As health care professionals, we are committed to continually improving our processes to safely deliver effective drug therapy to the patients we serve. However, the safe and effective delivery of parenteral nutrition (PN) has proven challenging over the last several years. Reports of PN contamination, ingredient shortages, and lack of compounding safety limits have compelled the health care community to reevaluate the systems and methods of PN delivery to improve safety through PN formula standardization. 

Although PN formula standardization is often thought to be synonymous with standardized, commercial PN products, this is not the case. A standardized PN formulation is simply one intended to meet the daily maintenance requirements of a specific patient population, and is differentiated by its route of administration (peripheral [osmolality 900–1000 mOsm/L] vs central [about 1500 mOsm/L]). When creating PN order forms, ensure that route of administration is clearly delineated. (Go to pppmag.com/PNforms to view sample premix and compounded PN order forms.) 

A standardized, commercial PN product or premixed product is a type of standardized PN solution that is available from a manufacturer and requires fewer compounding steps before administration.¹ Therefore, a premixed PN solution is an example of a standardized PN solution but certainly not the only example. Commercial two-compartment bags containing dextrose in one compartment and amino acids in the second compartment have been available in the US for years. These products are available from the manufacture in one- and two-liter volumes, both with and without added electrolytes. When the two compartment products are used, IV fat emulsion can be added to the container following the mixture of the amino acid and dextrose chambers or administered via a Y-connector into the primary IV catheter. 

Determine the Feasibility of Using Premixed PN Products 
Based in Springfield, Missouri, CoxHealth serves more than 900,000 people in a 25-county service area in southwest Missouri and northwest Arkansas. Our primary and specialty care services include three hospitals and more than 50 physician clinics in 20 communities. The pharmacy operates 24 hours a day, serving over 700 inpatient beds, and is staffed with approximately 60 pharmacists, 46 technicians, and a multidisciplinary nutrition support team that includes two nurses, two pharmacists, and three dietitians. Our pharmacy dispenses an average of 25 bags of PN daily—10 neonatal and 15 adult. Outsourcing is currently not an option for our facility because there are no local outsourced compounding services; therefore, we use an automated compounder to manage our in-house compounding process. 

Our pharmacy team originally performed a gap analysis and completed a process improvement plan in 2005 based on the ASPEN Safe Practices for Parenteral Nutrition guidelines,² and then reevaluated these steps in 2009 (see sidebar). At that time, we decided to incorporate premixed products because of extensive PN component shortages. In addition, we wanted to minimize the risks associated with IV compounding by adopting use of the premixed products, which require fewer steps to prepare. 

Safety Advantages of Commercial, Premixed PN Solutions
It is important to note that IV compounding errors have been regularly documented in the literature. 

• Information from US Pharmacopeia’s Medmarx database presented at the 2008 Summit on Preventing Patient Harm and Death from IV Medication Errors indicates that parenteral medication errors are almost three times as likely to cause harm or death than other types of errors, and the majority (79%) of harmful or fatal parenteral errors involves the IV route of administration.³
• A 1997 observational study at five US hospital pharmacies found that PN compounding was associated with more errors, including component omissions and unauthorized additions, than other types of IV compounding.⁴ 
• Results of the 2003 ASPEN Parenteral Nutrition Safe Practice Survey published in 2006 identified electrolytes, insulin, and dextrose as the components of PN most often associated with error.⁵ 

A primary advantage of switching from PN solutions mixed in the hospital pharmacy to commercial premixed PN solutions is that patient safety is improved through reduced handling of the products. Using premixed PN formulations—especially products containing electrolytes—reduces bag manipulations, which can decrease compounding errors and the risk of microbiological contamination. These points are particularly important for hospital pharmacies that do not use automated compounding devices.

Cost Considerations 
While commercial premixed solutions are often more costly than purchasing individual components, the extra expense is usually offset by the decrease in labor costs and the reduction of individual component product waste that results from switching. One way to assess the feasibility of a switch is to conduct a review of the last six months of adult PN compounding practices and compare the overall cost of preparing the mixes in house to the cost of available premixed solutions. Key factors to include in an analysis are items such as contract pricing and whether you will be able to completely switch to a premixed system. Vendors may be able to assist your facility with this type of analysis or you can complete one independently, as we did. A spreadsheet was created that listed amino acid concentrations (in grams %), dextrose concentrations (in grams %), and all of the electrolyte additions. This list was compared to the premixed products available for purchase. This analysis revealed that approximately 75% of our adult PN formulations could be supplied using premixed products. Upon completion of this analysis, it should be apparent what percentage of your facility’s PN needs can be satisfied using commercial premix, which premix products will best meet your needs, and the inventory levels required.  

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Due to safety concerns and the labor costs associated with the addition of individual electrolytes to premixed solutions, the decision was made to only use products already containing electrolytes. Because of this decision, the need for electrolyte restrictions was the most frequent limitation to premixed solution use. Other patient-specific factors—such as fluid intolerance, organ dysfunction, need for higher amino acid concentrations, and limited IV access—precluded us from a complete switch to premixed PN products. 

It is also important to note that the lack of availability of three-compartment premixed bags in the US decreases the cost advantage of these products because labor is involved in either mixing fat emulsion into the two-compartment bag or in hanging a separate container of fat emulsion. The additional cost of transfer sets and/or tubing required for staff to add or administer fat separately also should be weighed when deciding between the options. 

Clinical Considerations
A clinical advantage of commercial premixed PN solutions is the ability to expeditiously offer a start dose of PN to patients due to reduced preparation and turnaround times. Keep in mind that expeditious access should not preclude the opportunity for nutrition professionals (dietitians, pharmacists, or a multidisciplinary team) to clinically evaluate the need for PN and avoid inappropriate use. For example, we have reduced our PN use by 10% by recommending enteral nutrition via small bowel access. Thus, even after the addition of premixed PN bags to our system, we still require a clinical review prior to dispensing. 

One potential clinical concern is the currently limited number of commercial premixed PN formulas on the US market, as compared with those available in Europe. Additionally, volume sizes in the US are limited to 1- and 2-liter bags, whereas in Europe a variety of volumes are available. A third concern is that US commercial premixed products contain a maximum amino acid concentration of 5%, which limits their usefulness in critical care, wound care, and obese patient populations.

Several additional factors must be evaluated when deciding whether to convert to a commercial premixed PN system if an institution has a cut-off time for new or changed PN orders and a standardized hang time for PN. In most instances where a standardized hang time for PN is used, total nutrient admixtures are compounded and hung for 24 hours. Because only 1- and 2-liter volumes are available, maintenance of a standardized hang time may be problematic. To maintain a standardized hang time for patients requiring more than a 2-liter bag, a second bag will need to be hung; alternatively, if a patient does not require the full 2-liter volume to meet nutritional needs, but requires more than the 1-liter volume, there will be waste from the premixed PN bag along with a loss of vitamin and trace element dose under the standardized hang time approach. A possible solution would be to switch from a standard, 24-hour hang time, but this would require re-education of staff and potentially increase touch contamination if the patient requires more than one bag. A mechanism also would need to be instituted for patients requiring a low volume of PN in order to ensure that bags do not become unsafe by hanging more than 24 hours. Regardless, this conversion would certainly be an option for institutions that can make the switch to 100% premixed solutions. For institutions that are unable to make a total conversion, careful consideration of hang time safety, potential administration errors, and wastage needs to be evaluated.

Conclusion 
Commercial premixed PN solutions can offer cost and safety advantages over PN solutions compounded by an in-house pharmacy or outsourcing facility. Careful consideration and evaluation of current practices, including prescribing, compounding, distribution, and administration needs to be included to make an informed decision on whether premixed PN offers real advantages over your current system. These products are an excellent option for institutions that infrequently administer PN, serve primarily older children and adults, have limited IV room space for compounding, or do not have nutrition experts available. Larger institutions may choose to implement a hybrid system using commercial premixed PN solutions for specific patients, which could provide the advantage of quicker starts, improved safety, and conservation of compounding products during periods of shortage.

Note: See page 7 for a sample PN pharmacy department procedure.

References

1. Kochevar M, Guenter P, Holcombe B, Malone A, Mirtallo J, ASPEN Board of Directors and Task Force on Parenteral Nutrition Standardization. ASPEN statement on parenteral nutrition standardization. JPEN J Parenter Enteral Nutr. 2007;31(5):441-448.
2. Mirtallo J, Canada T, Johnson D, et al. Safe practice for parenteral nutrition [published correction appears in JPEN J Parenter Enteral Nutr. 2006;30(2):177]. JPEN J Parenter Enteral Nutr. 2004;28(suppl 6):S39-S70.
3. Proceeding of a summit on preventing patient harm and death from i.v. medication errors [published correction appears in Am J Health Syst Pharm. 2009;66(3):213]. Am J Health Syst Pharm. 2008;65:2367-2379.
4. Flynn EA, Pearson RE, Barker KN. Observational study of accuracy in compounding i.v. admixtures at five hospitals [published correction appears in Am J Health Syst Pharm. 1997;54(9):1110]. Am J Health Syst Pharm. 1997;54(8):904-912.
5. Seres D, Sack GS, Pederson CA, et al. Parenteral nutrition safe practices:  results of the 2003 American Society for Parenteral and Enteral Nutrition survey. JPEN J Parenter Enteral Nutr. 2006;30(3):259-265.

Karrie Derenski, PharmD, BCNSP, CNSC, is the coordinator of the nutrition support service at CoxHealth, Springfield, Missouri. She received her pharmacy degree from the University of Missouri-Kansas City College of Pharmacy and completed a residency in nutrition support at the University of Colorado. Her professional interests include safe and effective use of parenteral and enteral nutrition, diabetes care, and teaching.

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