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HYPERMAGNESÆMIA AND PLATELET FUNCTION IN URÆMIC BLEEDING
301 Sectional efficiency and sectional economy must clearly be seen benefit the part as well as the whole. Backing Britain is well, but backing Little- Puddleton is a good incentive.
to
F. PYGOTT.
PSYCHIATRY RAMPANT SiR,—Iwas surprised to read Dr. Denis Williams’ remarks, as reported in your annotation,! for I felt that he was reintroducing an old problem which I thought had been adequately discussed and settled more than twenty years ago. The point which perhaps seems to demand a comment from me is his apparent criticism of the Army for taking on everything. It is not quite true to say that the Army tried to take on everything. We refused many requests for help and advice, either because there was not time to study the matter and give that advice, or because we felt that what we had to contribute was not worth much emphasis. Dr. Williams is correct in saying that there were not enough good psychiatrists to do all the jobs; that applied not merely to the Army, but to the other two Services as well. Partly because the other Services had prior choice of personnel, and the Army had to take what was left, we had rather fewer men who had had first-rate training, and the whole work of our team in psychiatry was in part a form of training for our men and women doctors. We had, however, quite a large number of people with excellent background training. I have often smiled to myself at the fact that we had twenty or thirty fully qualified psychoanalysts, but so far as I am aware not one of them ever analysed a patient during the 1939-45 war: they were too busy using their knowledge of pathology in trying to solve some of the problems of other people in other arms of the Services. Finally I would like to say how very happy I am about the work that Prof. Linford Rees is doing at Barts; it is a real advance in the teachins of nsvchiatrv.
J. R. REES.
EMPTYING THE KIIL KIDNEY
SIR,-We were interested by the letter of Dr. van Hooff and Dr. Wijdeveld (Jan. 6, p. 51) reporting the advantage of an air-rinsing method of emptying the Kiil dialyser. We reported2 last year at the meeting of the European Dialysis and Transplant Association similar favourable results by a method using only sterile air. Internal gasket dialysers with
clamp were used. They were not tilted before the end of the dialysis. Dialysate flow was not modified during the emptying of the
dialyser. After disconnection of the arterial line, the line was occluded. Air was injected through a sterile filter into the arterial line, up to a pressure of 200 mm. Hg. Injection was then stopped and the venous line was opened, allowing the blood to flow into the patient. When the pressure inside the dialyser had fallen to 100 mm. Hg., the venous line was again occluded. The whole procedure was repeated, until venous
air reached the bubble catcher. The blood remaining in the dialyser and in the blood lines after rinsing has been evaluated 62 times by cutting the membranes and the tubing in small pieces and dipping them in heparinised isotonic saline solution. The amount of blood recovered averaged 123 ml. whole blood after rinsing with 1 litre isotonic glucose solution and 42 ml. whole blood after air rinsing. The difference is highly significant (P < O’OOl). The amount of blood needed to maintain a haemoglobin value of 9.5 g. per 100 ml. was evaluated in six patients. It fell from an average of 3 units packed-cell volume (P.c.v.) per month, when the glucose-rinsing method was used, to an average of 2 units P.c.v. per month with the air-rinsing method. The difference is significant (p < 0-01). 1. Lancet, 1967, ii, 976. 2. Stragier, A., van Ypersele de Ass (in the press).
Strihou, C.
Proc. Eur. Dial.
Transpl.
The
now been used in over 1200 without untoward effects. No air embolism has occurred. This method requires only a few minutes, and has the obvious advantages of diminishing the transfusion requirements and of reducing the amount of fluid returned to the patient at the end of the dialysis. Renal Unit, Department of Medicine, A. STRAGIER
air-rinsing technique has
dialyses
University of Louvain, Louvain, Belgium.
C.
VAN
YPERSELE
DE
STRIHOU.
HYPERMAGNESÆMIA AND PLATELET FUNCTION IN URÆMIC BLEEDING SiR,—Hypermagnesaemia has been described in bilaterally nephrectomised dogs, and in acute renal failure 2and chronic nephritis 4-6 in man. Abnormal bleeding is common in uraemic patients,7 and has been ascribed to failure in the activation of platelet-factor 3.8 Horowitz et al. described a plasma constituent which inhibits platelet-factor-3. It has properties similar to guanidosuccinic acid and may be overcome by the addition of calcium. Stewart and Castaldihave shown that a reversible platelet defect in urxmic bleeding may be corrected by dialysis, but their attempts to reproduce the defect in vitro by the addition of various substances, including magnesium, to platelet-rich plasma (P.R.P.) were unsuccessful. However, their P.R.P. contained citrate,9 with consequent inactivation of calcium and magnesium ions-conditions in which the addition of sufficient magnesium induces platelet clumping.10 Addition of magnesium to fresh P.R.P. without anticoagulants prolongs platelet-clumping time and antagonises the clumping activity of adenosine diphosphate" 12; magnesium also prolongs the clotting-time of whole blood 13 and delays the peak thrombin-generation time in vitro and in vivo. 14 By the method we have described,12 fresh whole blood in plastic or siliconed containers may be centrifuged immediately and the supernatant P.R.P. examined microscopically at 5minute intervals to determine the clumping-time. During the early phases of such observations many of the platelets appear as rods-presumably because at this stage they maintain their disc shape and some of them are viewed end-on. As time progresses, the proportion of rod-shaped platelets diminishes until, in the preclumping phase, the rods disappear altogether. In the process of delaying platelet clumping, added magnesium salts increases the proportion and the duration of these rodshaped forms. Plasma-magnesium levels were measured by E.E.L. atomic absorption spectrophotometer giving a mean normal value of 2-34 ±0-008 (S.E.M.) mg. per 100 ml. Platelet-clumping time was recorded at the first appearance of 1001i clumps giving a In 3 patients with mean value of 301-03 (s.E.M.) minutes. urxmic bleeding the results were as follows:
In patients 2 and 3, fibrin appeared before platelet clumping had begun. In all 3 patients, the increased initial proportion 1. 2. 3. 4. 5.
6. 7.
8. 9. 10. 11. 12. 13. 14.
Schloerb, P. R. Metabolism, 1961, 10, 59. Wacker, W. E. C., Vallee, B. L. New Engl. J. Med. 1957, 257, 1254. Takayasu, H., Sato, S., Yamadori, H., Hirata, T. Acta med. biol., Niigata, 1962, 10, 117. Outa, T. Fukuoka Acta med. 1963, 54, 1208. Randall, R. E., Cohen, M. D., Spray, C. C., Rossmeisl, E. C. Ann. intern. Med. 1964, 61, 73. Breen, M., Marshall, R. T. J. Lab. clin. Med. 1966, 68, 701. Stewart, J. H., Castaldi, P. A. Q. Jl Med. 1967, 36, 409. Horowitz, H. I., Burton, D. C., Martinez, P., Papayoanou, M. F. Blood, 1967, 30, 331. Castaldi, P. A., Rozenberg, M. C., Stewart, J. H. Lancet, 1966, ii, 66. Brambel, C. E., in Henry Ford Symposium on Blood Platelets; p. 125. London, 1961. Hughes, A., Tonks, R. S. Lancet, 1965, i, 1044. Hughes, A., Tonks, R. S. Nature, Lond. 1966, 210, 106. Greville, G. D., Lehmann, H. ibid. 1943, 152, 81. Huntsman, R. G., Hurn, B. A. L., Lehmann, H. J. clin. Path. 1960, 13, 99.
302 of both patients. In each case, the modal chromosome number of thirty cells was 46; random loss accounted for cells with chromosome number less than 46; and No no cells with 47 or more chromosomes were found. abnormalities in the B group were present. Culture of the cells of the carcinoma was not attempted in our patients or in the patient of Dr. Pascasio and his colleagues, so that karyotypes of the malignant cells are unknown. In order to postulate that an apparent chromosome imbalance in the peripheral lymphocytes is related to the setiology of an adrenal neoplasm, it must be assumed that the same karyotype is present in the adrenal cells and that this imbalance or a derived karyotype pattern is carcinogenic3 for that cell type. This is indeterminable. Chromosome abnormalities have been described in solid neoplasms,4 but the transfer of a spontaneous cytogenetic alteration in an adrenal cell to a lymphocytic stemline is unlikely. Department of Pediatrics, University of Florida, L. C. ELLWOOD College of Medicine, H. A. PEARSON. Gainesville, Florida.
lymphocyte metaphases
Appearance of P.R.P. 20 minutes after venepuncture: (a) in normal blood, showing absence of rod forms; (b) in blood of a uraemic patient, showing persistence of rod-shaped platelets. (Unstained, x 1000.)
and abnormal persistence of rod-shaped platelets was clearly apparent (figs. 1 and 2). Thus, in association with other plasma factors, the hypermagnesxmia itself may partake in the prevention of normal platelet clumping in patients with urxmic bleeding. In controlling the hypermagnesaemia by dialysis, regard to the magnesium content of the dialysing fluid itself may repay attention. D. T. P. DAVIES ANEURIN HUGHES G. D. LOMAX Nevill Hall Hospital, R. S. TONKS. Abergavenny, Monmouthshire.
NORMAL LYMPHOCYTE KARYOTYPES IN ADRENOCORTICAL CARCINOMA SIR,-Pascasio et al.l described a five-year-old boy with anaplastic type of adrenal carcinoma with an extra large subto group B (pair 5) in most peripheral lymphocyte metaphases. We have lately analysed karyotypes from peripheral lymphocytes of two children with adrenocortical carcinoma cultured according to the method of Moorhead et al. using Difco chromosome-culture kits. Case 1.-A four-year-old girl was first noted to have signs of acquired adrenogenital syndrome with clitoral enlargement, pubic hair, and deepened voice pitch. She had increased excretion of 17-ketosteroids and 17-hydroxysteroids. Exploratory laparotomy showed no gross abnormality of the adrenal glands; corticosteroid therapy arrested progression of signs. A left upper-quadrant abdominal mass was first palpated at age nine years; an encapsulated mass was found within the substance of the left adrenal gland, which was removed in toto. Microscopically the tumour was an adrenocortical carcinoma. Widespread metastatic lung nodules appeared two months after operation, and o, p’ DDD therapy was begun. The lung metastases dramatically decreased in size, and remission was
metacentric chromosome similar
maintained for the next three years. The metastases then became resistant to o, p’DDD therapy, and the child died several months later. Blood for chromosome analysis was obtained two months before her death at twelve years of age. Case 2.-A thirteen-year-old girl developed Cushing’s syndrome with weight gain, hypertension, amenorrhoea, hirsutism, acne, abdominal striec, and emotional lability over six months. Urinary 17-ketosteroids and 17-hydroxysteroids were strikingly raised. Encapsulated mass, weighing 450 g., was removed from the left adrenal. Microscopy revealed adrenocortical carcinoma. No metastases were found at operation, and the patient improved thereafter. Normal female karyotypes (46, XX) were found in peripheral1. 2.
Pascasio, F. M., Jesalva, P. S., Cruz, E. P., Alikpala, S. Lancet, 1967, i, 1107. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Expl Cell Res. 1960, 20, 613.
HOSPITAL ADMISSIONS AND INVESTIGATIONS "
SiR,-Dr. Samuel (Jan. 20, p. 139) writes: There are few hospitals in the United Kingdom where admission of patients is correlated to the capacity of the X-ray departments or biochemical laboratories. More liaison in this area would surely eliminate many of the delays." Dr. Samuel does not tell us what are the kinds of patients he has in mind, but he is clearly not referring to emergencies, since their admission cannot be delayed for correlation purposes. Which non-urgent patients need to be admitted for their radiological and biochemical investigations ? I can think of very few. A most deplorable misuse of hospital beds is to occupy them with patients being investigated-however efficient the correlation. May I urge Dr. Samuel to use his great influence to dissuade his colleagues from indulging in this practice ? JOHN W. TODD.
HYPOTENSION AFTER ORAL PROPRANOLOL an episode of profound hypotension
SiR,-Ireport here
after a small oral dose of propranolol (’ Inderal’). The patient is a 49-year-old publican with severe alcoholic cardiomyopathy. He developed atrial fibrillation with left bundle-branch block, and his rapid ventricular rate (150 per minute) was refractory to digoxin. He was given a single oral dose of 10 mg. propranolol. Two hours later he was moribund, with systolic blood-pressure (B.P.) 60 mm. Hg, cold clammy extremities, peripheral cyanosis, and mental confusion. The ventricular rate was slower (100 per minute). Intravenous infusion of isoprenaline (0-03 mg. per minute) in dextrose solution produced improvement in his B.P. and cardiac output. Electrocardiographic monitoring did not disclose ventricular ectopic beats during this infusion, despite the large dose necessary. Isoprenaline was required for over 24 hours. Several weeks later sinus rhythm returned spontaneously. Hypotension can of course follow the intravenous administration of propranolol. The drug is valuable in controlling arrhythmias, or in the treatment of angina, and I have used doses of up to 600 mg. daily; I have not previously noted dangerous hypotension when it is given orally. I feel that this patient may have been unduly sensitive to the hypotensive effect of propranolol because of his severe heart-disease. Since this experience I feel it is prudent to observe the effect of a small dose (e.g., 25 mg.) before prescribing a course of
propranolol. Regional Cardiac Unit, Papworth Hospital, J. H. N. BETT. Cambridgeshire. 3. Conen, P. Can. med. Ass. J. 1967, 96, 1599. 4. Miles, C. P. Cancer, N.Y. 1967, 20, 1253.
to
F. PYGOTT.
PSYCHIATRY RAMPANT SiR,—Iwas surprised to read Dr. Denis Williams’ remarks, as reported in your annotation,! for I felt that he was reintroducing an old problem which I thought had been adequately discussed and settled more than twenty years ago. The point which perhaps seems to demand a comment from me is his apparent criticism of the Army for taking on everything. It is not quite true to say that the Army tried to take on everything. We refused many requests for help and advice, either because there was not time to study the matter and give that advice, or because we felt that what we had to contribute was not worth much emphasis. Dr. Williams is correct in saying that there were not enough good psychiatrists to do all the jobs; that applied not merely to the Army, but to the other two Services as well. Partly because the other Services had prior choice of personnel, and the Army had to take what was left, we had rather fewer men who had had first-rate training, and the whole work of our team in psychiatry was in part a form of training for our men and women doctors. We had, however, quite a large number of people with excellent background training. I have often smiled to myself at the fact that we had twenty or thirty fully qualified psychoanalysts, but so far as I am aware not one of them ever analysed a patient during the 1939-45 war: they were too busy using their knowledge of pathology in trying to solve some of the problems of other people in other arms of the Services. Finally I would like to say how very happy I am about the work that Prof. Linford Rees is doing at Barts; it is a real advance in the teachins of nsvchiatrv.
J. R. REES.
EMPTYING THE KIIL KIDNEY
SIR,-We were interested by the letter of Dr. van Hooff and Dr. Wijdeveld (Jan. 6, p. 51) reporting the advantage of an air-rinsing method of emptying the Kiil dialyser. We reported2 last year at the meeting of the European Dialysis and Transplant Association similar favourable results by a method using only sterile air. Internal gasket dialysers with
clamp were used. They were not tilted before the end of the dialysis. Dialysate flow was not modified during the emptying of the
dialyser. After disconnection of the arterial line, the line was occluded. Air was injected through a sterile filter into the arterial line, up to a pressure of 200 mm. Hg. Injection was then stopped and the venous line was opened, allowing the blood to flow into the patient. When the pressure inside the dialyser had fallen to 100 mm. Hg., the venous line was again occluded. The whole procedure was repeated, until venous
air reached the bubble catcher. The blood remaining in the dialyser and in the blood lines after rinsing has been evaluated 62 times by cutting the membranes and the tubing in small pieces and dipping them in heparinised isotonic saline solution. The amount of blood recovered averaged 123 ml. whole blood after rinsing with 1 litre isotonic glucose solution and 42 ml. whole blood after air rinsing. The difference is highly significant (P < O’OOl). The amount of blood needed to maintain a haemoglobin value of 9.5 g. per 100 ml. was evaluated in six patients. It fell from an average of 3 units packed-cell volume (P.c.v.) per month, when the glucose-rinsing method was used, to an average of 2 units P.c.v. per month with the air-rinsing method. The difference is significant (p < 0-01). 1. Lancet, 1967, ii, 976. 2. Stragier, A., van Ypersele de Ass (in the press).
Strihou, C.
Proc. Eur. Dial.
Transpl.
The
now been used in over 1200 without untoward effects. No air embolism has occurred. This method requires only a few minutes, and has the obvious advantages of diminishing the transfusion requirements and of reducing the amount of fluid returned to the patient at the end of the dialysis. Renal Unit, Department of Medicine, A. STRAGIER
air-rinsing technique has
dialyses
University of Louvain, Louvain, Belgium.
C.
VAN
YPERSELE
DE
STRIHOU.
HYPERMAGNESÆMIA AND PLATELET FUNCTION IN URÆMIC BLEEDING SiR,—Hypermagnesaemia has been described in bilaterally nephrectomised dogs, and in acute renal failure 2and chronic nephritis 4-6 in man. Abnormal bleeding is common in uraemic patients,7 and has been ascribed to failure in the activation of platelet-factor 3.8 Horowitz et al. described a plasma constituent which inhibits platelet-factor-3. It has properties similar to guanidosuccinic acid and may be overcome by the addition of calcium. Stewart and Castaldihave shown that a reversible platelet defect in urxmic bleeding may be corrected by dialysis, but their attempts to reproduce the defect in vitro by the addition of various substances, including magnesium, to platelet-rich plasma (P.R.P.) were unsuccessful. However, their P.R.P. contained citrate,9 with consequent inactivation of calcium and magnesium ions-conditions in which the addition of sufficient magnesium induces platelet clumping.10 Addition of magnesium to fresh P.R.P. without anticoagulants prolongs platelet-clumping time and antagonises the clumping activity of adenosine diphosphate" 12; magnesium also prolongs the clotting-time of whole blood 13 and delays the peak thrombin-generation time in vitro and in vivo. 14 By the method we have described,12 fresh whole blood in plastic or siliconed containers may be centrifuged immediately and the supernatant P.R.P. examined microscopically at 5minute intervals to determine the clumping-time. During the early phases of such observations many of the platelets appear as rods-presumably because at this stage they maintain their disc shape and some of them are viewed end-on. As time progresses, the proportion of rod-shaped platelets diminishes until, in the preclumping phase, the rods disappear altogether. In the process of delaying platelet clumping, added magnesium salts increases the proportion and the duration of these rodshaped forms. Plasma-magnesium levels were measured by E.E.L. atomic absorption spectrophotometer giving a mean normal value of 2-34 ±0-008 (S.E.M.) mg. per 100 ml. Platelet-clumping time was recorded at the first appearance of 1001i clumps giving a In 3 patients with mean value of 301-03 (s.E.M.) minutes. urxmic bleeding the results were as follows:
In patients 2 and 3, fibrin appeared before platelet clumping had begun. In all 3 patients, the increased initial proportion 1. 2. 3. 4. 5.
6. 7.
8. 9. 10. 11. 12. 13. 14.
Schloerb, P. R. Metabolism, 1961, 10, 59. Wacker, W. E. C., Vallee, B. L. New Engl. J. Med. 1957, 257, 1254. Takayasu, H., Sato, S., Yamadori, H., Hirata, T. Acta med. biol., Niigata, 1962, 10, 117. Outa, T. Fukuoka Acta med. 1963, 54, 1208. Randall, R. E., Cohen, M. D., Spray, C. C., Rossmeisl, E. C. Ann. intern. Med. 1964, 61, 73. Breen, M., Marshall, R. T. J. Lab. clin. Med. 1966, 68, 701. Stewart, J. H., Castaldi, P. A. Q. Jl Med. 1967, 36, 409. Horowitz, H. I., Burton, D. C., Martinez, P., Papayoanou, M. F. Blood, 1967, 30, 331. Castaldi, P. A., Rozenberg, M. C., Stewart, J. H. Lancet, 1966, ii, 66. Brambel, C. E., in Henry Ford Symposium on Blood Platelets; p. 125. London, 1961. Hughes, A., Tonks, R. S. Lancet, 1965, i, 1044. Hughes, A., Tonks, R. S. Nature, Lond. 1966, 210, 106. Greville, G. D., Lehmann, H. ibid. 1943, 152, 81. Huntsman, R. G., Hurn, B. A. L., Lehmann, H. J. clin. Path. 1960, 13, 99.
302 of both patients. In each case, the modal chromosome number of thirty cells was 46; random loss accounted for cells with chromosome number less than 46; and No no cells with 47 or more chromosomes were found. abnormalities in the B group were present. Culture of the cells of the carcinoma was not attempted in our patients or in the patient of Dr. Pascasio and his colleagues, so that karyotypes of the malignant cells are unknown. In order to postulate that an apparent chromosome imbalance in the peripheral lymphocytes is related to the setiology of an adrenal neoplasm, it must be assumed that the same karyotype is present in the adrenal cells and that this imbalance or a derived karyotype pattern is carcinogenic3 for that cell type. This is indeterminable. Chromosome abnormalities have been described in solid neoplasms,4 but the transfer of a spontaneous cytogenetic alteration in an adrenal cell to a lymphocytic stemline is unlikely. Department of Pediatrics, University of Florida, L. C. ELLWOOD College of Medicine, H. A. PEARSON. Gainesville, Florida.
lymphocyte metaphases
Appearance of P.R.P. 20 minutes after venepuncture: (a) in normal blood, showing absence of rod forms; (b) in blood of a uraemic patient, showing persistence of rod-shaped platelets. (Unstained, x 1000.)
and abnormal persistence of rod-shaped platelets was clearly apparent (figs. 1 and 2). Thus, in association with other plasma factors, the hypermagnesxmia itself may partake in the prevention of normal platelet clumping in patients with urxmic bleeding. In controlling the hypermagnesaemia by dialysis, regard to the magnesium content of the dialysing fluid itself may repay attention. D. T. P. DAVIES ANEURIN HUGHES G. D. LOMAX Nevill Hall Hospital, R. S. TONKS. Abergavenny, Monmouthshire.
NORMAL LYMPHOCYTE KARYOTYPES IN ADRENOCORTICAL CARCINOMA SIR,-Pascasio et al.l described a five-year-old boy with anaplastic type of adrenal carcinoma with an extra large subto group B (pair 5) in most peripheral lymphocyte metaphases. We have lately analysed karyotypes from peripheral lymphocytes of two children with adrenocortical carcinoma cultured according to the method of Moorhead et al. using Difco chromosome-culture kits. Case 1.-A four-year-old girl was first noted to have signs of acquired adrenogenital syndrome with clitoral enlargement, pubic hair, and deepened voice pitch. She had increased excretion of 17-ketosteroids and 17-hydroxysteroids. Exploratory laparotomy showed no gross abnormality of the adrenal glands; corticosteroid therapy arrested progression of signs. A left upper-quadrant abdominal mass was first palpated at age nine years; an encapsulated mass was found within the substance of the left adrenal gland, which was removed in toto. Microscopically the tumour was an adrenocortical carcinoma. Widespread metastatic lung nodules appeared two months after operation, and o, p’ DDD therapy was begun. The lung metastases dramatically decreased in size, and remission was
metacentric chromosome similar
maintained for the next three years. The metastases then became resistant to o, p’DDD therapy, and the child died several months later. Blood for chromosome analysis was obtained two months before her death at twelve years of age. Case 2.-A thirteen-year-old girl developed Cushing’s syndrome with weight gain, hypertension, amenorrhoea, hirsutism, acne, abdominal striec, and emotional lability over six months. Urinary 17-ketosteroids and 17-hydroxysteroids were strikingly raised. Encapsulated mass, weighing 450 g., was removed from the left adrenal. Microscopy revealed adrenocortical carcinoma. No metastases were found at operation, and the patient improved thereafter. Normal female karyotypes (46, XX) were found in peripheral1. 2.
Pascasio, F. M., Jesalva, P. S., Cruz, E. P., Alikpala, S. Lancet, 1967, i, 1107. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Expl Cell Res. 1960, 20, 613.
HOSPITAL ADMISSIONS AND INVESTIGATIONS "
SiR,-Dr. Samuel (Jan. 20, p. 139) writes: There are few hospitals in the United Kingdom where admission of patients is correlated to the capacity of the X-ray departments or biochemical laboratories. More liaison in this area would surely eliminate many of the delays." Dr. Samuel does not tell us what are the kinds of patients he has in mind, but he is clearly not referring to emergencies, since their admission cannot be delayed for correlation purposes. Which non-urgent patients need to be admitted for their radiological and biochemical investigations ? I can think of very few. A most deplorable misuse of hospital beds is to occupy them with patients being investigated-however efficient the correlation. May I urge Dr. Samuel to use his great influence to dissuade his colleagues from indulging in this practice ? JOHN W. TODD.
HYPOTENSION AFTER ORAL PROPRANOLOL an episode of profound hypotension
SiR,-Ireport here
after a small oral dose of propranolol (’ Inderal’). The patient is a 49-year-old publican with severe alcoholic cardiomyopathy. He developed atrial fibrillation with left bundle-branch block, and his rapid ventricular rate (150 per minute) was refractory to digoxin. He was given a single oral dose of 10 mg. propranolol. Two hours later he was moribund, with systolic blood-pressure (B.P.) 60 mm. Hg, cold clammy extremities, peripheral cyanosis, and mental confusion. The ventricular rate was slower (100 per minute). Intravenous infusion of isoprenaline (0-03 mg. per minute) in dextrose solution produced improvement in his B.P. and cardiac output. Electrocardiographic monitoring did not disclose ventricular ectopic beats during this infusion, despite the large dose necessary. Isoprenaline was required for over 24 hours. Several weeks later sinus rhythm returned spontaneously. Hypotension can of course follow the intravenous administration of propranolol. The drug is valuable in controlling arrhythmias, or in the treatment of angina, and I have used doses of up to 600 mg. daily; I have not previously noted dangerous hypotension when it is given orally. I feel that this patient may have been unduly sensitive to the hypotensive effect of propranolol because of his severe heart-disease. Since this experience I feel it is prudent to observe the effect of a small dose (e.g., 25 mg.) before prescribing a course of
propranolol. Regional Cardiac Unit, Papworth Hospital, J. H. N. BETT. Cambridgeshire. 3. Conen, P. Can. med. Ass. J. 1967, 96, 1599. 4. Miles, C. P. Cancer, N.Y. 1967, 20, 1253.