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On the role of magnesium depletion in severely malnourished children
Volume 84 Number 5
Letters to the Editor
Between March 1 and November 30, 1969, 100 infants and children were admitted to our service with acute pneumonia. Lung puncture-aspiration was performed in 31 of these patients. 3 One infant, 8 months of age, with lobar pneumonia had H. influenzae, type b, in the lung-puncture specimen, laryngeal specimen, and blood culture. In two children of 20 months and 3 years of age with interstitial pneumonia, H. influenzae was identified in direct smear; in one of these it was also present in the lung aspirate culture. Hugo Trujillo, M.D. Diana G. de Olarte, M.D. Department o f Pediatrics and Infectious Disease Service University o f Antioquia Apartado aereo No. 1226 Medellin, Colombia, South America REFERENCES
1. Honig, P. J., Pasquariello, P. S., Jr., and Stool, S. E.: H. influenzae pneumonia in infants and children, J. PEDIATR. 83: 215, 1973. 2. Mimica, I., Donoso, E., Howard, J. E., and Lederman, G. W.: Lung puncture in the etiological diagnosis of pneumonia, Am. J. Dis. Child. 122: 278, 1971. 3. Garcia, de, O. D., Trujillo, S. H., Uribe, P. A., and Agudelo, O. N.: Lung puncture-aspiration as a bacteriologic diagnostic procedure in acute pneumonias of infants and children, Clin. Pediatr. 10: 346, 1971.
On the role of magnesium depletion in severely malnourished children To the Editor: Kingston 1 deserves great credit for his work in Liberia in reducing the mortality in severe kwashiorkor from 100 per cent to 15 per cent. I should like to comment on several points he made in his report. He said that magnesium depletion has been considered to be the most important electrolyte disturbance in Nigeria (referring to Caddell and Goddard2), but not elsewhere (referring to Garrow and associates3). Caddell and Goddard selected only seriously ill children with histories of chronic, severe gastroenteritis and reported very low plasma values of magnesium, sodium, potassium, chloride, bicarbonate, total serum protein, and serum albumin, and emphasized, "This study in no way suggests that magnesium is of any greater importance than potassium or any other ion known to be essential to myocardial metabolism" (p. 539). Garrow and associates 3 reviewed the major published work on potassium and magnesium m e t a b o l i s m in m a l n o u r i s h e d c h i l d r e n and c o n c l u d e d "malnourished children are usually magnesium deficient" and "it is sensible to give additional magnesium, as well as potassium, routinely to all severely malnourished children." The degree of concomitant gastroenteritis largely dictates the extent of depletion of these ions; not every malnourished child will have serious depletion of potassium or magnesium. 3'4 Dr. Kingston attributed to hypokalemia alone a list of initial
781
nonspecific changes that included apathy, reduced motor ability, weakness, hypotonia, and electrocardiograph changes such as ST depression, fiat T waves, and "supraventricular tachyarrhythmias." However, other known problems in these patients might well have contributed to their symptoms. These included insufficient protein and calories; dehydration; alkalosis; hyponatremia; hypomagnesemia; systemic effects of known bacterial infection, malaria, and helminthiasis; and possibly anemia and vitamin B deficiencies (not stated). The patients were fed a formula which consisted of calcium caseinate, sugar, cottonseed oil, and added sodium, potassium, and magnesium salts. This formula provided practically no vitamins and trace minerals, including iron, and there was no other source of vitamins or trace minerals mentioned in the report. Malaria and helminthic infestations have been found to increase the severity of anemia usually found in kwashiorkorS; iron-deficient anemia might be anticipated in patients who had been fed a diet of rice, cassava, and breast milk. Dr. Kingston concluded that the malnourished child with hypokalemia requires less potassium (presumably on a weight basis) than the normally nourished child with hypokalemia, and that this had important implications for treatment. The plasma values of the two major intracellular cations, potassium and magnesium, do not accurately reflect the total body stores)' 4 They must be considered together, since potassium is constantly associated with magnesium in muscle in the proportion of 5.67 to 1, and depletion of either has an effect on the content of the other. 6 Whether or not a malnourished child 24 or animal 7 is initially depleted of these ions, he will require large amounts of both to maintain normal composition of the new tissue being made during the accelerated growth period that occurs during recovery. The need for potassium during this period has been well established after many years of extensive research. 3 More recently, it has been shown that failure to provide sufficient magnesium as well as potassium during recovery from malnutrition will result in profound clinical disturbances in the young growing child2, 4, 5 or animal. 7 Joan Caddell Department o f Pediatrics School o f Medicine St. Louis University 1402 S. Grand Blvd. St. Louis, Mo. 63104 REFERENCES
1.
Kingston, M.: Electrolyte disturbances in Liberian children with kwashiorkor, J. PEDIAT~. 83: 859, 1973. 2. Caddell, J. L., and Goddard, D. R.: Studies in protein calorie malnutrition, N. Engl. J: Med. 276: 533, 535, 1967. 3. Garrow, J. S., Smith, R., and Ward, E. E.: Electrolyte metabolism in severe infantile malnutrition, Oxford, 1968, Pergamon Press, Inc., pp. 62, 77, 83, 87. 4. Caddell, J. L., and Olson, R. E.: An evaluation of the electrolyte status of malnourished Thai children, J. PEDIATR.83: 124, 129, 1973. 5. Allen, D. M., and Dean, R. F. A.: The anaemia of kwashiorkor in Uganda, Trans. R. Soc. Trop. Med. Hyg. 59: 326, 1965. 6. Baldwin, D., Robinson, P. K., Zierler, K. L., and Lilienthal,
782
Letters to the Editor
J. L., Jr.: Interrelations of magnesium, potassium, phosphorous, and creatine in skeletal muscle of man, J. Clin. Invest. 31: 850, 1952. 7. Caddell, J. L., and Olson, R. E.: Effect of dietary protein and magnesium on selected ATP phosphotransferases and neuromuscular behavior in young rats, J. Nutr. 103: 1385, 1973.
Repty To the Editor: In the paper 1 referred to above it was not written that magnesium depletion did not occur in areas other than Nigeria but that it was considered to be the most important disturbance there. Apart from the single reference to hypokalemia, which referred to myocardial metabolism, quoted above, the content of the papers by Caddell and Goddard 2 referred almost exclusively to magnesium depletion and its importance in malnourished children. This was surprising because hypokalemia was a more severe aberration than hypomagnesemia. It should be noted that the lower limit or normal for magnesium (1.4 mEq. per liter) quoted in their paper is probably abnormally high because magnesium is partly bound to albumin, which is low in malnourished children. It has not been satisfactorily established that magnesium depletion "usually" occurs in malnourished children: it is invalid to generalize from data--in itself inconclusive--from a few geographic areas. Vis and associates, 3 for example, did not find that depletion was common in the Congo. Although diarrhea is the route of abnormal losses of potassium and magnesium in malnourished children, their dietary intake of these ions, which varies considerably in different geographic areas, probably determines whether depletion of these ions will occur. Evidence that the manifestations quoted in my paper were due to hypokalemia was based on their resolution in association with potassium but not magnesium infusion; a more detailed analysis is to be the subject of a further paper on hypokalemia. The electrocardiograph changes quoted were not nonspecific but were typical of hypokalemia. There is no good evidence that these changes result from the conditions specified by Dr. Caddell, with the possible exception of hypomagnesemia. I emphasized that apathy, weakness, and hypotonia were also characteristic of kwashiorkor. I am aware that the formula given to the subjects and foods previously ingested by them were deficient in iron, folic acid, and vitamins; supplements of these were given routinely to all hospitalized children. I concluded that the malnourished children with hypokalemia required considerably less potassium repletion than hypokalemic children of normal nutrition relative to age--not weight. The following example illustrates the importance and implications of this: the potassium capacity of two 18-month-old children, one severely malnourished (weight 5 kilograms), the other of normal nutrition (weight 12 kilograms) is likely to be approximately 150 mEq. (30 mEq. per kilograms • 5) and 540 mEq. (45 mEq. per kilograms • 12), respectively. If both
The Journal of Pediatrics May 1974
children have a 20 per cent decrease in their total body potassium, perhaps reflecting a serum potassium of 2.2 mEq. per liter, they will require 30 and 108 mEq. of potassium, respectively, for correction of their deficit--an amount of potassium contained in one liter of Darrows solution or 750 ml. of fullstrength cow's milk in the former case. Sufficient potassium and magnesium, the main intracellular cations, are obviously required for growth but in considerably less amounts than that required for repletion of a deficit. Hyperkalemia may result when children are fed large oral supplements of potassium (Allenye and associates,4 Darrow, 5 and personal observations). Alleyne and associates4 stated that it is only in the very severely depleted children with total body potassium below 30 mEq. per kilograms that high doses of potassium supplements should be given; and that high oral doses (6 to 8 mEq. per kilograms per day) of potassium supplement may lead to hyperkalemia. There is no satisfactory evidence that the serum potassium correctly interpreted fails to reflect potassium depletion either in the reference cited by Caddell or elsewhere. Several authors have based their conclusions on the inaccuracy of the serum K as a guide .to potassium status on inadequate evidence of potassium depletion. 1Scribner and Burnell 6 have stated: "the review just completed supports the view that the serum potassium concentration, properly interpreted, reflects with a high degree of accuracy the potassium needs of patients because it reflects K R, the relation between the total body potassium and potassium capacity." Finally the data of Caddell and Olson is insufficient to justify their conclusion that the serum magnesium concentration fails to reflect magnesium depletion: individual results of retention of magnesium, serum concentrations of magnesium before and after magnesium repletion, the subjects weight, and serum albumin should be analyzed to justify this conclusion. Michael E. Kingston, M.R.C.P., D.T.M.H., D.A. Calgary General Hospital Calgary, Alberta, Canada
REFERENCES 1. Kingston, M.: Electrolyte disturbances in Liberian children with kwashiorkor, J. PEDIATR. 83: 859, 1973. 2. CaddeU, J. L., and Goddard, D. R.: Studies in protein-calorie malnutrition, N. Engl. J. Med. 276: 533, 555, 1967. 3. Vis, H., Dubois, R., Vanderborght, H., and de Maeyer, E.: Etudes des troubles electrolytiques accompagnant le kwashiorkor marastique, Rev. Fr. Etud. Clin. Biol. 10: 729, 1965. 4. Alleyne, G. A. O., Millward, D. J., and Scullard, G. H.: Total body potassium, muscle electrolytes and glycogen in malnourished children, J. PEDIATR.76: 75, 1970. 5. Darrow, D. C.: The retention of potassium during recovery from severe dehydration due to diarrhea, J. PEDIAT~. 28: 515, 1946. 6. Scribner, B. S., and Burnell, J. M.: Interpretation of the serum potassium concentration, Metabolism 5: 468, 1965. 7. Caddell, J. L., and Olson, R. E.: An evaluation of the electrolyte status of malnourished Thai children, J. PEDIATR. 83: 124, 129, 1973.
Letters to the Editor
Between March 1 and November 30, 1969, 100 infants and children were admitted to our service with acute pneumonia. Lung puncture-aspiration was performed in 31 of these patients. 3 One infant, 8 months of age, with lobar pneumonia had H. influenzae, type b, in the lung-puncture specimen, laryngeal specimen, and blood culture. In two children of 20 months and 3 years of age with interstitial pneumonia, H. influenzae was identified in direct smear; in one of these it was also present in the lung aspirate culture. Hugo Trujillo, M.D. Diana G. de Olarte, M.D. Department o f Pediatrics and Infectious Disease Service University o f Antioquia Apartado aereo No. 1226 Medellin, Colombia, South America REFERENCES
1. Honig, P. J., Pasquariello, P. S., Jr., and Stool, S. E.: H. influenzae pneumonia in infants and children, J. PEDIATR. 83: 215, 1973. 2. Mimica, I., Donoso, E., Howard, J. E., and Lederman, G. W.: Lung puncture in the etiological diagnosis of pneumonia, Am. J. Dis. Child. 122: 278, 1971. 3. Garcia, de, O. D., Trujillo, S. H., Uribe, P. A., and Agudelo, O. N.: Lung puncture-aspiration as a bacteriologic diagnostic procedure in acute pneumonias of infants and children, Clin. Pediatr. 10: 346, 1971.
On the role of magnesium depletion in severely malnourished children To the Editor: Kingston 1 deserves great credit for his work in Liberia in reducing the mortality in severe kwashiorkor from 100 per cent to 15 per cent. I should like to comment on several points he made in his report. He said that magnesium depletion has been considered to be the most important electrolyte disturbance in Nigeria (referring to Caddell and Goddard2), but not elsewhere (referring to Garrow and associates3). Caddell and Goddard selected only seriously ill children with histories of chronic, severe gastroenteritis and reported very low plasma values of magnesium, sodium, potassium, chloride, bicarbonate, total serum protein, and serum albumin, and emphasized, "This study in no way suggests that magnesium is of any greater importance than potassium or any other ion known to be essential to myocardial metabolism" (p. 539). Garrow and associates 3 reviewed the major published work on potassium and magnesium m e t a b o l i s m in m a l n o u r i s h e d c h i l d r e n and c o n c l u d e d "malnourished children are usually magnesium deficient" and "it is sensible to give additional magnesium, as well as potassium, routinely to all severely malnourished children." The degree of concomitant gastroenteritis largely dictates the extent of depletion of these ions; not every malnourished child will have serious depletion of potassium or magnesium. 3'4 Dr. Kingston attributed to hypokalemia alone a list of initial
781
nonspecific changes that included apathy, reduced motor ability, weakness, hypotonia, and electrocardiograph changes such as ST depression, fiat T waves, and "supraventricular tachyarrhythmias." However, other known problems in these patients might well have contributed to their symptoms. These included insufficient protein and calories; dehydration; alkalosis; hyponatremia; hypomagnesemia; systemic effects of known bacterial infection, malaria, and helminthiasis; and possibly anemia and vitamin B deficiencies (not stated). The patients were fed a formula which consisted of calcium caseinate, sugar, cottonseed oil, and added sodium, potassium, and magnesium salts. This formula provided practically no vitamins and trace minerals, including iron, and there was no other source of vitamins or trace minerals mentioned in the report. Malaria and helminthic infestations have been found to increase the severity of anemia usually found in kwashiorkorS; iron-deficient anemia might be anticipated in patients who had been fed a diet of rice, cassava, and breast milk. Dr. Kingston concluded that the malnourished child with hypokalemia requires less potassium (presumably on a weight basis) than the normally nourished child with hypokalemia, and that this had important implications for treatment. The plasma values of the two major intracellular cations, potassium and magnesium, do not accurately reflect the total body stores)' 4 They must be considered together, since potassium is constantly associated with magnesium in muscle in the proportion of 5.67 to 1, and depletion of either has an effect on the content of the other. 6 Whether or not a malnourished child 24 or animal 7 is initially depleted of these ions, he will require large amounts of both to maintain normal composition of the new tissue being made during the accelerated growth period that occurs during recovery. The need for potassium during this period has been well established after many years of extensive research. 3 More recently, it has been shown that failure to provide sufficient magnesium as well as potassium during recovery from malnutrition will result in profound clinical disturbances in the young growing child2, 4, 5 or animal. 7 Joan Caddell Department o f Pediatrics School o f Medicine St. Louis University 1402 S. Grand Blvd. St. Louis, Mo. 63104 REFERENCES
1.
Kingston, M.: Electrolyte disturbances in Liberian children with kwashiorkor, J. PEDIAT~. 83: 859, 1973. 2. Caddell, J. L., and Goddard, D. R.: Studies in protein calorie malnutrition, N. Engl. J: Med. 276: 533, 535, 1967. 3. Garrow, J. S., Smith, R., and Ward, E. E.: Electrolyte metabolism in severe infantile malnutrition, Oxford, 1968, Pergamon Press, Inc., pp. 62, 77, 83, 87. 4. Caddell, J. L., and Olson, R. E.: An evaluation of the electrolyte status of malnourished Thai children, J. PEDIATR.83: 124, 129, 1973. 5. Allen, D. M., and Dean, R. F. A.: The anaemia of kwashiorkor in Uganda, Trans. R. Soc. Trop. Med. Hyg. 59: 326, 1965. 6. Baldwin, D., Robinson, P. K., Zierler, K. L., and Lilienthal,
782
Letters to the Editor
J. L., Jr.: Interrelations of magnesium, potassium, phosphorous, and creatine in skeletal muscle of man, J. Clin. Invest. 31: 850, 1952. 7. Caddell, J. L., and Olson, R. E.: Effect of dietary protein and magnesium on selected ATP phosphotransferases and neuromuscular behavior in young rats, J. Nutr. 103: 1385, 1973.
Repty To the Editor: In the paper 1 referred to above it was not written that magnesium depletion did not occur in areas other than Nigeria but that it was considered to be the most important disturbance there. Apart from the single reference to hypokalemia, which referred to myocardial metabolism, quoted above, the content of the papers by Caddell and Goddard 2 referred almost exclusively to magnesium depletion and its importance in malnourished children. This was surprising because hypokalemia was a more severe aberration than hypomagnesemia. It should be noted that the lower limit or normal for magnesium (1.4 mEq. per liter) quoted in their paper is probably abnormally high because magnesium is partly bound to albumin, which is low in malnourished children. It has not been satisfactorily established that magnesium depletion "usually" occurs in malnourished children: it is invalid to generalize from data--in itself inconclusive--from a few geographic areas. Vis and associates, 3 for example, did not find that depletion was common in the Congo. Although diarrhea is the route of abnormal losses of potassium and magnesium in malnourished children, their dietary intake of these ions, which varies considerably in different geographic areas, probably determines whether depletion of these ions will occur. Evidence that the manifestations quoted in my paper were due to hypokalemia was based on their resolution in association with potassium but not magnesium infusion; a more detailed analysis is to be the subject of a further paper on hypokalemia. The electrocardiograph changes quoted were not nonspecific but were typical of hypokalemia. There is no good evidence that these changes result from the conditions specified by Dr. Caddell, with the possible exception of hypomagnesemia. I emphasized that apathy, weakness, and hypotonia were also characteristic of kwashiorkor. I am aware that the formula given to the subjects and foods previously ingested by them were deficient in iron, folic acid, and vitamins; supplements of these were given routinely to all hospitalized children. I concluded that the malnourished children with hypokalemia required considerably less potassium repletion than hypokalemic children of normal nutrition relative to age--not weight. The following example illustrates the importance and implications of this: the potassium capacity of two 18-month-old children, one severely malnourished (weight 5 kilograms), the other of normal nutrition (weight 12 kilograms) is likely to be approximately 150 mEq. (30 mEq. per kilograms • 5) and 540 mEq. (45 mEq. per kilograms • 12), respectively. If both
The Journal of Pediatrics May 1974
children have a 20 per cent decrease in their total body potassium, perhaps reflecting a serum potassium of 2.2 mEq. per liter, they will require 30 and 108 mEq. of potassium, respectively, for correction of their deficit--an amount of potassium contained in one liter of Darrows solution or 750 ml. of fullstrength cow's milk in the former case. Sufficient potassium and magnesium, the main intracellular cations, are obviously required for growth but in considerably less amounts than that required for repletion of a deficit. Hyperkalemia may result when children are fed large oral supplements of potassium (Allenye and associates,4 Darrow, 5 and personal observations). Alleyne and associates4 stated that it is only in the very severely depleted children with total body potassium below 30 mEq. per kilograms that high doses of potassium supplements should be given; and that high oral doses (6 to 8 mEq. per kilograms per day) of potassium supplement may lead to hyperkalemia. There is no satisfactory evidence that the serum potassium correctly interpreted fails to reflect potassium depletion either in the reference cited by Caddell or elsewhere. Several authors have based their conclusions on the inaccuracy of the serum K as a guide .to potassium status on inadequate evidence of potassium depletion. 1Scribner and Burnell 6 have stated: "the review just completed supports the view that the serum potassium concentration, properly interpreted, reflects with a high degree of accuracy the potassium needs of patients because it reflects K R, the relation between the total body potassium and potassium capacity." Finally the data of Caddell and Olson is insufficient to justify their conclusion that the serum magnesium concentration fails to reflect magnesium depletion: individual results of retention of magnesium, serum concentrations of magnesium before and after magnesium repletion, the subjects weight, and serum albumin should be analyzed to justify this conclusion. Michael E. Kingston, M.R.C.P., D.T.M.H., D.A. Calgary General Hospital Calgary, Alberta, Canada
REFERENCES 1. Kingston, M.: Electrolyte disturbances in Liberian children with kwashiorkor, J. PEDIATR. 83: 859, 1973. 2. CaddeU, J. L., and Goddard, D. R.: Studies in protein-calorie malnutrition, N. Engl. J. Med. 276: 533, 555, 1967. 3. Vis, H., Dubois, R., Vanderborght, H., and de Maeyer, E.: Etudes des troubles electrolytiques accompagnant le kwashiorkor marastique, Rev. Fr. Etud. Clin. Biol. 10: 729, 1965. 4. Alleyne, G. A. O., Millward, D. J., and Scullard, G. H.: Total body potassium, muscle electrolytes and glycogen in malnourished children, J. PEDIATR.76: 75, 1970. 5. Darrow, D. C.: The retention of potassium during recovery from severe dehydration due to diarrhea, J. PEDIAT~. 28: 515, 1946. 6. Scribner, B. S., and Burnell, J. M.: Interpretation of the serum potassium concentration, Metabolism 5: 468, 1965. 7. Caddell, J. L., and Olson, R. E.: An evaluation of the electrolyte status of malnourished Thai children, J. PEDIATR. 83: 124, 129, 1973.