- Email: [email protected]
Parenteral magnesium load evaluation of malnourished Thai children
July, 1973 T h e J o u r n a l o/ P - E D I A T R I C S
129
II Parenteral magnesium load evaluation of malnourished Thai children Parenteral magnesium load tests were conducted to evaluate the magnesium status o/ 32 malnourished Northern Thai children. A 56 hour test was elaborated to study electrolyte and creatinine excretion be/ore and a/ter an intramuscular magnesium load o / 0 . 4 9 mEq. per kilogram. No diurnal excretion p a t t e r n / o r magnesium was/ound, and the magnesium rejected by the kidney was excreted within 16 hours. A 24 hour test with an 8 hour preload and a 16 hour postload collection period provided the same in/ormation as the longer trial, and hence 24 hour tests were conducted. The mean retention on admission was 57.67 per cent, unchanged on Day 7, and 17.15 per cent on Day 70. T h e magnesium load increased the urinary excretion o / c a l c i u m and sodium but not that o/ potassium, creatinine, or water. Low plasma magnesium values usually related to high magnesium retention, but some patients with high retention had normal plasm a values. Low magnesium content o / u r i n e on admission was not a use/ul guide to the magnesium status. High magnesium retention was related to severe antecedent gastroenteritis.
Joan L. Caddell, M.D.,'* Robert Suskind, M.D., Helen Sillup, R.N., and Robert E. Olson, M.D., Ph.D., C h i a n g M a i , T k a i l a n d
T~E PURPOSE of this study was to determine the magnesium status of 32 malnourished Northern Thai children by application of an abbreviated parenteral magnesium load test. Harris and WiIkinson 1 designed a 48 hour pediatric load test that required a From the Anemia and Malnutrition Research Center, Faculty, o/Medicine, Chiang Mai University, and the Departments of Pediatrics and Biochemistry; St. Louis Unive(sity School o/Medicine. Supported by the National Institute o[ Arthritis and Metabolic Diseases, National Institutes o/ Health, 5 F3-AM-39,696-O1 and 02 and 5 R22-AM-11044-05. "~'Reprint address: St. Louis University School oJ Medicine, 1402 S. Grand Blvd., St. Louis, Mo. 63104.
24 hour control urinary collection period, administration of a 10ad of 0.5 mEq. per kilogram of body weight intramuscularly, followed by a 24 hour postcollection period. They suggested that retention of more than 40 per cent of the load indicated magnesium depletion. In order to shorten the test period and thus accommodate ill children on a metabolic frame in our pediatric ward, studies were made 'of the diurnal excretion pattern of magnesium and the time required to excrete the parenteral load. The final test devised was a 24 hour magnesium load test consisting of an 8 hour control period and a 16 hour experimental period. A significant Vol. 83, No. 1, pp. 129-135
13 0
Caddell et al.
The Journal o[ Pediatrics July 1973
T a b l e I. M e a n plasma cation values (in mill•
I
Day 1
I
Day 2
per liter)
I Days 3-5
I Days 6-8
] Days 12-29 I
Day 84
Magnesium Mean S.D. N
1.634 -+0.243 32
1.755 -+0.331 32
1.651 -+0.294 27
1.619 -+0.223 18
1.653 -+0.174 18
1.656 -+0.150 20
4.0'38 -+0.438 32
3.759 -+0.464 32
3.977 -+0.533 27
3.796 -+0.5323 15
4.050 -+0.4055 17
4.791 -+0.555 20
2.569 -+0.958 32
3.376 +-0.9433 32
4.559 .+0.6848 27
4.228 .+0.5775 15
3.901 .+0.643 17
4.050 -+0.358 20
134.7 -+7.985 32
136.6 .+6.803 32,
136.8 -+5.875 27
139.7 -+8.815 13
137.7 -+4.595 17
139.6 -+5.546 20
Calcium Mean S.D. N
Potassium Mean S.D. N
Sodium Mean
S.D. N
T a b l e II. D a t a from 56 hour parenteral m a g n e s i u m load tests: 6 patients on Day 84
Urinary components
Period 1 (8 hr.)
Period 2 (8 hr.)
Magnesium 0.7155 1.094 (mEq. +- S.D.) - + 0 . 3 5 5 +0.720 mEq. magnesium/ 19.90 21.73 Gm. creatinine -+5.43 -+11.04 Calcium 0.639 0.812 (mEq. • S.D.) . + 0 . 7 7 3 +-0.859 mEq. calcium/ 16.80 15.03 Gm. creatinine -+16.81 -+13.34 Potassium 2.988 3.708 (mEq. -+ S.D.) - + I . 5 2 5 -+2.671 mEq. potassium/ 95.61 77.61 Gm. creatinine -+55.0 .+46.5 Sodium 15.14 20.65 (mEq. -+ S.D.) -+8.874 -+16.50 mEq. sodium/ 387.9 363.9 Gm. creatinine -+139.11 -+216.0 Creatinine 36.73 44.41 (mg. -+ S.D.) -+18.15 +31.49
Magnesium load 0.492 mEq./Kg. I.M. Period 3 Period 7 (8.819-+ 1.329 Period 4 Period 5 Period 6 (7.930-+0.237 hr.) ~(8 hr.) (8 hr.) (8 hr.) hr.) 1.390 -+0.741 21.83 -+5.36 1.603 -+2.045 19.48 +-16.14 7.472 +2.913 121.21 .+32.22 26.52 -+17.47 392.9 -+165.8 63.43 -+26.90
degree of m a g n e s i u m depletion in T h a i children with protein-calorie malnutrition ( P C M ) was found.
M A T E R I A L S AND M E T H O D S Patients. Thirty-two malnourished T h a i children studied between September, 1970, and June, 1971, constitute the m a i n group presented in this report. Two other children were studied only for 56 hours in October, 1971. Laboratory investigations. Investigations
4.308 1.478 1.229 +1.170 - + 0 . 8 1 8 -+0.709 91.66 36.80 21.70 +25.86 +17.47 .+4.55 1.979 1.413 1.566 -+1.140 - + 0 . 9 0 0 -+1.800 44.43 37.78 24.01 -+27.61 - + 2 4 . 5 4 -+20.90 4.560 2.626 6.267 -+1.702 +0.720 .+2.372 100.1 69.71 134.68 +27.07 . + 1 5 . 5 4 -+48.79 39.93 22.68 26.78 -+28.39 - + 1 0 . 2 3 -+18.56 779.1 566.7 467.3 -+373.0 - + 1 7 7 . 4 -+219.0 48.35 39.78 53.23 -+20.65 - + 1 4 . 6 4 -+21.97
1.153 -+0.572 22.88 +7.18 1.231 -+1.291 26.01 +20.17 4.288 -+1.152 87.96 .+17.0 39.16 -+15.31 874.9 -+527.8 50.55 -+17.64
pertinent to this report include serial plasma evaluation of magnesium, calcium, sodium, a n d potassium on admission, on Days 2, 3, and 4, at one or more intervals between Days 6 and 29, a n d on Days 50, 70, a n d 84. T h e 56 hour parenteral m a g n e s i u m load tests were carried out on 4 children on admission a n d on 6 children on Day 84, following repletion therapy. T h e 24 hour parenteral magnesium load tests were conducted on 30 children on Day 1, on 21 on Day 7, and on 19 on Day 70.
Volume 83 Number 1
Magnesium states in malnutrition
13 1
Table III. Data from 56 hour parenteral magnesium load tests: 4 patients on admission Magnesium load 0.492 mEq./Kg. I.M. Urinary components
Period 1 (8 hr.)
Magnesium (mEq. + S.D.) mEq. magnesium/ Gm. creatinine Calcium (mEq. -+ S.D.) mEq. calcium/ Gm. creatinine Sodiums (mEq..+ S.D.) mEq. sodium/ Gm. creatinine Potassium* (mEq. +- S.D.) mEq. potassium/ Gm. creatinine Creatinine (rag. +- S.D.)
"2--0.234 9.425 -+10.31 0.186 +0.172 9.175 +9.201 3.157 -+3.122 150.7 -+143.5 1.544 -+1.616 70.25 +-70'.09 15.87 +9.33
0.20'2
Period 2 (8 hr.)
Period 3 (8.7 .+1.0 hr.)
Period 4 (8 hr.)
0.178 -+0.096 9.075 -+7.447 0.106 -+0.068 4.675 -+4.524 9.531 -+3.811 372.0 +156.6 2.681 +-1.625 111.2 .+96.13 30.55 +-21.18
0.244 -+0.221 15.075
1.584 +0.832 89.80 -+69.66 0.316 -+0.202 19.77 -+12.46 5.951 .+1.333 334.5
-+17.32
0.047 +0.036 2.975 .+2.712 7.566 -+2.851 385.0 +-234.7
3.911 +-2.969 151.2 +-68.4 22.72 +-9.429
Period 5 (8 hr.)
Period 6 (8 hr.)
Period 7 (8.65 -+ 0.45 hr.)
0.994 0.407 0.225 -+0.556 +0.254 -+0.132 38.87 17.07 11.56 -+21.58 +I1.00 +-8.92 0.386 0.098 0.248 -+0.274 +0.144 .+0.159 14.52 7.475 13.12 .+9.414 .+8.456 -+12.86 7.360 9.677 3.294 -+4.663 -+8.827 +3.804 310.1 395.4 221.6 +-122.5 -+222.0 -+418.8 -+315.9 3.418 3.809 3.889 3.693 +2.595 +-1.751 +-2.325 +-0.733 145.0 153.2 169.0 181.8 +-54.6 .+70.6 -+144.0 +-106.8 20.17 38.85 20.15 24.22 +-8.78 +-21.58 +-16.43 -+7.803
"ZPatients receive intravenous sodium and potassium.
The 56 hour parenteral magnesium load tests. These studies were carried out on a metabolic frame. Blood was analyzed for plasma magnesium, calcium, potassium, and sodium. There were seven 8 hour urine collection periods, 3 before and 4 following a parenteral magnesium load. A load of 0.49 mEq. of magnesium per kilogram of body weight (0.12 c.c. of 50 per cent magnesium sulfate heptahydrate per kilogram) was given intramuscularly before the Period 4 collection was begun. Plasma magaaesium was determined one hour after the injection and at the end of the seventh collection period. The 7 collections of urine were analyzed for magnesium, calcium, sodium, potassium, and creatinine. The 24 hour parenteral magnesium load tests. The load test was divided into: (1) a control period of approximately 8 hours which ended as soon as the child voided, (2) an intramuscular magnesium l'oad of 0.49 mEq. per kilogram of body weight, (3) followed by a collection period of approximately 16 hours which ended when the patient voided. The percentage of the magnesium load retained was calculateci from the data
from the base period and the net excretion after the load. Blood was drawn for plasma cation evaluation only at the beginning of the test. Methods for analysis. The methods and standards reported in Part I were employed in this study. Study plan. During the first week, children were treated with necessary medications, fluids, and the same dietary regimen which increased from 1 Gin. of protein and 25 calories per kilogram on Day 2 to 1 Gin. of protein and 100 calories per kilogram on Day 7. During this period the diet provided 0.35 mEq. of magnesium per kilogram. The intramuscular magnesium loads on Days 1 and 7 were 0.49 mEq. per kilogram, while the supplemental intramuscular dose was 0.41 mEq. per kilogram given on Days 2 through 6. Because of a parallel study, the children received 1 of 4 study diets between Weeks 1 and 4; after that all received a repletion diet that provided 4 Gin. of protein, 175 calories, and 1.4 mEq. of dietary magnesium per kilogram of body weight per day. Therefore, all patients studied on Day 70 had received this repletion diet for at least 6
13 2
Caddell et al.
The Journal o[ Pediatrics ]uly 1973
Table IV. Data 24 hour parenteral magnesium load test
Day of study I
Preload collection time (hr.)
7O
Postload collection time (hr.)
10.11 -+2.140" (3o)f 8.388 -+0.609 (21) 9.956 -+3.652 (19)
Preload collection of magnesium (mEq.)
16.42 -+1.041 (30) 16.61 -+1.0'18 (21) 16.97 +1.768 (19)
0.248 -+0.198 (30) 0.515 • (21) 1.031 +0..609 (19)
Preload collection o[ magnesium corrgcted to postload time (mEq.)
0.405 +O.298 (3,0) 0.998 -+0.991 (21) 1.779 -+0.769 (19)
*Mean and standard deviation. tNumber in parentheses refers to number of patients making up the mean. ~When magnesium excretion exceeded the load, or when preload excretion exceeded postload excretion, negative values were
weeks. All children received a salt supplement that included adequate zinc, manganese, copper, fluoride, and iodine. RESULTS Clinical findings at the time of admission. There were 17 boys and 15 girls, with a mean age 25.62 _+ 10.95 months. The mean height was 72.61 • 6.66 cm. which is 83.41 _+ 4.89 per cent of the mean height of the anthropometric chart of the Children's Medical Center, Boston. The mean weight was 6.5 Kg. • 1.55, which is 56.94 per cent of the normal value for local Thai children and 51.97 • 8.35 per cent of the mean Boston standard. The children had been breast-fed for a mean period of 11.1 months and had been fed polished glutenous rice and small amounts of vegetables, meat, and milk. Seventeen children had had moderate to severe diarrhea intermittently for 10 days to several months, 15 had had mild or no diarrhea, and 8 had vomited intermittently for 5 days or more. The diagnoses were: kwashiorkor in 3, marasmus in 12, and marasmic kwashiorkor in 17. Mean plasma cation values are expressed in Table I.
The 56 hour parenteral magnesium load tests in treated children. Table I I presents the data on the excretion of 4 cations in the urine of 6 treated children on Day 84. The data, are expressed in terms of milliequivalents of cation per period and milliequivalents
of cation per gram of creatinine. Although the patients did not void at exactly the end of 8 hour collection periods 1, 2, and 4, 5, and 6, the variations in the actual collection timeg are reasonably well corrected by dividing the cation excreted by grams of creatinine. The control collection time was corrected to 24 hours and divided into equal A.M. and P.M. periods. The excretion of each cation during the 2 periods was not significantly different. The mean plasma magnesium value increased from 1.85 _+ 0.17 mEq. per liter to 2.68 _+ 0.36 mEq. per liter one hour after the magnesium load. It returned to 1.79 _+ 0.24 mEq. per liter at the end of Period 7, not significantly different from the beginning of the load test. Of the total 24 hour postload magnesium excretion, 64 + 10 per cent was excreted during the first 8 hours and 20 • 5 per cent, during the second 8 hours. Since the third 8 hour excretion value equalled the mean baseline excretion value, the magnesium rejected was totally excreted at the end of 16 hours. One can therefore use an 8 hour control period and a 16 hour excretion period for this test. When the 56 hour load test data were recalculated as for the 24 hour test, using only the 8 hour preload and the 16 hour postload collection values, no significant difference was found. The magnesium load increased the urinary
Volume 83 Number 1
Magnesium states in malnutrition
Magnesium load (mEq.)
Postload magnesium excretion (mEq.)
3.156 • (30) 3.195 • (21) 4.024 • (19)
1.744 • (30) 2.268 • (21) 5.109 • (19)
Postload magnesium excretion minus corrected preload magnesium excretion$ (mEq.)
Net magnesium retentions (mEq.)
1.360 • (30) 1.383 • (21) 3.329 • (19)
133
Per cent o[ magnesium load retainedS
1.821 • (30) 1.832 • (21) 0.677 • (19)
57.67 • (30) 54.59 • (21) 17.15 • (19)
assigned the number O.
excretion of calcium and sodium without a significant effect on potassium, creatinine, or water. Since the magnesium load did not affect creatinine excretion, the urinary creatinine can serve as a useful base for expressing changes in ion excretion. T h e 56 hour parenteral magnesium load tests in malnourished children. A study of 4 children admitted with moderate malnutrition revealed no diurnal variation of magnesium excretion, and the rejected fraction of the load was excreted within 16 hours. T h e design of the 24 hour test is therefore appropriate for malnourished as well as for treated children. The mean plasma magnesium value was not significantly different at the beginning and the end of the test (Table I I I ) . The 24 hour magnesium load tests. T h e 24 hour magnesium load tests revealed no significant difference in magnesium retention during the first week, even though the children received a total of 3.03 mEq. of magnesium per kilogram of body weight intramuscularly and 2.1 mEq. of magnesium per kilogram by mouth during that period. However, by D a y 70 the mean retention was 17.15 per cent, well within the reported limits of normal (Table IV, Fig. 1). The low preload magnesium excretion was not a helpful guide to the child's magnesium status. Seven of 25 children who excreted less than 1 mEq. per 24 hours had no evi-
PARENTALMAGNESIUMLOADTESTS
1|
i
" |
80
I
i
m
+,+,
i
"
: ..
4o
.
!
\
9
1
|
7
Daily I.M.-Mg.
9
70
DAY OF STUDY
Fig. l. Per cent retention of intramuscular magnesium loads given on Days 1, 7, 70, and 84. Each point represents the retention by a single child. The accepted upper limit of normal for children is 40 per cent, represented by a broken line (@ refers to reference in text). dence of magnesium deficiency, and they retained a mean of only 23.3 per cent of the magnesium load. No significant correlation was found between magnesium retention and the presence or absence of edema, but a significant correlation was found between retention of the
13 4
Caddell et al.
initial magnesium load and the severity of recent diarrhea. Fifteen children with no or mild diarrhea retained 26.98 _+ 23.53 per cent, whereas 15 with more severe diarrhea retained 73.01 _+ 19.8 per cent of the magnesium load. The lowest plasma magnesium values could be related to the highest magnesium retention on admission, but the reverse was not true: Children with high retention of magnesium sometimes had normal plasma magnesium values. Therefore, only low plasma magnesium was a helpful guide to the magnesium status. DISCUSSION
Plasma magnesium values. The patients in this series, admitted after the peak of the malnutrition (rainy) season, had relatively mild hypomagnesemia. Significant changes developed in 5 patients who had severe antecedent diarrhea and who were fed the highprotein, high-calorie diet. Evaluation of the magnesium load test. Pretoad or control magnesium excretion. The control magnesium excretion in patients with PCM on admission was usually significantly low, less than 1 mEq. per 24 hours. Since any individual with good renal function will sharply curtail his renal output of magnesium to that low value when magnesium intake is reduced, 2 reduced output might reflect magnesium depletion or avid renal conservation secondary to reduced dietary intake or reduced intestinal absorption. The magnesium load distinguished between these alternatives. Failure to demonstrate a diurnal pattern of magnesium and calcium might be explained by the elimination of two variables that influence the renal handling of these ions. Ingestion of food, which increases excretion, ~ was distributed over 5 or 6 equal feedings per 24 hours. Exercise, which decreases excretion, 4 was curtailed during metabolic studies. A test dose of 0.5 mEq. of magnesium per kilogram of body weight is safe. The dose should be given intramuscularly or slowly
The Journal o[ Pediatrics July 1973
intravenously I because of the uncertain intestinal absorption of magnesium in PCM. 5 Sixteen hours was found to be an adequate postload collection period for both malnourished and treated children. Excretion of other urinary components. Increased calcium excretion following a magnesium load has previously been reported5 The excretion of neither sodium nor potassium is influenced by exercise or ingestion of food? An increased excretion of sodium following a magnesium load was seen in normal individuals in one study, ~ but only in men experimentally deprived of magnesium in another studyY No significant changes in urine volume were found in treated children. In a study of guinea pigs, magnesium sulfate had no effect on the urine volume of control animals, but the urine volume of magnesiumdeficient animals doubled following magnesium therapy. 8 Results of the 24 hour magnesium load tests. The initial elevation of the percentage of magnesium retention and the normal values by Day 70 correspond with the findings of Pretorius and associater who noted a retention of 60 per cent of parenteral magnesium on about Day 6 and of 33 per cent on about Day 21. Conclusions. The parenteral magnesium load test is a direct and useful means for assessing the magnesium status of the malnourished child. The modification with an 8 hour preload collection and a 16 hour postload collection is justified. We gratefully acknowledge the help of Dr. Ousa Thanangkul, who referred the patients from the Malnutrition Clinic, Chiang Mai General Hospital. REFERENCES
1. Harris, I., and Wilkinson, A. W.: Magnesium depletion in children, Lancet 2: 735, 1971. 2. Keynes, W. M., Barnes, 13. A., and Cope, O.: Urinary excretion of calcium and magnesium ir~ man using a diet with a very low content of these minerals, Proc. R. Soc. Med. 64: 152, 1971. 3. Heaton, F. W., and Hodgkinson, A.: External factors affecting diurnal variation in electrolyte excretion with particular reference to
Volume 83 Number 1
calcium and magnesium, Clin. Chim. Acta 8: 246, 1963. 4. Fiorica, V., Burr, M. J., and Moses, R.: Contribution of activity to the circadian rhythm in excretion of magnesium and calcium, Aerospace Med. 39: 714, 1968. 5. 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.
M a g n e s i u m states in malnutrition
135
6. Barker, E. S., Elkinton, J. R., and Clark, J. K.: Studies of the renal excretion of magnesium in man, J. Clin. Invest. 38: t733, 1959. 7. Fitzgerald, M. G., and Fourman, P.: An experimental study of magnesium deficiency in man, Clin. Sci. 15: 635, 1956. 8. Morris, E. R., and O'Dell, B. L.: Effect of magnesium deficiency in guinea pigs on kidney function and plasma ultrafiltrable ions, Proc. Soc. Exp. Biol. Med. 132: 105, 1969.
129
II Parenteral magnesium load evaluation of malnourished Thai children Parenteral magnesium load tests were conducted to evaluate the magnesium status o/ 32 malnourished Northern Thai children. A 56 hour test was elaborated to study electrolyte and creatinine excretion be/ore and a/ter an intramuscular magnesium load o / 0 . 4 9 mEq. per kilogram. No diurnal excretion p a t t e r n / o r magnesium was/ound, and the magnesium rejected by the kidney was excreted within 16 hours. A 24 hour test with an 8 hour preload and a 16 hour postload collection period provided the same in/ormation as the longer trial, and hence 24 hour tests were conducted. The mean retention on admission was 57.67 per cent, unchanged on Day 7, and 17.15 per cent on Day 70. T h e magnesium load increased the urinary excretion o / c a l c i u m and sodium but not that o/ potassium, creatinine, or water. Low plasma magnesium values usually related to high magnesium retention, but some patients with high retention had normal plasm a values. Low magnesium content o / u r i n e on admission was not a use/ul guide to the magnesium status. High magnesium retention was related to severe antecedent gastroenteritis.
Joan L. Caddell, M.D.,'* Robert Suskind, M.D., Helen Sillup, R.N., and Robert E. Olson, M.D., Ph.D., C h i a n g M a i , T k a i l a n d
T~E PURPOSE of this study was to determine the magnesium status of 32 malnourished Northern Thai children by application of an abbreviated parenteral magnesium load test. Harris and WiIkinson 1 designed a 48 hour pediatric load test that required a From the Anemia and Malnutrition Research Center, Faculty, o/Medicine, Chiang Mai University, and the Departments of Pediatrics and Biochemistry; St. Louis Unive(sity School o/Medicine. Supported by the National Institute o[ Arthritis and Metabolic Diseases, National Institutes o/ Health, 5 F3-AM-39,696-O1 and 02 and 5 R22-AM-11044-05. "~'Reprint address: St. Louis University School oJ Medicine, 1402 S. Grand Blvd., St. Louis, Mo. 63104.
24 hour control urinary collection period, administration of a 10ad of 0.5 mEq. per kilogram of body weight intramuscularly, followed by a 24 hour postcollection period. They suggested that retention of more than 40 per cent of the load indicated magnesium depletion. In order to shorten the test period and thus accommodate ill children on a metabolic frame in our pediatric ward, studies were made 'of the diurnal excretion pattern of magnesium and the time required to excrete the parenteral load. The final test devised was a 24 hour magnesium load test consisting of an 8 hour control period and a 16 hour experimental period. A significant Vol. 83, No. 1, pp. 129-135
13 0
Caddell et al.
The Journal o[ Pediatrics July 1973
T a b l e I. M e a n plasma cation values (in mill•
I
Day 1
I
Day 2
per liter)
I Days 3-5
I Days 6-8
] Days 12-29 I
Day 84
Magnesium Mean S.D. N
1.634 -+0.243 32
1.755 -+0.331 32
1.651 -+0.294 27
1.619 -+0.223 18
1.653 -+0.174 18
1.656 -+0.150 20
4.0'38 -+0.438 32
3.759 -+0.464 32
3.977 -+0.533 27
3.796 -+0.5323 15
4.050 -+0.4055 17
4.791 -+0.555 20
2.569 -+0.958 32
3.376 +-0.9433 32
4.559 .+0.6848 27
4.228 .+0.5775 15
3.901 .+0.643 17
4.050 -+0.358 20
134.7 -+7.985 32
136.6 .+6.803 32,
136.8 -+5.875 27
139.7 -+8.815 13
137.7 -+4.595 17
139.6 -+5.546 20
Calcium Mean S.D. N
Potassium Mean S.D. N
Sodium Mean
S.D. N
T a b l e II. D a t a from 56 hour parenteral m a g n e s i u m load tests: 6 patients on Day 84
Urinary components
Period 1 (8 hr.)
Period 2 (8 hr.)
Magnesium 0.7155 1.094 (mEq. +- S.D.) - + 0 . 3 5 5 +0.720 mEq. magnesium/ 19.90 21.73 Gm. creatinine -+5.43 -+11.04 Calcium 0.639 0.812 (mEq. • S.D.) . + 0 . 7 7 3 +-0.859 mEq. calcium/ 16.80 15.03 Gm. creatinine -+16.81 -+13.34 Potassium 2.988 3.708 (mEq. -+ S.D.) - + I . 5 2 5 -+2.671 mEq. potassium/ 95.61 77.61 Gm. creatinine -+55.0 .+46.5 Sodium 15.14 20.65 (mEq. -+ S.D.) -+8.874 -+16.50 mEq. sodium/ 387.9 363.9 Gm. creatinine -+139.11 -+216.0 Creatinine 36.73 44.41 (mg. -+ S.D.) -+18.15 +31.49
Magnesium load 0.492 mEq./Kg. I.M. Period 3 Period 7 (8.819-+ 1.329 Period 4 Period 5 Period 6 (7.930-+0.237 hr.) ~(8 hr.) (8 hr.) (8 hr.) hr.) 1.390 -+0.741 21.83 -+5.36 1.603 -+2.045 19.48 +-16.14 7.472 +2.913 121.21 .+32.22 26.52 -+17.47 392.9 -+165.8 63.43 -+26.90
degree of m a g n e s i u m depletion in T h a i children with protein-calorie malnutrition ( P C M ) was found.
M A T E R I A L S AND M E T H O D S Patients. Thirty-two malnourished T h a i children studied between September, 1970, and June, 1971, constitute the m a i n group presented in this report. Two other children were studied only for 56 hours in October, 1971. Laboratory investigations. Investigations
4.308 1.478 1.229 +1.170 - + 0 . 8 1 8 -+0.709 91.66 36.80 21.70 +25.86 +17.47 .+4.55 1.979 1.413 1.566 -+1.140 - + 0 . 9 0 0 -+1.800 44.43 37.78 24.01 -+27.61 - + 2 4 . 5 4 -+20.90 4.560 2.626 6.267 -+1.702 +0.720 .+2.372 100.1 69.71 134.68 +27.07 . + 1 5 . 5 4 -+48.79 39.93 22.68 26.78 -+28.39 - + 1 0 . 2 3 -+18.56 779.1 566.7 467.3 -+373.0 - + 1 7 7 . 4 -+219.0 48.35 39.78 53.23 -+20.65 - + 1 4 . 6 4 -+21.97
1.153 -+0.572 22.88 +7.18 1.231 -+1.291 26.01 +20.17 4.288 -+1.152 87.96 .+17.0 39.16 -+15.31 874.9 -+527.8 50.55 -+17.64
pertinent to this report include serial plasma evaluation of magnesium, calcium, sodium, a n d potassium on admission, on Days 2, 3, and 4, at one or more intervals between Days 6 and 29, a n d on Days 50, 70, a n d 84. T h e 56 hour parenteral m a g n e s i u m load tests were carried out on 4 children on admission a n d on 6 children on Day 84, following repletion therapy. T h e 24 hour parenteral magnesium load tests were conducted on 30 children on Day 1, on 21 on Day 7, and on 19 on Day 70.
Volume 83 Number 1
Magnesium states in malnutrition
13 1
Table III. Data from 56 hour parenteral magnesium load tests: 4 patients on admission Magnesium load 0.492 mEq./Kg. I.M. Urinary components
Period 1 (8 hr.)
Magnesium (mEq. + S.D.) mEq. magnesium/ Gm. creatinine Calcium (mEq. -+ S.D.) mEq. calcium/ Gm. creatinine Sodiums (mEq..+ S.D.) mEq. sodium/ Gm. creatinine Potassium* (mEq. +- S.D.) mEq. potassium/ Gm. creatinine Creatinine (rag. +- S.D.)
"2--0.234 9.425 -+10.31 0.186 +0.172 9.175 +9.201 3.157 -+3.122 150.7 -+143.5 1.544 -+1.616 70.25 +-70'.09 15.87 +9.33
0.20'2
Period 2 (8 hr.)
Period 3 (8.7 .+1.0 hr.)
Period 4 (8 hr.)
0.178 -+0.096 9.075 -+7.447 0.106 -+0.068 4.675 -+4.524 9.531 -+3.811 372.0 +156.6 2.681 +-1.625 111.2 .+96.13 30.55 +-21.18
0.244 -+0.221 15.075
1.584 +0.832 89.80 -+69.66 0.316 -+0.202 19.77 -+12.46 5.951 .+1.333 334.5
-+17.32
0.047 +0.036 2.975 .+2.712 7.566 -+2.851 385.0 +-234.7
3.911 +-2.969 151.2 +-68.4 22.72 +-9.429
Period 5 (8 hr.)
Period 6 (8 hr.)
Period 7 (8.65 -+ 0.45 hr.)
0.994 0.407 0.225 -+0.556 +0.254 -+0.132 38.87 17.07 11.56 -+21.58 +I1.00 +-8.92 0.386 0.098 0.248 -+0.274 +0.144 .+0.159 14.52 7.475 13.12 .+9.414 .+8.456 -+12.86 7.360 9.677 3.294 -+4.663 -+8.827 +3.804 310.1 395.4 221.6 +-122.5 -+222.0 -+418.8 -+315.9 3.418 3.809 3.889 3.693 +2.595 +-1.751 +-2.325 +-0.733 145.0 153.2 169.0 181.8 +-54.6 .+70.6 -+144.0 +-106.8 20.17 38.85 20.15 24.22 +-8.78 +-21.58 +-16.43 -+7.803
"ZPatients receive intravenous sodium and potassium.
The 56 hour parenteral magnesium load tests. These studies were carried out on a metabolic frame. Blood was analyzed for plasma magnesium, calcium, potassium, and sodium. There were seven 8 hour urine collection periods, 3 before and 4 following a parenteral magnesium load. A load of 0.49 mEq. of magnesium per kilogram of body weight (0.12 c.c. of 50 per cent magnesium sulfate heptahydrate per kilogram) was given intramuscularly before the Period 4 collection was begun. Plasma magaaesium was determined one hour after the injection and at the end of the seventh collection period. The 7 collections of urine were analyzed for magnesium, calcium, sodium, potassium, and creatinine. The 24 hour parenteral magnesium load tests. The load test was divided into: (1) a control period of approximately 8 hours which ended as soon as the child voided, (2) an intramuscular magnesium l'oad of 0.49 mEq. per kilogram of body weight, (3) followed by a collection period of approximately 16 hours which ended when the patient voided. The percentage of the magnesium load retained was calculateci from the data
from the base period and the net excretion after the load. Blood was drawn for plasma cation evaluation only at the beginning of the test. Methods for analysis. The methods and standards reported in Part I were employed in this study. Study plan. During the first week, children were treated with necessary medications, fluids, and the same dietary regimen which increased from 1 Gin. of protein and 25 calories per kilogram on Day 2 to 1 Gin. of protein and 100 calories per kilogram on Day 7. During this period the diet provided 0.35 mEq. of magnesium per kilogram. The intramuscular magnesium loads on Days 1 and 7 were 0.49 mEq. per kilogram, while the supplemental intramuscular dose was 0.41 mEq. per kilogram given on Days 2 through 6. Because of a parallel study, the children received 1 of 4 study diets between Weeks 1 and 4; after that all received a repletion diet that provided 4 Gin. of protein, 175 calories, and 1.4 mEq. of dietary magnesium per kilogram of body weight per day. Therefore, all patients studied on Day 70 had received this repletion diet for at least 6
13 2
Caddell et al.
The Journal o[ Pediatrics ]uly 1973
Table IV. Data 24 hour parenteral magnesium load test
Day of study I
Preload collection time (hr.)
7O
Postload collection time (hr.)
10.11 -+2.140" (3o)f 8.388 -+0.609 (21) 9.956 -+3.652 (19)
Preload collection of magnesium (mEq.)
16.42 -+1.041 (30) 16.61 -+1.0'18 (21) 16.97 +1.768 (19)
0.248 -+0.198 (30) 0.515 • (21) 1.031 +0..609 (19)
Preload collection o[ magnesium corrgcted to postload time (mEq.)
0.405 +O.298 (3,0) 0.998 -+0.991 (21) 1.779 -+0.769 (19)
*Mean and standard deviation. tNumber in parentheses refers to number of patients making up the mean. ~When magnesium excretion exceeded the load, or when preload excretion exceeded postload excretion, negative values were
weeks. All children received a salt supplement that included adequate zinc, manganese, copper, fluoride, and iodine. RESULTS Clinical findings at the time of admission. There were 17 boys and 15 girls, with a mean age 25.62 _+ 10.95 months. The mean height was 72.61 • 6.66 cm. which is 83.41 _+ 4.89 per cent of the mean height of the anthropometric chart of the Children's Medical Center, Boston. The mean weight was 6.5 Kg. • 1.55, which is 56.94 per cent of the normal value for local Thai children and 51.97 • 8.35 per cent of the mean Boston standard. The children had been breast-fed for a mean period of 11.1 months and had been fed polished glutenous rice and small amounts of vegetables, meat, and milk. Seventeen children had had moderate to severe diarrhea intermittently for 10 days to several months, 15 had had mild or no diarrhea, and 8 had vomited intermittently for 5 days or more. The diagnoses were: kwashiorkor in 3, marasmus in 12, and marasmic kwashiorkor in 17. Mean plasma cation values are expressed in Table I.
The 56 hour parenteral magnesium load tests in treated children. Table I I presents the data on the excretion of 4 cations in the urine of 6 treated children on Day 84. The data, are expressed in terms of milliequivalents of cation per period and milliequivalents
of cation per gram of creatinine. Although the patients did not void at exactly the end of 8 hour collection periods 1, 2, and 4, 5, and 6, the variations in the actual collection timeg are reasonably well corrected by dividing the cation excreted by grams of creatinine. The control collection time was corrected to 24 hours and divided into equal A.M. and P.M. periods. The excretion of each cation during the 2 periods was not significantly different. The mean plasma magnesium value increased from 1.85 _+ 0.17 mEq. per liter to 2.68 _+ 0.36 mEq. per liter one hour after the magnesium load. It returned to 1.79 _+ 0.24 mEq. per liter at the end of Period 7, not significantly different from the beginning of the load test. Of the total 24 hour postload magnesium excretion, 64 + 10 per cent was excreted during the first 8 hours and 20 • 5 per cent, during the second 8 hours. Since the third 8 hour excretion value equalled the mean baseline excretion value, the magnesium rejected was totally excreted at the end of 16 hours. One can therefore use an 8 hour control period and a 16 hour excretion period for this test. When the 56 hour load test data were recalculated as for the 24 hour test, using only the 8 hour preload and the 16 hour postload collection values, no significant difference was found. The magnesium load increased the urinary
Volume 83 Number 1
Magnesium states in malnutrition
Magnesium load (mEq.)
Postload magnesium excretion (mEq.)
3.156 • (30) 3.195 • (21) 4.024 • (19)
1.744 • (30) 2.268 • (21) 5.109 • (19)
Postload magnesium excretion minus corrected preload magnesium excretion$ (mEq.)
Net magnesium retentions (mEq.)
1.360 • (30) 1.383 • (21) 3.329 • (19)
133
Per cent o[ magnesium load retainedS
1.821 • (30) 1.832 • (21) 0.677 • (19)
57.67 • (30) 54.59 • (21) 17.15 • (19)
assigned the number O.
excretion of calcium and sodium without a significant effect on potassium, creatinine, or water. Since the magnesium load did not affect creatinine excretion, the urinary creatinine can serve as a useful base for expressing changes in ion excretion. T h e 56 hour parenteral magnesium load tests in malnourished children. A study of 4 children admitted with moderate malnutrition revealed no diurnal variation of magnesium excretion, and the rejected fraction of the load was excreted within 16 hours. T h e design of the 24 hour test is therefore appropriate for malnourished as well as for treated children. The mean plasma magnesium value was not significantly different at the beginning and the end of the test (Table I I I ) . The 24 hour magnesium load tests. T h e 24 hour magnesium load tests revealed no significant difference in magnesium retention during the first week, even though the children received a total of 3.03 mEq. of magnesium per kilogram of body weight intramuscularly and 2.1 mEq. of magnesium per kilogram by mouth during that period. However, by D a y 70 the mean retention was 17.15 per cent, well within the reported limits of normal (Table IV, Fig. 1). The low preload magnesium excretion was not a helpful guide to the child's magnesium status. Seven of 25 children who excreted less than 1 mEq. per 24 hours had no evi-
PARENTALMAGNESIUMLOADTESTS
1|
i
" |
80
I
i
m
+,+,
i
"
: ..
4o
.
!
\
9
1
|
7
Daily I.M.-Mg.
9
70
DAY OF STUDY
Fig. l. Per cent retention of intramuscular magnesium loads given on Days 1, 7, 70, and 84. Each point represents the retention by a single child. The accepted upper limit of normal for children is 40 per cent, represented by a broken line (@ refers to reference in text). dence of magnesium deficiency, and they retained a mean of only 23.3 per cent of the magnesium load. No significant correlation was found between magnesium retention and the presence or absence of edema, but a significant correlation was found between retention of the
13 4
Caddell et al.
initial magnesium load and the severity of recent diarrhea. Fifteen children with no or mild diarrhea retained 26.98 _+ 23.53 per cent, whereas 15 with more severe diarrhea retained 73.01 _+ 19.8 per cent of the magnesium load. The lowest plasma magnesium values could be related to the highest magnesium retention on admission, but the reverse was not true: Children with high retention of magnesium sometimes had normal plasma magnesium values. Therefore, only low plasma magnesium was a helpful guide to the magnesium status. DISCUSSION
Plasma magnesium values. The patients in this series, admitted after the peak of the malnutrition (rainy) season, had relatively mild hypomagnesemia. Significant changes developed in 5 patients who had severe antecedent diarrhea and who were fed the highprotein, high-calorie diet. Evaluation of the magnesium load test. Pretoad or control magnesium excretion. The control magnesium excretion in patients with PCM on admission was usually significantly low, less than 1 mEq. per 24 hours. Since any individual with good renal function will sharply curtail his renal output of magnesium to that low value when magnesium intake is reduced, 2 reduced output might reflect magnesium depletion or avid renal conservation secondary to reduced dietary intake or reduced intestinal absorption. The magnesium load distinguished between these alternatives. Failure to demonstrate a diurnal pattern of magnesium and calcium might be explained by the elimination of two variables that influence the renal handling of these ions. Ingestion of food, which increases excretion, ~ was distributed over 5 or 6 equal feedings per 24 hours. Exercise, which decreases excretion, 4 was curtailed during metabolic studies. A test dose of 0.5 mEq. of magnesium per kilogram of body weight is safe. The dose should be given intramuscularly or slowly
The Journal o[ Pediatrics July 1973
intravenously I because of the uncertain intestinal absorption of magnesium in PCM. 5 Sixteen hours was found to be an adequate postload collection period for both malnourished and treated children. Excretion of other urinary components. Increased calcium excretion following a magnesium load has previously been reported5 The excretion of neither sodium nor potassium is influenced by exercise or ingestion of food? An increased excretion of sodium following a magnesium load was seen in normal individuals in one study, ~ but only in men experimentally deprived of magnesium in another studyY No significant changes in urine volume were found in treated children. In a study of guinea pigs, magnesium sulfate had no effect on the urine volume of control animals, but the urine volume of magnesiumdeficient animals doubled following magnesium therapy. 8 Results of the 24 hour magnesium load tests. The initial elevation of the percentage of magnesium retention and the normal values by Day 70 correspond with the findings of Pretorius and associater who noted a retention of 60 per cent of parenteral magnesium on about Day 6 and of 33 per cent on about Day 21. Conclusions. The parenteral magnesium load test is a direct and useful means for assessing the magnesium status of the malnourished child. The modification with an 8 hour preload collection and a 16 hour postload collection is justified. We gratefully acknowledge the help of Dr. Ousa Thanangkul, who referred the patients from the Malnutrition Clinic, Chiang Mai General Hospital. REFERENCES
1. Harris, I., and Wilkinson, A. W.: Magnesium depletion in children, Lancet 2: 735, 1971. 2. Keynes, W. M., Barnes, 13. A., and Cope, O.: Urinary excretion of calcium and magnesium ir~ man using a diet with a very low content of these minerals, Proc. R. Soc. Med. 64: 152, 1971. 3. Heaton, F. W., and Hodgkinson, A.: External factors affecting diurnal variation in electrolyte excretion with particular reference to
Volume 83 Number 1
calcium and magnesium, Clin. Chim. Acta 8: 246, 1963. 4. Fiorica, V., Burr, M. J., and Moses, R.: Contribution of activity to the circadian rhythm in excretion of magnesium and calcium, Aerospace Med. 39: 714, 1968. 5. 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.
M a g n e s i u m states in malnutrition
135
6. Barker, E. S., Elkinton, J. R., and Clark, J. K.: Studies of the renal excretion of magnesium in man, J. Clin. Invest. 38: t733, 1959. 7. Fitzgerald, M. G., and Fourman, P.: An experimental study of magnesium deficiency in man, Clin. Sci. 15: 635, 1956. 8. Morris, E. R., and O'Dell, B. L.: Effect of magnesium deficiency in guinea pigs on kidney function and plasma ultrafiltrable ions, Proc. Soc. Exp. Biol. Med. 132: 105, 1969.