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An evaluation of the electrolyte status of malnourished Thai children
TROPICAL
PEDIATRICS
DerrickB. Jelliffe, Editor
I. An ,evaluation of the electrolyte status of malnourished Thai children Thirty Northern Thai children with protein-calorie malnutrition (PCM) were studied to determine the cation composition o/several tissues on admission and during subsequent treatment. All children received 5 to 10 mEq. o[ magnesium [rom milk/ormula and up to 8.5 mEq. o[ magnesium/tom so[t diet every day. In addition, 9 children received 0.41 to 0.5 mEq. o/magnesium per kilogram o[ body weight intramuscularly [rom Days 2 through 11. On admission, 44 per cent had plasma magnesium levels below 1.4 mEq. per liter, and 64 per cent had plasma potassium values below 3.5 mEq. per liter. Ninety-three per cent excreted less than 1 mEq. o[ m~agnesium per 24 hours. The severity o/symptoms was roughly related to the degree o[ hypomagnesemia; there/ore, a low plasma magnesium is an important finding in PCM. However, normal plasma and low urine magnesium values, the usual findings when a child with PCM is admitted to the hospital, are not reliable guides to magnesium status at this time.
Joan L. Caddell, M.D.,* and Robert E. Olson, M.D., Ph.D., Chiang Mai, Thailand
E LE C T R O L Y T E
imbalance, including
magnesium deficiency, has been well documented in protein-calori e malnutrition (PCM). 17 Magnesium deficiency was expected to be part of the PCM syndrome in Northern Thailand, because of the high
From the Anemia and Malnutrition Research Center, Faculty o[ Medicine, Chiang Mai University, and the Departments o[ Pediatrics and Biochemistry, St. Louis University School o/Medicine. Supported by the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, 5 F3-AM-39-696-O1 and -02 and 5 R22-AM-11044-05. *Rep~int address: St, Louis University School o[ Medicine, 1402 S. Grand Blvd,, St. Louis, Mo. 63104.
Vol. 83; No. I, pp, 124-128
incidence of diarrhea in pediatric admissions to Chiang Mai Hospital (75 per cent) s and because the dietary staple, pdished rice, is a poor source of magnesium. The purpose of this study was to investigate changes in concentrations of magnesium, calcium, sodium, and potassium in plasma, muscle, and urine of children with PCM in Northern Thailand and to demonstrate the extent to which clinical improvement is associated with changes in urine and tissue electrolytes. MATERIALS
AND
METHODS
Thirty children between 12 and 50 months of age were admitted to the Anemia and Malnutrition Research Center, Chiang Mai,
Volume 83 Number 1
Thailand, between July, 1969, and February, 1970, for a 12 week period of study. Laboratory investigations. Plasma cations were measured on a Model 303 Perkin Elmer atomic absorption spectrophotometer by established methods 9 on admission and usually on Days 2, 4, 7, and 10 and at Weeks 3, 6, 9, and 12. The urine cations 9 and creatinine determinations ~~ were made on admission and at 3 week intervals. A total o f 3 9 muscle samples were taken from the pectoralis major muscle within 3 days of admission and at 3 and 11 weeks, and were analyzed by a standard method 1~ with minor modifications. Therapy. Fluid and electrolyte administration was based upon the clinical state and the plasma electrolyte values. Nine children received 0.41 to 0.50 mEq. of magnesium per kilogram of body weight intramuscularly daily from Days 2 to 11. The formulas of whole milk 'and dextrose supplied (per liter): 5 to 10 mEq. of magnesium, 35 to 70 mEq. of calcium, 11 to 22 mEq. of sodium, and 20 to 40 mEq. of potassium. A mixed diet that supplied up to 8.5 mEq. of magnesium was then fed. The m a x i m u m diet supplied 180 to 200 calories and 6.6 Gm. of protein per kilogram of body weight per day. Vitamins were routinely given in doses greater than those recommended by the Food and Nutrition Board, the National Research Council, United States. In vitamin deficiency states, therapeutic doses were given. Antibiotic therapy, cortisone, blood transfusions, and other drugs were given as indicated.
RESULTS Clinical findings at the time of admission. There were 14 boys and 16 girls in the study with a mean age of 24.5 4- 8.8 months and a mean weight of 6.8 _+ 1.7 Kg., which is 60.5 + 10.7 per cent of the local Thai standard a2 and 54.4 +_ 9.4 per cent of the mean weight of the Children's Medical Center, Boston, anthropometric chart, a3 They had been breast-fed for a mean period of 14.7 months and had been fed polished glutenous rice (Oryza glutinosa) and small
Electrolyte status in malnutrition
125
amounts of vegetables, milk, and meat. Fifteen had had anorexia, 27 had intermittent diarrhea over a mean period of 30 days, and 5 had intermittent vomiting over a 2 week period. Nine were markedly dehydrated and 12 had grade 3 to 4 peripheral edema. They were classified as follows: marasmus in 7, marasmic kwashiorkor in 15, and kwashiorkor in 8. None of these children developed convulsions or tetany during the first 2 days. During that time, none had plasma magnesium values below 1.0 mEq. per liter, but 10 had total plasma calcium values between 2.1 and 3.5 mEq. per liter.
Laboratory findings at the time of admission. The values of the 4 major cations measured in plasma, urine, and muscle are presented in Tables I, II, and lII. Magnesium. On admission, 44 per cent of the children had plasma magnesium values slightly below the lower limits of normal of 1.4 mEq. per liter. 1,~,G Following about 16 hours of parenteral magnesium-free fluid therapy, 56 per cent of the values were decreased. Ninety-three per cent of the initim 24 hour urine values were less than 1.0 mEq., which is significantly low. ~ The mean initial muscle magnesium value of 8.81 _+ 1.6 mEq. per kilogram wet weight or 49.9 _+ 7.9 mEq. per kilogram of fat-free dry tissue was below published normal values for children of 16.3 to 20.0 mEq. per kilogram wet weight2 Other cations. The mean plasma calcium value decreased 0.44 mEq. per liter following initial calcium-free rehydration therapy. The mean muscle calcium value was slightly elevated. Fifty-three per cent of a mean sodium intake of 47 mEq. was retained in the first 24 hours, as was 76 per cent of the mean potassium intake of 26 mEq. Twentytwo children excreted less than 1.1 mEq. of potassium per 24 hours, indicating good renal conservation of the ion.
Course of clinical changes with treatment. Of the 30 patients studied on admission, 6 were assigned to another study after Day 2 and 2 died, one of staphylococcus pneumonia and the other during initial rehydra-
12 6
Caddell and Olson
The ]ournal o[ Pediatrics ]uly 1973
T a b l e I. C a t i o n values for p l a s m a (in milliequivalents p e r liter) No.
o/ patients
Day
30 ~ 27 ~ 19t 18t
1 2 21 84
Magnesium (mean + S.D.) 1.44 1.36 1.67 1.63
• 0.25 +- 0.28 • 0.69 -+ 0.11
Calcium (mean + S.D.) 3.80 3.53 4.35 5.02
• 0.73 -+ 0.56 + 0.49 + 0.42
Sodium (mean +- S.D.) 133 • 7.1 135 + 6.5 137 + 5.8 138 + 3.3
Potassium (mean +- S.D.) 2.68 • 1.08 3.83 -+ 0.91 4.42 • 0.48 4.42 -+ 0.45
~Three less for Mg and K (hemolysis). tOne less for Mg and K (hemolysis).
T a b l e I I . C a t i o n values for urine (in milliequivalents per 24 hours' No.
o/ patients 30 19 18
Day 1 21 84
Creatinine Magnesium Calcium Sodium Potassium (mg./Kg. (mean + S.D.) (mean +- S.D.) (mean • S.D.) (mean • S.D.) body weight) 0.33 -+ 0.31 0.69 + 0.73 22.1 • 23.2 6.45 + 7.5 10.64 -+ 3.88 1.52 + 1.08 1.85 • 1.75 78.7 -+ 38.3 19.9 • 8.7 17.18 +- 4.34 3.25 • 1.14 2.30 -+ 1.45 93.6 +- 68.4 16.6 -+ 4.6 15.63 -+ 2.93
T a b l e I I I . C a t i o n values in (milliequivalents per kilogram) of d r y fat-free muscle weight Mean dry
fat-/ree
Day o[ study
children
weight
1 21 77
18 15 6
20.5 22.1 15.3
(me.)
Per cent water Magnesium (mean +- S.D.) (mean • S.D.) 81.12 +- 2.56 79.2 -+ 3.16 79.0 -+ 1.05
49.9 -+ 7.9 48.6 '+- 9.2 71.4 • 16.0
tion t h e r a p y . T h e following d a t a are from 22 patients. T h e lowest p l a s m a m a g n e s i u m values developed between Days 5 and 14, when the c o n c e n t r a t i o n of most electrolytes and p l a s m a a l b u m i n were r e t u r n i n g to normal. T h e incidence of clinical changes in patients with a b n o r m a l l y low p l a s m a m a g n e s i u m values was c o m p a r e d to those with n o r m a l p l a s m a m a g n e s i u m levels. Food intake. T e n children with p l a s m a magnesium values below 1.2 mEq. p e r liter accepted soft diets at a m e a n of 14.5 days and consumed a m e a n of 61 calories p e r kilogram p e r day for the first 21 days. Twelve children with p l a s m a values m a i n tained above 1.2 mEq. per liter accepted soft diets at a m e a n of 7 days a n d consumed a m e a n of 114 calories p e r kilogram p e r day for the first 21 days. T h e difference in the caloric intake between these 2 groups is highly significant, p < 0.0005.
(mS:lc us. ) (meUi?7 ) 21.6 • 5.2 19.6 -+ 5.4 26.5 • 9.0
274 + 65.7 249 + 61.1 249 + 56.3
Potassium (mean +- S.D.) 164 + 59.5 208 + 81.3 222.7 +- 58.7
N e t weight gain. Children with p l a s m a magnesium values below 1.2 mEq. p e r liter h a d a weight gain of 0.35 Kg. in 21 days, whereas those h a v i n g higher p l a s m a magnesium values h a d a m e a n weight gain of 1.2 Kg. in 21 days; the difference is significant at a 0.005 level of probability, This difference disappeared when it was c o m p a r e d at 84 days. Persistence o[ edema. Twelve children had 3 to 4 plus e d e m a on admission. Visible e d e m a persisted until D a y 18 in 9 children with h y p o m a g n e s e m i a (a m e a n of 0.87 mEq. p e r liter), a n d until D a y 8 in 3 children w h o m a i n t a i n e d n o r m a l plasma magnesium values ( m e a n 1.55 mEq. per liter). T h e sample size was too small for statistical comparison. Neurologic signs and symptoms. Between Days 5 a n d 14, 4 out of 5 children with p l a s m a m a g n e s i u m values below 1.0 mEq. p e r liter developed one or m o r e neurologic
Volume 83 Number 1
signs. At that time, their mean plasma cation values, in milliequivalents per liter, were: magnesium 0.75, calcium 3.68, sodium 136, and potassium 4.18. Blood sugar and cerebrospinal fluid examinations were normal. Neurologic signs included facial twitching and grimacing in one child, local and generalized convulsions followed by transient right arm palsy in one, oculogyric crises in two, fixed opthalmoplegia with infrequent blinking in one, episodes of rigid hyperextension of the neck and back in one, and brief apnea while sucking a bottle in one. Transient cyanosis was an associated finding in three. Of the 17 children with plasma magnesium values above 1.0 mEq. per liter, only one had a neurologic symptom, a seizure when his blood sugar was 15 mg. per 100 ml. Serial electrocardiograph changes. The major changes found on admission, generalized dwarfing, of electrical complexes and isoelectric or negative T waves, could not be correlated with any single biochemical abnormality. Within a few days of beginning vitamin B and potassium-supplemented rehydration therapy, the electrocardiogram usually improved. However~ between Days 5 and 14 the T waves subsequently deteriorated, usually with decreased amplitude or inversion, in patients Who developed hypomagnesemia but whose other cation values were improving or normal. Course of laboratory changes with treatment. Magnesium. The initial differences in the values between magnesium-supplemented and unsupplemented children gradually disappeared with refeeding or magnesium supplementation. Seventeen children developed a mean plasma magnesium value of 1.0 mEq. per liter, despite m~ignesium supplementation in 5 of them. Major contributing factors appeared to be persistent diarrhea, prolonged intravenous fluid therapy, and failure to accept the mixed soft diet. At 3 weeks, only one child had a low plasma magnesium value, but about 30 per cent of children still had low 24 hour urine magnesium values. Magnesium-unsupplerhented children
Electrolyte status in malnutrition
127
excreted a mean of 1.25 mEq. and magnesium-supplemented children, 2.12 mEq. per 24 hours. The muscle magnesium values increased but were still below the normal value at 11 weeks. Other cations. Values for plasma and urine became normal, but normal values for muscle were not achieved during the period of observation. DISCUSSION Plasma magnesium. On admission, the plasma magnesium values in PCM patients are usually normal or low normal. 5, G However, while the patients were receiving therapy that preferentially restored cations other than magnesium and that provided nutrients for protein anabolism, they developed significant hypomagnesemia, a,~ as in this study, indicating low magnesium reserves. The onset of anorexia, neuromuscular hyperirritability, and electrocardiographic changes, all previously described in magnesium deficiency,a, ~, 6 correlated best with the plasma magnesium value. The critical factor is probably the balance between ionized magnesium and calcium, sodium, and potassium ions. It is concluded that since low plasma magnesium values may be associated with severe symptomatology, hypomagnesemia is an important finding. Nonetheless, a normal plasma magnesium value, by itself, does not indicate adequacy of body stores of magnesium. Urine magnesium. Excretion of less than 1 mEq. of magnesium per 24 hours has usually been interpreted as a sign of magnesium deficiency in PCM?, 5 This concept is critically evaluated in Part II of this study. Muscle cations. The content of cations in muscle observed in this study 1' 2, G, ~ and the inability to achieve complete repletion of magnesium and potassium 1' ~' 7 compare favorably with data in other reports. Increased muscle collagen and decreased binding sites for magnesium and potassium in malnourished muscle might contribute to low muscle values5 ~ Alleyne and associates 7 suggested that the differential loss of potas-
128
Caddell and Olson
sium in relation to magnesium m i g h t be exp l a i n e d by the fact t h a t a g r e a t e r p r o p o r tion of potassium is stored in muscle, whereas bone is the m a i n reservoir for magnesium. O t h e r cations. T h e p l a s m a a n d urine values for calcium were low on admission. T h e lack of symptoms m a y be explained b y the low serum a l b u m i n c o n c e n t r a t i o n a n d the relatively high p r o p o r t i o n of u n b o u n d , physiologically active p l a s m a calcium. Olson 1. r e p o r t e d m a r k e d intolerance to sodium in a p a t i e n t who h a d fasted for 30 days. I t has also been shown t h a t increased sodium retention m a y a c c o m p a n y potassium ~ a n d m a g n e s i u m 11 depletion, a n d t h a t increased sodium excretion m a y follow potassium a~ a n d magnesium t h e r a p y ? s CONCLUSIONS This study of m a l n o u r i s h e d N o r t h e r n T h a i children revealed significant potassium and m a g n e s i u m depletion a n d electrolyte imbalance. However, the indexes e m p l o y e d were u n c e r t a i n guides to the m a g n e s i u m status of the child. This led to the second study in which the m a g n e s i u m status was assessed by the p a r e n t a l m a g n e s i u m load test; these d a t a are recorded in P a r t II. REFERENCES
1. Montgomery, R. D.: Magnesium metabolism in infantile protein malnutrition, Lancet 2: 74, 1960. 2. Meteoff, J., Frenk, S., Antonowicz, I., Gordillo, G., and Lopez, E.: Relations of intracellular ions to metabolite sequences in muscle in kwashiorkor, Pediatrics 26: 960, 1960. 3. Back, E. H., Montgomery, R. D., and Ward, E. E.: Neurological manifestations of magnesium deficiency in infantile gastroenteritis and malnutrition, Arch. Dis. Child. 37: 106, 1962.
The Journal o[ Pediatrics July 1973
4. Pretorius, P. J., Wehmeyer, A. S., and Theron, J. J.: Magnesium balance studies in South African Bantu children with kwashiorkor, Am. J. Clin. Nutr. 13: 331, 1963. 5. Linder, G. C., Hansen, J. D. L., and Karabus, C. D.: Metabolism of magnesium and other inorganic cations and of nitrogen in acute kwashiorkor, Pediatrics 31: 552, 1963. 6. Caddell, J. L., and Goddard, D. R.: Studies in protein-calorie malnutrition, N. Engl. J. Med. 276: 533, 1967. 7. Alleyne, G. A. O., Millward, D. J., and Soullard, G. H.: Total body potassium, muscle electrolytes, and glycogen in malnourished children, J. PEDIATR. 76: 75, 1970. 8. Thanangkul, O., Whitaker, J. A., and Fort, E. G.: Malnutrition in Northern Thailand, Am. J. Clin. Nutr. 18: 379, 1966. 9. Anonymous: Analytical methods for atomic absorption spectrophotometry, Norwalk, Conn., November, 1966, Perkin Elmer Corp. 10. Lambert, G. F.: The determination of creatine and creatinine, J. Biol. Chem. 161: 679, 1945. I I. MacIntyre, I., and Davidsson, D.: The production of secondary potassium depletion, sodium retention, nephrocalcinosis, and hypercalcaemia by magnesium deficiency, Biochem. J. 70: 456, 1958. 127 Unpublished data: Department of Preventive Medicine, Chiang Mai University, Chiang Mai, Thailand, 1971. 13. Anthropometric chart, The Children's Medical Center, Boston, in Nelson, W. E., Vaughan, V. C., III, and McKay, R. J., editors: Textbook of pediatrics, ed. 9, Philadelphia, 1969, W. B. Saunders Company, pp. 40-41. 14. Keynes, W. M., Barnes, B. A., and Cope, O.: Urinary excretion of calcium and magnesium in man using a diet with a very low content of these minerals, Proc. R. Soc. IVied. 64: 152, 1971. I5. Picou, D., Halliday, D., and Garrow, J. S.: Total body protein, collagen, and non-collagen protein in infantile protein malnutrition, Clin. Sci. 30: 345, 1966. 16. Olson, R. E.: Role of hormones in protein metabolism, J. A. M. A. 164: 1758, 1957. 17. Schwartz, W. B., and Relman, A. S.: Effects of electrolyte disorders on renal structure and function, N. Engl. J. Med. 276: 383, 1967. 18. Fitzgerald, M. G., and Fourman, P.: An experimental study of magnesium deficiency in man, Clin. Sci. 15: 635, 1956.
PEDIATRICS
DerrickB. Jelliffe, Editor
I. An ,evaluation of the electrolyte status of malnourished Thai children Thirty Northern Thai children with protein-calorie malnutrition (PCM) were studied to determine the cation composition o/several tissues on admission and during subsequent treatment. All children received 5 to 10 mEq. o[ magnesium [rom milk/ormula and up to 8.5 mEq. o[ magnesium/tom so[t diet every day. In addition, 9 children received 0.41 to 0.5 mEq. o/magnesium per kilogram o[ body weight intramuscularly [rom Days 2 through 11. On admission, 44 per cent had plasma magnesium levels below 1.4 mEq. per liter, and 64 per cent had plasma potassium values below 3.5 mEq. per liter. Ninety-three per cent excreted less than 1 mEq. o[ m~agnesium per 24 hours. The severity o/symptoms was roughly related to the degree o[ hypomagnesemia; there/ore, a low plasma magnesium is an important finding in PCM. However, normal plasma and low urine magnesium values, the usual findings when a child with PCM is admitted to the hospital, are not reliable guides to magnesium status at this time.
Joan L. Caddell, M.D.,* and Robert E. Olson, M.D., Ph.D., Chiang Mai, Thailand
E LE C T R O L Y T E
imbalance, including
magnesium deficiency, has been well documented in protein-calori e malnutrition (PCM). 17 Magnesium deficiency was expected to be part of the PCM syndrome in Northern Thailand, because of the high
From the Anemia and Malnutrition Research Center, Faculty o[ Medicine, Chiang Mai University, and the Departments o[ Pediatrics and Biochemistry, St. Louis University School o/Medicine. Supported by the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, 5 F3-AM-39-696-O1 and -02 and 5 R22-AM-11044-05. *Rep~int address: St, Louis University School o[ Medicine, 1402 S. Grand Blvd,, St. Louis, Mo. 63104.
Vol. 83; No. I, pp, 124-128
incidence of diarrhea in pediatric admissions to Chiang Mai Hospital (75 per cent) s and because the dietary staple, pdished rice, is a poor source of magnesium. The purpose of this study was to investigate changes in concentrations of magnesium, calcium, sodium, and potassium in plasma, muscle, and urine of children with PCM in Northern Thailand and to demonstrate the extent to which clinical improvement is associated with changes in urine and tissue electrolytes. MATERIALS
AND
METHODS
Thirty children between 12 and 50 months of age were admitted to the Anemia and Malnutrition Research Center, Chiang Mai,
Volume 83 Number 1
Thailand, between July, 1969, and February, 1970, for a 12 week period of study. Laboratory investigations. Plasma cations were measured on a Model 303 Perkin Elmer atomic absorption spectrophotometer by established methods 9 on admission and usually on Days 2, 4, 7, and 10 and at Weeks 3, 6, 9, and 12. The urine cations 9 and creatinine determinations ~~ were made on admission and at 3 week intervals. A total o f 3 9 muscle samples were taken from the pectoralis major muscle within 3 days of admission and at 3 and 11 weeks, and were analyzed by a standard method 1~ with minor modifications. Therapy. Fluid and electrolyte administration was based upon the clinical state and the plasma electrolyte values. Nine children received 0.41 to 0.50 mEq. of magnesium per kilogram of body weight intramuscularly daily from Days 2 to 11. The formulas of whole milk 'and dextrose supplied (per liter): 5 to 10 mEq. of magnesium, 35 to 70 mEq. of calcium, 11 to 22 mEq. of sodium, and 20 to 40 mEq. of potassium. A mixed diet that supplied up to 8.5 mEq. of magnesium was then fed. The m a x i m u m diet supplied 180 to 200 calories and 6.6 Gm. of protein per kilogram of body weight per day. Vitamins were routinely given in doses greater than those recommended by the Food and Nutrition Board, the National Research Council, United States. In vitamin deficiency states, therapeutic doses were given. Antibiotic therapy, cortisone, blood transfusions, and other drugs were given as indicated.
RESULTS Clinical findings at the time of admission. There were 14 boys and 16 girls in the study with a mean age of 24.5 4- 8.8 months and a mean weight of 6.8 _+ 1.7 Kg., which is 60.5 + 10.7 per cent of the local Thai standard a2 and 54.4 +_ 9.4 per cent of the mean weight of the Children's Medical Center, Boston, anthropometric chart, a3 They had been breast-fed for a mean period of 14.7 months and had been fed polished glutenous rice (Oryza glutinosa) and small
Electrolyte status in malnutrition
125
amounts of vegetables, milk, and meat. Fifteen had had anorexia, 27 had intermittent diarrhea over a mean period of 30 days, and 5 had intermittent vomiting over a 2 week period. Nine were markedly dehydrated and 12 had grade 3 to 4 peripheral edema. They were classified as follows: marasmus in 7, marasmic kwashiorkor in 15, and kwashiorkor in 8. None of these children developed convulsions or tetany during the first 2 days. During that time, none had plasma magnesium values below 1.0 mEq. per liter, but 10 had total plasma calcium values between 2.1 and 3.5 mEq. per liter.
Laboratory findings at the time of admission. The values of the 4 major cations measured in plasma, urine, and muscle are presented in Tables I, II, and lII. Magnesium. On admission, 44 per cent of the children had plasma magnesium values slightly below the lower limits of normal of 1.4 mEq. per liter. 1,~,G Following about 16 hours of parenteral magnesium-free fluid therapy, 56 per cent of the values were decreased. Ninety-three per cent of the initim 24 hour urine values were less than 1.0 mEq., which is significantly low. ~ The mean initial muscle magnesium value of 8.81 _+ 1.6 mEq. per kilogram wet weight or 49.9 _+ 7.9 mEq. per kilogram of fat-free dry tissue was below published normal values for children of 16.3 to 20.0 mEq. per kilogram wet weight2 Other cations. The mean plasma calcium value decreased 0.44 mEq. per liter following initial calcium-free rehydration therapy. The mean muscle calcium value was slightly elevated. Fifty-three per cent of a mean sodium intake of 47 mEq. was retained in the first 24 hours, as was 76 per cent of the mean potassium intake of 26 mEq. Twentytwo children excreted less than 1.1 mEq. of potassium per 24 hours, indicating good renal conservation of the ion.
Course of clinical changes with treatment. Of the 30 patients studied on admission, 6 were assigned to another study after Day 2 and 2 died, one of staphylococcus pneumonia and the other during initial rehydra-
12 6
Caddell and Olson
The ]ournal o[ Pediatrics ]uly 1973
T a b l e I. C a t i o n values for p l a s m a (in milliequivalents p e r liter) No.
o/ patients
Day
30 ~ 27 ~ 19t 18t
1 2 21 84
Magnesium (mean + S.D.) 1.44 1.36 1.67 1.63
• 0.25 +- 0.28 • 0.69 -+ 0.11
Calcium (mean + S.D.) 3.80 3.53 4.35 5.02
• 0.73 -+ 0.56 + 0.49 + 0.42
Sodium (mean +- S.D.) 133 • 7.1 135 + 6.5 137 + 5.8 138 + 3.3
Potassium (mean +- S.D.) 2.68 • 1.08 3.83 -+ 0.91 4.42 • 0.48 4.42 -+ 0.45
~Three less for Mg and K (hemolysis). tOne less for Mg and K (hemolysis).
T a b l e I I . C a t i o n values for urine (in milliequivalents per 24 hours' No.
o/ patients 30 19 18
Day 1 21 84
Creatinine Magnesium Calcium Sodium Potassium (mg./Kg. (mean + S.D.) (mean +- S.D.) (mean • S.D.) (mean • S.D.) body weight) 0.33 -+ 0.31 0.69 + 0.73 22.1 • 23.2 6.45 + 7.5 10.64 -+ 3.88 1.52 + 1.08 1.85 • 1.75 78.7 -+ 38.3 19.9 • 8.7 17.18 +- 4.34 3.25 • 1.14 2.30 -+ 1.45 93.6 +- 68.4 16.6 -+ 4.6 15.63 -+ 2.93
T a b l e I I I . C a t i o n values in (milliequivalents per kilogram) of d r y fat-free muscle weight Mean dry
fat-/ree
Day o[ study
children
weight
1 21 77
18 15 6
20.5 22.1 15.3
(me.)
Per cent water Magnesium (mean +- S.D.) (mean • S.D.) 81.12 +- 2.56 79.2 -+ 3.16 79.0 -+ 1.05
49.9 -+ 7.9 48.6 '+- 9.2 71.4 • 16.0
tion t h e r a p y . T h e following d a t a are from 22 patients. T h e lowest p l a s m a m a g n e s i u m values developed between Days 5 and 14, when the c o n c e n t r a t i o n of most electrolytes and p l a s m a a l b u m i n were r e t u r n i n g to normal. T h e incidence of clinical changes in patients with a b n o r m a l l y low p l a s m a m a g n e s i u m values was c o m p a r e d to those with n o r m a l p l a s m a m a g n e s i u m levels. Food intake. T e n children with p l a s m a magnesium values below 1.2 mEq. p e r liter accepted soft diets at a m e a n of 14.5 days and consumed a m e a n of 61 calories p e r kilogram p e r day for the first 21 days. Twelve children with p l a s m a values m a i n tained above 1.2 mEq. per liter accepted soft diets at a m e a n of 7 days a n d consumed a m e a n of 114 calories p e r kilogram p e r day for the first 21 days. T h e difference in the caloric intake between these 2 groups is highly significant, p < 0.0005.
(mS:lc us. ) (meUi?7 ) 21.6 • 5.2 19.6 -+ 5.4 26.5 • 9.0
274 + 65.7 249 + 61.1 249 + 56.3
Potassium (mean +- S.D.) 164 + 59.5 208 + 81.3 222.7 +- 58.7
N e t weight gain. Children with p l a s m a magnesium values below 1.2 mEq. p e r liter h a d a weight gain of 0.35 Kg. in 21 days, whereas those h a v i n g higher p l a s m a magnesium values h a d a m e a n weight gain of 1.2 Kg. in 21 days; the difference is significant at a 0.005 level of probability, This difference disappeared when it was c o m p a r e d at 84 days. Persistence o[ edema. Twelve children had 3 to 4 plus e d e m a on admission. Visible e d e m a persisted until D a y 18 in 9 children with h y p o m a g n e s e m i a (a m e a n of 0.87 mEq. p e r liter), a n d until D a y 8 in 3 children w h o m a i n t a i n e d n o r m a l plasma magnesium values ( m e a n 1.55 mEq. per liter). T h e sample size was too small for statistical comparison. Neurologic signs and symptoms. Between Days 5 a n d 14, 4 out of 5 children with p l a s m a m a g n e s i u m values below 1.0 mEq. p e r liter developed one or m o r e neurologic
Volume 83 Number 1
signs. At that time, their mean plasma cation values, in milliequivalents per liter, were: magnesium 0.75, calcium 3.68, sodium 136, and potassium 4.18. Blood sugar and cerebrospinal fluid examinations were normal. Neurologic signs included facial twitching and grimacing in one child, local and generalized convulsions followed by transient right arm palsy in one, oculogyric crises in two, fixed opthalmoplegia with infrequent blinking in one, episodes of rigid hyperextension of the neck and back in one, and brief apnea while sucking a bottle in one. Transient cyanosis was an associated finding in three. Of the 17 children with plasma magnesium values above 1.0 mEq. per liter, only one had a neurologic symptom, a seizure when his blood sugar was 15 mg. per 100 ml. Serial electrocardiograph changes. The major changes found on admission, generalized dwarfing, of electrical complexes and isoelectric or negative T waves, could not be correlated with any single biochemical abnormality. Within a few days of beginning vitamin B and potassium-supplemented rehydration therapy, the electrocardiogram usually improved. However~ between Days 5 and 14 the T waves subsequently deteriorated, usually with decreased amplitude or inversion, in patients Who developed hypomagnesemia but whose other cation values were improving or normal. Course of laboratory changes with treatment. Magnesium. The initial differences in the values between magnesium-supplemented and unsupplemented children gradually disappeared with refeeding or magnesium supplementation. Seventeen children developed a mean plasma magnesium value of 1.0 mEq. per liter, despite m~ignesium supplementation in 5 of them. Major contributing factors appeared to be persistent diarrhea, prolonged intravenous fluid therapy, and failure to accept the mixed soft diet. At 3 weeks, only one child had a low plasma magnesium value, but about 30 per cent of children still had low 24 hour urine magnesium values. Magnesium-unsupplerhented children
Electrolyte status in malnutrition
127
excreted a mean of 1.25 mEq. and magnesium-supplemented children, 2.12 mEq. per 24 hours. The muscle magnesium values increased but were still below the normal value at 11 weeks. Other cations. Values for plasma and urine became normal, but normal values for muscle were not achieved during the period of observation. DISCUSSION Plasma magnesium. On admission, the plasma magnesium values in PCM patients are usually normal or low normal. 5, G However, while the patients were receiving therapy that preferentially restored cations other than magnesium and that provided nutrients for protein anabolism, they developed significant hypomagnesemia, a,~ as in this study, indicating low magnesium reserves. The onset of anorexia, neuromuscular hyperirritability, and electrocardiographic changes, all previously described in magnesium deficiency,a, ~, 6 correlated best with the plasma magnesium value. The critical factor is probably the balance between ionized magnesium and calcium, sodium, and potassium ions. It is concluded that since low plasma magnesium values may be associated with severe symptomatology, hypomagnesemia is an important finding. Nonetheless, a normal plasma magnesium value, by itself, does not indicate adequacy of body stores of magnesium. Urine magnesium. Excretion of less than 1 mEq. of magnesium per 24 hours has usually been interpreted as a sign of magnesium deficiency in PCM?, 5 This concept is critically evaluated in Part II of this study. Muscle cations. The content of cations in muscle observed in this study 1' 2, G, ~ and the inability to achieve complete repletion of magnesium and potassium 1' ~' 7 compare favorably with data in other reports. Increased muscle collagen and decreased binding sites for magnesium and potassium in malnourished muscle might contribute to low muscle values5 ~ Alleyne and associates 7 suggested that the differential loss of potas-
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Caddell and Olson
sium in relation to magnesium m i g h t be exp l a i n e d by the fact t h a t a g r e a t e r p r o p o r tion of potassium is stored in muscle, whereas bone is the m a i n reservoir for magnesium. O t h e r cations. T h e p l a s m a a n d urine values for calcium were low on admission. T h e lack of symptoms m a y be explained b y the low serum a l b u m i n c o n c e n t r a t i o n a n d the relatively high p r o p o r t i o n of u n b o u n d , physiologically active p l a s m a calcium. Olson 1. r e p o r t e d m a r k e d intolerance to sodium in a p a t i e n t who h a d fasted for 30 days. I t has also been shown t h a t increased sodium retention m a y a c c o m p a n y potassium ~ a n d m a g n e s i u m 11 depletion, a n d t h a t increased sodium excretion m a y follow potassium a~ a n d magnesium t h e r a p y ? s CONCLUSIONS This study of m a l n o u r i s h e d N o r t h e r n T h a i children revealed significant potassium and m a g n e s i u m depletion a n d electrolyte imbalance. However, the indexes e m p l o y e d were u n c e r t a i n guides to the m a g n e s i u m status of the child. This led to the second study in which the m a g n e s i u m status was assessed by the p a r e n t a l m a g n e s i u m load test; these d a t a are recorded in P a r t II. REFERENCES
1. Montgomery, R. D.: Magnesium metabolism in infantile protein malnutrition, Lancet 2: 74, 1960. 2. Meteoff, J., Frenk, S., Antonowicz, I., Gordillo, G., and Lopez, E.: Relations of intracellular ions to metabolite sequences in muscle in kwashiorkor, Pediatrics 26: 960, 1960. 3. Back, E. H., Montgomery, R. D., and Ward, E. E.: Neurological manifestations of magnesium deficiency in infantile gastroenteritis and malnutrition, Arch. Dis. Child. 37: 106, 1962.
The Journal o[ Pediatrics July 1973
4. Pretorius, P. J., Wehmeyer, A. S., and Theron, J. J.: Magnesium balance studies in South African Bantu children with kwashiorkor, Am. J. Clin. Nutr. 13: 331, 1963. 5. Linder, G. C., Hansen, J. D. L., and Karabus, C. D.: Metabolism of magnesium and other inorganic cations and of nitrogen in acute kwashiorkor, Pediatrics 31: 552, 1963. 6. Caddell, J. L., and Goddard, D. R.: Studies in protein-calorie malnutrition, N. Engl. J. Med. 276: 533, 1967. 7. Alleyne, G. A. O., Millward, D. J., and Soullard, G. H.: Total body potassium, muscle electrolytes, and glycogen in malnourished children, J. PEDIATR. 76: 75, 1970. 8. Thanangkul, O., Whitaker, J. A., and Fort, E. G.: Malnutrition in Northern Thailand, Am. J. Clin. Nutr. 18: 379, 1966. 9. Anonymous: Analytical methods for atomic absorption spectrophotometry, Norwalk, Conn., November, 1966, Perkin Elmer Corp. 10. Lambert, G. F.: The determination of creatine and creatinine, J. Biol. Chem. 161: 679, 1945. I I. MacIntyre, I., and Davidsson, D.: The production of secondary potassium depletion, sodium retention, nephrocalcinosis, and hypercalcaemia by magnesium deficiency, Biochem. J. 70: 456, 1958. 127 Unpublished data: Department of Preventive Medicine, Chiang Mai University, Chiang Mai, Thailand, 1971. 13. Anthropometric chart, The Children's Medical Center, Boston, in Nelson, W. E., Vaughan, V. C., III, and McKay, R. J., editors: Textbook of pediatrics, ed. 9, Philadelphia, 1969, W. B. Saunders Company, pp. 40-41. 14. Keynes, W. M., Barnes, B. A., and Cope, O.: Urinary excretion of calcium and magnesium in man using a diet with a very low content of these minerals, Proc. R. Soc. IVied. 64: 152, 1971. I5. Picou, D., Halliday, D., and Garrow, J. S.: Total body protein, collagen, and non-collagen protein in infantile protein malnutrition, Clin. Sci. 30: 345, 1966. 16. Olson, R. E.: Role of hormones in protein metabolism, J. A. M. A. 164: 1758, 1957. 17. Schwartz, W. B., and Relman, A. S.: Effects of electrolyte disorders on renal structure and function, N. Engl. J. Med. 276: 383, 1967. 18. Fitzgerald, M. G., and Fourman, P.: An experimental study of magnesium deficiency in man, Clin. Sci. 15: 635, 1956.