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EFFECTS OF PHENACETIN ON KIDNEY
243
Udhoji et al.3, in a small group of patients with primary bacterasmic shock, found the peripheral resistance increased, the circulation-time prolonged, and the venous return diminished. But the blood-volume and central venous pressure were unaffected. Thus there is no rationale for either rapid intravenous fluid therapy or pressor amines, either or both cf which are widely advocated. McHenry and Martinopposed rapid fluid therapy and favoured pressor amines. Naqui and Tranter’s recent article1 reversed this view. Lillehei2 recommended moderate infusions combined with vasodilators, and, in particular, the " subtle adrenergic-blocking effects of hydrocortisone in huge doses5 (15 to 25 mg. per kg. per 24 hours). McGowan and Walters believe that rapid infusion to raise the central venous pressure to high normal levels is of the utmost importance. In the face of such varying opinions amongst authorities on the subject, it is perhaps permissible to argue from a single case. Our patient showed pure bactersemic shock, uncomplicated by other conditions likely to produce hypovolsemia. She had warm extremities, no sweating, and continuing urinary output in the presence of profound hypotension. Cardiac failure was precipitated by little more than a litre of fluid, and there was complete recovery without further fluid, pressor agents, or effective doses of vasodilators. It seems that in this case recovery followed redistribution of body fluids when the infection was overcome by the appropriate antibiotics. "
We are indebted this case.
to
Bolingbroke Hospital, London, S.W.11.
Mr. G. D. Pinker for
permission
to
publish
R. J. HEALD R. L. STRICKLAND.
POTASSIUM CHLORIDE AND INTESTINAL ULCERATION SIR,-We have read with interest your annotation (July 3) and the letter by Professor Goodwin and Dr. Oakley (July 17)
potassium supplements. Whilst we agree that it is necessary for chloride to be given in association with potassium, we do not feel that varnished potassium chloride tablets or combined thiazide/potassium preparations offer the best solution to the problem. The combined preparations do not permit variation of the amount of potassium in accordance with the needs of the patient, and in any event contain potassium chloride in an on
enteric-coated form. Since recognising the need for chloride to be included in the formulation, we have been using for the past three years an effervescent tablet which contains potassium chloride 0-30 g., potassium bicarbonate 0-50 g., tartaric acid 0-25 g., citric acid 0.15 g., and saccharin sodium 0-005 g. Each tablet contains 9 mEq. of potassium and 4 mEq. of chloride. The preparation dissolves in water to provide a well-tolerated solution. Tablets made according to the above formula are difficult to prepare, and there might be technical difficulties in producing them on a large scale. Royal Free Hospital, London, W.C.1.
J. W. HADGRAFT S. SHALDON.
SIR,-As a surgeon I hesitate to disagree with Professor Goodwin and Dr. Oakley, but the impression given in their letter that combined thiazide/potassium preparations will not produce intestinal ulceration is incorrect. Your annotation (July 3) rightly disapproves of these preparations, for the majority of recently reported cases of circumferential ulcer of the small bowel were associated with the administration of a combined thiazide/potassium chloride tablet. A recent of our own illustrates this point. A 76-year-old man became breathless in July, was started on ’ Hydrosaluric-K ’, one tablet March, 1965, he developed colicky postprandial
case
1964, and
daily. In epigastric
V. N., Weil, M. H., Samghi, M. P., Rossoff, L. Am. J. Med. 1963, 34, 461. 4. McHenry, M. C., Martin, W. J. Proc. Staff. Meet. Mayo Clin. 1962, 37, 162. 5. McGowan, G. K., Walters, G. Br. J. Surg. 1963, 50, 821. 3.
Udhoji,
pain, distension, and constipation. Barium meal and barium enema revealed nothing abnormal, but his appearance suggested malignant disease. At laparotomy, on May 21, a 1 cm.-long stricture was found in the upper jejunum, with dilatation of the proximal bowel. 8 cm. of jejunum was reseceed, and was found to be almost completely occluded by the stricture. There was a circumferential ulcer immediately proximal to the narrowed area. The appearances closely resembled the lesion which has been described in association with enteric-coated potassium chloride.1 Histological examination showed hypertrophy and fibrosis, especially in the muscularis mucosse, with non-specific ulceration proximally. The patient is now symptom-free. Almost all the commonly used combined thiazide/potassium tablets contain, like hydrosaluric-K, an enteric-coated centre of potassium chloride, and on present evidence these can be considered far from safe. I
am
grateful to Mr.
T. Rowntree for permission
Southampton General Hospital.
to
report this
case.
T. B. HUGH.
EFFECTS OF PHENACETIN ON KIDNEY SiR,ŅThe work of Dr. Prescott (July 17)confirms that of my colleagues and myself2 with regard to the appearance of large numbers of renal tubular cells in the urine after taking aspirin. His results with other drugs tested are also of interest although quantitatively much less striking. Not least is he to be congratulated on finding 60 volunteers who had taken no analgesics in the preceding six weeks-I found this surprisingly difficult. Your annotation (July 24) emphasises, as we did, the need for care in relating these findings to the possibility of chronic renal damage. I recently summarised some reasons for believing that phenacetin, rather than aspirin, is the main cause of so-called analgesic nephropathy,3 but the question is an open one. Dr. Prescott and your annotation
spoke of the use of in minor discomforts and neurosis, the treatment of analgesics but failed to mention the more important function of salicylates in the management of rheumatic disorders, particularly rheumatoid arthritis, where by relieving pain they permit muscular exercise and the prevention of deformity. The possibility that their prolonged administration can produce renal disease is one which naturally causes concern to these patients and their doctors, but many will still feel that the value of salicylates is not offset by what remains a hypothetical disadvantage. Medical School, London, W.12.
Postgraduate
J. T. SCOTT.
HÆMORRHAGIC DISEASE AND TICK BITES SiR.ŅThe history of fibrinolytic purpura is now 24 years old, and fibrinogenopenia and fibrinolysis are given due importance in the investigation of hxmorrhagic disease. It is customary for every haematological laboratory to carry out routinely the clot observation test for the detection of critical fibrinogenopenia. The normal range of plasma-fibrinogen is 220-400 mg. per 100 ml. The critical level, below which fibrinogenopenic or fibrinolytic purpura is inevitable, is 150-75 mg. per 100 ml. The clot observation test is positive when the plasma-fibrinogen is below 200 mg. per 100 ml. A negative clot observation test, therefore, rules out fibrinogenopenia which may result in overt hxmorrhagic manifestations. More elaborate methods for estimation of
plasma-fibrinogen
and the
blood-fibrinolytic activity
are
only
indicated when the clot observation test is positive or when surgery is envisaged in a suspected case. If Dr. Rao (June 26) is of the opinion that investigation of any hxmorrhagic disorder is incomplete without routine Morgenstern, L., Freilich, M., Panish, J. F. J. Am. med. Ass. 1965, 191, 637. 2. Scott, J. T., Denman, M. A., Dorling, J. Lancet, 1963, i, 344. 3. Scott, J. T. ibid. 1964, i, 827. 1.
Udhoji et al.3, in a small group of patients with primary bacterasmic shock, found the peripheral resistance increased, the circulation-time prolonged, and the venous return diminished. But the blood-volume and central venous pressure were unaffected. Thus there is no rationale for either rapid intravenous fluid therapy or pressor amines, either or both cf which are widely advocated. McHenry and Martinopposed rapid fluid therapy and favoured pressor amines. Naqui and Tranter’s recent article1 reversed this view. Lillehei2 recommended moderate infusions combined with vasodilators, and, in particular, the " subtle adrenergic-blocking effects of hydrocortisone in huge doses5 (15 to 25 mg. per kg. per 24 hours). McGowan and Walters believe that rapid infusion to raise the central venous pressure to high normal levels is of the utmost importance. In the face of such varying opinions amongst authorities on the subject, it is perhaps permissible to argue from a single case. Our patient showed pure bactersemic shock, uncomplicated by other conditions likely to produce hypovolsemia. She had warm extremities, no sweating, and continuing urinary output in the presence of profound hypotension. Cardiac failure was precipitated by little more than a litre of fluid, and there was complete recovery without further fluid, pressor agents, or effective doses of vasodilators. It seems that in this case recovery followed redistribution of body fluids when the infection was overcome by the appropriate antibiotics. "
We are indebted this case.
to
Bolingbroke Hospital, London, S.W.11.
Mr. G. D. Pinker for
permission
to
publish
R. J. HEALD R. L. STRICKLAND.
POTASSIUM CHLORIDE AND INTESTINAL ULCERATION SIR,-We have read with interest your annotation (July 3) and the letter by Professor Goodwin and Dr. Oakley (July 17)
potassium supplements. Whilst we agree that it is necessary for chloride to be given in association with potassium, we do not feel that varnished potassium chloride tablets or combined thiazide/potassium preparations offer the best solution to the problem. The combined preparations do not permit variation of the amount of potassium in accordance with the needs of the patient, and in any event contain potassium chloride in an on
enteric-coated form. Since recognising the need for chloride to be included in the formulation, we have been using for the past three years an effervescent tablet which contains potassium chloride 0-30 g., potassium bicarbonate 0-50 g., tartaric acid 0-25 g., citric acid 0.15 g., and saccharin sodium 0-005 g. Each tablet contains 9 mEq. of potassium and 4 mEq. of chloride. The preparation dissolves in water to provide a well-tolerated solution. Tablets made according to the above formula are difficult to prepare, and there might be technical difficulties in producing them on a large scale. Royal Free Hospital, London, W.C.1.
J. W. HADGRAFT S. SHALDON.
SIR,-As a surgeon I hesitate to disagree with Professor Goodwin and Dr. Oakley, but the impression given in their letter that combined thiazide/potassium preparations will not produce intestinal ulceration is incorrect. Your annotation (July 3) rightly disapproves of these preparations, for the majority of recently reported cases of circumferential ulcer of the small bowel were associated with the administration of a combined thiazide/potassium chloride tablet. A recent of our own illustrates this point. A 76-year-old man became breathless in July, was started on ’ Hydrosaluric-K ’, one tablet March, 1965, he developed colicky postprandial
case
1964, and
daily. In epigastric
V. N., Weil, M. H., Samghi, M. P., Rossoff, L. Am. J. Med. 1963, 34, 461. 4. McHenry, M. C., Martin, W. J. Proc. Staff. Meet. Mayo Clin. 1962, 37, 162. 5. McGowan, G. K., Walters, G. Br. J. Surg. 1963, 50, 821. 3.
Udhoji,
pain, distension, and constipation. Barium meal and barium enema revealed nothing abnormal, but his appearance suggested malignant disease. At laparotomy, on May 21, a 1 cm.-long stricture was found in the upper jejunum, with dilatation of the proximal bowel. 8 cm. of jejunum was reseceed, and was found to be almost completely occluded by the stricture. There was a circumferential ulcer immediately proximal to the narrowed area. The appearances closely resembled the lesion which has been described in association with enteric-coated potassium chloride.1 Histological examination showed hypertrophy and fibrosis, especially in the muscularis mucosse, with non-specific ulceration proximally. The patient is now symptom-free. Almost all the commonly used combined thiazide/potassium tablets contain, like hydrosaluric-K, an enteric-coated centre of potassium chloride, and on present evidence these can be considered far from safe. I
am
grateful to Mr.
T. Rowntree for permission
Southampton General Hospital.
to
report this
case.
T. B. HUGH.
EFFECTS OF PHENACETIN ON KIDNEY SiR,ŅThe work of Dr. Prescott (July 17)confirms that of my colleagues and myself2 with regard to the appearance of large numbers of renal tubular cells in the urine after taking aspirin. His results with other drugs tested are also of interest although quantitatively much less striking. Not least is he to be congratulated on finding 60 volunteers who had taken no analgesics in the preceding six weeks-I found this surprisingly difficult. Your annotation (July 24) emphasises, as we did, the need for care in relating these findings to the possibility of chronic renal damage. I recently summarised some reasons for believing that phenacetin, rather than aspirin, is the main cause of so-called analgesic nephropathy,3 but the question is an open one. Dr. Prescott and your annotation
spoke of the use of in minor discomforts and neurosis, the treatment of analgesics but failed to mention the more important function of salicylates in the management of rheumatic disorders, particularly rheumatoid arthritis, where by relieving pain they permit muscular exercise and the prevention of deformity. The possibility that their prolonged administration can produce renal disease is one which naturally causes concern to these patients and their doctors, but many will still feel that the value of salicylates is not offset by what remains a hypothetical disadvantage. Medical School, London, W.12.
Postgraduate
J. T. SCOTT.
HÆMORRHAGIC DISEASE AND TICK BITES SiR.ŅThe history of fibrinolytic purpura is now 24 years old, and fibrinogenopenia and fibrinolysis are given due importance in the investigation of hxmorrhagic disease. It is customary for every haematological laboratory to carry out routinely the clot observation test for the detection of critical fibrinogenopenia. The normal range of plasma-fibrinogen is 220-400 mg. per 100 ml. The critical level, below which fibrinogenopenic or fibrinolytic purpura is inevitable, is 150-75 mg. per 100 ml. The clot observation test is positive when the plasma-fibrinogen is below 200 mg. per 100 ml. A negative clot observation test, therefore, rules out fibrinogenopenia which may result in overt hxmorrhagic manifestations. More elaborate methods for estimation of
plasma-fibrinogen
and the
blood-fibrinolytic activity
are
only
indicated when the clot observation test is positive or when surgery is envisaged in a suspected case. If Dr. Rao (June 26) is of the opinion that investigation of any hxmorrhagic disorder is incomplete without routine Morgenstern, L., Freilich, M., Panish, J. F. J. Am. med. Ass. 1965, 191, 637. 2. Scott, J. T., Denman, M. A., Dorling, J. Lancet, 1963, i, 344. 3. Scott, J. T. ibid. 1964, i, 827. 1.