Heba Elkholy, Pharm. D A. Senior Clinical Pharmacist, SKMC

1. Heba Elkholy, Pharm. D A. Senior Clinical Pharmacist, SKMC

2. Goals • To provide a brief explanation about TPN. • To illustrate one common problem which could occur when writing TPN prescription and how it could be avoided. • To discuses the current Canadian guidelines recommendation supported by evidence based. • To briefly go through some calculations related to PPO TPN at SKMC

3. Total Parenteral Nutrition • Normal Diet • Protein • Carbohydrates • Fat • Vitamins • Minerals • Water

4. Total Parenteral Nutrition Normal Diet TPN • Protein………………...Amino Acids • Carbohydrates…….Dextrose • Fat……………………….Lipid Emulsion • Vitamins………………Multivitamin Infusion • Minerals……………….Electrolytes and Trace Elements

5. Carbohydrate-CHO • The most commonly used carbohydrate energy substrate is dextrose. • 1gm dextrose= 3.4 kcal/g. • According to the United States Pharmacopoeia (USP), dextrose are acidic, with a pH ranging from 3.5 to 6.5, and vary in osmolarity depending upon their concentration.

6. Carbohydrate-CHO • Higher dextrose concentrations (greater than 10%) are generally reserved for central venous administration • the propensity to cause thrombophlebitis in peripheral veins.

7. Use your brain True or false? Dextrose 10% can be given as peripheral?

8. Protein • Crystalline amino acids . • 4 kcal/g. • essential and nonessential amino acids.

9. Electrolytes • Daily Electrolyte Requirements • Sodium 1–2 mEq/kg • Chloride As needed to maintain acid–base balance • Acetate As needed to maintain acid–base balance • Calcium 10–15 mEq • Magnesium 8–20 mEq • Phosphate 20–40 mmol

10. How to Measure the Energy requirement? Harris–Benedict Equation • Men: Energy expenditure= 66 + 13.75 (wt in kg)+ 5 (ht) in cm -68 (age) • Women: Energy expenditure= 655 + 9.6 (wt in kg)+ 1.8 (ht in cm) -4.78 (age)

11. Energy for critically ill patient Swinmer: RMR (Kcal/day)= BSA (941)-age(6.3)+T (104)+RR(24)+Vt (804)-4243. Penn State: RMR (Kcal/day)= HBE (0.85)+Ve(33)+Tm (175)-6433

12. Special population Spontaneously Breathing Patients IJEE (s) = 629 − 11(A) + 25(W) − 609(O) Ventilator-Dependent Patients IJEE (v)=1784−11(A) + 5(W) + 244(S) + 239T+804(B).

13. TPN complication • Underfeeding: • Decreased respiratory muscle strength • Decreased ventilatory drive • Failure to wean from mechanical ventilation • Impaired organ function • Immunosuppression • Poor wound healing • Increased risk of nosocomial infection

14. TPN complication • Overfeeding: • Hyperglycemia • Azotemia • Hypertriglyceridemia • Electrolyte imbalance • Immunosuppression • Alterations in hydration status • Hepatic steatosis

15. osmolarity • Osmolarity is dependent on the dextrose, amino acid, and electrolyte Content. • PN is a hypertonic to body fluid. • Inappropriate administration can lead to venous thrombosis , thrombophlebitis, and extravasation. • For Peripheral TPN, maximum allowed osmolarity is 900 mosm/L.

16. Use your brain Which of the following may increase the risk of phlebitis with peripherally administered parenteral nutrition (PPN)? • A. Osmolarity ≤900 mOsm/L • B. Potassium 100 mEq/L • C. Intravenous fat emulsion (IVFE) piggybacked with PPN. • D. Addition of heparin to the PPN

17. When is TPN recommended? Criteria for 2007 A.S.P.E.N Guidelines • Patient has failed EN trial with appropriate tube placement (postpyloric). • When EN is contraindicated or the intestinal tract has severely diminished function due to the following: • Paralytic ileus • Mesenteric ischemia • Small bowel obstruction • GI fistula except when enteral access may be placed posterior to the fistula.

18. Critically ill patients • Gut failure in critically ill patients is common. • In critically ill patients, PN is indicated if EN is not possible, and hypermetabolism is expected to last more than 4 to 5 days. • Critically ill patients requiring PN are those who are: hemodynamically stable and have: • a paralytic ileus. • acute GI bleeding. • Complete bowel obstruction

19. Problem • What problem could occur when mixing TPN?

20. Calcium – Phosphorus compound • Calcium and phosphorus are common essential electrolytes in PN solutions . • If mixing in high conc.…… insoluble precipitate of ca-phosphate compound could occur. • PE secondary to ca-phosphate ppt. has been reported.

21. Calcium-Phosphate compatibility • Factors which affect stability • Additive concentration • Choice of calcium salt • Order of mixing • Amino acid product (brand) • Amino acid concentration • Dextrose Concentration • Temperature (not what you think) • Storage time • Addition of l-cysteine (neonatal)

22. Case report • Microvascular Pulmonary Emboli Secondary to Precipitated Crystals in a Patient Receiving Total Parenteral Nutrition, • 21-year-old man receiving immunosuppressive therapy and TPN developed fever, shortness of breath, and chest tightness. • This patient’s calcium-phosphate product was at times as high as 47.5 mmol/L • CHEST 1999; 115:892–895).

23. In response to this, the Food and Drug Administration (FDA) issued a safety alert warning of the hazards of TPN and offered guidelines that may help prevent future morbidity.

24. Different image of lung poorly marginated micronodules throughout all lung zones

25. Calcium-Phosphate compatibility How to minimize calcium phosphate precipitation • Additive concentration……..……....use lower the conc. • Choice of Ca ……..…..…...use Ca Gluconate, not CaCl2 • Order of mixing…....add phosphate first, calcium last • Amino acid product …Aminosyn best, FreAmine worst • Amino acid concentration……….…use higher AA conc. • Dextrose concentration………use higher Dextrose conc. • Temperature………………………………………….…Refrigerate • Storage time……………………....Minimized storage time • l-cysteine (neonatal) ……..greatly increases solubility

26. How can the physician help? • Please, Keep the total amount of calcium and phosphorus less than 45meq/L.

27. Calcium-Phosphate compatibility • Ca-Po4 chart

28. What are we doing regarding Pediatric patients? Compatibility of calcium and phosphate in four parenteral nutrition solutions for preterm neonates, LUIS PEREIRA-DA-SILVA, M.D., NURMAMODO, et al , Am J Health-Syst Pharm. 2003; 60:1041-4 . An inorganic source of phosphorus (monobasic sodium phosphate,NaH2PO4 27.5%) was used in mixtures A and C, while an organic source (sodium glycerophosphate [Glycophos] was used in mixtures B and D. Organic phosphates have been recommended as sources of phosphorus in PN solutions for premature infants because of their higher compatibility with calcium than inorganic phosphates.

29. What is new? Glutamine • amino acid that is reported to become “conditionally essential” during critical illness. • It is vital fuel for rapidly dividing cells such as fibroblasts, reticuloendothelial cells, malignant cell, and gut epithelial cells.

30. Glutamine • clinical conditions, such as exercise, trauma, and sepsis, the body’s glutamine requirement exceeds its ability to synthesize glutamine; this leads to a fall in plasma and intracellular glutamine which increased mortality.

31. Glutamine evidence-base • Efficacy of glutamine dipeptide-supplemented total parenteral nutrition in critically ill patients: a prospective, double-blind randomized trial. • Method: 53 assigned to Glu-TPN and 64 to S-TPN. • Critical Care 2008, 12(Suppl 2):P146.

32. Glutamine evidence-base Result: • Less new infections occurred in Glu-TPN patients: nosocomial pneumonia 8.04 versus 29.25 episodes-urinary tract infections 2.5 versus 16.7 episodes. • no differences in the incidence of catheter-related sepsis, primary bacteremia and intra-abdominal infections.

33. Glutamine evidence-base • Conclusion: Glu-TPN used in critically ill patients for longer than 3 days significantly reduces the incidence of nosocomial pneu-monias and urinary tract infections, and decreases the severity of organ failures.

34. Glutamine in different studies • glutamine supplementation reduces length of stay, particularly among surgical patients. • parenteral glutamine supplementation nutrition led to a statistically significant decrease in infectious complications and insulin resistance in critically ill patients. • The use of intravenous glutamine supplementation in critically ill patients on total parenteral nutrition is currently the standard of care.

35. Canadian Clinical Practice Guidelines,January 8th 2007 • Based on 4 level 1 studies and 5 level 2 studies, when parenteral nutrition is prescribed to critically ill patients, parenteral supplementation with glutamine, where available, is recommended. • There are insufficient data to generate recommendations for intravenous glutamine in critically ill patients who are receiving enteral nutrition.

36. TPN at SKMC

37. TPN at SKMC • Calculation of Peripheral TPN: • 2.75%=2.75gm /100ml= 27.5gm/1L. • Each 1gm AA give 4gm Kcal, • 1L of 2.75%AA has 110 kcal • 10% dextrose= 10gm/100ml= 100gm/1L • Each 1gm dextrose give 3.4Kcal • 1L of 10% dextrose= 340 Kcal • Total calories PPN = 110+ 340=450Kcal

38. TPN at SKMC • Calculation of central TPN: • 5%=5gm /100ml= 50gm/1L. • Each 1gm AA give 4gm Kcal, • 1L of 2.75%AA has 200 kcal • 25% dextrose= 25gm/100ml= 250gm/1L • Each 1gm dextrose give 3.4Kcal • 1L of 10% dextrose= 850 Kcal • Total calories central = 850+ 200=1050Kcal

39. Finally • Potential complications can be minimized if special attention is paid to each step of the preparation and administration of total parenteral nutrition solutions. • Cooperation between physician, pharmacist , dietitian and nurse results in the best outcome for those patients who are candidates for TPN administration.

40. The End • Thanks for your attention