- Email: [email protected]
CARDIORESPIRATORY ARREST IN DIABETES
504 provement, which remained and was increased after each dose. His cumulative improvement has been sustained and dramatic: he now easily turns over, gets out of bed, walks 6 miles daily, does a push-up and deep-knee bend, climbs 120 steps, and holds a heavy chair over his head. Distal muscles of finger function have improved, but not strikingly so far. Interferon levels increased from zero to 100-500 units with each polyI.C.L.c. dose. C.S.F. protein is now 36 mg/dl and motor-nerve conduction velocity is 40 m/s in the median nerve and 27 in the ulnar. In the three polY-I.c.L.c.-treated patients, leucocytes were studied with each dose (39 total doses), usually thrice daily for 2 days and then daily until the next dose (more than 250 studies altogether). All three responded similarly. Lymphocytes fell to 17% of baseline, having a nadir in 1-2 days, and returned to baseline by the 4th or 5th day; the granulocyte response was biphasic, with a 3-fold rise at 6-24 h, a 30% fall from baseline at 2-3 days, and return to baseline by 3-5 days. We propose that POlY-I.C.L.C. has been responsible for the striking clinical improvement of this patient and that this benefit may have been the result of an "anti-dysimmune" action of poly-l.c.L.c. acting by lymphocyte suppression rather than increasing interferon or stress-induced corticoids. POlY-I.C.L.C. would then be a new type of immunosuppressant drug potentially beneficial in other kinds of dysimmune diseases (and perhaps in lymphocytoproliferative disorders). If it acts through interferon, POlY-I.C.L.C. would provide new insight into the pathogenesis of relapsing neuropathy and a new treatment. Medical Neurology Branch, National Institute of Neurological and Communicative Disorders, National Institutes of Health, Bethesda, Maryland 20014, U.S.A.
W. KING ENGEL RICHARD A. CUNEO HILTON B. LEVY
A.L.G. IN APLASTIC ANÆMIA
S!R,—The preliminary report by Speck et al. on the use of antilymphocyte globulin (A.L.G.) with or without partially compatible bone-marrow for treating severe aplastic anaemia is intriguing. However, as Speck et al. say, aplastic anaemia, even when severe, has a variable course. Thus, to assess the contribution of A.L.G. to survival, a control group treated identically except for A.L.G. is required. The controls and A.L.G. treated patients should be comparable in disease severity, interval from diagnosis to entry into study, and other factors, such as age, sex, and infection, that may affect survival. In the absence of concurrent controls, results of relatively small series may be misleading. For example, the trials of A.L.G. + incompatible marrow by Mathe et awl. were uncontrolled. Survival of 5/24 patients treated in this manner is no different than the survival of patients with severe aplastic anaemia receiving supportive care alone.3 Similarly, early uncontrolled reports of improved survival with androgen therapy for severe aplastic anaemia were not confirmed when these agents were evaluated in a controlled trial.4.5 Speck et al. recognise the limitations of their work. I hope that they will design follow-up trials to define the role of A.L.G. in treating severe aplastic anaemia. Department of Pediatrics, Midwest Children’s Cancer Center, Milwaukee Children’s Hospital, Milwaukee, Wisconsin 3233, U.S.A.
1.
Speck, B., Gluckman, E., Haak, H. L.,
BRUCE M. CAMITTA
van
ANTI-HBs IMMUNE GLOBULIN TO PREVENT HEPATITIS B
SiR,—Frosner et al.’ described three cases of hepatitis, after sexual contact or accidental needlestick exposure, despite administration of anti-HBs immune globulin (H.B.I.G.). They concluded that H.B.I.G. had not prevented hepatitis B but had merely extended the incubation period. We disagree with this conclusion, especially for the third case. If H.B.I.G. failed in the first two cases, it was probably because prophylaxis was attempted too late after exposure (12 days or more in the first case of sexual contact and 15 days in the second case). Such cases are not really failures of im-
munotherapy. In the third case, hepatitis B in a nurse 205 days after needlestick exposure, a second, undetected exposure 2-4 months after the detected incident is the more likely explanation. We have seen a similar case (hepatitis B 6 months after exposure and H.B.I.G.).3,4 This case was interpreted as a later, undetected contamination. The permanent exposure risk in haunodialysis units was the incentive for us to try repeated H.B.I.G. injections to achieve permanent protection.3,4 We have found that 5 ml H.B.LG., with the same activity as the international reference, protects for only 2 months5 despite weak levels of passive anti-HBs beyond this period. This residual anti-HBs is too weak to guarantee effective protection. In our experience H.B.I.G. prevents hepatitis B if the H.B.I.G. titre is at least as potent as the international reference, the dose is 0-08 ml/kg, the injection is given no more than 8 days after exposure, and the H.B.I.G. injections are repeated every 2 months if the risk of exposure is great and permanent. ’
Etablissement Cabanel, Centre National de Transfusion Sanguine, 75739 Paris, France
A. M. COUROUCE
Centre Edouard Rist, Paris
C. NARET C. CIANCIONNI S. DELONS
CARDIORESPIRATORY ARREST IN DIABETES
S:R,—We have similar
to
seen
cardiorespiratory arrest in a diabetic by Dr Page and Dr Watkins (Jan. 7,
that described
p. 14). A 49-year-old
male with a 20-year history of insulin-dependent diabetes mellitus presented with acute shortness of breath and diarrhoea. His supine blood-pressure was 150/80 mm Hg. Examination showed advanced diabetic retinopathy, postural hypotension, sinus tachycardia, bilateral rales, and extensive peripheral neuropathy. There was evidence of neurogenic bladder. Chest X-ray showed pulmonary oedema but no significant change in heart size. Blood-glucose was 160 mg/dl and serum-electrolytes were normal but there was hypoxia and hyper-
capnia.
,
While being treated, he suddenly stopped breathing. At that moment, the cardiac monitor showed sinus rhythm and the blood-pressure did not fall. Spontaneous respiration began again after several minutes of respiratory resuscitation. During his stay in the hospital, Holter monitoring did not show any rhythm disturbance. He had two more episodes of respiratory arrest during which cardiac function was unchanged but there was X-ray evidence of pulmonary cedema. 8 h of artificial ventilation were required after one of these episodes before spontaneous respiration returned. The patient left the hospital in a stable condition but a few weeks later was found dead in bed.
Rood, J. J. Lancet, 1977, ii,
1145. 2. Mathé, G., Schwartzenberg, L. Exp. Hæmat. 1976, 4, 256. 3. Williams, D. M., Lynch, R. E., Cartwright, G. E. Sem. Hemat. 1973, 10, 195. 4. Camitta, B. M., Thomas, E. D., Nathan, D. G., Santos, G., Gordon-Smith, E. C., Gale, R. P., Rappaport, J. M., Storb, R. Blood, 1976, 48, 63. 5. Camitta, B. M., Thomas, D., Nathan, D., Santos, G., Gordon-Smith, E., Rappaport, J. ibid. 1977, 48, suppl., p. 313.
1. Frösner, G.
G., Frösner, H.-R., Dienhardt, F., Haussman, W., Knabe, U. H. Lancet, 1977, ii, 1023. 2. Soulier, J. P., Couroucé-Pauty, A. M., Benamon-Djiane, D. Rev. fr. Transf.
1972, 15, 377. 3. Delons, S., and others. Proc. Eur. Dial. Transpl. Ass. 1974, 11, 237. 4. Couroucé-Pauty, A. M., Delons, S., Soulier, J. P. Am. J. med. Sci. 1975, 375. 5. Couroucé-Pauty, A. M., and others. Archs Malad. profess. (in the press).
270,
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.
W. KING ENGEL RICHARD A. CUNEO HILTON B. LEVY
A.L.G. IN APLASTIC ANÆMIA
S!R,—The preliminary report by Speck et al. on the use of antilymphocyte globulin (A.L.G.) with or without partially compatible bone-marrow for treating severe aplastic anaemia is intriguing. However, as Speck et al. say, aplastic anaemia, even when severe, has a variable course. Thus, to assess the contribution of A.L.G. to survival, a control group treated identically except for A.L.G. is required. The controls and A.L.G. treated patients should be comparable in disease severity, interval from diagnosis to entry into study, and other factors, such as age, sex, and infection, that may affect survival. In the absence of concurrent controls, results of relatively small series may be misleading. For example, the trials of A.L.G. + incompatible marrow by Mathe et awl. were uncontrolled. Survival of 5/24 patients treated in this manner is no different than the survival of patients with severe aplastic anaemia receiving supportive care alone.3 Similarly, early uncontrolled reports of improved survival with androgen therapy for severe aplastic anaemia were not confirmed when these agents were evaluated in a controlled trial.4.5 Speck et al. recognise the limitations of their work. I hope that they will design follow-up trials to define the role of A.L.G. in treating severe aplastic anaemia. Department of Pediatrics, Midwest Children’s Cancer Center, Milwaukee Children’s Hospital, Milwaukee, Wisconsin 3233, U.S.A.
1.
Speck, B., Gluckman, E., Haak, H. L.,
BRUCE M. CAMITTA
van
ANTI-HBs IMMUNE GLOBULIN TO PREVENT HEPATITIS B
SiR,—Frosner et al.’ described three cases of hepatitis, after sexual contact or accidental needlestick exposure, despite administration of anti-HBs immune globulin (H.B.I.G.). They concluded that H.B.I.G. had not prevented hepatitis B but had merely extended the incubation period. We disagree with this conclusion, especially for the third case. If H.B.I.G. failed in the first two cases, it was probably because prophylaxis was attempted too late after exposure (12 days or more in the first case of sexual contact and 15 days in the second case). Such cases are not really failures of im-
munotherapy. In the third case, hepatitis B in a nurse 205 days after needlestick exposure, a second, undetected exposure 2-4 months after the detected incident is the more likely explanation. We have seen a similar case (hepatitis B 6 months after exposure and H.B.I.G.).3,4 This case was interpreted as a later, undetected contamination. The permanent exposure risk in haunodialysis units was the incentive for us to try repeated H.B.I.G. injections to achieve permanent protection.3,4 We have found that 5 ml H.B.LG., with the same activity as the international reference, protects for only 2 months5 despite weak levels of passive anti-HBs beyond this period. This residual anti-HBs is too weak to guarantee effective protection. In our experience H.B.I.G. prevents hepatitis B if the H.B.I.G. titre is at least as potent as the international reference, the dose is 0-08 ml/kg, the injection is given no more than 8 days after exposure, and the H.B.I.G. injections are repeated every 2 months if the risk of exposure is great and permanent. ’
Etablissement Cabanel, Centre National de Transfusion Sanguine, 75739 Paris, France
A. M. COUROUCE
Centre Edouard Rist, Paris
C. NARET C. CIANCIONNI S. DELONS
CARDIORESPIRATORY ARREST IN DIABETES
S:R,—We have similar
to
seen
cardiorespiratory arrest in a diabetic by Dr Page and Dr Watkins (Jan. 7,
that described
p. 14). A 49-year-old
male with a 20-year history of insulin-dependent diabetes mellitus presented with acute shortness of breath and diarrhoea. His supine blood-pressure was 150/80 mm Hg. Examination showed advanced diabetic retinopathy, postural hypotension, sinus tachycardia, bilateral rales, and extensive peripheral neuropathy. There was evidence of neurogenic bladder. Chest X-ray showed pulmonary oedema but no significant change in heart size. Blood-glucose was 160 mg/dl and serum-electrolytes were normal but there was hypoxia and hyper-
capnia.
,
While being treated, he suddenly stopped breathing. At that moment, the cardiac monitor showed sinus rhythm and the blood-pressure did not fall. Spontaneous respiration began again after several minutes of respiratory resuscitation. During his stay in the hospital, Holter monitoring did not show any rhythm disturbance. He had two more episodes of respiratory arrest during which cardiac function was unchanged but there was X-ray evidence of pulmonary cedema. 8 h of artificial ventilation were required after one of these episodes before spontaneous respiration returned. The patient left the hospital in a stable condition but a few weeks later was found dead in bed.
Rood, J. J. Lancet, 1977, ii,
1145. 2. Mathé, G., Schwartzenberg, L. Exp. Hæmat. 1976, 4, 256. 3. Williams, D. M., Lynch, R. E., Cartwright, G. E. Sem. Hemat. 1973, 10, 195. 4. Camitta, B. M., Thomas, E. D., Nathan, D. G., Santos, G., Gordon-Smith, E. C., Gale, R. P., Rappaport, J. M., Storb, R. Blood, 1976, 48, 63. 5. Camitta, B. M., Thomas, D., Nathan, D., Santos, G., Gordon-Smith, E., Rappaport, J. ibid. 1977, 48, suppl., p. 313.
1. Frösner, G.
G., Frösner, H.-R., Dienhardt, F., Haussman, W., Knabe, U. H. Lancet, 1977, ii, 1023. 2. Soulier, J. P., Couroucé-Pauty, A. M., Benamon-Djiane, D. Rev. fr. Transf.
1972, 15, 377. 3. Delons, S., and others. Proc. Eur. Dial. Transpl. Ass. 1974, 11, 237. 4. Couroucé-Pauty, A. M., Delons, S., Soulier, J. P. Am. J. med. Sci. 1975, 375. 5. Couroucé-Pauty, A. M., and others. Archs Malad. profess. (in the press).
270,
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.