1. BY:DR.B.IMANI ASSISTANT PROF OF PEDIATRICS TPN

2. Introduction Total parenteral nutrition (TPN) The goal of TPN is to initially provide sufficient nutrients to prevent negative energy and nitrogen balance and essential fatty acid deficiency and support normal growth of appropriate composition without increased significant morbidity.

3. Introduction short-term outcomes : lower propensity to infection and shortened hospital stay longer-term outcomes :decreased growth deficits, improved neurodevelopment, and overall morbidity

4. Clinical Indications Gastrointestinal surgery(gastroschisis, meconium and paralytic ileus, short bowel syndrome ) Extreme prematurity Necrotizing enterocolitis severe illness such as septicemia or cardiac failure – often with ileus. malabsorption respiratory distress (Preterm who will not reach full feeds in 3-4 days or term babies where oral feeds not possible for 7 days).

5. General indications TPN therapy is indicated for patients: Requiring long-term (>10 days) supplemental nutrition. Requiring total nutrition because of severe gut dysfunction or inability to tolerate enteral feedings. When enteral feeding cannot be established, TPN is usually helpful: After major surgery. In patients with enterocutaneous fistulas, both high and low. In patients with inflammatory bowel disease.

6. Specific indications TPN therapy is part of routine care in: Patients who cannot eat or absorb nutrients through the GI tract because of: Massive bowel resection Diseases of the small bowel Radiation enteritis Malnourished patients undergoing high-dose chemotherapy or radiation therapy. Patients with severe necrotizing pancreatitis when enteral feeding is not possible. Patients with severe malnutrition and nonfunctional gut. Severely catabolic patients whose gut cannot be used within 5 to 7 days.

7. Clinical Considerations NEONATE: <1500 grams should be started on TPN by 48 hours of age unless they are expected to be tolerating full feeds within 24-48 hours. NEONATE>1500 grams should be started on TPN by 72 hours of age if they are not expected to be enterally fed by day 5.

8. INFUSION ROUTES 1. Peripheral route is used for partial or supplemental PN. This route is usually used for short-term nutritional support. Peripheral PN solutions cannot exceed 12.5% dextrose or 3.5% amino acids due to the risk of thrombophlebitis and should not contain calcium because of the serious complications resulting from extravasation of calcium. 2. Central PN is delivered by a venous catheter with the tip in a central location (DW30%).This route is used for patients who require long-term nutritional support, usually TPN.

9. Components of TPN Solutions TPN provides some or all nutrients of basal metabolism and growth for: fluid, energy, macronutrients (protein, carbohydrate, and fat) and micronutrients (electrolytes, major minerals, trace minerals, and vitamins).

10. Daily Energy Requirements (Nonprotein kcal/kg) Age Non-protein(kcal/kg) Preterm 120-140 Term 100-120 < 6 months90-120 6-12 months80-100 1-7 yr75-90 7-1260-75 >12-1830-60

11. Increase caloric requirements Fever12% for each degree above 37oC Cardiac Failure 5-25% Major Surgery20-50% Burnsup to 100% Long term growth failure50-100% Protein calorie malnutrition50-100%

12. Fluid

13. Maintenance requirements for fluid Body weight Fluid requirements per day 1-10 kg. 100ml/kg 11-20 kg.1000 mls plus 50 ml/kg for each kg > 10 kg. > 20 kg.1500 mls plus 20 ml/kg for each kg > 20 kg.

14. Macronutrients Energy needs may be increased with: infection, chronic lung disease, healing, growth, and in babies who have experienced intrauterine growth restriction (IUGR). Energy needs may be decreased with: sedation, mechanical ventilation, and after tracheostomy placement.

15. Micronutrients Electrolytes. Sodium, potassium, and chloride are essential to life and requirements are dependent on obligatory losses, abnormal losses, and amounts necessary for growth.

16. Major Minerals Calcium, phosphorus, and magnesium are the most abundant minerals in the body. They are closely interrelated to each other in metabolism, the formation of tissue structure, and function.

17. Preterm infants and term infants receiving long-term parenteral nutrition are at increased risk for bone demineralization and fractures. Calcium (Ca) and phosphorus (P) delivery should be maximized for all infants receiving PN. (approximately 1 mEq Ca=2mg Calcium gluconate)

18. Clinical Considerations 1. Sodium: Very small infants with poor renal tubular function may need as much as 8-10 mmol/kg/day. In premature infants who suffer from persistent metabolic acidosis due to urinary loss of bicarbonate it may be helpful to give 50% of the sodium as acetate. 2. Potassium: May require adjustment if the infant is on diuretics or has poor urine output. 3. Chloride: Ordinarily this amount is delivered automatically as a side effect of the usual doses of NaCL and KCL in the IV.

19. Clinical Considerations 4. Magnesium: An abnormally high magnesium level may be due to maternal treatment with magnesium sulfate. * Remove Mg from TPN if serum Mg is greater than 1.25 mmol/L. Resume Mg when levels normalize. The renal clearance of magnesium is poor during the first few days and infants may accumulate magnesium given in the TPN solution and reach even higher levels with no warning. Do not start magnesium until the serum level is <2.5 mg/dL. 5. Calcium: Higher risk infants may require higher doses of calcium. *Ensure Ca:Phos molar ratio is 1:1 – 1.3:1 for optimal mineral retention.

20. Major Minerals ElementDaily Amount Sodium2-5 meq/kg Potassium2-5 meq/kg Chloride2-5 meq/kg Magnesium0.25-0.5 mEq/kg Calcium gluconate*0.5-2.5 mEq/kg Phosphorous1-2 mmol/kg * 110 mg is used in standard pediatric TPN; gluconate is the recommended Calcium salt in Parenteral Nutrition solutions since this salt dissociates less than chloride salt.

21. Trace Minerals Copper, selenium, molybdenum, and iron can be delivered separately also..Copper and manganese are discontinued from TPN solutions with the complication of cholestasis, and amounts of chromium, selenium, and molybdenum are reduced or omitted when renal output is low. Minimal enteral feedings are also a source of copper within the first two weeks.

22. Iron Parenteral iron supplementation may be delayed until two months of age in premature infants and three months of age in term infants and considered for those infants who do not receive regular blood. Iron - is not a standard part of TPN solutions, but may be added to solutions as Iron Dextran when oral iron therapy is precluded by GI problems. Monitor serum ferritin levels. A test dose of iron dextran must be given.

23. Trace Elements 1. Cholestatic Liver Disease: Conjugated Bilirubin > 2.5 mg/dL reduce trace elements to twice weekly. If receiving enteral nutrition, discontinue trace elements. 2. Persistent diarrhea and GI loss: Increase Zinc

24. Trace elements Trace elements are recommended as 0.2 mL/kg/d of trace element solution containing zinc, manganese, copper, and chromium. Preterm infants need additional zinc (300 mcg/kg/d) and selenium (2 mcg/kg/d). Term infants need additional zinc (200 mcg/kg/d) and selenium (2 mcg/kg/d). For infants with cholestasis discontinue the trace element solution and give: Zinc 400 mcg/kg/d TOTAL (preterm infants) 300 mcg/kg/d TOTAL (term infants) Chromium 0.2 mcg/kg/d Selenium 2 mcg/kg/d Discontinue selenium with patients on renal dialysis.

25. Vitamins. MVI Pediatric is the only parenteral multivitamin solution designed for pediatric. The standard dose of 2 mL/kg/d with a maximum intake of 5 mL/d provides lower amounts of vitamin A and higher amounts of most of the B vitamins. Furthermore, intravenous vitamin delivery may be less due to photodegradation of vitamins A, D, E, K, B2, B6, B12, C, and folic acid and absorption of vitamins A, D, and E into the vinyl delivery bags and tubing.

26. Heparin (1 unit/mL) is added to all central venous lines and to all peripheral infusions running at <2 mL/hr in order to maintain catheter patency.

27. Initiation and Advancement of Macronutrients in TPN Solutions Provision of greater than 70 kcal/kg/d and 2.7 to 3.5 g protein/kg/d has been demonstrated to support growth and positive nitrogen balance in preterm infants.

28. Carbohydrate Carbohydrate is delivered in 2.5 to 30% dextrose solutions that provide 3.4 kcal/g. Glucose is the energy source for all cells and is essential for the central nervous system (CNS), erythrocytes, and other tissues. 4 to 6 mg/kg/min; 8 to 10 mg/kg/min in ELBW infants provides 40 to 50 kcal/kg/d and preserves carbohydrate stores. Advance by 1-3 mg/kg/min daily to a maximum of 12 mg/kg/min (up to 15 mg/kg/min in selected cases).

29. Carbohydrates Dextrose mg/kg/ min g/kg/day Initial dose 6 – 8 7 Avg. daily increase 1 – 3 0.5 – 1 Maximum dose 12 – 14 10 – 17 Energy value 3.4 kcal/g; 2.8 kJ/mmol (14.3 kJ) Conversions 1 mmol = 0.2 g = 200 mg = 2.8 kJ (0.67 kcal)

30. Adjust the percent dextrose daily according to the infant's tolerance as measured by glucometer, blood sugars and urine dipsticks. Note: The maximum percent dextrose should not exceed 12.5% when delivered peripherally or 30% centrally. 2. If plasma glucose concentration is greater than 8.3 mmol/L sepsis should be evaluated and treated.

31. Potential complications/risks include: Hyperglycemia or hypoglycemia Glycosuria and potential osmotic diuresis Excess co2 production Cholestasis and/or hepatic steatosis with high caloric intake usually from long-term high concentration infusion.

32. protein Amino acid solutions provide 4.0 kcal/g of protein. provision of at least 1 g/kg/d of amino acids can decrease catabolism. ELBW infants can generally receive 2 g/kg/d of amino acids on the first day of life. Protein requirements may be increased to counter catabolic or excretory losses in clinical conditions such as postoperative wound- healing, chronic lung disease treated with steroids, lymphatic injury with a sustained chyle leak, and/or during sustained periods when infants require limited or withheld enteral feeding or higher amounts of protein for catch- up growth.

33. New ESPGHAN Guidelines 2010 Recommendation of two different protein intakes: Preterm babies <1000 g : 3.6 – 4.1 g/100 kcal Preterm babies 1000-1800 g: 3.2 – 3.6 g/100 kcal

34. Protein Protein g/kg/day Initial dose (by 48 hrs) 1.5 Avg. daily increase 0.5 Max usual dose 3.8 Energy Value: 4 Kcal/g (16.8 kJ/g) 1. Restrict protein dose in renal failure and hepatic failure to 0.5-1.5 g/kg/day. 2. For infants with sepsis, high cardio-pressor support, or significant birth asphyxia, start at 1g/kg/day and advance as tolerated.

35. Daily protein requirements (g/kg) Neonates 2.5-3 gm/kg Infants2.0-2.5 gm/kg Children 1.5-2.0 gm/kg Adolescents0.8-2.0 gm/kg Critically Ill1.5-2.0 gm/kg

36. Complications of Excess Protein Administration Azotemia Abnormal Plasma Aminograms Acidosis Elevated BUN Hyperammonemia Cholestasis with prolonged administration

37. Fat Fat is delivered as lipid emulsions of neutral triglycerides (TG), primarily polyunsaturated fatty acids (PUFA) that are essential for normal growth and development, retinal development and function, brain development, and cell structure and function. Lipid emulsions provide a concentrated source of energy, 10 kcal/g of fat. Adequate administration of lipids prevents essential fatty acid deficiency, promotes positive nitrogen balance, and optimizes energy utilization.

38. Fat The lipid emulsion is advanced as tolerated in incremental rates of 0.5 to 1 g/kg/d to a typical maximum of 3 g/kg/d.In a balanced TPN solution, this generally approximates about 30% of total calories from fat. Fluid-restricted, growth-compromised patients or those limited to peripheral line access may require as high as 3.5 to 4 grams fat/kg/d to achieve adequate energy for growth and protein sparing.

39. Lipids Lipids Initiate by 48h of Age_ Initial dose (g/kg/day) 1 g/kg/day Increase every 2-3 days 0.5 g/kg/day Maximum dose (g/kg/day) 3-4 g/kg/day _ Energy Value 20% - 2 kcal/mL; 8.4 kJ/mL and 0.2 g/mL

40. Check TG level after each incremental increase in IV lipid. 2. Maintain serum TG level below 2.26 mmol/L. *If TG > 2.26 mmol/L reduce or discontinue IV lipid and ensure at least 0.5-1 g/kg/day of fat to prevent essential fatty acid deficiency (EFAD).

41. Clinical Considerations 3. Infants with sepsis or with severe compromise in oxygenation and/or severe hyperbilirubinema should be maintained at 0.5 – 1 g/kg/day. 4. Initiate IV lipids within the first 3 days of life to prevent essential fatty acid deficiency (EFAD). Minimum intake to prevent EFAD is 0.5 – 1 g/kg/day. **Reported complications of high lipid levels a) Enhancement of RBC and platelet clumping. b) Competition of free fatty acids with bilirubin for albumin binding sites. c) An adverse effect of the oxygen diffusion capacity in the lungs. d) Deposition on intravenous lipids in the RES (reticuloendothelial system) and potential blocking of RES function.

42. lipid infusion rates less than or equal to 0.15 g/kg/h are recommended to span over 24 hours. The delivery of 3 g/kg/d of a 20% lipid emulsion equates to an infusion rate of 0.125 g/kg/h.Premature infants have limited fat stores and lipoprotein lipase concentrations that may hinder their ability to clear plasma lipids following infusions of intravenous fat.

43. Fat: There are potential safety concerns regarding administration of lipid emulsions to very low birth weight infants and infants with hyperbilirubinemia, pulmonary hypertension and serious pulmonary disease. To maximize benefits of lipids and minimize their adverse effects, use the following guidelines: (a) provide sufficient lipids to prevent essential fatty acid deficiency; (b)monitor for evidence of lipid intolerance; (c) adjust lipid dose based on clinical status.

44. GUIDELINES FOR ADMINISTERING 20% LIPID EMULSION (2)(6) PrematureFull-TermOlder SGA InfantsAGA InfantsChildren Initial Dose0.5 gm/kg/day1gm/kg/day 1gm/kg/day (2.5ml/kg/day)(5ml/kg/day) (5ml/kg/day) Increase Daily Dose by0.25 gm/kg/day 0.5 gm/kg/day 1gm/kg/day (1.25ml/kg/day) (2.5ml/kg/day)(5ml/kg/day) Maximum Dose3 gm/kg/day4 gm/kg/day 2 gm/kg/day (15 ml/kg/day)(20 ml/kg/day) (10 ml/kg/day)

45. Complication Hyperlipidemia Potential risk of kernicterus at low levels of unconjugated bilirubin because of displacement of bilirubin from albumin binding sites by free fatty acids. As a general rule, do not advance lipids beyond 0.5 g/kg/d until bilirubin is below threshold for phototherapy Potential increased risk or exacerbation of chronic lung disease Potential exacerbation of Persistent Pulmonary Hypertension (PPHN) Lipid overload syndrome with coagulopathy and liver failure

46. Clinical Monitoring of Nutrient Adequacy, Compatibility, and Tolerance of TPN Solutions Accurate and routine monitoring of growth measures is necessary to prevent over- or undernutrition from TPN support. Further, routine monitoring of solution compatibility and tolerance is required to prevent morbidity.

47. requires 0.4 cc of blood in each of 2 microtainer tubes (i.e., 0.8 cc total). It is usually drawn on mondays with additional individual labs as needed or suggested above. Test Initial When stable Electrolytes, BUN/creatinine Daily 2-3x/week Chemstrip/glucose q6hr-daily Daily, more frequently when changing CHO Calcium, ionized daily 2-3x/week Total calcium, phosphorus, magnesium, bilirubin (T/D), ALT, alkaline phosphatase, GGT, albumin Baseline weekly Triglycerides When lipid infusion reaches 1.5 g fat/kg/d and 3 g fat/kg/d weekly CBC/Diff and platelets

48. Growth Monitoring Weekly lengths and head measurements, in addition to daily weights, are important to ensure that overall growth is occurring and not simply weight gain. Although accurate and reproducible lengths are more difficult to obtain among clinicians, they are a better indicator of lean body mass and not influenced significantly by edema. For infants to grow optimally, ongoing assessment of growth in relation to daily estimates of nutrient intake is necessary. It is critical for practitioners to be cognizant of the actual amount of TPN that is delivered to a patient and not to assume that it approximates 100% of what is ordered.

49. TPN WEANING GUIDELINES When the patient is tolerating >50 ml/kg/day of feedings, the TPN should be gradually tapered off.

50. DISCONTINUING PARENTERAL NUTRITION: PN may be stopped when the infant is tolerating ≥100-120 cc/kg of enteral feedings or is receiving ≤25 cc/kg/d of PN. The rate of dextrose administration should be tapered to prevent rebound hypoglycemia. Chemstrips should be done q6h. Newborns need a slower tapering than older children and require continued monitoring of glucose after the solution has been stopped. Lipids may be stopped without tapering. If the PN catheter clots or infiltrates, start another IV with dextrose concentration ≤12.5% depending on the current glucose concentration

51. Transitional Feeds Reduce IV Lipid by 50% when infant tolerates > 50% of TFI as enteral feeds Discontinue TPN when an infant is tolerating 75% of full enteral feeds.

52. CONTRAINDICATIONS Contraindications to the initiation of enteral nutrition include bowel obstruction, severe and protracted ileus, major upper gastrointestinal bleeding, intractable vomiting or diarrhea, hemodynamic instability, significant bowel wall edema, gastrointestinal ischemia, a high output fistula, and a gastrointestinal anastomosis distal to the infusion site. Contraindications to parenteral feeding include severe hyperglycemia, hyperosmolality, and severe fluid and electrolyte abnormalities.