The safety of parenteral nutrition (PN) administration in critically ill patients has been the subject of much controversy. Historically, PN administration has been associated with an increased risk of bacterial and fungal infections, leading to significant morbidity and mortality. Much of the data showing increased infectious complications compared with either no nutrition or enteral nutrition was derived from early studies conducted in the 1980s–2000s. Poor glucose control and hyperalimentation are confounding factors in many early studies, making it difficult to determine the true PN infection risks. While PN studies conducted during the past 10 years have failed to show the same infection rates, these risks continue to be cited as dogma. Potential reasons for such discordant results include improved glycemic control, avoidance of overfeeding, and improved sterility and central venous catheter care. Understanding the true infectious risk of PN administration in the intensive care unit is necessary to optimize patient care, as inappropriately withholding such nutrition is potentially deleterious. This review is meant to serve as a practical guide to the bedside clinician who is evaluating the risks and benefits of initiating PN in a critically ill patient. Each component of PN will be evaluated based on risk of infection, and the potential ways to mitigate risks will be discussed.
Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med. 1991;325(8):525-532.
2.
MooreFAMooreEEJonesTNMcCroskeyBLPetersonVM. TEN versus TPN following major abdominal trauma—reduced septic morbidity. J Trauma. 1989;29(7):916-923.
3.
KudskKACroceMAFabianTC. Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215(5):503-513.
4.
KalfarentzosFKehagiasJMeadNKokkinisKGogosCA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg. 1997;84(12):1665-1669.
5.
DoigGSimpsonFSweetmanE. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA. 2013;309(20):2130-2138.
6.
AltintasNDAydinKTurkogluMAAbbasogluOTopeliA. Effect of enteral versus parenteral nutrition on outcome of medical patients requiring mechanical ventilation. Nutr Clin Pract. 2011;26(3):322-329.
7.
HarveySEParrottFHarrisonDA; CALORIES Trial Investigators. Trial of the route of early nutritional support in critically ill adults. N Engl J Med. 2014;371(18):1673-1684.
8.
McClaveSATaylorBEMartindaleRG. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016;40(2):159-211.
9.
KoretzRLLipmanTOKleinS. AGA technical review on parenteral nutrition. Gastroenterology. 2001;121(4):970-1001.
10.
DissanaikeSSheltonMWarnerKO’KeefeG. The risk for bloodstream infections is associated with increased parenteral caloric intake in patients receiving parenteral nutrition. Critical Care. 2007;11(5):R114.
11.
FinferSHeritierS, Committee NSM, Committee SSE. The NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) study: statistical analysis plan. Crit Care Resusc. 2009;11(1):46-57.
12.
WoodcockNPZeiglerDPalmerMDBuckleyPMitchellCJMacFieJ. Enteral versus parenteral nutrition: a pragmatic study. Nutrition. 2001;17(1):1-12.
13.
MooreFAFelicianoDVAndrassyRJ. Early enteral feeding, compared with parenteral, reduces postoperative septic complications: the results of a meta-analysis. Ann Surg. 1992;216(2):172-183.
14.
SimpsonFDoigGSParenteralvs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005;31(1):12-23.
15.
DriscollDFBistrianBR. Clinical issues in the therapeutic monitoring of total parenteral nutrition. Clin Lab Med. 1987;7(3):699-714.
16.
BtaicheIFKhalidiN. Metabolic complications of parenteral nutrition in adults, part 1. Am J Health Syst Pharm. 2004;61(18):1938-1949.
17.
MadeoMLowryL. Infection rates associated with total parenteral nutrition. J Hosp Infect. 2011;79(4):373-374.
O’GradyNPAlexanderMBurnsLA. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4)(suppl 1):S1-S34.
20.
MakiDGKlugerDMCrnichCJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc. 2006;81(9):1159-1171.
21.
O’GradyNPAlexanderMDellingerEP. Guidelines for the prevention of intravascular catheter-related infections. Infect Control Hosp Epidemiol. 2002;23(12):759-769.
22.
Centers for Disease Control and Prevention. 2013 National and state healthcare-associated infections progress report. January14, 2015. www.cdc.gov/hai/progress-report/index.html. Accessed June 6, 2016.
23.
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(5):574-586.
24.
Pontes-ArrudaALiuFXTurpinRSMercaldiCJHiseMZalogaG. Bloodstream infections in patients receiving manufactured parenteral nutrition with vs without lipids: is the use of lipids really deleterious?JPEN J Parenter Enteral Nutr. 2012;36(4):421-430.
25.
TurpinRSCanadaTRosenthalV. Bloodstream infections associated with parenteral nutrition preparation methods in the United States: a retrospective, large database analysis. JPEN J Parenter Enteral Nutr. 2012;36(2):169-176.
26.
MuhlebachSFrankenCStangaZ. Practical handling of AIO admixtures—guidelines on Parenteral Nutrition, Chapter 10. Ger Med Sci. 2009;7:Doc18.
27.
MuhlebachS. Practical aspects of multichamber bags for total parenteral nutrition. Curr Opin Clin Nutr Metab Care. 2005;8(3):291-295.
28.
U.S. Pharmacopeial Convention. Pharmaceutical compounding-sterile preparations (chapter 797). In: The United States Pharmacopeia Compounding Compendium. 39th revision. Rockville, MD: U.S. Pharmacopeial Convention; 2016:44-45.
29.
TrisselLAGentempoJAAndersonRWLajeunesseJD. Using a medium-fill simulation to evaluate the microbial contamination rate for USP medium-risk-level compounding. Am J Health Syst Pharm. 2005;62(3):285-288.
30.
HansenEWNielsenPL. Intrinsic and extrinsic microbial contamination of home total parenteral nutrition manufactured in eva-infusion bags (the i.v. bag). J Clin Pharm Ther. 1987;12(5):325-331.
31.
RichDSFrickerMPJrCohenMRLevineSR. Guidelines for the safe preparation of sterile compounds: results of the ISMP Sterile Preparation Compounding Safety Summit of October 2011. Hosp Pharm. 2013;48(4):282-294.
BoullataJIGilbertKSacksG. A.S.P.E.N. clinical guidelines: parenteral nutrition ordering, order review, compounding, labeling, and dispensing. JPEN J Parenter Enteral Nutr. 2014;38(3):334-377.
34.
SchaibleUEKaufmannSHE. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med. 2007;4(5):e115.
35.
ButlerSOBtaicheIFAlanizC. Relationship between hyperglycemia and infection in critically ill patients. Pharmacotherapy. 2005;25(7):963-976.
36.
HostetterMK. Handicaps to host defense: effects of hyperglycemia on C3 andCandida albicans. Diabetes. 1990;39(3):271-275.
37.
BagdadeJDNielsonKLBulgerRJ. Reversible abnormalities in phagocytic function in poorly controlled diabetic patients. Am J Med Sci. 1972;263(6):451-456.
38.
BlackCTHennesseyPJAndrassyRJ. Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin. J Trauma. 1990;30(7):830-833.
39.
van den BergheGWoutersPWeekersF. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367.
40.
Van den BergheGWoutersPJBouillonR. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med. 2003;31(2):359-366.
41.
Van den BergheGWilmerAHermansG. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449-461.
42.
McMahonMMNystromEBraunschweigCMilesJCompherC. A.S.P.E.N. clinical guidelines: nutrition support of adult patients with hyperglycemia. JPEN J Parenter Enteral Nutr. 2013;37(1):23-36.
43.
WolfeRRO’DonnellTFJrStoneMDRichmandDABurkeJF. Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition. Metabolism. 1980;29(9):892-900.
44.
BurkeJFWolfeRRMullanyCJMathewsDEBierDM. Glucose requirements following burn injury: parameters of optimal glucose infusion and possible hepatic and respiratory abnormalities following excessive glucose intake. Ann Surg. 1979;190(3):274-285.
45.
RosmarinDKWardlawGMMirtalloJ. Hyperglycemia associated with high, continuous infusion rates of total parenteral nutrition dextrose. Nutr Clin Pract. 1996;11(4):151-156.
46.
RosenthalMDVanzantELMartindaleRGMooreFA. Evolving paradigms in the nutritional support of critically ill surgical patients. Curr Probl Surg. 2015;52(4):147-182.
47.
WeijsPStapelSde GrootS. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort study. JPEN J Parenter Enteral Nutr. 2012;36:60-68.
48.
WiernikAJarstrandCJulanderI. The effect of Intralipid on mononuclear and polymorphonuclear phagocytes. Am J Clin Nutr. 1983;37(2):256-261.
49.
HeylandDKDhaliwalRDroverJWGramlichLDodekP. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27(5):355-373.
50.
StapletonRDMartinJMMayerK. Fish oil in critical illness: mechanisms and clinical applications. Crit Care Clin. 2010;26(3):501-514, ix.
51.
NishiwakiHIriyamaKAsamiH. Influences of an infusion of lipid emulsion on phagocytotic activity of cultured Kupffer’s cells in septic rats. JPEN J Parenter Enteral Nutr. 1986;10(6):614-616.
52.
CalderPCSherringtonEJAskanaziJNewsholmeEA. Inhibition of lymphocyte proliferation in vitro by two lipid emulsions with different fatty acid compositions. Clin Nutr. 1994;13(2):69-74.
53.
SriramKMeguidMM. Addition of lipids to parenteral nutrition does not cause fungal infections. Nutrition. 2015;31(11-12):1443-1446.
54.
BattistellaFDWidergrenJTAndersonJTSieplerJKWeberJCMacCollK. A prospective, randomized trial of intravenous fat emulsion administration in trauma victims requiring total parenteral nutrition. J Trauma. 1997;43(1):52-60.
55.
McCowenKCFrielCSternbergJ. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications—a randomized clinical trial. Crit Care Med. 2000;28(11):3606-3611.
56.
GerlachATThomasSMurphyCV. Does delaying early intravenous fat emulsion during parenteral nutrition reduce infections during critical illness?Surg Infect (Larchmt). 2011;12(1):43-47.
57.
ArrazcaetaJLemonS. Evaluating the significance of delaying intravenous lipid therapy during the first week of hospitalization in the intensive care unit. Nutr Clin Pract. 2014;29(3):355-359.
58.
ChhengMLHeidbrederCBtaicheIFBlackmerAB. Infectious complications with nondaily versus daily infusion of intravenous fat emulsions in non-critically ill adults. Nutr Clin Pract. 2013;28(6):737-744.
59.
PradelliLMayerKMuscaritoliMHellerAR. n-3 Fatty acid–enriched parenteral nutrition regimens in elective surgical and ICU patients: a meta-analysis. Crit Care. 2012;16(5):R184.
60.
PalmerAJHoCKAjibolaOAvenellA. The role of omega-3 fatty acid supplemented parenteral nutrition in critical illness in adults: a systematic review and meta-analysis. Crit Care Med. 2013;41(1):307-316.
61.
ManzanaresWDhaliwalRJurewitschBStapletonRDJeejeebhoyKNHeylandDK. Alternative lipid emulsions in the critically ill: a systematic review of the evidence. Intensive Care Med. 2013;39(10):1683-1694.
62.
UmpierrezGESpiegelmanRZhaoV. A double-blind, randomized clinical trial comparing soybean oil–based versus olive oil–based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition. Crit Care Med. 2012;40(6):1792-1798.
63.
Grau-CarmonaTBonet-SarisAGarcia-de-LorenzoA. Influence of n-3 polyunsaturated fatty acids enriched lipid emulsions on nosocomial infections and clinical outcomes in critically ill patients: ICU lipids study. Crit Care Med. 2015;43(1):31-39.
64.
RuanSYHuangCT. Influence of lipid emulsions on nosocomial infections: measurement with cumulative incidence or incidence density may make a difference. Crit Care Med. 2015;43(5):e157-e158.
65.
ManzanaresWLangloisPLDhaliwalRLemieuxMHeylandDK. Intravenous fish oil lipid emulsions in critically ill patients: an updated systematic review and meta-analysis. Crit Care. 2015;19:167.
66.
BarrLHDunnGDBrennanMF. Essential fatty acid deficiency during total parenteral nutrition. Ann Surg. 1981;193(3):304-311.
67.
BronteVZanovelloP. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005;5(8):641-654.
68.
KurpadAV. The requirements of protein & amino acid during acute & chronic infections. Indian J Med Res. 2006;124(2):129-148.
69.
HeysSDWalkerLGSmithIEreminO. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg. 1999;229(4):467-477.
70.
HeylandDKNovakFDroverJWJainMSuXSuchnerU. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286(8):944-953.
71.
van ZantenARSztarkFKaisersUX. High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA. 2014;312(5):514-524.
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