- Email: [email protected]
INTENSIVE INTRAVENOUS POTASSIUM REPLACEMENT THERAPY
809
of iron T.D.I. infusions may be assumed to give the maximum haemoglobin response possible with iron therapy alone. In uncomplicated cases the response was very satisfactory, yet over three-quarters of these thirty-four patients had gastrointestinal disease or had already failed to respond to oral iron therapy. The immediate subjective improvement after these infusions is attributable to reversal of ill-effects of irondepletion other than anaemia. Stafford (1965) pointed out that the symptoms of long-standing iron-deficiency anemia were due to a combination of circulatory hypoxia with the effects of depression of tissue enzymes dependent on iron, whereby reduction-oxidation at cellular level became inefficient. Before parenteral iron preparations were introduced, correction of iron-deficiency was too slow to differentiate between the effects of increased hxmoglobin and the remission of non-hsemic features, such as lassitude, buccal epithelial degradation, dysphagia, koilonychia, psychical disturbances, and undue motor
fatigue. Although the serum-iron level may vary in health (Zilva and Patson 1966), the mean levels shown in table iv can be taken to indicate a general trend. None of these thirty-four patients had advanced malignant disease or chronic suppuration, and it may be inferred that the low serum-iron levels reflected serious depletion of iron available for hxmoglobin synthesis within one to two weeks after a major hxmorrhage. Low serum-folate levels due to dietary deficiency, often without anxmia, are common in the elderly (Read et al. 1965, Hurdle and Williams 1966). 28% of adults of all ages with gastrointestinal disease in the present series had low serum-folate levels. Thus, even in the absence of macrocytosis, pending serum-folate and vitamin-B12 estimations, there is a case for giving supplementary folic acid to all those with severe iron-deficiency anxmia who have gastrointestinal disease or who are elderly.
INTENSIVE INTRAVENOUS POTASSIUM REPLACEMENT THERAPY M.B.
REGISTRAR* M.B.
A. DOIG Edin., F.R.C.P.E., M.R.C.P.
CONSULTANT PHYSICIAN AND SENIOR LECTURER IN MEDICINE
M.B.
ANNE T. LAMBIE Edin., F.R.C.P.E., M.R.C.P.
SENIOR LECTURER IN THERAPEUTICS
From the
University departments of medicine and therapeutics and the Royal Infirmary of Edinburgh
intravenous replacement of instituted in a patient with potassium diabetic acidosis who had severe potassium depletion and muscle paralysis. In the first 24 hours of treatment, the patient received 860 mEq. of potassium, 600 mEq. of which was given intravenously. Improvement in the muscle paralysis and a rise of the serum-potassium could only be obtained by the intravenous infusion of potassium at rates greatly exceeding those currently recommended.
Summary
Intensive
was
Introduction
SEVERE potassium depletion is potentially lethal and demands urgent replacement. Because of the dangers of intravenous administration of potassium, most standard textbooks recommend that the rate of infusion should not exceed 10-25 mEq. per hour and 100-200 mEq. per day. We suggest that these recommendations should be reconsidered, since recent case-reports (Stephens 1949, Clementsen 1962, Seftel and Kew 1966, Abramson and Arky 1966), including one described here, indicate that survival in severe potassium depletion may depend upon the intravenous administration of potassium at rates considerably in excess of those advised at the present time.
rapid
Conclusions For the
H. PULLEN Edin., M.R.C.P.E., D.T.M. & H.
Case-report of
surgical problem patient with a level of less than 11 hxmoglobin g. per 100 ml. after or is more rational than a T.D.I. operation haemorrhage, " topping-up transfusion, and, incidentally, economises in the use of blood. It is also useful before early elective surgery, and in many cases of anaemia secondary to malignant disease. Correction of iron-deficiency brings about an increase in well-being over and above that due to an increase in haemoglobin alone. Folic-acid deficiency should be excluded in gastrointestinal disease associated with iron-deficiency anaemia. In the absence of complicating factors, elderly patients respond well to T.D.I. The response may be good, despite infection, provided that there is no suppuration.
A
33-year-old labourer
was admitted to the Royal Infirmary, Edinburgh, on April 14,1966, in a semicomatose state. He had apparently been in good health until 4 weeks previously, when his illness began with a sore throat, severe thirst, and polyuria. During the week before admission, he became anorexic and vomited several times each day; these symptoms were accompanied by progressive muscle weakness which caused the patient to believe that he had " infantile paralysis ". He had become drowsy on the day before admission. He was a well-built young man, weighing 69 kg. (152 lb.) with clinical features of keto-acidosis, moderate dehydration, and flaccid paresis of the muscles of the limbs and neck. Bowel sounds were present. Pulse 130 per minute; blood-pressure 120/70 mm. Hg; respiration 50 per minute; and temperature 98-2°F (36-8°C). Clinical and radiological examination of chest was negative. I wish to thank Dr. V. W. Pugh for much help and valuable advice; Urinanalysis disclosed severe glycosuria and ketonuria; there Mr. R. W. T. Gaze for carrying out the many serum-iron estimations; was no proteinuria, and there were no abnormal findings on Mr. P. Mills for help with some of the statistics; the surgeons of microscopical examination of the centrifuged deposit. HxmoLeicester Royal Infirmary for inviting me to treat their patients; and globin was 18.3 g. per 100 ml.; haematocrit was 49%; total Dr. J. G. Humble and Dr. J. F. Zilva for their comments. white-cell-count was 12,200 per c.mm.; and erythrocyte-
common
a
"
Basu, Lancet, i, Coleman, D. H., Stevens, A. R., Finch, C. A. (1955) Blood, 10, Hurdle, A. D. F., Williams, T. C. P. (1966) Br. med. J. ii, 202. Newcombe, R. L. G. (1966) J. Therap. 1, 20. Read, A. E., Gough, K. R., Pardoe, J. L., Nicholas, A. (1965) 1430.
ii, 843. Stafford, J. L. (1965) Ann. R. Coll. Surg. 36, 280. Waters, A. H., Mollin, D. L. (1961) J. clin. Path. 14, Young, D. S., Hicks, J. M. (1965) ibid. 18, 98. Zilva, J. F., Patson, V. J. (1966) Lancet, i, 549.
rate was 1 mm. in the first hour (Westergren). Pre-treatment blood chemistry: glucose 340 mg. per 100 ml.; urea 60 mg. per 100 ml.; plasma-sodium 132 mEq. per litre; plasma-potassium 2-9 mEq. per litre, and plasma-bicarbonate 6-0 mEq. per litre. Figs. 1 and 2 give details of treatment during the first 24 hours after admission together with the changes in plasma electrolytes, blood-glucose, and urinary excretion of potassium.
sedimentation
REFERENCES
S. K. (1963)
335.
567.
Br. med. J.
*
Present
appointment: lecturer
in
therapeutics, University of Edinburgh.
Q3
810
Fig. 2-Potassium intake and plasmapotassium during first 24 hours of treatment (urinary potassium excretion not
Fig. 1-Intravenous fluid therapy and blood chemistry during
first 24 hours of treatment.
During this period, the urinary output was 6 litres. No stools passed, and there was no recurrence of vomiting. The low pre-treatment plasma-potassium concentration suggested severe potassium depletion; after the abnormally low result had been confirmed, replacement therapy was begun with potassium chloride given intravenously and potassium effervescent tablets orally (these contained potassium bicarbonate 500 mg. and potassium acid tartrate 300 mg.). Within 5 hours the patient became alert and fully orientated, but the limb and neck muscles remained extremely weak, and, despite the administration of 95 mEq. of potassium, the plasma concentration of potassium had fallen to 1.2 mEq. per litre. The electrocardiogram showed pronounced sagging of the ST
were
segment and flat T waves; there were no u waves. Between 4 and 81/2 hours (fig. 2), the fastest rate of intravenous
measured during first 6 hours).
potassium administration was 80 mEq. per hour, controlled by frequent estimations of the serum-potassium; at 81/2 hours, the plasma-potassium had risen to 1.5 mEq. per litre, the patient’s hand grip had become slightly stronger, and the rate of potassium administration was reduced to approximately 20 mEq. per hour. Although the plasma-potassium continued to show a gradual rise, the improvement in muscle power was not sustained; at 20 hours, when the plasma-potassium concentration was 2-4 mEq. per litre, the paresis became more severe and spread to the intercostal muscles. Increasing the rate of intravenous infusion to 40 mEq. per hour did not prevent the onset of severe respiratory distress; the muscle paralysis failed to improve until the rate of infusion had again been increased to 80 mEq. per hour and maintained at this high level for 50 minutes. Thereafter, further improve-
REPORTED CASES OF INTENSIVE INTRAVENOUS POTASSIUM-REPLACEMENT THERAPY
Potassium infused after 22 hours
not
included.
811 allowed progressive reductions in the rate of potassium infusion. Intravenous therapy was stopped 42 hours after admission. By this time, the serum-potassium was 4-4 mEq. per litre, the electrocardiogram showed only slight abnormalities and the intercostal muscle weakness had disappeared; the patient’s hand grip was stronger, but the weakness in the legs showed only slight improvement and took 4 weeks to recover ment
completely. The oral administration of
potassium bicarbonate and
potassium citrate was discontinued after 40 hours; thereafter the patient received a diet with a constant potassium content of mEq. per day. Potassium balance was attained on the 10th day after admission. During this 10-day period, potassium intake totalled 1836 mEq. and output 780 mEq. (urinary excretion 740 mEq. and faecal excretion 40 mEq.), the patient retaining 1056 mEq. of potassium. Renal function was assessed 3 weeks after admission: glomerular-filtration rate (12’Idiatrozoate clearance), 131 ml. per minute; tubular reabsorption of solute-free water (during mannitol diuresis and vasopressin infusion), 6-0 ml. per minute; lowest urinary pH (after ammonium chloride orally), 4-9. The diabetes mellitus was controlled on a diet containing 240 g. of carbohydrate with protamine zinc insulin, 28 i.u. daily, and soluble insulin, 28 i.u. daily. The patient has taken no potassium supplements for over a year, and there has been no recurrence of hypokalxmia.
85
Discussion
Hypokalsemia in untreated diabetic acidosis indicates unusually severe potassium depletion (Abramson and Arky 1966), the deficit in our patient amounting to almost a third of the total body potassium. Treatment of the diabetic acidosis further reduced plasma-potassium to dangerously low levels, which persisted throughout most of the first 24 hours, despite intensive potassium replacement. This protracted period of serious hypokalsemia can only be explained by a massive cellular uptake of potassium, since the urinary losses of potassium during intensive replacement were small. Factors responsible for the cellular uptake of potassium during treatment of diabetic acidosis include the administration of insulin (Smillie and Manery 1960) and glucose (Fenn 1939), and the correction of acidosis (Keating et al. 1953) accelerated by the administration of alkali. On account of the severity of the metabolic acidosis we gave our patient sodium bicarbonate. Though the initial concentration of serum-potassium would probably have fallen less rapidly had bicarbonate been avoided, the protracted period of dangerous hypokalasmia must be attributed to failure of the high rate of potassium administration to exceed significantly the rate of cellular potassium
uptake. The intercostal muscles became paralysed after the replacement of 670 mEq. of potassium. Although the serum-potassium at this stage had risen from 1.2 to 2-4 mEq. per litre, the intercostal paralysis was believed to have resulted from a disproportionate rise in cellular potassium, since an increase in the ratio of intracellular to extracellular potassium concentration may lead to interference with muscle function (Grob et al. 1957). The striking improvement in respiratory paralysis which followed doubling of the rate of potassium infusion, and the accompanying rise in plasma-potassium, lend some support to this hypothesis. The limitations of current recommendations on intravenous potassium replacement are illustrated by several recent reports. Kunin et al. (1962) reported significant reductions in serum-potassium in eight out of twenty-one patients with potassium depletion during the intravenous infusion of potassium with glucose at rates of 20 mEq. and
mEq. per hour. In reported cases of intensive intrapotassium-replacement therapy, where the amounts given within periods of 12 or 24 hours exceeded 30’) mEq. and 600 mEq. (see accompanying table), the rates of potassium infusion varied between 30 and 190 mEq. per hour. In the successful resuscitation of a paralysed moribund patient, Seftel and Kew (1966) infused potassium at a rate of 320 mEq. per hour over a period of
40
venous
15 minutes. It is apparent that the recommended
highest rates of intravenous potassium administration of 10-25 mEq. per hour and 100-200 mEq. per day may have to be exceeded several-fold in the treatment of severe potassium depletion. Replacement therapy of this intensity must be controlled by the results of frequent clinical, biochemical, and electrocardiographic observations. Since serial determinations of serum-potassium at short intervals are absolutely essential, arrangements must be made for the rapid transit of blood-samples to the laboratory, and the carrying out of estimations without delay. We thank the staff of the University department of clinical chemistry, Royal Infirmary, Edinburgh, particularly Dr. R. G. S. Leask, for the chemical analyses. Requests for reprints should be addressed to A. D., Department of Medicine, Royal Infirmary, Edinburgh 3. REFERENCES
Abramson, E., Arky, R. (1966) J. Am. med. Ass. 196, 401. Clementsen, H. J. (1962) Lancet, ii, 175. Fenn, W. O. (1939) J. biol. Chem. 128, 297. Grob, D., Johns, R. J., Liljestrand, A. (1957) Am. J. Med. 23, 356. Keating, R. E., Weichselbaum, T. E., Alanis, M., Margraf, H. W., Elman, R. (1953) Surgery Gynec. Obstet. 96, 323. Kunin, A. S., Surawicz, B., Sims, E. A. H. (1962) New Engl. J. Med. 266, 228. Seftel, H. C., Kew, M. C. (1966) Diabetes, 15, 694. Smillie, L. B., Manery, J. F. (1960) Am. J. Physiol. 198, 67. Stephens, F. I. (1949) Ann. intern. Med. 30, 1272.
Reviews of Books Infant Nutrition SAMUEL J. FOMON, M.D., professor of pediatrics, University of Iowa College of Medicine, Iowa City. London and Philadelphia: W. B. Saunders. 1967. Pp. 299. 73s. 6d.; §10.50.
Dr. Fomon has written this book to provide up-to-date information for practising clinicians. He has succeeded admirably. The chapters on protein, fat, carbohydrate, vitamins, and minerals provide a comprehensive summary of present knowledge. The book is particularly pleasing because Dr. Fomon thoughtfully defiries the area of the unknown as well as the territory which has already been mapped. He defines failure a rate of gain in length and/or weight less than to thrive as the value corresponding to two standard deviations below the mean during an interval of at least 56 days for infants less than three months of age and during an interval of at least three months for older infants." Infants below the 10th percentile values for length and weight should be regarded as suspect. While this definition may be acceptable, diagnosis and treatment of failure to thrive can seldom be delayed for eight weeks. He defines obesity as a gross discrepancy between length and weight in relation to the percentile tables ńa more satisfactory definition requires further study. To prevent iron-deficiency anaemia he suggests that 2000 mg. of iron should be provided by small daily increments during the first year of life. In discussing the future of infant nutrition, Dr. Fomon describes work which has shown that caloric restriction in rats at the time of weaning can increase longevity and prevent renal disease. He discusses, too, the relation of later atherosclerosis to the lipid content of the diet in infancy and the possibility that a high intake of sodium chloride may predispose to subsequent hypertension. Animal work has shown that nutrition in pregnancy and in the preweaning period "
of iron T.D.I. infusions may be assumed to give the maximum haemoglobin response possible with iron therapy alone. In uncomplicated cases the response was very satisfactory, yet over three-quarters of these thirty-four patients had gastrointestinal disease or had already failed to respond to oral iron therapy. The immediate subjective improvement after these infusions is attributable to reversal of ill-effects of irondepletion other than anaemia. Stafford (1965) pointed out that the symptoms of long-standing iron-deficiency anemia were due to a combination of circulatory hypoxia with the effects of depression of tissue enzymes dependent on iron, whereby reduction-oxidation at cellular level became inefficient. Before parenteral iron preparations were introduced, correction of iron-deficiency was too slow to differentiate between the effects of increased hxmoglobin and the remission of non-hsemic features, such as lassitude, buccal epithelial degradation, dysphagia, koilonychia, psychical disturbances, and undue motor
fatigue. Although the serum-iron level may vary in health (Zilva and Patson 1966), the mean levels shown in table iv can be taken to indicate a general trend. None of these thirty-four patients had advanced malignant disease or chronic suppuration, and it may be inferred that the low serum-iron levels reflected serious depletion of iron available for hxmoglobin synthesis within one to two weeks after a major hxmorrhage. Low serum-folate levels due to dietary deficiency, often without anxmia, are common in the elderly (Read et al. 1965, Hurdle and Williams 1966). 28% of adults of all ages with gastrointestinal disease in the present series had low serum-folate levels. Thus, even in the absence of macrocytosis, pending serum-folate and vitamin-B12 estimations, there is a case for giving supplementary folic acid to all those with severe iron-deficiency anxmia who have gastrointestinal disease or who are elderly.
INTENSIVE INTRAVENOUS POTASSIUM REPLACEMENT THERAPY M.B.
REGISTRAR* M.B.
A. DOIG Edin., F.R.C.P.E., M.R.C.P.
CONSULTANT PHYSICIAN AND SENIOR LECTURER IN MEDICINE
M.B.
ANNE T. LAMBIE Edin., F.R.C.P.E., M.R.C.P.
SENIOR LECTURER IN THERAPEUTICS
From the
University departments of medicine and therapeutics and the Royal Infirmary of Edinburgh
intravenous replacement of instituted in a patient with potassium diabetic acidosis who had severe potassium depletion and muscle paralysis. In the first 24 hours of treatment, the patient received 860 mEq. of potassium, 600 mEq. of which was given intravenously. Improvement in the muscle paralysis and a rise of the serum-potassium could only be obtained by the intravenous infusion of potassium at rates greatly exceeding those currently recommended.
Summary
Intensive
was
Introduction
SEVERE potassium depletion is potentially lethal and demands urgent replacement. Because of the dangers of intravenous administration of potassium, most standard textbooks recommend that the rate of infusion should not exceed 10-25 mEq. per hour and 100-200 mEq. per day. We suggest that these recommendations should be reconsidered, since recent case-reports (Stephens 1949, Clementsen 1962, Seftel and Kew 1966, Abramson and Arky 1966), including one described here, indicate that survival in severe potassium depletion may depend upon the intravenous administration of potassium at rates considerably in excess of those advised at the present time.
rapid
Conclusions For the
H. PULLEN Edin., M.R.C.P.E., D.T.M. & H.
Case-report of
surgical problem patient with a level of less than 11 hxmoglobin g. per 100 ml. after or is more rational than a T.D.I. operation haemorrhage, " topping-up transfusion, and, incidentally, economises in the use of blood. It is also useful before early elective surgery, and in many cases of anaemia secondary to malignant disease. Correction of iron-deficiency brings about an increase in well-being over and above that due to an increase in haemoglobin alone. Folic-acid deficiency should be excluded in gastrointestinal disease associated with iron-deficiency anaemia. In the absence of complicating factors, elderly patients respond well to T.D.I. The response may be good, despite infection, provided that there is no suppuration.
A
33-year-old labourer
was admitted to the Royal Infirmary, Edinburgh, on April 14,1966, in a semicomatose state. He had apparently been in good health until 4 weeks previously, when his illness began with a sore throat, severe thirst, and polyuria. During the week before admission, he became anorexic and vomited several times each day; these symptoms were accompanied by progressive muscle weakness which caused the patient to believe that he had " infantile paralysis ". He had become drowsy on the day before admission. He was a well-built young man, weighing 69 kg. (152 lb.) with clinical features of keto-acidosis, moderate dehydration, and flaccid paresis of the muscles of the limbs and neck. Bowel sounds were present. Pulse 130 per minute; blood-pressure 120/70 mm. Hg; respiration 50 per minute; and temperature 98-2°F (36-8°C). Clinical and radiological examination of chest was negative. I wish to thank Dr. V. W. Pugh for much help and valuable advice; Urinanalysis disclosed severe glycosuria and ketonuria; there Mr. R. W. T. Gaze for carrying out the many serum-iron estimations; was no proteinuria, and there were no abnormal findings on Mr. P. Mills for help with some of the statistics; the surgeons of microscopical examination of the centrifuged deposit. HxmoLeicester Royal Infirmary for inviting me to treat their patients; and globin was 18.3 g. per 100 ml.; haematocrit was 49%; total Dr. J. G. Humble and Dr. J. F. Zilva for their comments. white-cell-count was 12,200 per c.mm.; and erythrocyte-
common
a
"
Basu, Lancet, i, Coleman, D. H., Stevens, A. R., Finch, C. A. (1955) Blood, 10, Hurdle, A. D. F., Williams, T. C. P. (1966) Br. med. J. ii, 202. Newcombe, R. L. G. (1966) J. Therap. 1, 20. Read, A. E., Gough, K. R., Pardoe, J. L., Nicholas, A. (1965) 1430.
ii, 843. Stafford, J. L. (1965) Ann. R. Coll. Surg. 36, 280. Waters, A. H., Mollin, D. L. (1961) J. clin. Path. 14, Young, D. S., Hicks, J. M. (1965) ibid. 18, 98. Zilva, J. F., Patson, V. J. (1966) Lancet, i, 549.
rate was 1 mm. in the first hour (Westergren). Pre-treatment blood chemistry: glucose 340 mg. per 100 ml.; urea 60 mg. per 100 ml.; plasma-sodium 132 mEq. per litre; plasma-potassium 2-9 mEq. per litre, and plasma-bicarbonate 6-0 mEq. per litre. Figs. 1 and 2 give details of treatment during the first 24 hours after admission together with the changes in plasma electrolytes, blood-glucose, and urinary excretion of potassium.
sedimentation
REFERENCES
S. K. (1963)
335.
567.
Br. med. J.
*
Present
appointment: lecturer
in
therapeutics, University of Edinburgh.
Q3
810
Fig. 2-Potassium intake and plasmapotassium during first 24 hours of treatment (urinary potassium excretion not
Fig. 1-Intravenous fluid therapy and blood chemistry during
first 24 hours of treatment.
During this period, the urinary output was 6 litres. No stools passed, and there was no recurrence of vomiting. The low pre-treatment plasma-potassium concentration suggested severe potassium depletion; after the abnormally low result had been confirmed, replacement therapy was begun with potassium chloride given intravenously and potassium effervescent tablets orally (these contained potassium bicarbonate 500 mg. and potassium acid tartrate 300 mg.). Within 5 hours the patient became alert and fully orientated, but the limb and neck muscles remained extremely weak, and, despite the administration of 95 mEq. of potassium, the plasma concentration of potassium had fallen to 1.2 mEq. per litre. The electrocardiogram showed pronounced sagging of the ST
were
segment and flat T waves; there were no u waves. Between 4 and 81/2 hours (fig. 2), the fastest rate of intravenous
measured during first 6 hours).
potassium administration was 80 mEq. per hour, controlled by frequent estimations of the serum-potassium; at 81/2 hours, the plasma-potassium had risen to 1.5 mEq. per litre, the patient’s hand grip had become slightly stronger, and the rate of potassium administration was reduced to approximately 20 mEq. per hour. Although the plasma-potassium continued to show a gradual rise, the improvement in muscle power was not sustained; at 20 hours, when the plasma-potassium concentration was 2-4 mEq. per litre, the paresis became more severe and spread to the intercostal muscles. Increasing the rate of intravenous infusion to 40 mEq. per hour did not prevent the onset of severe respiratory distress; the muscle paralysis failed to improve until the rate of infusion had again been increased to 80 mEq. per hour and maintained at this high level for 50 minutes. Thereafter, further improve-
REPORTED CASES OF INTENSIVE INTRAVENOUS POTASSIUM-REPLACEMENT THERAPY
Potassium infused after 22 hours
not
included.
811 allowed progressive reductions in the rate of potassium infusion. Intravenous therapy was stopped 42 hours after admission. By this time, the serum-potassium was 4-4 mEq. per litre, the electrocardiogram showed only slight abnormalities and the intercostal muscle weakness had disappeared; the patient’s hand grip was stronger, but the weakness in the legs showed only slight improvement and took 4 weeks to recover ment
completely. The oral administration of
potassium bicarbonate and
potassium citrate was discontinued after 40 hours; thereafter the patient received a diet with a constant potassium content of mEq. per day. Potassium balance was attained on the 10th day after admission. During this 10-day period, potassium intake totalled 1836 mEq. and output 780 mEq. (urinary excretion 740 mEq. and faecal excretion 40 mEq.), the patient retaining 1056 mEq. of potassium. Renal function was assessed 3 weeks after admission: glomerular-filtration rate (12’Idiatrozoate clearance), 131 ml. per minute; tubular reabsorption of solute-free water (during mannitol diuresis and vasopressin infusion), 6-0 ml. per minute; lowest urinary pH (after ammonium chloride orally), 4-9. The diabetes mellitus was controlled on a diet containing 240 g. of carbohydrate with protamine zinc insulin, 28 i.u. daily, and soluble insulin, 28 i.u. daily. The patient has taken no potassium supplements for over a year, and there has been no recurrence of hypokalxmia.
85
Discussion
Hypokalsemia in untreated diabetic acidosis indicates unusually severe potassium depletion (Abramson and Arky 1966), the deficit in our patient amounting to almost a third of the total body potassium. Treatment of the diabetic acidosis further reduced plasma-potassium to dangerously low levels, which persisted throughout most of the first 24 hours, despite intensive potassium replacement. This protracted period of serious hypokalsemia can only be explained by a massive cellular uptake of potassium, since the urinary losses of potassium during intensive replacement were small. Factors responsible for the cellular uptake of potassium during treatment of diabetic acidosis include the administration of insulin (Smillie and Manery 1960) and glucose (Fenn 1939), and the correction of acidosis (Keating et al. 1953) accelerated by the administration of alkali. On account of the severity of the metabolic acidosis we gave our patient sodium bicarbonate. Though the initial concentration of serum-potassium would probably have fallen less rapidly had bicarbonate been avoided, the protracted period of dangerous hypokalasmia must be attributed to failure of the high rate of potassium administration to exceed significantly the rate of cellular potassium
uptake. The intercostal muscles became paralysed after the replacement of 670 mEq. of potassium. Although the serum-potassium at this stage had risen from 1.2 to 2-4 mEq. per litre, the intercostal paralysis was believed to have resulted from a disproportionate rise in cellular potassium, since an increase in the ratio of intracellular to extracellular potassium concentration may lead to interference with muscle function (Grob et al. 1957). The striking improvement in respiratory paralysis which followed doubling of the rate of potassium infusion, and the accompanying rise in plasma-potassium, lend some support to this hypothesis. The limitations of current recommendations on intravenous potassium replacement are illustrated by several recent reports. Kunin et al. (1962) reported significant reductions in serum-potassium in eight out of twenty-one patients with potassium depletion during the intravenous infusion of potassium with glucose at rates of 20 mEq. and
mEq. per hour. In reported cases of intensive intrapotassium-replacement therapy, where the amounts given within periods of 12 or 24 hours exceeded 30’) mEq. and 600 mEq. (see accompanying table), the rates of potassium infusion varied between 30 and 190 mEq. per hour. In the successful resuscitation of a paralysed moribund patient, Seftel and Kew (1966) infused potassium at a rate of 320 mEq. per hour over a period of
40
venous
15 minutes. It is apparent that the recommended
highest rates of intravenous potassium administration of 10-25 mEq. per hour and 100-200 mEq. per day may have to be exceeded several-fold in the treatment of severe potassium depletion. Replacement therapy of this intensity must be controlled by the results of frequent clinical, biochemical, and electrocardiographic observations. Since serial determinations of serum-potassium at short intervals are absolutely essential, arrangements must be made for the rapid transit of blood-samples to the laboratory, and the carrying out of estimations without delay. We thank the staff of the University department of clinical chemistry, Royal Infirmary, Edinburgh, particularly Dr. R. G. S. Leask, for the chemical analyses. Requests for reprints should be addressed to A. D., Department of Medicine, Royal Infirmary, Edinburgh 3. REFERENCES
Abramson, E., Arky, R. (1966) J. Am. med. Ass. 196, 401. Clementsen, H. J. (1962) Lancet, ii, 175. Fenn, W. O. (1939) J. biol. Chem. 128, 297. Grob, D., Johns, R. J., Liljestrand, A. (1957) Am. J. Med. 23, 356. Keating, R. E., Weichselbaum, T. E., Alanis, M., Margraf, H. W., Elman, R. (1953) Surgery Gynec. Obstet. 96, 323. Kunin, A. S., Surawicz, B., Sims, E. A. H. (1962) New Engl. J. Med. 266, 228. Seftel, H. C., Kew, M. C. (1966) Diabetes, 15, 694. Smillie, L. B., Manery, J. F. (1960) Am. J. Physiol. 198, 67. Stephens, F. I. (1949) Ann. intern. Med. 30, 1272.
Reviews of Books Infant Nutrition SAMUEL J. FOMON, M.D., professor of pediatrics, University of Iowa College of Medicine, Iowa City. London and Philadelphia: W. B. Saunders. 1967. Pp. 299. 73s. 6d.; §10.50.
Dr. Fomon has written this book to provide up-to-date information for practising clinicians. He has succeeded admirably. The chapters on protein, fat, carbohydrate, vitamins, and minerals provide a comprehensive summary of present knowledge. The book is particularly pleasing because Dr. Fomon thoughtfully defiries the area of the unknown as well as the territory which has already been mapped. He defines failure a rate of gain in length and/or weight less than to thrive as the value corresponding to two standard deviations below the mean during an interval of at least 56 days for infants less than three months of age and during an interval of at least three months for older infants." Infants below the 10th percentile values for length and weight should be regarded as suspect. While this definition may be acceptable, diagnosis and treatment of failure to thrive can seldom be delayed for eight weeks. He defines obesity as a gross discrepancy between length and weight in relation to the percentile tables ńa more satisfactory definition requires further study. To prevent iron-deficiency anaemia he suggests that 2000 mg. of iron should be provided by small daily increments during the first year of life. In discussing the future of infant nutrition, Dr. Fomon describes work which has shown that caloric restriction in rats at the time of weaning can increase longevity and prevent renal disease. He discusses, too, the relation of later atherosclerosis to the lipid content of the diet in infancy and the possibility that a high intake of sodium chloride may predispose to subsequent hypertension. Animal work has shown that nutrition in pregnancy and in the preweaning period "