 mg. per 100 ml. A few hours after admission the patient developed pulmonary oedema. Initially he was given digoxin and oxygen, and finally an intramuscular injection of 20 mg. frusemide. Within one minute after the injection, the patient suddenly died. The final E.C.G. showed cardiac arrest. Necropsy showed: pulmonary oedema; hepatosplenomegaly; nephrosclerosis; a benign, large, retroperitoneal tumour; enlarged heart, with sclerosis, but no thrombosis of coronary arteries, and a small area of discoloration on the posterior wall of the myocardium. To the best of my knowledge, these are the first two reported cases of sudden death after a single, parenteral, administration of frusemide-i.e., before it could have caused any electrolyte imbalance. Since the death in both these cases may have been fortuitous and unrelated to this fairly new drug, further observations on this subiect are needed. Beilinson Hospital, Petah Tikva, Israel.
I. MACHTEY.
PURPURA WITH HYPOGAMMAGLOBULINÆMIA SIR,-Cases of purpura with hypogammaglobulinxniia have been reported by Dr. Pouggouras and his colleagues,! and by Professor Cordeiro and Dr. Abecasis,2 and I report another here. A boy, aged 1 year 3 months, was first admitted here with a history of pyrexia, cough, and anorexia for 1 week, after having had chloramphenicol for a few days from the family doctor without improvement. He was the second child in the family, and had no history of previous diseases. His brother, a 3-yearold boy, and both parents were normal. The boy looked very ill, and his temperature was 103°F (39-5°C), but he showed no abnormalities apart from a very sore throat and small ulcers on the buccal mucosa. His blood showed: Hb 8-6 g. per 100 ml., white blood-cells 9300 per c.mm (granulocytes 0%, lymphocytes 95%, monocytes 5%), adequate platelets. Bone-marrow aspirate showed hyperplasia of the red series with a shift to the left, and a preponderance of eosinophils and reticulum cells; the polymorphs were maturing up to the stage of promyelocytes and myelocytes. Granulocytopenia due to chloramphenicol was diagnosed, and treatment was started with oxytetracycline, and with prednisone which the patient took for only 3 days (a total of 30 mg.). The temperature dropped very soon, and he was improving clinically, but his parents removed him before his blood-picture became normal. The patient was readmitted at 3 years 8 months, because of frequent respiratory infections and pyodermia of his face. A year before he had had pleurisy which had cleared with antibiotics. His blood showed Hb 85 g. per 100 ml., white bloodcells 8500 per c.mm (granulocytes 7%, lymphocytes 87%, eosinophils 6%), and adequate platelets; bone-marrow aspirate was normal. Electrophoresis of Hb showed the trait of p-thalasssemia, and that of proteins showed considerable decrease of y-globulins. Immunoelectrophoresis of y-globulins revealed complete lack of IgA and IgM and very small amounts of IgG. Chest X-ray and bronchography disclosed bronchiectasis of the left lower lobe. The patient was started on y-globulins, antibiotics (according to sensitivity cultures), and postural drainage. During a physiotherapy session he suddenly developed petechix all over his face and trunk. The mother then remembered that these punctate haemorrhages had appeared spontaneously many times in the past, lasting a few days on each occasion. Full hsematological investigation was normal, except for a positive Rumpel-Leede test. 1. 2.
Pouggouras, P., Simos, A., Papazacharias, A. Lancet, 1968, i, 141. Cordeiro, M., Abecasis, M. ibid. p. 534.