January 2019 Issue

Trends in Parenteral Nutrition
By Kristi L. King, MPH, RDN, CNSC, LD
Today's Dietitian
Vol. 21, No. 1, P. 36

Where We Are Today, and Where We're Heading Tomorrow

On average, approximately 34,000 patients in the United States receive parenteral nutrition (PN) each year.1 Interest in providing nutrients to the body via the circulatory system dates back to the late 1880s. Advancements in technology and science up to the 1960s has brought PN to where it is today.2 There's no doubt that PN inherently has saved thousands of lives over many decades and will continue to do so in the future.

Some health care practitioners may be wondering how PN practices have evolved and what's in store for the future. A few trends in PN have emerged over recent years; they all have an underlying focus on improving patient safety and clinical outcomes.

Lipid Emulsions
One of the first challenges with PN was finding a way to provide total energy requirements and essential fatty acids, since dextrose and amino acids alone can't meet these goals.2 Cottonseed oil was originally used as a fat source, but it caused many adverse effects in patients; therefore, a soybean oil lipid emulsion (SOLE) was created and has been the standard IV lipid emulsion in the United States since the 1970s.3

However, SOLE didn't come onto the scene without controversy, as it was tied to the development of PN-associated liver disease (PNALD). SOLEs are high in omega-6 polyunsaturated fatty acids, which tend to be more proinflammatory in higher doses and contain phytosterols thought to hinder liver function and ultimately contribute to the development of PNALD.3-5

Patients in high-risk populations, such as neonates and infants that have complex medical conditions (eg, necrotizing enterocolitis, gastroschisis, and prematurity), can develop PNALD within two weeks of receiving PN.6 These children often are on PN for extended periods—possibly for their entire lives. The condition eventually can lead to end-stage liver disease and require a liver transplant.6

At the turn of the century, alternative lipid emulsions were introduced; these included fat sources such as fish and olive oils to promote better patient outcomes.

Fish oil lipid emulsion (FOLE) has been attributed to the resolution of PNALD with normalization of direct bilirubin levels and improved patient clinical status.3 Health care practitioners raised concerns about the essential fatty acid profile of FOLEs. However, studies have yet to show essential fatty acid deficiency in patients receiving exclusive PN and FOLE.6

Until recently, one type of FOLE, Omegaven, could be used only as part of an approved research study or with consent from the FDA for compassionate use. The dosage of Omegaven came with a limit of 1 g/kg/day.

In August 2018, the FDA approved the use of Omegaven in the pediatric population after reviewing data from research collaborators. Steven A. Abrams, MD, a professor of pediatrics at the Dell Medical School at The University of Texas at Austin who previously served as the neonatologist leading Baylor College of Medicine's Omegaven research study, says, "Availability of Omegaven will vastly simplify access to this medication, which is critical for the care of infants with cholestasis. Simplified access will undoubtedly lead to early usage and fewer complications from cholestasis."

The randomized controlled trials haven't shown that FOLE is beneficial in preventing cholestasis, noting that it may work better as a rescue drug.6

Keli Hawthorne, MS, RD, LD, director of clinical research for the department of pediatrics at Dell Medical School, also played an important role in Baylor College of Medicine's Omegaven trial. She's optimistic about having a choice for her patients because "being able to provide an alternative to the proinflammatory omega-6 product is important to helping these patients survive and thrive."

Besides FOLEs, other new-generation lipid emulsions have emerged—some olive oil based and others containing a combination of medium-chain triglycerides and omega-3–based lipids.7 One meta-analysis showed new-generation lipids were associated with higher oleic acid concentrations compared with SOLEs. This suggests the newer lipid emulsions might be more nutritionally beneficial compared with the current standard soy-based lipids, such as Intralipid or Nutralipid.7

One particular solution, SMOF (soy, medium chain, olive, and fish oil), has been approved in the United States for adults receiving PN and is used off label for many pediatric patients with PNALD and those with impaired lipid clearance.

The addition of new-generation lipids to the market has increased lipid choices clinicians have available for their patients. But will these new-generation lipids become the next "standard" lipid solutions?

Ashley Ratliff, MS, RD, LD, CNSC, an advanced practice dietitian with the nutrition support team at the Cleveland Clinic, suggests waiting for more evidence to "justify a more robust use of new-generation lipids for the inpatient population." More randomized controlled trials and clinical outcomes studies on acute and critically ill patients may be needed before most hospitals will switch from using their standard lipids to a new-generation lipid such as SMOF.

Nevertheless, new-generation lipids appear to have an anti-inflammatory effect on the liver and may prevent PNALD. Therefore, clinicians working with patients on long-term PN and at risk of developing PNALD may see a "greater use for these types of lipids in the outpatient, long-term home PN patient," Ratliff says.

Whether it's SOLE, FOLE, or a lipid emulsion containing multiple fat sources, practitioners can take into account patient clinical status and availability of IV fat emulsion products to make the best decisions for their patients. Ultimately, no one knows the ideal composition of standard lipid emulsions, but with numerous choices available, clinicians have a better chance of maximizing positive clinical outcomes.

Premixed PN Formulations
Just as the variety of lipid emulsion products continues to evolve, so do best practices for using compounded vs premixed PN formulations. PN is compounded and administered in two ways: Hospital staff either will mix the PN formula themselves using standard hospital (or outpatient pharmacy) compounded bags or use multichamber bag solutions that contain commercially premixed solutions. Various team members, including physicians, nurses, pharmacists, dietitians, and pharmacy technicians, are involved in compounding PN formulations, suggesting that this practice may be one of the most complex processes to occur in hospital settings and leaving room for various human errors.8,9

In 2003, The Joint Commission issued a statement urging standardization of medications/formulations whenever possible to improve patient safety, since manufactured premixed medications/formulations are considered low risk for harboring contaminants and bacteria.10

Researchers have found that patients who receive multichamber bag solutions have a decreased risk of developing bloodstream infections during hospitalization compared with those receiving personalized compounded solutions.10 Studies also have shown that compounding, labeling, and administration errors are significantly higher when hospital staff use compounded bags vs premixed multichamber bag solutions.8 As a result, the American Society for Parenteral and Enteral Nutrition (ASPEN) established best practices for compounding PN and determined that premixed formulations or multichamber bag solutions would be valuable.9

Multichamber bag solutions are closed systems premade by a manufacturer. These premade solutions contain the various components of PN (eg, dextrose, amino acids, electrolytes, and lipids) in multiple chambers that are mixed together just before administration. These solutions can be shelf stable for up to 12 months or more, compared with individually compounded solutions whose shelf life is approximately seven to nine days.11

Despite the perceived benefits of premixed multichamber bag solutions, US hospitals have been slow to use them12 because they can't be tailored or customized to meet patients' individual medical needs. Multichamber bags tend to contain less protein and fewer electrolytes such as sodium, potassium, chloride, and acetate compared with personalized compounded solutions.12

Carol Ireton-Jones, PhD, RDN, LD, CNSC, FASPEN, who works with Nutrishare, Inc, a home infusion provider, in Dallas, says both premixed and multichamber bag solutions have a place in PN administration. For example, premixed solutions can work well for some clients while they're on vacation, she says, and they may work well for small hospitals. But for many home PN patients, personalized treatment is best, so multichamber bag solutions are less likely to work, she adds.

It should be noted that specific illnesses such as renal failure, liver dysfunction, electrolyte imbalances, and patients with increased metabolic needs may benefit more from personalized compounded solutions vs premixed solutions.13,14

Supplemental PN
During times of critical illness, supplemental PN may be the answer to how health care practitioners can prevent energy deficits in patients. It's well known that energy is needed for every function of the body, especially during health crises. A review study by Oshima and colleagues showed significant energy deficits in patients during ICU stays, a situation that could contribute to poor outcomes.15 Research shows supplemental PN may help prevent these energy deficits when enteral nutrition (EN) alone is insufficient for meeting patients' energy and protein needs.16

Various organizations have developed different guidelines for adding PN to feeding regimens, as research results have been mixed and are limited.17 According to guidelines from the Society of Critical Care Medicine and ASPEN, for "patients at either low or high nutrition risk, use of supplemental PN [should] be considered after seven to 10 days if unable to meet 60% of energy and protein requirements by the enteral route alone. Initiating supplemental PN prior to this seven-to-10-day period in critically ill patients on some EN does not improve outcomes and may be detrimental to the patient."18

In contrast, in 2017, the European Society of Parenteral and Enteral Nutrition recommended initiating supplemental PN within 24 to 48 hours in patients not expected to reach full nutrition goals within three days.19 The Canadian Clinical Practice Guidelines also make recommendations for combining PN and EN. The guidelines found supplemental PN to be associated with significant reductions in hospital stays compared with patients receiving only EN, whereas other studies have found mixed results.17

Pradelli and colleagues found that supplemental PN provided an average of 2,320 additional kcal in the first eight days of patients' ICU stays.16 The decreased energy deficit was found to be associated with significant improvement in mechanical ventilation, shorter length of stay, reduced infection risk, and lower overall resource consumption compared with those who didn't receive supplemental PN.16

The practice of supplementing EN with PN has been used for many years in the neonatal ICU when awaiting maturity of infants' gastrointestinal tracts. Given the release of the consensus statement that focused on malnutrition from the Academy of Nutrition and Dietetics and ASPEN in 2012, supplemental PN potentially could serve as a bridge to treating and preventing malnutrition.

Amy Nishnick, RD, LD, CNSC, a nutrition support team advanced practice dietitian in Cleveland, foresees "an increased use of appropriate PN usage due to increased physician awareness of negative outcomes associated with malnutrition."

What the Future Holds
Both lab science and clinical research continue to examine the use of PN regarding its components, safety profile, efficacy, and delivery systems. For example, subcutaneous nutrition, which involves administering PN directly under the skin, has been used outside of the United States for more than 30 years, although more research is needed, since current results stem from observational studies or small randomized controlled trials.20 Thus far, subcutaneous nutrition has been easily tolerated; this may help frail patients who have limited IV access in the future.20

Moreover, research on immune-enhancing nutrition supplements via PN likely will continue. Just in the past year, the use of iodine in long-term PN, the role of selenium, and the use of high doses of vitamins to combat infection and shorten hospital stays were given more attention.21-23

However, there's been concern about providing micronutrients using standard dosing for healthy individuals in that the doses may not be adequate for patients' acute or chronic illnesses. A review by Stehle and colleagues examined trace element recommendations by three different PN organizations and found that they were varied.24 Stehle and colleagues also noted that trace elements should be added individually.24 And in some cases, higher doses of the individual trace elements may be beneficial.24

Dietitians likely will see more research on these essential micronutrients as PN product shortages, such as trace elemental packages, continue.

According to Nishnick and Ireton-Jones, health care practitioners may see an increased use of PN in patients with gastroparesis, motility disorders, and overall global dysmotility. Supplemental PN at home also may be beneficial for those patients unable to meet 100% of their nutrient needs via EN or by mouth.

The practicing clinician should have regular conversations with facility management to determine new practices that can and should be implemented for their patient population. The trends in new-generation lipid emulsions, premixed PN solutions, and supplemental PN are more tools in the dietitian's toolbox to better improve patient safety and health outcomes—and to ultimately save lives.

— Kristi L. King, MPH, RDN, CNSC, LD, is a clinical instructor of pediatrics at Baylor College of Medicine and senior dietitian at Texas Children's Hospital. Her clinical expertise includes gastrointestinal disorders, such as short bowel syndrome, inflammatory bowel syndrome, motility disorders, and nutrition support.

Kristi L. King, MPH, RDN, CNSC, LD, reports the following relevant disclosure: She has received honorariums for giving educational presentations for Abbott Nutrition and Nutricia.

1. John J, Seifi A. Total parenteral nutrition usage trends in the United States. J Crit Care. 2017;40:312-313.

2. Dudrick SJ, Palesty JA. Historical highlights of the development of total parenteral nutrition. Surg Clin North Am. 2011;91(3):693-717.

3. de Meijer VE, Gura KM, Meisel JA, Le HD, Puder M. Parenteral fish oil monotherapy in the management of patients with parenteral nutrition-associated liver disease. Arch Surg. 2010;145(6):547-551.

4. Carter BA, Taylor OA, Prendergast DR, et al. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr Res. 2007;62(3):301-306.

5. Araujo F, Fenton TR, Lukmanji S, Raman M. Olive oil and soybean oil based intravenous lipid emulsions, liver biochemistry and clinical outcomes. Nutrients. 2018;10(6):658.

6. Guthrie G, Premkumar M, Burrin DG. Emerging clinical benefits of new-generation fat emulsions in preterm neonates. Nutr Clin Pract. 2017;32(3):326-336.

7. Dai YJ, Sun LL, Li MY, et al. Comparison of formulas based on lipid emulsions of olive oil, soybean oil, or several oils for parenteral nutrition: a systematic review and meta-analysis. Adv Nutr. 2016;7(2):279-286.

8. Berlana D, Almendral MA, Abad MR, et al. Cost, time, error assessment during preparation of parenteral nutrition: multichamber bags versus hospital-compound bags [published online August 29, 2018]. JPEN J Parenter Enteral Nutr. doi: 10.1002/jpen.1436.

9. Alfonso JE, Berlana D, Ukleja A, Boullata J. Clinical, ergonomic, and economic outcomes with multichamber bags compared with (hospital) pharmacy compounded bags and multibottle systems: a systematic literature review. JPEN J Parenter Enteral Nutr. 2017;41(7):1162-1177.

10. Turpin RS, Canada T, Liu FX, Mercaldi CJ, Pontes-Arruda A, Wischmeyer P. Nutrition therapy cost analysis in the US: pre-mixed multi-chamber bag vs compounded parenteral nutrition. Appl Health Econ Health Policy. 2011;9(5):281-292.

11. Pichard C, Schwarz G, Frei A, et al. Economic investigation of the use of three-compartment total parenteral nutrition bag: prospective randomized unblinded controlled study. Clin Nutr. 2000;19(4):245-251.

12. Beattie C, Allard J, Raman M. Comparison between premixed and compounded parenteral nutrition solutions in hospitalized patients requiring parenteral nutrition. Nutr Clin Pract. 2016;31(2):229-234.

13. Bozat E, Korubuk G, Onar P, Abbasoglu O. Cost analysis of premixed multichamber bags versus compounded parenteral nutrition: breakeven point. Hosp Pharm. 2014;49(2):170-176.

14. Singh A, Rauch D. Commercial premixed parenteral nutrition and its potential role in pediatrics. Hosp Pediatr. 2016;6(1):34-36.

15. Oshima T, Heidegger CP, Pichard C. Supplemental parenteral nutrition is the key to prevent energy deficits in critically ill patients. Nutr Clin Pract. 2016;31(4):432-437.

16. Pradelli L, Graf S, Pichard C, Berger MM. Supplemental parenteral nutrition in intensive care patients: a cost saving strategy. Clin Nutr. 2018;37(2):573-579.

17. Russell MK, Wischmeyer PE. Supplemental parenteral nutrition: review of the literature and current nutrition guidelines. Nutr Clin Pract. 2018;33(3):359-369.

18. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the critically ill adult 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.

19. Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr. 2009;28(4):387-400.

20. Caccialanza R, Constans T, Cotogni P, Zaloga GP, Pontes-Arruda A. Subcutaneous infusion of fluids for hydration or nutrition: a review. JPEN J Parenter Enteral Nutr. 2018;42(2):296-307.

21. Ikomi C, Cole CR, Vale E, Golekoh M, Khoury JC, Jones NY. Hypothyroidism and iodine deficiency in children on chronic parenteral nutrition. Pediatrics. 2018;141(4).

22. Freitas RGBON, Nogueira RJN, Cozzolino SMF, Vasques ACJ, Hessel G. Influence of selenium supplementation on patients with inflammation: a pilot double blind randomized study. Nutrition. 2017;41:32-36.

23. Askari R. Overview of perioperative nutritional support. UptoDate website. https://www.uptodate.com/contents/overview-of-perioperative-nutritional-support?search=immunonutrition&source=search_result&selectedTitle=1~6&usage_type=default&display_rank=1. Updated November 26, 2018. Accessed November 7, 2018.

24. Stehle P, Stoffel-Wagner B, Kuhn KS. Parenteral trace element provision: recent clinical research and practical conclusions. Eur J Clin Nutr. 2016:70(8);886-893.