Parenteral nutrition (PN) is a life-sustaining therapy designed to deliver essential nutrients to patients unable to meet nutrition needs via the enteral route. PN may be delivered via a 2-in-1 system (one solution containing amino acids, dextrose, electrolytes, vitamins, minerals, and fluids and one solution containing intravenous fat emulsions [IVFEs]) or via a 3-in-1 system (all nutrients mixed in one container). Although the use of 3-in-1 PN solutions is not necessarily therapeutically advantageous, certain benefits may exist such as the potential to reduce the risk of contamination due to decreased manipulations; ease of administration, particularly in the home care setting; possible cost savings; and reduced IVFE wastage. However, the incorporation of IVFE in 3-in-1 solutions also presents unique risks for the neonatal and pediatric population such as decreased stability, increased lipid globule size, decreased sterility and the potential for increased microbial growth/infectious complications, the need to use a larger filter size, precipitation and compatibility risks, and an increased chance of catheter occlusion. This review outlines the unique issues and challenges to be considered when formulating neonatal and pediatric 3-in-1 PN admixtures. While 3-in-1 PN solutions may be advantageous for certain pediatric populations, specifically those dependent on home PN, the risks do not outweigh the benefits in neonatal patients, and use should be avoided in this population.
SayeedFATrippMGSukumaranKBMikrutBAStelmachHARaihleJA. Stability of various total nutrient admixture formulations using Liposyn II and Aminosyn II. Am J Hosp Pharm. 1987;44:2280-2286.
DriscollDF. Physicochemical assessment of total nutrient admixture stability and safety: quantifying the risk. Nutrition. 1997;13:166-167.
14.
Globule size distribution in lipid injectable emulsions. Chapter <729>. In: United States Pharmacopeia 31/National Formulary 26. Vol I. Rockville, MD: United States Pharmacopeial Convention; 2008:285-287.
15.
DriscollDF. Total nutrient admixtures: theory and practice. Nutr Clin Pract. 1995;10:114-119.
16.
DriscollDFBhargavaHNLiLZaimRHBabayanVKBistrianBR. Physicochemical stability of total nutrient admixtures. Am J Health Syst Pharm. 1995;52:623-634.
17.
DriscollDFThomaAFrankeRKlutschKNehneJBistrianBR. Lipid globule size in total nutrient admixtures prepared in three-chamber plastic bags. Am J Health Syst Pharm. 2009;66:649-656.
18.
TuckerAYbarraJBinghamA. American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) standards of practice for nutrition support pharmacists. Nutr Clin Pract. 2015;30(1):139-146.
19.
DriscollDFNehneJPeterssHKlutschKBistrianBRNiemannW. Physicochemical stability of intravenous lipid emulsions as all-in-one admixtures intended for the very young. Clin Nutr. 2003;22:489-495.
20.
Ribeiro DdeOLoboBWVolpatoNMda VeigaVFCabralLMde SousaVP. Influence of the calcium concentration in the presence of organic phosphorus on the physicochemical compatibility and stability of all-in-one admixtures for neonatal use. Nutrition. 2009;8:51.
21.
KernerJAJrPooleRL. The use of IV fat in neonates. Nutr Clin Pract. 2006;21:374-380.
22.
WalesPWAllenNWorthingtonP. A.S.P.E.N. clinical guidelines: support of pediatric patients with intestinal failure at risk of parenteral nutrition–associated liver disease. JPEN J Parenter Enteral Nutr. 2014;38:538-557.
23.
RollinsMDWardRMJacksonWD. Effect of decreased parenteral soybean lipid emulsion on hepatic function in infants at risk for parenteral nutrition–associated liver disease: a pilot study. J Pediatr Surg. 2013;48:1348-1356.
24.
ColombVJobert-GiraudALacailleFGouletOFournetJCRicourC. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. JPEN J Parenter Enteral Nutr. 2000;24:345-350.
25.
RollinsMDScaifeERJacksonWDMeyersRLMulroyCWBookLS. Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome. Nutr Clin Pract. 2010;25:199-204.
26.
CoberMPKilluGBrattainAWelchKBKunisakiSMTeitelbaumDH. Intravenous fat emulsions reduction for patients with parenteral nutrition–associated liver disease. J Pediatr. 2012;160:421-427.
27.
GuraKMLeeSValimC. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition–associated liver disease. Pediatrics. 2008;121:e678-e686.
28.
de MeijerVEGuraKMLeHDMeiselJAPuderM. Fish oil–based lipid emulsions prevent and reverse parenteral nutrition–associated liver disease: the Boston experience. JPEN J Parenter Enteral Nutr. 2009;33:541-547.
29.
de MeijerVEGuraKMMeiselJALeHDPuderM. Parenteral fish oil as monotherapy for patients with parenteral nutrition–associated liver disease. Pediatr Surg Int. 2009;25:123-124.
30.
LeeSIValimCJohnstonP. Impact of fish oil–based lipid emulsion on serum triglyceride, bilirubin, and albumin levels in children with parenteral nutrition–associated liver disease. Pediatr Res. 2009;66:698-703.
31.
PuderMValimCMeiselJA. Parenteral fish oil improves outcomes in patients with parenteral nutrition–associated liver injury. Ann Surg. 2009;250:395-402.
32.
GouletOAntebiHWolfC. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2010;34:485-495.
33.
SanchezSEBraunLPMercerLDSherrillMStevensJJavidPJ. The effect of lipid restriction on the prevention of parenteral nutrition–associated cholestasis in surgical infants. J Pediatr Surg. 2013;48:573-578.
34.
DurfeeSMAdamsSCArthurE. A.S.P.E.N. standards for nutrition support: home and alternate site care. Nutr Clin Pract. 2014;29:542-555.
35.
DriscollDFSilvestriAPBistrianBR. Stability of MCT/LCT-based total nutrient admixtures for neonatal use over 30 hours at room temperature: applying pharmacopeial standards. JPEN J Parenter Enteral Nutr. 2010;34:305-312.
36.
O’GradyNPAlexanderMBurnsLA. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39:S1-34.
37.
WalsheCMBonerKSBourkeJHoneRPhelanD. Diagnosis of catheter-related bloodstream infection in a total parenteral nutrition population: inclusion of sepsis defervescence after removal of culture-positive central venous catheter. J Hosp Infect. 2010;76:119-123.
38.
Pontes-ArrudaADos SantosMCMartinsLF. Influence of parenteral nutrition delivery system on the development of bloodstream infections in critically ill patients: an international, multicenter, prospective, open-label, controlled study—EPICOS study. JPEN J Parenter Enteral Nutr. 2012;36:574-586.
39.
GerlachATThomasSMurphyCV. Does delaying early intravenous fat emulsion during parenteral nutrition reduce infections during critical illness?Surg Infect (Larchmt). 2011;12:43-7.
40.
YilmazGKoksalIAydinKCaylanRSucuNAksoyF. Risk factors of catheter-related bloodstream infections in parenteral nutrition catheterization. JPEN J Parenter Enteral Nutr. 2007;31:284-287.
41.
DissanaikeSSheltonMWarnerKO’KeefeGE. The risk for bloodstream infections is associated with increased parenteral caloric intake in patients receiving parenteral nutrition. Crit Care. 2007;11:R114.
42.
ChhengMLHeidbrederCBtaicheIFBlackmerAB. Infectious complications with nondaily versus daily infusion of intravenous fat emulsions in non-critically ill adults. Nutr Clin Pract. 2013;28:737-744.
43.
MirtalloJMDastaJFKleinschmidtKCVaronJ. State of the art review: intravenous fat emulsions: current applications, safety profile, and clinical implications. Ann Pharmacother. 2010;44:688-700.
44.
MellyMAMengHCSchaffnerW. Microbiol growth in lipid emulsions used in parenteral nutrition. Arch Surg. 1975;110:1479-1481.
45.
GilbertMGallagherSCEadsMElmoreMF. Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion. JPEN J Parenter Enteral Nutr. 1986;10:494-497.
46.
O’GradyNPAlexanderMDellingerEP. Guidelines for the prevention of intravascular catheter-related infections. Infect Control Hosp Epidemiol. 2002;23:759-769.
47.
VasilakisAApelgrenKN. Answering the fat emulsion contamination question: three in one admixture vs conventional total parenteral nutrition in a clinical setting. JPEN J Parenter Enteral Nutr. 1988;12:356-359.
48.
TurpinRSSolemCPontes-ArrudaA. The impact of parenteral nutrition preparation on bloodstream infection risk and costs. Eur J Clin Nutr. 2014;68:953-958.
49.
KovacevichDSFrederickAKellyD. Standards for specialized nutrition support: home care patients. Nutr Clin Pract. 2005;20:579-590.
50.
KitchenPForbesA. Intravenous nutrition: focus on delivery (3-in-1 bags or not?). Curr Opin Gastroenterol. 2000;16:184-187.
51.
UsluSOzdemirHComertSBolatFNuhogluA. The effect of low-dose heparin on maintaining peripherally inserted percutaneous central venous catheters in neonates. J Perinatol. 2010;30:794-799.
52.
TangJLiXHWangHXiongYMuDZ. Administration of low-dose heparin in total nutrient admixture prevents central venous catheter–related infections in neonates [in Chinese]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:983-985.
53.
LimMSChoiCWKimBIYangHR. Clinical factors affecting lipid metabolism and optimal dose of heparin in preterm infants on parenteral nutrition. Pediatr Gastroenterol Hepatol Nutr. 2013;16:116-122.
54.
BirchPOgdenSHewsonM. A randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: the Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial. Arch Dis Child Fetal Neonatal Ed. 2010;95:F252-F257.
55.
MoclairABatesI. The efficacy of heparin in maintaining peripheral infusions in neonates. Eur J Pediatr. 1995;154:567-570.
56.
SilversKMDarlowBAWinterbournCC. Pharmacologic levels of heparin do not destabilize neonatal parenteral nutrition. JPEN J Parenter Enteral Nutr. 1998;22:311-314.
57.
TrisselLAGilbertDLMartinezJFBakerMBWalterWVMirtalloJM. Compatibility of medications with 3-in-1 parenteral nutrition admixtures. JPEN J Parenter Enteral Nutr. 1999;23:67-74.
58.
RyanDMDanielsCESomaniSM. Personnel costs and preparation time in a centralized intravenous admixture program. Am J Hosp Pharm. 1986;43:1222-1225.
59.
EskewJA. Fiscal impact of a total nutrient admixture program at a pediatric hospital. Am J Hosp Pharm. 1987;44:111-114.
60.
RollinsCJElsberryVAPollackKAPollackPFUdallJNJr.Three-in-one parenteral nutrition: a safe and economical method of nutritional support for infants. JPEN J Parenter Enteral Nutr. 1990;14:290-294.
61.
ErdmanSHMcElweeCLKramerJMZuppanCWWhiteJJGrillBB. Central line occlusion with three-in-one nutrition admixtures administered at home. JPEN J Parenter Enteral Nutr. 1994;18:177-181.
CorkinsM, ed. Pediatric Nutrition Support Core Curriculum. Silver Springs, MD: American Society for Parenteral and Enteral Nutrition; 2010.
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