505
patient had three isolated respiratory arrests with unchanged cardiac function. A similar arrest may have caused his death. He was not on any drugs known to depress respiration before the arrests and had non-cardiac pulmonary oedema which may have induced hypoxia, depressing chemotactic centres and delaying the recovery of respiratory reflexes. In view of the potential danger of cardiorespiratory arrest, diabetic patients’ use of drugs which could depress respiration should be carefully considered. This
tries were less likely to have asthma and other atopic diseases than children of the same race born in Britain, as a result of environmental and cultural factors including breast-feeding. Thus, as Buisseret states, early exposure to cow’s milk may be an important factor in the development of atopic disease —specifically, I would suggest, atopic eczema. Addenbrooke’s
Hospital,
Cambridge
ROGER
J. WOLSTENHOLME
Division of Internal Medicine,
Department of Medicine,
GIRIYAPPA SRINIVASAN GARY SANDERS
University of Louisville School of Medicine Louisville, Kentucky 40202, U.S.A.
LEVEEN v SHUNTS %7&A %d.Llq a o JUJU
SIR,-The LeVeen peritoneo-venous shunt, discussed in (Feb. 11, p. 311), is useful in selected cases of ascites. However, malignant ascites is a different probhepatic lem ; the increase in peritoneal fluid is partly due to the deyour editorial
creased reabsorption of fluid via blocked lymphatics, following their obstruction by malignant cells, rather than the increased production of hepatic lymph. Furthermore the fluid often contains more protein and tends to coagulate, and it may also contain clumps of malignant cells. Despite these disadvantages, peritoneo-venous shunts have been used successfully in the control of malignant ascites,’ and we have lately inserted LeVeen shunts into three patients with advanced malignancy whose disease was relatively stable and whose ascites required repeated paracentesis. In two patients, one with gastric and the other with colonic adenocarcinoma, the ascites was controlled after insertion of the shunt. In the third (ovarian carcinoma) the operation was not successful in reducing the ascites. In all three patients we looked for malignant cells in the peripheral blood before and after the procedure. In the first two patients, whose ascites was controlled and in whom the shunt was working, venous blood taken immediately after a period of inspiration against a negative pressure of 15 cm water contained no detectable circulating cancer cells.2 We suggest that peritoneo-venous shunting may be useful in patients with malignant as well as hepatic ascites if the condition is not rapidly progressive. Shunting does not seem to disseminate malignant cells. Department of Surgery, Royal Marsden Hospital, London SW3 6JJ
RICHARD S. ARNOT HARVEY WHITE
ATOPY AND COW’S MILK
SiR,-Dr Buisseret (Feb. 11, eczema
provoked by cow’s
milk
p.
304)
drew attention to manifestation of
as a common
allergy in children. While working in
the southern Maldives, a chain of islands south-west of Sri-Lanka, I noted a high incidence of bronchial asthma in the population. Of 137 asthmatics 28 had allergic rhinitis and/or conjunctivitis but only 2 showed evidence of atopic eczema. This low frequency of atopic eczema in patients with bronchial asthma may have been associated with a lack of cow’s milk in the diet. The staple diet is fish and rice, infants almost always being breast-fed. Warrell et awl. noted a striking absence of eczema in Nigerian asthmatics and suggested that the prolonged breast feeding that is common in African countries might be a factor. Morrison Smith4 suggested that children born in poor tropical counPollock, A. V. Br. J. Surg. 1975, 62, 104. Salisbury, A. J. M.D. thesis, University of Cambridge, 1964. 3. Warrell, D. A., Fawcett, I. W., Harrison, B. D. W., Agamah, J. O., Pope, H. M., Maberly, D. J. Q. J. Med. 1975, 44, 325. 4. Morrison Smith J. Br. J. Dis. Chest, 1976, 70, 73. 1. 2.
A.
J., Ibu,
TREATMENT OF MASSIVE DIGITOXIN OVERDOSE BY CHARCOAL HÆMOPERFUSION AND CHOLESTYRAMINE
SIR,-We have seen a patient early after intoxication with digitoxin and have monitored the concentration of the drug in plasma before and after charcoal haemoperfusion and cholestyramine treatment. A 47-year-old woman was admitted to our hospital 7 h after ingestion of about a hundred ’Digimerck’ tablets of 0.1 mg digitoxin in a suicide attempt. Gastric lavage had been done 3 h after drug ingestion. On admission the patient had symptoms of severe digitalis intoxication (nausea, vomiting, and seconddegree atrioventricular block, QT shortening, and widespread ST depression). She also had severe hyperventilation, suggesting that high doses of digitalis may be neuroexcitatory.’ Serum electrolytes were consistently normal. 12 h after ingestion of digitoxin the patient had ventricular fibrillation. She was resuscitated and given ugnocaine (4 g in 24 h). The plasmadigitoxin on admission (radioimmunoassay) was 150 ng/ml indicating that large amounts of the drug had been absorbed. 21 h after ingestion of digitoxin charcoal hasmoperfusion with ’Hxmocol’ (Dr E. Fresenius KG, Bad Homburg) filled with 300 g activated charcoal coated to 2% with acryl hydrogel was started. The plasma-digitoxin was then 125 ng/ml. Over 8 h of haemoperfusion 1.24 mg of the drug was removed, as indicated by hourly calculations of pre and post column concentration differences.2 1 h later a second haemoperfusion was started, and 0.87 mg digitoxin was removed. At this time the plasma-digitoxin had fallen to 70 ng/ml and most of the symptoms of intoxication had disappeared. Thereafter 4 g cholestyramine was given three times daily for 5 days and plasma-digitoxin was measured twice daily. The elimination half-life found during this period was 62 h. 3 weeks later 0-73 mg digitoxin was given intravenously to the patient, and plasma concentration of the drug was monitored for 17 days. Under these conditions the half-life of digitoxin was 145 h. Charcoal hmmoperfusion can remove digitoxin in laboratory conditions both in vitro and in vivo.3 Our patient had very severe digitalis intoxication, and to our knowledge such high plasma levels have not been reported previously in man. The rapid improvement in the clinical picture, the reduction of digitalis-induced E.c.G. changes, and the dramatic fall in plasmadigitoxin show that charcoal haemoperfusion can remove significant amounts of digitoxin in patients with life-threatening digitoxin intoxication. Cholestyramine enhances the elimination of digitoxin in digitalis-intoxicated animals by interrupting the enterohepatic recycling of the drug.4 Cholestyramine seems to do this in man also, and this effect could be of value for the treatment of less dramatic digitoxin intoxication.
II Medizinische Klinik, Universität Mainz, D-6500 Mainz, West Germany
HANS-JOACHIM GILFRICH WOLFGANG KASPER THOMAS MEINERTZ STEFAN OKONEK RENATE BORK
1. Gilhs, R. A., Pearle, D. L., Levitt, B. Circulation, 1975, 52, 739. 2. Winchester, J. F., Edwards, R. O., Tilstone, W. J., Woodcock, B. G. Toxicol. appl. Pharmac. 1975, 31, 120. 3. Gilfrich, H. J., Okonek, S., Manns, M., Schuster, C. J. Klin. Wschr. (in the
4.
press). Caldwell, J. H., Greenberger, N. J. J. clin. Invest. 1971, 50, 2626.
patient had three isolated respiratory arrests with unchanged cardiac function. A similar arrest may have caused his death. He was not on any drugs known to depress respiration before the arrests and had non-cardiac pulmonary oedema which may have induced hypoxia, depressing chemotactic centres and delaying the recovery of respiratory reflexes. In view of the potential danger of cardiorespiratory arrest, diabetic patients’ use of drugs which could depress respiration should be carefully considered. This
tries were less likely to have asthma and other atopic diseases than children of the same race born in Britain, as a result of environmental and cultural factors including breast-feeding. Thus, as Buisseret states, early exposure to cow’s milk may be an important factor in the development of atopic disease —specifically, I would suggest, atopic eczema. Addenbrooke’s
Hospital,
Cambridge
ROGER
J. WOLSTENHOLME
Division of Internal Medicine,
Department of Medicine,
GIRIYAPPA SRINIVASAN GARY SANDERS
University of Louisville School of Medicine Louisville, Kentucky 40202, U.S.A.
LEVEEN v SHUNTS %7&A %d.Llq a o JUJU
SIR,-The LeVeen peritoneo-venous shunt, discussed in (Feb. 11, p. 311), is useful in selected cases of ascites. However, malignant ascites is a different probhepatic lem ; the increase in peritoneal fluid is partly due to the deyour editorial
creased reabsorption of fluid via blocked lymphatics, following their obstruction by malignant cells, rather than the increased production of hepatic lymph. Furthermore the fluid often contains more protein and tends to coagulate, and it may also contain clumps of malignant cells. Despite these disadvantages, peritoneo-venous shunts have been used successfully in the control of malignant ascites,’ and we have lately inserted LeVeen shunts into three patients with advanced malignancy whose disease was relatively stable and whose ascites required repeated paracentesis. In two patients, one with gastric and the other with colonic adenocarcinoma, the ascites was controlled after insertion of the shunt. In the third (ovarian carcinoma) the operation was not successful in reducing the ascites. In all three patients we looked for malignant cells in the peripheral blood before and after the procedure. In the first two patients, whose ascites was controlled and in whom the shunt was working, venous blood taken immediately after a period of inspiration against a negative pressure of 15 cm water contained no detectable circulating cancer cells.2 We suggest that peritoneo-venous shunting may be useful in patients with malignant as well as hepatic ascites if the condition is not rapidly progressive. Shunting does not seem to disseminate malignant cells. Department of Surgery, Royal Marsden Hospital, London SW3 6JJ
RICHARD S. ARNOT HARVEY WHITE
ATOPY AND COW’S MILK
SiR,-Dr Buisseret (Feb. 11, eczema
provoked by cow’s
milk
p.
304)
drew attention to manifestation of
as a common
allergy in children. While working in
the southern Maldives, a chain of islands south-west of Sri-Lanka, I noted a high incidence of bronchial asthma in the population. Of 137 asthmatics 28 had allergic rhinitis and/or conjunctivitis but only 2 showed evidence of atopic eczema. This low frequency of atopic eczema in patients with bronchial asthma may have been associated with a lack of cow’s milk in the diet. The staple diet is fish and rice, infants almost always being breast-fed. Warrell et awl. noted a striking absence of eczema in Nigerian asthmatics and suggested that the prolonged breast feeding that is common in African countries might be a factor. Morrison Smith4 suggested that children born in poor tropical counPollock, A. V. Br. J. Surg. 1975, 62, 104. Salisbury, A. J. M.D. thesis, University of Cambridge, 1964. 3. Warrell, D. A., Fawcett, I. W., Harrison, B. D. W., Agamah, J. O., Pope, H. M., Maberly, D. J. Q. J. Med. 1975, 44, 325. 4. Morrison Smith J. Br. J. Dis. Chest, 1976, 70, 73. 1. 2.
A.
J., Ibu,
TREATMENT OF MASSIVE DIGITOXIN OVERDOSE BY CHARCOAL HÆMOPERFUSION AND CHOLESTYRAMINE
SIR,-We have seen a patient early after intoxication with digitoxin and have monitored the concentration of the drug in plasma before and after charcoal haemoperfusion and cholestyramine treatment. A 47-year-old woman was admitted to our hospital 7 h after ingestion of about a hundred ’Digimerck’ tablets of 0.1 mg digitoxin in a suicide attempt. Gastric lavage had been done 3 h after drug ingestion. On admission the patient had symptoms of severe digitalis intoxication (nausea, vomiting, and seconddegree atrioventricular block, QT shortening, and widespread ST depression). She also had severe hyperventilation, suggesting that high doses of digitalis may be neuroexcitatory.’ Serum electrolytes were consistently normal. 12 h after ingestion of digitoxin the patient had ventricular fibrillation. She was resuscitated and given ugnocaine (4 g in 24 h). The plasmadigitoxin on admission (radioimmunoassay) was 150 ng/ml indicating that large amounts of the drug had been absorbed. 21 h after ingestion of digitoxin charcoal hasmoperfusion with ’Hxmocol’ (Dr E. Fresenius KG, Bad Homburg) filled with 300 g activated charcoal coated to 2% with acryl hydrogel was started. The plasma-digitoxin was then 125 ng/ml. Over 8 h of haemoperfusion 1.24 mg of the drug was removed, as indicated by hourly calculations of pre and post column concentration differences.2 1 h later a second haemoperfusion was started, and 0.87 mg digitoxin was removed. At this time the plasma-digitoxin had fallen to 70 ng/ml and most of the symptoms of intoxication had disappeared. Thereafter 4 g cholestyramine was given three times daily for 5 days and plasma-digitoxin was measured twice daily. The elimination half-life found during this period was 62 h. 3 weeks later 0-73 mg digitoxin was given intravenously to the patient, and plasma concentration of the drug was monitored for 17 days. Under these conditions the half-life of digitoxin was 145 h. Charcoal hmmoperfusion can remove digitoxin in laboratory conditions both in vitro and in vivo.3 Our patient had very severe digitalis intoxication, and to our knowledge such high plasma levels have not been reported previously in man. The rapid improvement in the clinical picture, the reduction of digitalis-induced E.c.G. changes, and the dramatic fall in plasmadigitoxin show that charcoal haemoperfusion can remove significant amounts of digitoxin in patients with life-threatening digitoxin intoxication. Cholestyramine enhances the elimination of digitoxin in digitalis-intoxicated animals by interrupting the enterohepatic recycling of the drug.4 Cholestyramine seems to do this in man also, and this effect could be of value for the treatment of less dramatic digitoxin intoxication.
II Medizinische Klinik, Universität Mainz, D-6500 Mainz, West Germany
HANS-JOACHIM GILFRICH WOLFGANG KASPER THOMAS MEINERTZ STEFAN OKONEK RENATE BORK
1. Gilhs, R. A., Pearle, D. L., Levitt, B. Circulation, 1975, 52, 739. 2. Winchester, J. F., Edwards, R. O., Tilstone, W. J., Woodcock, B. G. Toxicol. appl. Pharmac. 1975, 31, 120. 3. Gilfrich, H. J., Okonek, S., Manns, M., Schuster, C. J. Klin. Wschr. (in the
4.
press). Caldwell, J. H., Greenberger, N. J. J. clin. Invest. 1971, 50, 2626.
