What s In The Bag? 3-in-1 versus 2-in-1 PN

Transcription

1 What s In The Bag? 3-in-1 versus 2-in-1 PN Amber Verdell, PharmD, BCPS, BCNSP Assistant Professor, Pharmacy Practice West Coast University, Los Angeles, CA

2 Disclosures I have no commercial relationships to disclose

3 Learning Objectives Upon completion of this session, the learner will be able to.. Identify factors affecting stability of 3-in-1 PN solutions and recognize conditions that may lead to destabilization Describe the risks and benefits of compounding PN solutions as 3-in-1 versus 2-in-1 admixtures in various populations

4 Introduction 3-in-1 PN use was first reported in 1974 Increased efficiency but also increased complexity 3-in-1 PN is a complex mixture with up to 40 individual components Many clinicians have concerns regarding restrictions for 3-in-1 PN Chief concern is destabilization of the emulsion Solassol et al 1974

5 Factors That Affect 3-in-1 Stability Order of admixture Final ph Amino acid product used Final concentra;on of macronutrients AA>4% D>10% L>2% Electrolyte concentra;ons Addi;ves Storage condi;ons Aging/end use date

6 ph, (charge), and Emulsion Emulsifier provides a negative charge around the outside of the lipid droplet Acidic ph or positive charge cause the emulsifier to degrade and lipid droplets to aggregate 5 micron

7 ph, (charge), and Emulsion Emulsifier provides a negative charge around the outside of the lipid droplet Acidic ph or positive charge cause the emulsifier to degrade and lipid droplets to aggregate 5 micron

8 ph, (charge), and Emulsion 3-in-1 most stable at ph of 6.3 to 9 In contrast to a low ph desired for calcium-phosphate solubility Commercial lipid emulsion product adjusted to ph 8 At ph <5 or >10, fat droplets lose negative charge and aggregate Emulsion becomes unstable Also at ph < 5, egg-yolk phospholipid denaturates

9 Dextrose and Amino Acids Order of admixture Dextrose ph = 4 Final ph Should not be added directly to lipids Amino acid product ph is primary determinant of final ph Buffering capacity provided by amino acids Final ph of emulsion is often identical to amino acid ph

10 Choice of Amino Acid Product ph is the critical factor FreAmine (ph 6 6.5) Travasol (ph 6) Aminosyn II (ph ) Aminosyn (ph 5.3) TrophAmine (ph 5-5.5) Aminosyn PF (ph 5.4) Amino acid solutions with a ph of 5.3 or less should not be used for 3-in-1 compounding

11 Final Concentrations Amino Acid final concentration > 4% or 40 g/l Dextrose final concentration > 10% or 100 g/l Lipid final concentration > 2% or 20 g/l G/day limits depend on total volume

12 Electrolytes and Additives Divalent cations calcium, magnesium Very high concentrations will disrupt emulsion Neutralizes negative charge of emulsifier Generally, Ca meq/l + Mg meq/l < 30, but can go higher depending on formulation Trivalent Cations Iron dextran Stable in dextrose-based PN DO NOT admix or infuse with TPN formulation or lipid emulsion Other parenteral irons DO NOT admix or infuse with either dextrose-based PN or TPN

13 Storage and Aging Storage conditions High temperature will destabilize faster Aging/end use date stable for up to 30 hours at room temperature (25 C) or for 9 days refrigerated (5 C) followed by 24 hours at room temperature

14 Factors That Affect 3-in-1 Stability Order of admixture Final ph Amino acid product used Final concentra;on of macronutrients AA>4% D>10% L>2% Electrolyte concentra;ons Addi;ves Storage condi;ons Aging/end use date

15 Question Is the following 3-in-1 PN likely to be stable? 2.5 L; AA75g; D250g; L50g AA 30g/L; D 100g/L; L 20 g/l Why not? Which component should be changed? Which patients are unlikely to benefit from 3- in-1 PN?

16 Advantages of 3-in-1 Disadvantages of 3-in-1 Compounding: asep;cally compounded by pharmacy, more efficient, less manipula;on Administra;on less risk of contamina;on, inhibited bacterial growth, less nursing ;me, less supply and equipment, home advantages Clinical Improved dextrose and venous tolerance, possible fluid restric;on advantage, may be more cost effec;ve, fat clearance Ordering limita;ons on macronutrients and electrolytes Compounding difficult to visualize par;culate, less stable over ;me Administra;on can t use 0.2 micron filter, certain medica;ons are incompa;ble Clinical catheter occlusion more common Boullata et al 2014

17 Differences in Catheter Occlusion There is only one retrospective study that evaluated catheter occlusion rates with 3-in-1 vs 2-in-1 Increased rates of catheter failure and replacement in pediatric patients receiving 3- in-1 at home; 89% vs 25%, p=0.025 Erdman et al 1994

18 Differences in Catheter Occlusion

19 Advantages of 3-in-1 Disadvantages of 3-in-1 Compounding: asep;cally compounded by pharmacy, more efficient, less manipula;on Administra;on less risk of contamina;on, inhibited bacterial growth, less nursing ;me, less supply and equipment, home advantages Clinical Improved dextrose and venous tolerance, possible fluid restric;on advantage, may be more cost effec;ve, fat clearance Ordering limita;ons on macronutrients and electrolytes Compounding difficult to visualize par;culate, less stable over ;me Administra;on can t use 0.2 micron filter, certain medica;ons are incompa;ble Clinical Boullata et al 2014

20 Bacterial Contamination and Growth in 3-in-1 Gilbert et al inoculated three formulations with Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans *TPN=2-in-1, Combined=3-in-1 Gilbert et al 1986

21 Bacterial Growth and Sepsis in 3-in-1 Vasilakis et al 1988

22 Advantages of 3-in-1 Disadvantages of 3-in-1 Compounding: asep;cally compounded by pharmacy, more efficient, less manipula;on Administra;on less risk of contamina;on, inhibited bacterial growth, less nursing ;me, less supply and equipment, home advantages Clinical Improved dextrose and venous tolerance, possible fluid restric;on advantage, may be more cost effec;ve, fat clearance Ordering limita;ons on macronutrients and electrolytes Compounding difficult to visualize par;culate, less stable over ;me Administra;on can t use 0.2 micron filter, certain medica;ons are incompa;ble Clinical Boullata et al 2014

23 Specific Populations Which patients may benefit most from 3-in-1 formulations? Require daily lipids Glucose intolerance Severe fluid restriction Elevated TG with 12 hour lipid infusion Home patients For which patients are 2-in-1 formulations preferred? High fluid requirements Very high Ca or Mg requirements Neonates

24 Question JM is a 38 y/o M patient with multiple EC fistula. He is currently stable on: 3.5 L 2-in-1 formula containing: AA 84 g/day Dextrose 382 g/day with IL20% 250 ml 3x/week What are the concerns for transitioning to a 3-in-1 formula for home? High fluid volume -> may result in low final concentrations? High magnesium requirements Outside IV fluids may not be covered by insurance

25 References 1. Solassol C, Joyeux H, Etco L, Pujol H, Romieu C. New techniques for long-term intravenous feeding: an ar;ficial gut in 75 pa;ents. Ann Surg. 1974;179(4): Boullata JI, Gilbert K, Sacks G, Labossiere RJ, Crill C, Goday P, Kumpf VJ, Mamox TW, Plogsted S, Holcombe B; American Society for Parenteral and Enteral Nutri;on. A.S.P.E.N. clinical guidelines: parenteral nutri;on ordering, order review, compounding, labeling, and dispensing. JPEN J Parenter Enteral Nutr Mar-Apr; 38(3): Driscoll DF. Compounding TPN admixtures: then and now. JPEN J Parenter Enteral Nutr Nov-Dec;27(6): Ayers P, Adams S, Boullata J, Gervasio J, Holcombe B, Krao MD, Marshall N, Neal A, Sacks G, Seres DS, Worthington P; American Society for Parenteral and Enteral Nutri;on. A.S.P.E.N. parenteral nutri;on safety consensus recommenda;ons. JPEN J Parenter Enteral Nutr Mar-Apr;38(3): Erdman SH, McElwee CL, Kramer JM, Zuppan CW, White JJ, Grill BB. Central line occlusion with three-in-one nutri;on admixtures administered at home. JPEN J Parenter Enteral Nutr. 1994;18(2): Didier ME, Fischer S, Maki DG. Total nutrient admixtures appear safer than lipid emulsion alone as regards microbial contamina;on: growth proper;es of microbial pathogens at room temperature. JPEN J Parenter Enteral Nutr Sep-Oct;22(5): Gilbert M, Gallagher SC, Eads M, Elmore MF. Microbial growth pamerns in a total parenteral nutri;on formula;on containing lipid emulsion. JPEN J Parenter Enteral Nutr Sep-Oct;10(5): Vasilakis A, Apelgren KN. Answering the fat emulsion contamina;on ques;on: three in one admixture vs conven;onal total parenteral nutri;on in a clinical seqng. JPEN J Parenter Enteral Nutr Jul-Aug;12(4):

26 What s In The Bag? 3-in-1 versus 2-in-1 PN Amber Verdell, PharmD, BCPS, BCNSP Assistant Professor, Pharmacy Practice West Coast University, Los Angeles, CA