Continuous medical education on total parenteral nutrition

Total parenteral nutrition

1. Total Parenteral Nutrition Dr Subhash Chandra Shaw MD, DNB, MNAMS, DM (Neo) Command Hospital, Kolkata

2. 2 Slide courtesy: Dr Ashish Jain, MAMC, New Delhi

3. Objectives Rationale Indications Constituents Calculation Complications

4. What is optimal growth? Growth that approximates the in utero growth of a normal fetus Objectives: Preventing negative energy balance by providing sufficient calories and amino acids Promoting appropriate weight gain Means: Enteral nutrition and if not feasible parenteral nutrition

5. What is so unique about ELBW? Minimal accretion, limited nutrition stores at birth Take time to establish enteral feeding Gut immaturity Feeding skills Different requirements Higher fluid requirement Illnesses Need rapid growth Possibility of intervention high Supplementation

6. Why is nutrition important? Fetal growth ~ adult onset diseases Poor growth low brain volume adverse neurodevelopmental outcome Infection, gut atrophy, bone fracture

7. Why is it important to maintain growth ? Maximizing growth is of paramount importance to minimize the risk of poor neurologic outcomes. In extremely low birth weight (ELBW) infants, the risk of neurologic impairment at 18 months of age increased from 29% in infants gaining an average of 21 g/kg/d to 55% in those gaining an average of only 12 g/kg/d . Ehrenkranz et al. , Seminars in Perinatology , Vol 27, No 4 (August), 2003

8. Consequences of under nutrition Short term Long term Increased vulnerability to infection Greater free radical damage Greater need of ventilator support Poor growth Poor neurodevelopment outcome Susceptibility to cardiovascular diseases Reduced cell growth in specific organ systems (heart, kidney, pancreas Lucas A, Randomized trial of early diet in preterm infants. BMJ 1998

9. A case study Baby X, birth weight: 960 gm Not tolerating enteral feeds Day 10 of life N/5 in 10% Dextrose @ 150 ml/kg/day Calories: 48 kCal /day Caloric requirement: 120 kCal /day Proteins ? Fats ? Vitamins ? Trace elements? Huge caloric deficit Catabolic state

10. Glucose alone as nutrition

11. Postnatal weight loss

12. Aggressive nutrition to prevent extrauterine growth restriction Aggressive nutrition to prevent extrauterine growth restriction Adamkin DH. J Perinatol . 2005;25( suppl ):S7–S11

13. Why is TPN not used? Think TPN is not needed Nutrient solutions not available Do not know how to give TPN Not trained for central venous access Do not have pharmacy support Afraid of sepsis/other complications My patients can not afford it There are no ready made standardized PN bags

14. Candidates for PN Before starting parenteral nutrition or any component of it answer following questions: Is it needed? (Why?) Is it safe? If needed and can be provided safely: When to start? How much to start? How to make increments? Maximum? What to monitor?

15. Indications Birth weight < 1 kg Birth weight 1- 1.5 kg and significant enteral intake not expected for > 3 days Birth weight > 1.5 kg and significant enteral intake not expected for > 5 days AIIMS Protocol: A neonate not likely to be on at least 50% of expected energy intake by enteral route at day 7 of life e.g. all ELBW babies

16. Indications (cont..) Surgical conditions Omphalocele Gastroschisis Intestinal atresia Meconium peritonitis CDH Short bowel syndrome Medical indications NEC ECMO Meconium ileus

17. Constituents Protein Lipid Carbohydrate Electrolytes Vitamins Trace elements

18. Ideal amino acid solution Should provide- essential and conditionally essential amino acids Should contain taurine, cysteine No excessive glycine, methionine No sorbitol

19. Preparations-amino acids

20. Available amino acid mixtures Amino-acid preperation Glycine Sorbitol Taurine Cysteine Hermin excess + - - Alamin excess + - - Astymin-3 excess + + + A minodrip excess - + - Aminoplasma p * + - - + Aminoven* + - + +

21. Aminoven infant 10%

22. Amino acids – how much?

23. Amino acids - how much? Minimum 1 - 1.5 gm/kg/day to avoid catabolism Standard protocol: To start at 1 gm/kg/day and increase by 0.5 - 1 gm/kg/day to maximum 4 gm/kg/day Aggressive protocol: Start at 2.5 - 3.0 gm/kg/day within 24 hours of life and increase to 4 gm/kg/day Nahed O. ElHassan and Jeffrey R. Kaiser Parenteral Nutrition in the Neonatal Intensive Care Unit, Neoreviews 2011

24. Energy and protein Edmond K, Bahl R Optimal feeding of low-birth-weight infants.

25. Carbohydrate Main energy substrate for fetus and neonate especially preterm Largest glucose utilizing organ is brain Glucose utilization rate is twice as high early in gestation Glycogen deposition starting in third trimester Glucose utilization directly related to plasma glucose level

26. Carbohydrate Glucose utilization rate at 28 weeks 6-8mg/kg/min- Term infants-3-5mg/kg/min Additional requirement of 2 -3 mg/kg/minute for each gm/kg of protein needed for protein accretion

27. Carbohydrates - what? Glucose available as 5% to 50% Osmolarity increases 255 mOsm /Lt. for D5W to 1010 mOsm /Lt. for D20W < 12.5% in peripheral line and >12.5% in central line Energy: 3.4 Kcal/gram

28. Carbohydrates Standard/Aggressive protocol: Start at 4 - 6 mg/kg/min and increase by 1 -2 mg/kg/min to 11 - 14 mg/kg/min Higher glucose infusion - conversion into fat - Increased O 2 consumption and CO 2 production Probably 18 mg/kg/day is maximal* * DeCurtis M, Rigo J. The nutrition of preterm infants. Early Human Dev 2012

29. Role of Insulin Helps control plasma glucose concentration, increases energy intake, promotes nitrogen retention and growth Start with a dose of 0.05 IU/kg/hr Evidence* No improvement in growth, sepsis, intracranial haemorrhage , NEC, CLD More episodes of hypoglycemia, mortality below 28 days Use only if remains hyperglycemic despite minimum glucose infusion rate, current evidence does not support routine use *Sinclair JC, Cochrane 2011, Bottinno M, Cochrane 2011

30. Lipid Why? Non protein energy source (Nitrogen sparing effect) Low volume isotonic energy dense Essential fatty acids Long chain polyunsaturated fatty acids (LC-PUFAs)

31. Lipid Essential fatty acids Deficiency can develop within 72 hours if external supply not provided (Foote KD/Am J Clin Nutr /1992) Deficiency can be prevented by 0.5 - 1.0 gm/kg/day of intravenous lipids Gutcher GR, Am J Clin Nutr 2012

32. Lipid What? Neutral triglycerides derived from soybean/safflower Phopholipids from egg yolk for emulsification Glycerol Only safflower oil not used as associated with deficiency of omega -3-fatty acids

33. Lipids Standard: <1 kg: start at 0.5-1.0 gm/kg/day Increase by 0.5 gm/kg/day to 3 gm/kg/day Do not increase above in ELBWs above 1.0gm/kg/day if significant NNH Lipids can be started at 3 g/kg per day* * Vlaardingerbroek H, Veldhorst MA, Spronk S, et al. Parenteral lipid administration to very-low-birth-weight infants—early introduction of lipids and use of new lipid emulsions: a systematic review and meta-analysis. Am J Clin Nutr . 2012 Torrazza R, Neu J. Evidence-based guidelines for optimization of nutrition for the very low birthweight infant. NeoReviews . 2013

34. Lipid-safety Concerns especially in ELBW neonates Pulmonary vascular resistance CLD Bilirubin displacement Oxidative stress Function of platelets and neutrophils Mortality Lipid infusion rates in excess of 0.25 g/kg per hour can be associated with decrease in oxygenation

35. SMOFlipid and other fish oil emulsions SMOFlipid (30% MCT, 30% soyabin oil, 25% olive oil and 15% fish oil) Anti inflammatory Immunomodulatory effects due to increased incorporation of W-3 FA Inhibits TNF, IL6, IL1b Modulates production of IL10 Better triglyceride clearance and increased lipid oxidation Considered to be useful in decreasing sepsis and chiolestatic liver disease

36. Carnitine Transport of LCFAs across mitochondrial membrane Limited ability to synthesize carnitine TPN infusion free of carnitine Low carnitine status status in preterm especially if TPN > 4 weeks Cochrane 2000: Carnitine supplementation of parenterally fed neonates no evidence of effect on weight gain, lipid utilization or ketogenesis

37. Vitamins PN- should contain mixture of fat and water soluble vitamin Vitamins to administer on daily basis except Vit K Fat soluble vitamins to mix with lipid to increase stability Adult formulations containing propylene glycol and polysorbate additive –not recommended

38. Suggested Parenteral vitamin intake Vitamin Term (daily dose) Preterm (dose/kg/day) MVI (1ML) Vitamin A (IU) 2300 1640 1000IU Vitamin D (IU) 400 160 100IU Vitamin E (IU) 7 2.8 0.5 mg Vitamin K (µg) 200 80 Vitamin B6 (µg) 1000 180 1.5 mg Vitamin B12 (µg) 1 0.3 Vitamin C (mg) 80 25 50mg Biotin (µg) 20 6 Folic acid (µg) 140 56 Niacin (mg) 17 6.8 10mg Pantothenic acid (mg) 5 2 2.5 mg Riboflavin (µg) 1400 150 1.4 mg Thiamin (µg) 1200 350 5 mg

39. Vitamins No ideal MVI prep. Vitamin-K to be given as Inj. 1 mg weekly Need for Vit-B12 and folic acid

40. Trace elements ( Celecel ) Zn - D1 Other trace elements >2 weeks Term ( µ g) Preterm( µ g/kg/day) Zinc 250 400(150 in< 2weeks) Copper 20 20 Selenium 2.0 2.0 Manganese 1.0 1.0 Molybdenum 0.25 0.25 Iodide 1.0 1.0 Chromium 0.20 0.20

41. Electrolytes Requirements Sodium 2-3mEq/kg/d (<1week); 3-6 mEq /kg/d (>1week) Potassium 1-2mEq/kg/d (after 48 hours) Chloride 2-3 mEq /kg/d Calcium 150- 200 mg/kg/d Magnesium 15-25 mg/d Phosphate 20-40 mg/kg/d

42. Calcium-Phosphorus Calcium-Phosphorus Ratio The desired ratio by weight of calcium to phosphorus in the parenteral nutrition 1.7 A normal calcium-phosphorus ratio - optimal bone mineralization. A reversed calcium-phosphorus ratio hypocalcemia an increase in PTH secretion (which leads to increased phosphate loss in the urine) osteopenia

43. Recommended Energy intake Committee Minimum Energy intake (kcal/kg/day) Maximum Energy intake (kcal/kg/day) American Academy of Pediatrics 105 130 Canadian Pediatric Society 105 135 European society for Gastroenterology and Nutrition 98 128 Life Sciences Research Office 110 135

44. Energy distribution Adequate balance between nitrogen and non-protein energy sources to promote protein accretion Protein/Energy ratio: 3-4 gm/100 Kcal Balance between carbohydrates and fat to prevent excessive fat deposition and excessive production of CO 2

45. Energy distribution Carbohydrates 50 – 55% Proteins 10 – 15% Fat 35 – 40%

46. TPN protocol Amino Acids Lipids Glucose Start on D1 D1-2 D1 Start at 1-2 gm/kg/day 1 gm/kg/day 6 mg/kg/min Increase by 1 gm/kg/day 1 gm/kg/day 2 mg/kg/minute Maximum 3-3.5 gm/kg/day 3 gm/kg/day 12 mg/kg/min Use 10% Aminoven 10% Intralipid PLR 20% Intralipid 5-50% Dextrose

47. TPN protocol Na K Ca Mg Trace elements MVI Start on D3 D3 D1 D1 D1/D14 D1 Dose 3-5 mEq /kg/d 2-3 mEq /kg/d 0.5-5 mEq /kg/d 0.25-0.5 mEq /kg/d Calculate by Zn 250-400 mcg/kg/day Calculate by Vitamin A 1500IU/kg/day Use 3% NaCl (0.5 mEq /ml) KCl (2 mEq /ml) 10% Calcium gluconate (4 ml/kg/d) 50% MgSO4 0.2 ml/kg TMA/ Celcel 0.6 ml/kg/d Generic MVI 1.5 ml/kg/d

48. Route of administration PICC and CVC should be used for PN CVC tip – to lie outside pericardial sac 0.5 cm in small infant, 1 cm large infant Tip of femoral catheter to lie above renal veins Perforation – with acute angle of catheter and vessel wall

49. Venous access Neonate- UVC can be used for PN- uvc-14 days and UAC 5 days Lipid emulsion to infuse separately Syringe – should not be less than 10 ml

50. Role of Heparin Prophylactic use of heparin 0.5 IU/kg/hr Reduces occlusion rate Duration of PICC line- no difference Prophylactic use of heparin for peripherally placed PCVC allows a greater number of infants to complete their intended use (complete therapy) by reducing occlusion Shah PS, Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters, Cochrane 2008

51. Assessment points Met Not met Presence of PICC team Identify and assess patient (history, time of last feed, coagulation tests etc as applicable) Obtain informed consent Pain relief Vein used for insertion (avoid use of femoral vein) Hand hygiene with soap and water before and after palpating insertion site Hand hygiene with soap and water before and after inserting PICC line Maximal barrier precautions (sterile gown, sterile gloves, surgical mask, cap) for inserter Maximal barrier precautions (sterile gown, sterile gloves, surgical mask, cap) for assistant Large sterile drape used and not small sterile fenestrated drape Disinfect skin with 2% chlorhexidine (Back and forth scrubbing motion for 30 sec) Sterile field maintained throughout procedure Use sterile transparent semi permeable dressing or sterile gauze to cover insertion site Catheter cap/clamp placed on all lumens Document placement in patient chart after confirming position Evaluation done daily for signs of infection(document on nurses chart) Dressing change done aseptically (if damp, soiled or loose) Scrubbing of hub by 2% chlorhexidine before inserting new i.v . tubing (document on nurses chart) Daily review of catheter necessity (document on nurses chart) Prompt removal if not necessary Minimum catheter access ports Heparin 0.5 units/ml added to TPN Investigation for any undesired outcome Checklist for PICC insertion and maintenance Patient Name CR No Date of Birth Name of Inserter and signature Name of Assistant and signature Signature of Chief Nurse/Leader PICC team

52. Laminar flow system for preparation of parenteral nutrition

53. Risks associated with parenteral nutrition Sepsis - both fungal and bacterial Mechanical complications related to venous line placement Occlusion, thrombosis, embolism Miscalculations and errors while preparation or administration

54. Risks associated with parenteral nutrition (cont..) Metabolic derangements Electrolyte imbalance Hypoglycemia Hyperglycemia Hypocalcemia Hypercalcemia Hypophosphatemia Hepatic dysfunction, cholestasis

55. PNALD Multiple factors Sepsis Hemodynamic instability Hypoxia Duration of TPN Degree of immaturity Delayed enteral feeding

56. Treatment of PNALD Decrease AA infusion Continue Lipid infusion, monitor triglyceride Change to SMOF-lipid if possible Start ursodeoxycholic acid (15 – 20 mg/ kg/ day) Treat sepsis if needed

57. Which units should make parenteral nutrition ? Good quality control Strict asepsis while preparation Strict asepsis while administration Multidisciplinary team including committed nurses

58. Ann Nutr Metab 2013;62(suppl 3):8–11

59. Take home messages Nutrition an important part of management including long term outcome Practical considerations for optimal parenteral nutrition Need of monitoring, asepsis, quality control and team work

60. Thank You