Subject Review Efficacy and Safety of Total Parenteral Nutrition in Pediatric Patients
JOHN R. WESLEY, M.D., Division ofPediatric Surgery Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-tobenefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents.
Pediatric patients differ from adult patients in the need for nutritional support, not only for maintenance and healing but also for ongoing growth and development. For example, one of the most critical periods of brain growth is between the 30th week of gestation and the 5th month of life.' Animal studies have shown that compromised nutrition during this time may result in decreased brain growth that cannot be reversed, despite later provisions of adequate nutrition.r" In addition, pediatric patients, especially premature infants, have a proportionately smaller nutritional reserve, and their metabolic rate per unit of weight can be 3 times greater than that in adults. During conditions of total starvation, a fullterm infant has sufficient energy reserves to survive for approximately 1 month, but a 2,OOO-g premature infant has only enough reserves to survive for 4!12 days.' Therefore, Address reprint requests to Dr. J. R. Wesley, Division of Pediatric Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:671-675,1992
whatever medical or surgical treatment is rendered, nutritional support must be provided early because of the pediatric patient's limited stores of energy and other essential nutrients. Because weight gain (15 to 25 g per day in newborns and 0.5% of body weight in older children) is the single best measure of adequate growth of lean body mass in pediatric patients," failure to gain weight is as much a problem in pediatric patients as weight loss is in adult patients. Although the pediatric age-group is commonly defined as newborn to age 18 years, the rest of this discussion will mainly focus on newborns and children up to the age of 5 years.
POTENTIAL BENEFITS OF TOTAL PARENTERAL NUTRITION An important consideration in assessing the potential benefits of total parenteral nutrition (TPN) is to determine the expected outcome. In some patients, TPN may improve the 671
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actual outcome of the disease; in other patients, it may simply maintain or restore nutritional integrity. Measures of outcome of nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins with a short half-life, immunocompetence, decreased morbidity, fast recovery, and improved survival." An additional variable that is worth considering, but difficult to measure, is the patient's quality of life. 9 Generally, because of the limited nutritional reserves in pediatric patients from birth to 4 years of age, parenteral nutrition should be initiated if the patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids. Five days is the threshold for patients aged 5 to 18 years.v'? Indications for parenteral nutrition in pediatric patients are listed in Table 1 and include all those for adults plus several that are unique to pediatric patients. For this review, the discussion is limited to four of the indications unique to pediatric patients-namely, gastroschisis, shortbowel syndrome, intensive care of low-birth-weight or premature infants, and necrotizing enterocolitis. The detrimental and disastrous effects of total or almost total starvation in children (up to age 18 years) are well documented; thus, whenever the therapeutic choice is between starvation and parenteral nutrition, no choice exists, and the decision must be to initiate parenteral nutrition. Controlled trials are inappropriate and unethical. Rather, the decision to institute parenteral nutrition reflects clinical judgment and the need to balance the risks of starvation, malnutrition, and developmental failure against the risks of metabolic, septic, and mechanical complications of TPN in individual patients. I 1,12 The challenge is to recognize potential malnutrition early and to correct deficits of nutrients and energy before serious depletion occurs. Two examples, gastroschisis and short-bowel syndrome, illustrate this point. Gastroschisis.-Gastroschisis is a congenital full-thickness defect of the abdominal wall in conjunction with herniation of various amounts of uncovered intestines that, because they have been exposed to the chemical irritation of amniotic fluid in utero, are edematous, matted, and covered with a gelatinous exudate; these factors cause temporary nonfunction of the intestines. After the exposed bowel is reduced primarily or housed temporarily in a Silastic chimney for staged reduction, 3 to 5 weeks must elapse before the thick peel on the bowel wall resolves and normal peristalsis and digestive function occur. The mortality rate of patients with gastroschisis before 1964 was 80 to 90%. After the introduction of the Silastic chimney but before TPN was available, the mortality rate during the obligatory recovery period of the intestine was 30 to 40%, primarily because ofthe ravages
Mayo CUn Proc, JUly 1992, Vol 67
Table I.-Indications for Parenteral Nutrition in Pediatric Patients Surgical disordersof the gastrointestinal tract: gastroschisis, omphalocele, tracheoesophageal fistula, intestinalatresia, Hirschsprung's disease, meconium ileus, peritonitis, diaphragmatic hernia Short-bowelsyndrome Necrotizing enterocolitis Intractablediarrheaof infancy Intensivecare of low-birth-weight or prematureinfants Renal failure Fistula of the gastrointestinal tract Inflammatoryboweldisease Pancreatitis Hepatic failure Cancer Hypermetabolic states: severe bums, sepsis, and trauma Chylothorax and chylousascites
of malnutrition. 13 Since the advent of TPN in the late 1960s, the mortality from gastroschisis has been significantly decreased; in some series, the survival rate exceeds 95%.14-16 Although anesthesia and intensive care have improved during this period, the factor most commonly deemed responsible for this increased survival has been TPN. Short-Bowel Syndrome.-Short-bowel syndrome may be the result of a congenitally short intestine or massive surgical resection in association with one of several intestinal problems, including necrotizing enterocolitis, malrotation and volvulus, trauma, and Crohn's disease. Before the advent of TPN, patients with any of the aforementioned disorders had an extremely high mortality rate, which stemmed ultimately from the ill effects of malnutrition.F:" In a 1972 review of the literature, Wilmore" concluded that a minimum of 30 em of intact small bowel with an ileocecal valve was necessary to ensure survival. Infants with 15 to 29 em of remaining small bowel had a 50% survival rate, but survival was impossible with less than 15 em of small intestine. Since the advent of TPN as supportive therapy and because of the ability of infant intestine to grow in length as well as in surface area, some patients with less than 15 em of bowel can now survive, and the expectation of being weaned from TPN to enteral nutrition is reasonable.i? In a recent series of patients with short-bowel syndrome who had residual small intestine that was less than 25% of the normal length expected for gestational age, the long-term survival rate was 86%, primarily because of the supportive advantage provided by TPN,2I Premature and Low-Birth-Weight Infants.- The use of TPN in the intensive care of premature and low-birth-weight
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infants has become part of the management protocol in most stead, these infants received nutrition parenterally. In the neonatal centers throughout the United States. Low-birth- other group of 18 neonates, incremental enteric feedings of weight infants frequently have major problems, such as re- diluted infant formula or breast milk were administered durspiratory distress syndrome, congenital cardiac disease, im- ing the first 2 weeks of life. The overall incidence of mature kidneys, and an immature digestive system, that limit necrotizing enterocolitis in the parenterally fed group was 60% (12 of 20) in comparison with 22% (4 of 18) in the their ability to ingest and absorb adequate calories. In a controlled study of peripheral lipid-based TPN in group who received early oral feedings. The study showed infants with respiratory distress syndrome, Gunn and co- that withholding oral feedings for 2 weeks postnatally does workers-' showed that, in 40 premature infants, TPN neither not decrease the incidence of necrotizing enterocolitis; in favorably altered the course of respiratory distress syndrome fact, it may promote its occurrence. As a result of this and nor worsened the infants' pulmonary status. Infants with other studies, low-birth-weight infants are frequently being respiratory distress syndrome who weighed less than 1,500 g managed with a combination of enteral and parenteral nutriand who received TPN had an increased survival rate, how- tion and with a gradual increase in and conversion to total ever, in comparison with control subjects (71% and 37%, enteral nutrition as the infant's gastrointestinal tract marespectively). These data should not be interpreted to sug- tures. 26•27 Attributing improved survival of low-birth-weight gest that only infants who weigh less than 1,500 g should infants to better nutritional support is tempting; however, receive TPN. The current emphasis should be on the impor- other aspects of neonatal and obstetric care have improved tance of nutritional support, by either the parenteral or the considerably. Hence, the contribution of nutritional support enteral route, in all compromised infants. Use of the enteral is difficult to isolate in this group of high-risk infants." route, if possible, is always preferred because it is more physiologic and less expensive than the parenteral route. CONTRAINDICATIONS TO TPN Nonetheless, the more premature the infant, the greater the Contraindications to parenteral nutrition include severe conhazards of enteral nutrition because of the immaturity of the genital (usually genetic) defects (for example, trisomy 13 gastrointestinal tract; this factor shifts the balance in favor of and pentalogy of Cantrell) and terminal cancer, disorders in which life expectancy and quality of life are severely dethe parenteral route. The immature digestive system of premature and low- creased. Because withdrawal of TPN is always difficult, the birth-weight infants is associated with frequent incompe- decision to initiate intravenous nutrition in patients with such tence of the gastroesophageal sphincter, delayed gastric conditions should be carefully evaluated. Physician-family emptying, intestinal dysmotility, and a decreased gastroin- interaction and individual moral considerations are obvitestinal immune response-all of which make the provision ously important. In patients in whom life expectancy is of adequate enteral calories difficult and hazardous and in- limited, physicians should consider comfort and quality of crease the probability of occurrence of necrotizing entero- life provided by intravenous fluids for hydration rather than colitis. Thus, the intravenous administration of calories is by TPN. Generally, TPN should be reserved for those innecessary while the gastrointestinal tract is continuing to fants who receive active medical or surgical treatment. In develop and become more functional." Yu and co-workers> addition, because of potentially serious metabolic and catheconducted a controlled trial of TPN in 34 preterm infants ter-related complications, TPN should be used only in those whose birth weights were less than 1,200 g. The infants who children who cannot be nourished by bolus or continuous received TPN had a greater mean daily weight gain during tube feeding. TPN should not be regarded as an alternative the second week of life and regained birth weight sooner to enteral feeding, nor as a substitute for appropriate medical than did the control infants. Necrotizing enterocolitis devel- or surgical therapy. oped in four infants in the milk-fed control group but in none who received TPN. TEAM APPROACH AND SAFETY OF TPN Necrotizing Enterocolitis.-The term "necrotizing en- The team approach to parenteral and enteral nutrition in terocolitis" denotes a clinical state of intestinal inflammation pediatric patients is necessary and has substantially deand infarction detected most commonly in low-birth-weight creased the associated mechanical problems, catheter sepsis, or premature infants and associated with major stresses that and metabolic complications. In addition, the team approach frequently accompany prematurity. In order to test the hy- provides important education for floor nurses and patients pothesis that delayed oral feedings would decrease the inci- and their families." Stable patients who are receiving longdence of necrotizing enterocolitis in neonates who weighed term nutritional support, including infants, should be considless than 1,500 g, LaGamma and co-workers" compared two ered for home parenteral nutrition. The cost can he dematched groups of newborns. In one group of 20 newborns, creased by 50% or more when patients are transferred from no oral feedings were offered during a 2-week period; in- an inpatient to an outpatient environment for treatment."
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Parenteral nutntion is safe in pediatric patients when administered by protocol; short-term risks, such as catheter sepsis, mild reversible liver dysfunction, and cholelithiasis, are similar to those in adults. Long-term risks, including hepatic toxicity and failure, are more serious than short-term risks-because of the immaturity, and hence greater vulnerability, of the infant liver." Long-term risks in children older than I year of age are similar to those in adults; the major differences are compromised growth and development in children up to the late teenage years.
COST AND ETHICAL ISSUES OF TPN In properly selected pediatric patients, direct and indirect costs for parenteral nutrition may be significantly less than those in adults but are frequently similar." Pediatric patients, however, potentially have a more favorable cost-tobenefit ratio than do adult patients when life expectancy, parental pleasure, and potential work productivity are considered. The implications for third-party payers are generally positive for short-term use but negative for lifetime requirements. Ethical and social issues in initiating and discontinuing parenteral nutrition must be individualized and are best decided during thorough empathic discussions between physicians and parents. The critical decisions hinge on choosing between what can be done and what should be done for an individual patient." Legal concerns, particularly in consideration of the dimensions of denying adequate nutrition, are often complex, disruptive, and difficult to resolve. Psychologic implications of long-term use of TPN are extremely variable and must be assessed individually. Experience with parenteral nutrition has led to an enhanced understanding of nutritional biochemistry and gastrointestinal physiology and has enabled physicians to achieve bowel rest for their patients and to induce healing that would not otherwise be possible.
3.
"4.
5.
6.
7.
8.
9. 10.
11.
12.
13.
14.
CONCLUSION TPN, when properly used, is extremely valuable in the care of pediatric patients in whom enteral feedings are impossible, inadequate, or hazardous. Selection and management of patients must be carefully assessed to avoid unnecessary exposure to the potential complications of this treatment modality.
REFERENCES 1. Denson SE: Nutrient considerations in IV support of the neonate. In The Compromised Neonate. Edited by AG Coran, SE Denson, AB Fletcher, B Bernard. Berkeley, California, Cutter Laboratories, 1980, pp 10-15; 24 2. Dickerson JWT, Dobbing J, McCance RA: The effect of undernutrition on the postnatal development of the brain
15.
16. 17.
18. 19.
and cord in pigs. Proc R Soc Lond [Biol] 166:396-407, 1966-67 Winick M, Rosso P: The effect of severe early malnutrition on cellular growth of human brain. Pediatr Res 3:181-184, 1969 Dobbing J: The later development of the brain and its vulnerability. In Scientific Foundations of Paediatrics. Edited by JA Davis, J Dobbing. Philadelphia, WB Saunders Company, 1974, pp 565-577 Heird WC, Driscoll 1M Jr, Schullinger IN, Grebin B, Winters RW: Intravenous alimentation in pediatric patients. J Pediatr 80:351-372,1972 Wesley JR, Khalidi N, Faubion WC, Kovacevich DS, Braunschweig CL, Maksym CJ, Revesz SM, Perez AM, Wilson DD, Marikis B, Coran AG: The University of Michigan Medical Center Parenteral and Enteral Nutrition Manual. Chicago, Abbott Laboratories, Hospital Products Division, 1990, pp 54-69 Holcomb GW III, Ziegler MM Jr: Nutrition and cancer in children. Surg Annu 22:129-142,1990 Kerner JA Jr: Indications for parenteral nutrition in pediatrics. In Manual of Pediatric Parenteral Nutrition. Edited by JA Kerner Jr. New York, John Wiley & Sons, 1983, pp 3-17 Weber TR, Tracy T Jr, Connors RH: Short-bowel syndrome in children: quality of life in an era of improved survival. Arch Surg 126:841-846,1991 Coran A, Wesley JR: The pediatric patient. In Nutrition and Metabolism in the Surgical Patient. Edited by JR Kirkpatrick. Mount Kisco, New York, Futura Publishing Company, 1983, pp 461-482 Pereira GR, Glassman M: Parenteral nutrition in the neonate. In Parenteral Nutrition. Edited by JL Rombeau, MD Caldwell. Philadelphia, WB Saunders Company, 1986, pp 702-720 Varma RN, Suskind RM: Parenteral nutrition in the pediatric patient. In Parenteral Nutrition. Edited by JL Rombeau, MD Caldwell. Philadelphia, WB Saunders Company, 1986, pp 721-730 Bill AH Jr: Gastroschisis. In Pediatric Surgery. Vol 1. Second edition. Edited by WT Mustard, MM Ravitch, WH Snyder Jr, KJ Welch, CD Benson. Chicago, Year Book Medical Publishers, 1969, pp 685 c689 Dudrick SJ, Copeland EM III, MacFadyen BV Jr: Long-term parenteral nutrition: its current status. Hosp Pract (Off Ed) 10:47-,58, 1975 Wesley JR, Drongowski R, Coran AG: Intragastric pressure measurement: a guide for reduction and closure of the silastic chimney in omphalocele and gastroschisis. J Pediatr Surg 16:264-270,1981 Wagner CW, Parrish RA: Gastroschisis. Am Surg 47:174177,1981 Benson CD: Miscellaneous causes of small bowel obstruction. In Pediatric Surgery. Vol 2. Second edition. Edited by WT Mustard, MM Ravitch, WH Snyder Jr, KJ Welch, CD Benson. Chicago, Year Book Medical Publishers, 1969, pp 868-872 Heird WC, Winters RW: Total parenteral nutrition: the state of the art. J Pediatr 86:2-16,1975 Wilmore DW: Factors correlating with a successful outcome following extensive intestinal resection in newborn infants. J Pediatr 80:88-95, 1972
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20. 21. 22.
23. 24. 25.
26.
Klish WJ, Putnam TC: The short gut. Am J Dis Child 135:1056-1061, 1981 Caniano DA, Starr J, Ginn-Pease ME: Extensive short-bowel syndrome in neonates: outcome in the 1980s. Surgery 105:119-124,1989 Gunn T, Reaman G, Outerbridge EW, Colle E: Peripheral total parenteral nutrition for premature infants with the respiratory distress syndrome: a controlled study. J Pediatr 92:608-613, 1978 Kerner JA Jr, Sunshine P: Parenteral alimentation. Semin Perinatol 3:417-434, October 1979 Yu VYH, James B, Hendry P, MacMahon RA: Total parenteral nutrition in very low birthweight infants: a controlled trial. Arch Dis Child 54:653-661, 1979 LaGamma EF, Ostertag SG, Birenbaum H: Failure of delayed oral feedings to prevent necrotizing enterocolitis: results of study in very-Iow-birth-weight neonates. Am J Dis Child 139:385-389, 1985 Farrell MK, Balistreri WF: Parenteral nutrition and hepatobiliary dysfunction. Clin Perinatol 13:197-212, March 1986
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27.
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Grosfeld JL, Cheu H, Schlatter M, West KW, Rescorla FJ: Changing trends in necrotizing enterocolitis: experience with 302 cases in two decades. Ann Surg 214:300-306, 1991 28. Panel report on nutritional support of pediatric patients. Am J Clin Nutr 34:1223-1234,1981 29. Faubion WC, Wesley JR, Khalidi N, Silva J: Total parenteral nutrition catheter sepsis: impact of the team approach. JPEN J Parenter Enteral Nutr 10:642-645, 1986 30. Wesley JR, Khalidi N, Faubion WC, Ryan ML, de Leon RF: Home parenteral nutrition: a hospital-based program with commercial logistic support. JPEN J Parenter Enteral Nutr 8:585-588, 1984 31. Wesley JR, Ryan M, Faubion W, Haggerty R, Byron R, August D: A university-based wholly-owned home infusion program with commercial logistic support (submitted for publication) 32. Caniano DA, Kanoti GA: Newborns with massive intestinal loss: difficult choices. N Engl J Med 318:703"707, 1988
JOHN R. WESLEY, M.D., Division ofPediatric Surgery Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-tobenefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents.
Pediatric patients differ from adult patients in the need for nutritional support, not only for maintenance and healing but also for ongoing growth and development. For example, one of the most critical periods of brain growth is between the 30th week of gestation and the 5th month of life.' Animal studies have shown that compromised nutrition during this time may result in decreased brain growth that cannot be reversed, despite later provisions of adequate nutrition.r" In addition, pediatric patients, especially premature infants, have a proportionately smaller nutritional reserve, and their metabolic rate per unit of weight can be 3 times greater than that in adults. During conditions of total starvation, a fullterm infant has sufficient energy reserves to survive for approximately 1 month, but a 2,OOO-g premature infant has only enough reserves to survive for 4!12 days.' Therefore, Address reprint requests to Dr. J. R. Wesley, Division of Pediatric Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:671-675,1992
whatever medical or surgical treatment is rendered, nutritional support must be provided early because of the pediatric patient's limited stores of energy and other essential nutrients. Because weight gain (15 to 25 g per day in newborns and 0.5% of body weight in older children) is the single best measure of adequate growth of lean body mass in pediatric patients," failure to gain weight is as much a problem in pediatric patients as weight loss is in adult patients. Although the pediatric age-group is commonly defined as newborn to age 18 years, the rest of this discussion will mainly focus on newborns and children up to the age of 5 years.
POTENTIAL BENEFITS OF TOTAL PARENTERAL NUTRITION An important consideration in assessing the potential benefits of total parenteral nutrition (TPN) is to determine the expected outcome. In some patients, TPN may improve the 671
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actual outcome of the disease; in other patients, it may simply maintain or restore nutritional integrity. Measures of outcome of nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins with a short half-life, immunocompetence, decreased morbidity, fast recovery, and improved survival." An additional variable that is worth considering, but difficult to measure, is the patient's quality of life. 9 Generally, because of the limited nutritional reserves in pediatric patients from birth to 4 years of age, parenteral nutrition should be initiated if the patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids. Five days is the threshold for patients aged 5 to 18 years.v'? Indications for parenteral nutrition in pediatric patients are listed in Table 1 and include all those for adults plus several that are unique to pediatric patients. For this review, the discussion is limited to four of the indications unique to pediatric patients-namely, gastroschisis, shortbowel syndrome, intensive care of low-birth-weight or premature infants, and necrotizing enterocolitis. The detrimental and disastrous effects of total or almost total starvation in children (up to age 18 years) are well documented; thus, whenever the therapeutic choice is between starvation and parenteral nutrition, no choice exists, and the decision must be to initiate parenteral nutrition. Controlled trials are inappropriate and unethical. Rather, the decision to institute parenteral nutrition reflects clinical judgment and the need to balance the risks of starvation, malnutrition, and developmental failure against the risks of metabolic, septic, and mechanical complications of TPN in individual patients. I 1,12 The challenge is to recognize potential malnutrition early and to correct deficits of nutrients and energy before serious depletion occurs. Two examples, gastroschisis and short-bowel syndrome, illustrate this point. Gastroschisis.-Gastroschisis is a congenital full-thickness defect of the abdominal wall in conjunction with herniation of various amounts of uncovered intestines that, because they have been exposed to the chemical irritation of amniotic fluid in utero, are edematous, matted, and covered with a gelatinous exudate; these factors cause temporary nonfunction of the intestines. After the exposed bowel is reduced primarily or housed temporarily in a Silastic chimney for staged reduction, 3 to 5 weeks must elapse before the thick peel on the bowel wall resolves and normal peristalsis and digestive function occur. The mortality rate of patients with gastroschisis before 1964 was 80 to 90%. After the introduction of the Silastic chimney but before TPN was available, the mortality rate during the obligatory recovery period of the intestine was 30 to 40%, primarily because ofthe ravages
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Table I.-Indications for Parenteral Nutrition in Pediatric Patients Surgical disordersof the gastrointestinal tract: gastroschisis, omphalocele, tracheoesophageal fistula, intestinalatresia, Hirschsprung's disease, meconium ileus, peritonitis, diaphragmatic hernia Short-bowelsyndrome Necrotizing enterocolitis Intractablediarrheaof infancy Intensivecare of low-birth-weight or prematureinfants Renal failure Fistula of the gastrointestinal tract Inflammatoryboweldisease Pancreatitis Hepatic failure Cancer Hypermetabolic states: severe bums, sepsis, and trauma Chylothorax and chylousascites
of malnutrition. 13 Since the advent of TPN in the late 1960s, the mortality from gastroschisis has been significantly decreased; in some series, the survival rate exceeds 95%.14-16 Although anesthesia and intensive care have improved during this period, the factor most commonly deemed responsible for this increased survival has been TPN. Short-Bowel Syndrome.-Short-bowel syndrome may be the result of a congenitally short intestine or massive surgical resection in association with one of several intestinal problems, including necrotizing enterocolitis, malrotation and volvulus, trauma, and Crohn's disease. Before the advent of TPN, patients with any of the aforementioned disorders had an extremely high mortality rate, which stemmed ultimately from the ill effects of malnutrition.F:" In a 1972 review of the literature, Wilmore" concluded that a minimum of 30 em of intact small bowel with an ileocecal valve was necessary to ensure survival. Infants with 15 to 29 em of remaining small bowel had a 50% survival rate, but survival was impossible with less than 15 em of small intestine. Since the advent of TPN as supportive therapy and because of the ability of infant intestine to grow in length as well as in surface area, some patients with less than 15 em of bowel can now survive, and the expectation of being weaned from TPN to enteral nutrition is reasonable.i? In a recent series of patients with short-bowel syndrome who had residual small intestine that was less than 25% of the normal length expected for gestational age, the long-term survival rate was 86%, primarily because of the supportive advantage provided by TPN,2I Premature and Low-Birth-Weight Infants.- The use of TPN in the intensive care of premature and low-birth-weight
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infants has become part of the management protocol in most stead, these infants received nutrition parenterally. In the neonatal centers throughout the United States. Low-birth- other group of 18 neonates, incremental enteric feedings of weight infants frequently have major problems, such as re- diluted infant formula or breast milk were administered durspiratory distress syndrome, congenital cardiac disease, im- ing the first 2 weeks of life. The overall incidence of mature kidneys, and an immature digestive system, that limit necrotizing enterocolitis in the parenterally fed group was 60% (12 of 20) in comparison with 22% (4 of 18) in the their ability to ingest and absorb adequate calories. In a controlled study of peripheral lipid-based TPN in group who received early oral feedings. The study showed infants with respiratory distress syndrome, Gunn and co- that withholding oral feedings for 2 weeks postnatally does workers-' showed that, in 40 premature infants, TPN neither not decrease the incidence of necrotizing enterocolitis; in favorably altered the course of respiratory distress syndrome fact, it may promote its occurrence. As a result of this and nor worsened the infants' pulmonary status. Infants with other studies, low-birth-weight infants are frequently being respiratory distress syndrome who weighed less than 1,500 g managed with a combination of enteral and parenteral nutriand who received TPN had an increased survival rate, how- tion and with a gradual increase in and conversion to total ever, in comparison with control subjects (71% and 37%, enteral nutrition as the infant's gastrointestinal tract marespectively). These data should not be interpreted to sug- tures. 26•27 Attributing improved survival of low-birth-weight gest that only infants who weigh less than 1,500 g should infants to better nutritional support is tempting; however, receive TPN. The current emphasis should be on the impor- other aspects of neonatal and obstetric care have improved tance of nutritional support, by either the parenteral or the considerably. Hence, the contribution of nutritional support enteral route, in all compromised infants. Use of the enteral is difficult to isolate in this group of high-risk infants." route, if possible, is always preferred because it is more physiologic and less expensive than the parenteral route. CONTRAINDICATIONS TO TPN Nonetheless, the more premature the infant, the greater the Contraindications to parenteral nutrition include severe conhazards of enteral nutrition because of the immaturity of the genital (usually genetic) defects (for example, trisomy 13 gastrointestinal tract; this factor shifts the balance in favor of and pentalogy of Cantrell) and terminal cancer, disorders in which life expectancy and quality of life are severely dethe parenteral route. The immature digestive system of premature and low- creased. Because withdrawal of TPN is always difficult, the birth-weight infants is associated with frequent incompe- decision to initiate intravenous nutrition in patients with such tence of the gastroesophageal sphincter, delayed gastric conditions should be carefully evaluated. Physician-family emptying, intestinal dysmotility, and a decreased gastroin- interaction and individual moral considerations are obvitestinal immune response-all of which make the provision ously important. In patients in whom life expectancy is of adequate enteral calories difficult and hazardous and in- limited, physicians should consider comfort and quality of crease the probability of occurrence of necrotizing entero- life provided by intravenous fluids for hydration rather than colitis. Thus, the intravenous administration of calories is by TPN. Generally, TPN should be reserved for those innecessary while the gastrointestinal tract is continuing to fants who receive active medical or surgical treatment. In develop and become more functional." Yu and co-workers> addition, because of potentially serious metabolic and catheconducted a controlled trial of TPN in 34 preterm infants ter-related complications, TPN should be used only in those whose birth weights were less than 1,200 g. The infants who children who cannot be nourished by bolus or continuous received TPN had a greater mean daily weight gain during tube feeding. TPN should not be regarded as an alternative the second week of life and regained birth weight sooner to enteral feeding, nor as a substitute for appropriate medical than did the control infants. Necrotizing enterocolitis devel- or surgical therapy. oped in four infants in the milk-fed control group but in none who received TPN. TEAM APPROACH AND SAFETY OF TPN Necrotizing Enterocolitis.-The term "necrotizing en- The team approach to parenteral and enteral nutrition in terocolitis" denotes a clinical state of intestinal inflammation pediatric patients is necessary and has substantially deand infarction detected most commonly in low-birth-weight creased the associated mechanical problems, catheter sepsis, or premature infants and associated with major stresses that and metabolic complications. In addition, the team approach frequently accompany prematurity. In order to test the hy- provides important education for floor nurses and patients pothesis that delayed oral feedings would decrease the inci- and their families." Stable patients who are receiving longdence of necrotizing enterocolitis in neonates who weighed term nutritional support, including infants, should be considless than 1,500 g, LaGamma and co-workers" compared two ered for home parenteral nutrition. The cost can he dematched groups of newborns. In one group of 20 newborns, creased by 50% or more when patients are transferred from no oral feedings were offered during a 2-week period; in- an inpatient to an outpatient environment for treatment."
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Parenteral nutntion is safe in pediatric patients when administered by protocol; short-term risks, such as catheter sepsis, mild reversible liver dysfunction, and cholelithiasis, are similar to those in adults. Long-term risks, including hepatic toxicity and failure, are more serious than short-term risks-because of the immaturity, and hence greater vulnerability, of the infant liver." Long-term risks in children older than I year of age are similar to those in adults; the major differences are compromised growth and development in children up to the late teenage years.
COST AND ETHICAL ISSUES OF TPN In properly selected pediatric patients, direct and indirect costs for parenteral nutrition may be significantly less than those in adults but are frequently similar." Pediatric patients, however, potentially have a more favorable cost-tobenefit ratio than do adult patients when life expectancy, parental pleasure, and potential work productivity are considered. The implications for third-party payers are generally positive for short-term use but negative for lifetime requirements. Ethical and social issues in initiating and discontinuing parenteral nutrition must be individualized and are best decided during thorough empathic discussions between physicians and parents. The critical decisions hinge on choosing between what can be done and what should be done for an individual patient." Legal concerns, particularly in consideration of the dimensions of denying adequate nutrition, are often complex, disruptive, and difficult to resolve. Psychologic implications of long-term use of TPN are extremely variable and must be assessed individually. Experience with parenteral nutrition has led to an enhanced understanding of nutritional biochemistry and gastrointestinal physiology and has enabled physicians to achieve bowel rest for their patients and to induce healing that would not otherwise be possible.
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CONCLUSION TPN, when properly used, is extremely valuable in the care of pediatric patients in whom enteral feedings are impossible, inadequate, or hazardous. Selection and management of patients must be carefully assessed to avoid unnecessary exposure to the potential complications of this treatment modality.
REFERENCES 1. Denson SE: Nutrient considerations in IV support of the neonate. In The Compromised Neonate. Edited by AG Coran, SE Denson, AB Fletcher, B Bernard. Berkeley, California, Cutter Laboratories, 1980, pp 10-15; 24 2. Dickerson JWT, Dobbing J, McCance RA: The effect of undernutrition on the postnatal development of the brain
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and cord in pigs. Proc R Soc Lond [Biol] 166:396-407, 1966-67 Winick M, Rosso P: The effect of severe early malnutrition on cellular growth of human brain. Pediatr Res 3:181-184, 1969 Dobbing J: The later development of the brain and its vulnerability. In Scientific Foundations of Paediatrics. Edited by JA Davis, J Dobbing. Philadelphia, WB Saunders Company, 1974, pp 565-577 Heird WC, Driscoll 1M Jr, Schullinger IN, Grebin B, Winters RW: Intravenous alimentation in pediatric patients. J Pediatr 80:351-372,1972 Wesley JR, Khalidi N, Faubion WC, Kovacevich DS, Braunschweig CL, Maksym CJ, Revesz SM, Perez AM, Wilson DD, Marikis B, Coran AG: The University of Michigan Medical Center Parenteral and Enteral Nutrition Manual. Chicago, Abbott Laboratories, Hospital Products Division, 1990, pp 54-69 Holcomb GW III, Ziegler MM Jr: Nutrition and cancer in children. Surg Annu 22:129-142,1990 Kerner JA Jr: Indications for parenteral nutrition in pediatrics. In Manual of Pediatric Parenteral Nutrition. Edited by JA Kerner Jr. New York, John Wiley & Sons, 1983, pp 3-17 Weber TR, Tracy T Jr, Connors RH: Short-bowel syndrome in children: quality of life in an era of improved survival. Arch Surg 126:841-846,1991 Coran A, Wesley JR: The pediatric patient. In Nutrition and Metabolism in the Surgical Patient. Edited by JR Kirkpatrick. Mount Kisco, New York, Futura Publishing Company, 1983, pp 461-482 Pereira GR, Glassman M: Parenteral nutrition in the neonate. In Parenteral Nutrition. Edited by JL Rombeau, MD Caldwell. Philadelphia, WB Saunders Company, 1986, pp 702-720 Varma RN, Suskind RM: Parenteral nutrition in the pediatric patient. In Parenteral Nutrition. Edited by JL Rombeau, MD Caldwell. Philadelphia, WB Saunders Company, 1986, pp 721-730 Bill AH Jr: Gastroschisis. In Pediatric Surgery. Vol 1. Second edition. Edited by WT Mustard, MM Ravitch, WH Snyder Jr, KJ Welch, CD Benson. Chicago, Year Book Medical Publishers, 1969, pp 685 c689 Dudrick SJ, Copeland EM III, MacFadyen BV Jr: Long-term parenteral nutrition: its current status. Hosp Pract (Off Ed) 10:47-,58, 1975 Wesley JR, Drongowski R, Coran AG: Intragastric pressure measurement: a guide for reduction and closure of the silastic chimney in omphalocele and gastroschisis. J Pediatr Surg 16:264-270,1981 Wagner CW, Parrish RA: Gastroschisis. Am Surg 47:174177,1981 Benson CD: Miscellaneous causes of small bowel obstruction. In Pediatric Surgery. Vol 2. Second edition. Edited by WT Mustard, MM Ravitch, WH Snyder Jr, KJ Welch, CD Benson. Chicago, Year Book Medical Publishers, 1969, pp 868-872 Heird WC, Winters RW: Total parenteral nutrition: the state of the art. J Pediatr 86:2-16,1975 Wilmore DW: Factors correlating with a successful outcome following extensive intestinal resection in newborn infants. J Pediatr 80:88-95, 1972
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