- Email: [email protected]
Total parenteral nutrition
180
January, 1971 T h e Journal o[ P E D I A T R I C S
Letters to the Editor
Reply* To the Editor: We appreciate the opportunity to reply to the letter from Drs. Crawford, Gellis, and Senior. Let us begin by pointing out that we are in no basic disagreement. Alternate-day steroid is an untested therapeutic regimen which may very well prove both effective and less toxic. Crawford and associates state that "At the present time, available evidence suggests that alternateday corticoid therapy appears worthy of wider trials." We agree with this also and must point out that we neither stated nor implied in our comment that alternate-day corticosteroid therapy should be abandoned, but rather made a plea that its usefulness should be tested. I With the use of rigorously designed experimental protocols, the International Study of Kidney Disease in Children is in the process of seeking answers to several questions concerning treatment of renal disease in children3 The opportunity and responsibility for such studies lies primarily within the academic community, which is quick to recommend them but too often reluctant to carry them out.
Mark Abramowicz, M.D. Chester M. Edelmann, Jr., M.D. Adrian Spitzer, M.D. Albert Einstein College o[ Medicine t300 Morris Park Ave. Bronx, N. Y. 10461 REFERENCES
1. Abramowiez, M., Edelmann, C. M., Jr., and Spitzer, A.: Dogma disputed: Alternate-day steroid therapy in the nephrotic syndrome of childhood, J. PEDIAT. 76: 336, 1970. 2. Abramowicz, M., Arneil, G. C., Barnett~ H. L., Barron, B. A., Edelmann, C. M., Jr., Gordillo-P, G., Greifer, I , Hallman, N., Kobayashi, O., and Tiddens, H. A.: Controlled trial of azathioprine in children with nephrotic ~Reply, omitted in error, to the letter by Drs. Crawford, GeUis, and Senior, "Avoidance of dogma: Alternate-day corticoid therapy in a variety of illnesses in childhood," which appeared in the October, 1970, issue of the JOURNAL.
Vol. 78, No. 1, pp. 180-185
syndrome. A report for the International Study of Kidney Disease in Children, Lancet I: 959, 1970.
Action for improved maternal and cbiM heahh To the Editor: Having served on the Task Force which developed "Action for Improved Maternal and Child Health," I believe that it is necessary to re-emphasize to the readers of T~E JOURNAL Or PEDIATRICS that any such report can never be a total concensus but is a concensus of appropriate ideas for action. It must be emphasized that recommendations of this nature are not necessarily dicta for action but are primarily to produce discussion for appropriate action. The Basic Assumptions mentioned initially are undoubtedly valid in the eyes of those who have worked with children. I think that this group clearly spoke to the need for continual reassessment o f goals and directions designed to serve children and the clear-cut need for the involvement of people both in state and local program development as consultants and producers of national policy goals. I, for one, believe that too many of our national goals and directions have been developed without adequate consultation from those who serve children at the state and local level. Theodore D. Scurletis, M.D., F.A.A.P. Director, Personal Health Division State Board o[ Health P.O. Box 2091 Raleigh, N. C. 27602
Total parenteral nutrition To the Editor: Total parenteral nutrition, utilizing infusion of hypertonic solutions into large veins, is being more and more widely used. We have recentIy noted the development of hepatic cholestasis and cir-
Volume 78 Number 1
rhosis in a 1.0 Kg. premature infant receiving total parenteral nutrition. The solution used contained 200 Gm. of glucose and 33 Gin. of protein per liter, plus appropriate electrolytes and vitamins,1 and was administered via superior vena cava catheter. An episode of osmotic diuresis, with hyperglycemia, hypernatremia, and marked dehydration, occurred 48 hours after total parenteral nutrition was started. This was corrected within 48 hours, and thereafter the infant's blood glucose, serum electrolytes, and state of hydration remained within normal limits. It was noted on the eighteenth day of total parenteral nutrition that the infant's liver had become palpable. At this time it was also discovered that the tip of the catheter had slipped into the hepatic outflow tract. The catheter tip was pulled back into the inferior vena cava, and an inferior venacavagram at that time revealed no abnormality. Total parenteral nutrition was continued. Hepatosplenomegaly increased gradually, and on the forty-eighth day of total parenteral nutrition the liver was palpable 5 cm., and the spleen 3 cm., below the costal margins. The infant's highest serum bilirubin was 10.7 rag. per cent on the fifth day of life and had fallen to normal before total parenteral nutrition was instituted. Numerous blood cultures were negative. The infant had been unable to tolerate oral or garage feedings because of apneic episodes. These episodes became more frequent, and the infant died on the seventy-first day of life. Postmortem examination revealed extensive pulmonary hemorrhage with evidence of early organization of this hemorrhage, and early cirrhosis with prominent bile duct reduplication and predominantly centrilobular cholestasis. Occasional hepatic parenchymal giant cells were present, and hematopoiesis was prominent. No inclusion bodies were seen. The extrahepatic biliary tree was patent, as were the veins within, and leading from, the liver. The basis for the hepatic changes was not evident from the gross or microscopic findings. A definite relationship between the total parenteral nutrition regimen and the development of cholestasis and cirrhosis cannot be established in this case. A number of possibly pertinent causative factors could be suggested: the period of hyperosmolar dehydration, the position of the catheter tip, venous spasm due to the hypertonic infusate, or the nature of the total parenteral nutrition infusate itself. It is of interest, also, that cholestasis (and probably bile duct reduplication) are increasingly considered to be sequelae
Letters to the Editor
18 1
of abnormal bile salt metabolism and/or deranged hepatocyte function.2 The problem of cholestasis and cirrhosis has not been reported in any of the literature dealing with total parenteral alimentation, nor has it been encountered in our experience with other infants receiving the infusate. We would be much interested in knowing whether other investigators in this field have experienced similar difficulty and if so, under what circumstances.
V. H. Peden, M.D. C. L. Witzleben, M.D. M. A. SkeIton, M.D. Departments of Pediatrics and Pathology St. Louis University School of Medicine Cardinal Glennon Memorial Hospital for Children St. Louis, Mo. REFERENCES
1. Filler, R. M., Eraklis, A. J., Rubin, V. G., et al.: Long-term total parenteral nutrition in infants, New Eng. J. Med. 281: 589, 1969. 2. Popper, H.: Cholestasis, Ann. Rev. Med. 19: 39, 1968.
Behavioral pediatrics in private practice To the Editor: The editorial by Dr. Stanford B. Friedman on "The challenge in behavioral pediatrics ''1 presents only one view of interest--that of medical students, house staff, and faculty. The other significant interest and need are for continuing education in "behavioral pediatrics" for pediatricians in practice, those in the front lines of delivering most of the health care. For example, the need was documented in Rochester, New York (Dr. Friedman's base of operations) in 1964, when all 52 pediatricians were personally interviewed to assay mental health aspects of their private practices. 2 From this survey it was hoped that continuing education opportunities would be started to narrow the gap between theory and practice. Educational efforts in this direction have been started in northern California, where pediatricians in practice are serving as a nucleus for action by the local chapter of the American
January, 1971 T h e Journal o[ P E D I A T R I C S
Letters to the Editor
Reply* To the Editor: We appreciate the opportunity to reply to the letter from Drs. Crawford, Gellis, and Senior. Let us begin by pointing out that we are in no basic disagreement. Alternate-day steroid is an untested therapeutic regimen which may very well prove both effective and less toxic. Crawford and associates state that "At the present time, available evidence suggests that alternateday corticoid therapy appears worthy of wider trials." We agree with this also and must point out that we neither stated nor implied in our comment that alternate-day corticosteroid therapy should be abandoned, but rather made a plea that its usefulness should be tested. I With the use of rigorously designed experimental protocols, the International Study of Kidney Disease in Children is in the process of seeking answers to several questions concerning treatment of renal disease in children3 The opportunity and responsibility for such studies lies primarily within the academic community, which is quick to recommend them but too often reluctant to carry them out.
Mark Abramowicz, M.D. Chester M. Edelmann, Jr., M.D. Adrian Spitzer, M.D. Albert Einstein College o[ Medicine t300 Morris Park Ave. Bronx, N. Y. 10461 REFERENCES
1. Abramowiez, M., Edelmann, C. M., Jr., and Spitzer, A.: Dogma disputed: Alternate-day steroid therapy in the nephrotic syndrome of childhood, J. PEDIAT. 76: 336, 1970. 2. Abramowicz, M., Arneil, G. C., Barnett~ H. L., Barron, B. A., Edelmann, C. M., Jr., Gordillo-P, G., Greifer, I , Hallman, N., Kobayashi, O., and Tiddens, H. A.: Controlled trial of azathioprine in children with nephrotic ~Reply, omitted in error, to the letter by Drs. Crawford, GeUis, and Senior, "Avoidance of dogma: Alternate-day corticoid therapy in a variety of illnesses in childhood," which appeared in the October, 1970, issue of the JOURNAL.
Vol. 78, No. 1, pp. 180-185
syndrome. A report for the International Study of Kidney Disease in Children, Lancet I: 959, 1970.
Action for improved maternal and cbiM heahh To the Editor: Having served on the Task Force which developed "Action for Improved Maternal and Child Health," I believe that it is necessary to re-emphasize to the readers of T~E JOURNAL Or PEDIATRICS that any such report can never be a total concensus but is a concensus of appropriate ideas for action. It must be emphasized that recommendations of this nature are not necessarily dicta for action but are primarily to produce discussion for appropriate action. The Basic Assumptions mentioned initially are undoubtedly valid in the eyes of those who have worked with children. I think that this group clearly spoke to the need for continual reassessment o f goals and directions designed to serve children and the clear-cut need for the involvement of people both in state and local program development as consultants and producers of national policy goals. I, for one, believe that too many of our national goals and directions have been developed without adequate consultation from those who serve children at the state and local level. Theodore D. Scurletis, M.D., F.A.A.P. Director, Personal Health Division State Board o[ Health P.O. Box 2091 Raleigh, N. C. 27602
Total parenteral nutrition To the Editor: Total parenteral nutrition, utilizing infusion of hypertonic solutions into large veins, is being more and more widely used. We have recentIy noted the development of hepatic cholestasis and cir-
Volume 78 Number 1
rhosis in a 1.0 Kg. premature infant receiving total parenteral nutrition. The solution used contained 200 Gm. of glucose and 33 Gin. of protein per liter, plus appropriate electrolytes and vitamins,1 and was administered via superior vena cava catheter. An episode of osmotic diuresis, with hyperglycemia, hypernatremia, and marked dehydration, occurred 48 hours after total parenteral nutrition was started. This was corrected within 48 hours, and thereafter the infant's blood glucose, serum electrolytes, and state of hydration remained within normal limits. It was noted on the eighteenth day of total parenteral nutrition that the infant's liver had become palpable. At this time it was also discovered that the tip of the catheter had slipped into the hepatic outflow tract. The catheter tip was pulled back into the inferior vena cava, and an inferior venacavagram at that time revealed no abnormality. Total parenteral nutrition was continued. Hepatosplenomegaly increased gradually, and on the forty-eighth day of total parenteral nutrition the liver was palpable 5 cm., and the spleen 3 cm., below the costal margins. The infant's highest serum bilirubin was 10.7 rag. per cent on the fifth day of life and had fallen to normal before total parenteral nutrition was instituted. Numerous blood cultures were negative. The infant had been unable to tolerate oral or garage feedings because of apneic episodes. These episodes became more frequent, and the infant died on the seventy-first day of life. Postmortem examination revealed extensive pulmonary hemorrhage with evidence of early organization of this hemorrhage, and early cirrhosis with prominent bile duct reduplication and predominantly centrilobular cholestasis. Occasional hepatic parenchymal giant cells were present, and hematopoiesis was prominent. No inclusion bodies were seen. The extrahepatic biliary tree was patent, as were the veins within, and leading from, the liver. The basis for the hepatic changes was not evident from the gross or microscopic findings. A definite relationship between the total parenteral nutrition regimen and the development of cholestasis and cirrhosis cannot be established in this case. A number of possibly pertinent causative factors could be suggested: the period of hyperosmolar dehydration, the position of the catheter tip, venous spasm due to the hypertonic infusate, or the nature of the total parenteral nutrition infusate itself. It is of interest, also, that cholestasis (and probably bile duct reduplication) are increasingly considered to be sequelae
Letters to the Editor
18 1
of abnormal bile salt metabolism and/or deranged hepatocyte function.2 The problem of cholestasis and cirrhosis has not been reported in any of the literature dealing with total parenteral alimentation, nor has it been encountered in our experience with other infants receiving the infusate. We would be much interested in knowing whether other investigators in this field have experienced similar difficulty and if so, under what circumstances.
V. H. Peden, M.D. C. L. Witzleben, M.D. M. A. SkeIton, M.D. Departments of Pediatrics and Pathology St. Louis University School of Medicine Cardinal Glennon Memorial Hospital for Children St. Louis, Mo. REFERENCES
1. Filler, R. M., Eraklis, A. J., Rubin, V. G., et al.: Long-term total parenteral nutrition in infants, New Eng. J. Med. 281: 589, 1969. 2. Popper, H.: Cholestasis, Ann. Rev. Med. 19: 39, 1968.
Behavioral pediatrics in private practice To the Editor: The editorial by Dr. Stanford B. Friedman on "The challenge in behavioral pediatrics ''1 presents only one view of interest--that of medical students, house staff, and faculty. The other significant interest and need are for continuing education in "behavioral pediatrics" for pediatricians in practice, those in the front lines of delivering most of the health care. For example, the need was documented in Rochester, New York (Dr. Friedman's base of operations) in 1964, when all 52 pediatricians were personally interviewed to assay mental health aspects of their private practices. 2 From this survey it was hoped that continuing education opportunities would be started to narrow the gap between theory and practice. Educational efforts in this direction have been started in northern California, where pediatricians in practice are serving as a nucleus for action by the local chapter of the American