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SIGNIFICANCE OF URINARY POTASSIUM CONCENTRATION IN NEONATAL HYPERBILIRUBINÆMIA
938 The younger infant had a petechial rash; both had acidotic breathing. The blood-sugar on admission was 12 mg. per 100 ml. in the first case and 30 in the second. The bicarbonate levels were 11’9 and 6-8 mEq. per litre. The flocculation tests for liver functions were normal but the serum glutamicoxaloacetic transaminase level was raised in the first patient. The four-month-old infant had an abnormal electrocardiogram and the second a diffuse abnormality of the electroencephalogram. Despite intravenous glucose, steroids, antibiotics, and anticonvulsants, intermittent fits occurred and both children went into coma and died. Necropsy showed cerebral oedema, fatty infiltration of the liver, and fatty infiltration of the proximal tubules of the kidneys. There was no history of exposure to toxic substances and virus studies were negative.
In a survey of possible cases of encephalitis at the Hospital for Sick Children, Great Ormond Street, over the past two years, this syndrome had not been seen. The
Hospital for Sick Children, London, W.C.1.
KEITHA CORLETT.
SIGNIFICANCE OF URINARY POTASSIUM CONCENTRATION IN NEONATAL HYPERBILIRUBINÆMIA SIR,-A practical problem often arises in neonatal hxmolytic disease of the newborn. When the indirect
serum-bilirubin reading approaches a critical threshold of 18-20 mg. per 100 ml. exchange transfusion may become necessary. A rapid rate of rise of the serumbilirubin-e.g., more than 0-5 mg. in two hours, is sometimes used as indication for transfusion: but this is often
impracticable
or
unsatisfactory.
We have previously reported1 that potassium (presumably derived mostly from destroyed red blood-cells) was found in higher concentrations in the urine of newborn infants with physiological jaundice and haemolytic disease of the newborn. The rise of serum-potassium is transitory, the excess being excreted in the urine. These findings prompted us to investigate the usefulness of this test as an index of active haemolysis. Our experience indicated that a urinary potassium concentration of less than 150 mg. per 100 ml. implies the cessation of active haemolysis, whereas a level clearly above 200 mg. per 100 ml. could be regarded as a sign of continued haemolysis. These findings may vary under different climatic conditions (warmer temperatures causing higher potassium concentration); hence in Great Britain the figures could be somewhat lower. In our fifteen cases of haemolytic disease of the newborn the indirect serum-bilirubin ranged between 18-24 mg. per 100 ml., and when a urinary potassium concentration of less than 150 mg. per 100 ml. was obtained exchange transfusion was deferred. Within 2 to 6 hours in each case a considerable fall of 2-5 mg. per 100 ml. of serum-bilirubin followed, and in each a downward trend continued in the serum-bilirubin and the urinary potassium concentration. In all cases and especially in borderline situations (for example, when the urinary potassium-concentration figures lie between 150-200 mg. per 100 ml.) repetition of the estimation within two and four hours was often helpful in reaching a decision. Urinary potassium-concentration data were found unreliable in infants who had abnormally high serum-potassium levels since in such cases urinary potassium excretion could also depend on renal factors. Other factors known to affect potassium levels, such as dehydration, acidosis, or anoxia, were found not to affect the validity of these findings tangibly. Criticism may be raised that random estimations of potassium are not sufficiently reliable because of urinary variations; collection of urine over long periods is almost impracticable in the newborn. But our results seem to show that these examinations were of sufficient practical value. For obvious reasons it is difficult to obtain a control group by deferring exchange transfusion in infants who 1.
Gotlieb, A., Pesach,
I.
Harefuah, 1962, 63,
174.
reach the recognised serum-bilirubin peak and still show active haemolysis on the basis of our criterion. But if the finding we report is consistently confirmed it may well save many unnecessary transfusions and some mortality. Pediatric Department A, A. GOTLIEB Government Hospital, Zahalon, I. PESACH. Tel-Aviv-Jaffa, Israel. LACK OF EFFECT OF CHOLESTYRAMINE RESIN ON HYPERBILIRUBINÆMIA OF PREMATURE INFANTS SIR,-We reported1 that in homozygous Gunn rats, feeding of cholestyramine resin significantly reduced the level ofhyperbilirubinaemia by preventing the reabsorption of unconjugated bilirubin which had been transferred into
the intestinal lumen across the mucosa. These results suggested that administration of this resin might prevent or alleviate the severe hyperbilirubinsemia often found in premature infants. To investigate this possibility the effect of cholestyramine on the hyperbilirubinsemia of premature infants was studied at the Cook County
Hospital. Premature infants with birthweights ranging from 1500 to 2000 g. were selected. Infants delivered by cxsarean section or
exhibiting respiratory distress, infection,
or
hsmolytic
disease were excluded. Infants were assigned numbers in the order of their birth. The numbers were previously assigned to either the control or the resin group by means of a random number table. Randomisation was carried out in blocks of ten to achieve two groups of comparable size. 24 hours after birth, the infants were fed on Olac formula, and the volume of the feedings was gradually increased. At 48 hours the condition of each infant was assessed, and if found satisfactory the infant was taken into the trial and his previously assigned number to the resin or control group was revealed. Infants whose condition was unsatisfactory at this age were dropped from the trial. Cholestyramine (250 mg. dry-weight) was mixed with the Olac formula immediately before the bottle was warmed for feeding, and was administered every 4 hours to infants in the resin group. The total amount of cholestyramine given per 24 hours was 1500 mg. and the treatment was given for six consecutive days. If required, additional formula without resin was also offered. Infants in the control group received formula without resin every 4 hours. In a few instances, the formula with or without resin was administered by gastric tube. Fluid and caloric requirements were determined on the basis of body-weight and age. Weight, general condition, and the amount of formula taken were recorded each day. The total number of infants accepted for the trial was 32. Of these, 1 from the control group and 1 from the resin group were dropped from the study on the third day because of respiratory disease. Another infant from the resin group was dropped from the study on the sixth day because he had mild diarrhoea. 29 infants, 16 in the control group and 13 in the resin group, remained for statistical assessment. Serum was obtained each morning, beginning during the first 24 hours after birth and continuing throughout the study, at about the same time for determination of serum-bilirubin concentration.2 The laboratory personnel did not know which infants were receiving the resin and the results remained unknown to the investigators caring for the infants until the conclusion of the trial. In each case, bilirubin levels in mg. per 100 ml. were plotted against age in hours, and straight lines were drawn between the individual points. Bilirubin concentrations at 48 hours and 168 hours were estimated from the two adjacent points. The area under the graph between 48 hours and 168 hours was computed. There was little difference between the mean 48-hour bilirubin levels of the resin group (7-2, standard deviation 2-71) and the control groups (8-8, standard deviation 1. Lester, R., Hammaker, L., Schmid, R. Lancet, 1962, ii, 1257. 2. Malloy, H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481.
In a survey of possible cases of encephalitis at the Hospital for Sick Children, Great Ormond Street, over the past two years, this syndrome had not been seen. The
Hospital for Sick Children, London, W.C.1.
KEITHA CORLETT.
SIGNIFICANCE OF URINARY POTASSIUM CONCENTRATION IN NEONATAL HYPERBILIRUBINÆMIA SIR,-A practical problem often arises in neonatal hxmolytic disease of the newborn. When the indirect
serum-bilirubin reading approaches a critical threshold of 18-20 mg. per 100 ml. exchange transfusion may become necessary. A rapid rate of rise of the serumbilirubin-e.g., more than 0-5 mg. in two hours, is sometimes used as indication for transfusion: but this is often
impracticable
or
unsatisfactory.
We have previously reported1 that potassium (presumably derived mostly from destroyed red blood-cells) was found in higher concentrations in the urine of newborn infants with physiological jaundice and haemolytic disease of the newborn. The rise of serum-potassium is transitory, the excess being excreted in the urine. These findings prompted us to investigate the usefulness of this test as an index of active haemolysis. Our experience indicated that a urinary potassium concentration of less than 150 mg. per 100 ml. implies the cessation of active haemolysis, whereas a level clearly above 200 mg. per 100 ml. could be regarded as a sign of continued haemolysis. These findings may vary under different climatic conditions (warmer temperatures causing higher potassium concentration); hence in Great Britain the figures could be somewhat lower. In our fifteen cases of haemolytic disease of the newborn the indirect serum-bilirubin ranged between 18-24 mg. per 100 ml., and when a urinary potassium concentration of less than 150 mg. per 100 ml. was obtained exchange transfusion was deferred. Within 2 to 6 hours in each case a considerable fall of 2-5 mg. per 100 ml. of serum-bilirubin followed, and in each a downward trend continued in the serum-bilirubin and the urinary potassium concentration. In all cases and especially in borderline situations (for example, when the urinary potassium-concentration figures lie between 150-200 mg. per 100 ml.) repetition of the estimation within two and four hours was often helpful in reaching a decision. Urinary potassium-concentration data were found unreliable in infants who had abnormally high serum-potassium levels since in such cases urinary potassium excretion could also depend on renal factors. Other factors known to affect potassium levels, such as dehydration, acidosis, or anoxia, were found not to affect the validity of these findings tangibly. Criticism may be raised that random estimations of potassium are not sufficiently reliable because of urinary variations; collection of urine over long periods is almost impracticable in the newborn. But our results seem to show that these examinations were of sufficient practical value. For obvious reasons it is difficult to obtain a control group by deferring exchange transfusion in infants who 1.
Gotlieb, A., Pesach,
I.
Harefuah, 1962, 63,
174.
reach the recognised serum-bilirubin peak and still show active haemolysis on the basis of our criterion. But if the finding we report is consistently confirmed it may well save many unnecessary transfusions and some mortality. Pediatric Department A, A. GOTLIEB Government Hospital, Zahalon, I. PESACH. Tel-Aviv-Jaffa, Israel. LACK OF EFFECT OF CHOLESTYRAMINE RESIN ON HYPERBILIRUBINÆMIA OF PREMATURE INFANTS SIR,-We reported1 that in homozygous Gunn rats, feeding of cholestyramine resin significantly reduced the level ofhyperbilirubinaemia by preventing the reabsorption of unconjugated bilirubin which had been transferred into
the intestinal lumen across the mucosa. These results suggested that administration of this resin might prevent or alleviate the severe hyperbilirubinsemia often found in premature infants. To investigate this possibility the effect of cholestyramine on the hyperbilirubinsemia of premature infants was studied at the Cook County
Hospital. Premature infants with birthweights ranging from 1500 to 2000 g. were selected. Infants delivered by cxsarean section or
exhibiting respiratory distress, infection,
or
hsmolytic
disease were excluded. Infants were assigned numbers in the order of their birth. The numbers were previously assigned to either the control or the resin group by means of a random number table. Randomisation was carried out in blocks of ten to achieve two groups of comparable size. 24 hours after birth, the infants were fed on Olac formula, and the volume of the feedings was gradually increased. At 48 hours the condition of each infant was assessed, and if found satisfactory the infant was taken into the trial and his previously assigned number to the resin or control group was revealed. Infants whose condition was unsatisfactory at this age were dropped from the trial. Cholestyramine (250 mg. dry-weight) was mixed with the Olac formula immediately before the bottle was warmed for feeding, and was administered every 4 hours to infants in the resin group. The total amount of cholestyramine given per 24 hours was 1500 mg. and the treatment was given for six consecutive days. If required, additional formula without resin was also offered. Infants in the control group received formula without resin every 4 hours. In a few instances, the formula with or without resin was administered by gastric tube. Fluid and caloric requirements were determined on the basis of body-weight and age. Weight, general condition, and the amount of formula taken were recorded each day. The total number of infants accepted for the trial was 32. Of these, 1 from the control group and 1 from the resin group were dropped from the study on the third day because of respiratory disease. Another infant from the resin group was dropped from the study on the sixth day because he had mild diarrhoea. 29 infants, 16 in the control group and 13 in the resin group, remained for statistical assessment. Serum was obtained each morning, beginning during the first 24 hours after birth and continuing throughout the study, at about the same time for determination of serum-bilirubin concentration.2 The laboratory personnel did not know which infants were receiving the resin and the results remained unknown to the investigators caring for the infants until the conclusion of the trial. In each case, bilirubin levels in mg. per 100 ml. were plotted against age in hours, and straight lines were drawn between the individual points. Bilirubin concentrations at 48 hours and 168 hours were estimated from the two adjacent points. The area under the graph between 48 hours and 168 hours was computed. There was little difference between the mean 48-hour bilirubin levels of the resin group (7-2, standard deviation 2-71) and the control groups (8-8, standard deviation 1. Lester, R., Hammaker, L., Schmid, R. Lancet, 1962, ii, 1257. 2. Malloy, H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481.