One of the most complex medications available to patients, parenteral nutrition (PN) typically involves sterile compounding of 10 to 15 components, each requiring customization to patient-specific requirements. This complexity is accompanied by the risk of serious consequences should sterile compounding practices be compromised. The recent, tragic deaths in Alabama hospitals that occurred when patients received PN bags contaminated with Serratia marcescens highlight the gravity with which PN must be managed. When this risk is coupled with critical shortages of intravenous fat emulsion (IVFE), amino acids, vitamins, trace elements, and electrolyte additives, pharmacy faces significant challenges in preparing safe PN formulations. The role of pharmacy is key in ensuring that PN is prescribed, prepared, labeled, and administered in a safe and effective manner.
Designing a Safe PN Prescription
The first step in prescribing a safe PN regimen is the development of an appropriate nutrition care plan that incorporates an assessment of nutrition status, an estimation of nutrient requirements, a monitoring plan, and therapeutic outcome goals. All hospitalized patients should be screened for risk of malnutrition and those who screen positive should undergo a more comprehensive nutrition assessment by a dietitian to guide intervention and desired outcomes. Because there is no single clinical or laboratory indicator to determine malnutrition, a nutrition assessment incorporates a collection of information from a variety of sources, including medical/surgical history, weight history, dietary history, physical exam, laboratory indicators, and functional performance. Keep in mind that those patients who are identified as underweight, malnourished, or have a history of starvation, are at risk of serious metabolic complications when nutrition support is initiated, especially if repletion is too aggressive.
Pharmacists managing patients at risk of metabolic alterations with nutrition repletion, or refeeding syndrome, should be cautious with initiation of calories, including the provision of dextrose-containing fluid replacement. Upon PN initiation, these patients should be monitored for electrolyte abnormalities, receive appropriate vitamin supplementation (particularly thiamine), and be aggressively treated with phosphorus, potassium, and magnesium replacement when needed. PN calories should be advanced in a controlled, stepwise fashion to avoid serious electrolyte abnormalities.
An estimation of nutrient requirements, including protein, carbohydrate, fat, fluid, electrolytes, vitamins, and trace elements serves as the basis for designing a safe PN prescription. Nutrient requirements are based on age, physiologic requirements, organ function, disease state, metabolic condition, and medication usage. As a member of a multidisciplinary nutrition support team, the pharmacist will assist with determination of patient-specific requirements and designing an appropriate PN prescription. Pharmacists who are not part of such a team but are otherwise involved in the care of patients receiving PN may also be called upon to assist with fluid and metabolic management in conjunction with the PN regimen. The nutrition care plan also must incorporate a monitoring plan to assess patient response to PN administration and to identify complications. PN therapy can be associated with significant metabolic complications, including electrolyte abnormalities, hyper- and hypoglycemia, metabolic disturbances, and fluid imbalance. Patients receiving PN are also at risk for central line-associated bloodstream infections. A monitoring plan is an important measure to identify complications early and guide therapeutic adjustments to the PN regimen (see Table 1). Finally, the nutrition care plan should incorporate a strategy for transitioning the patient to an oral diet or enteral nutrition whenever possible.
The pharmacist overseeing the PN compounding process must be familiar with normal nutrient requirements in order to assess the PN prescription for appropriateness prior to compounding. The American Society for Parenteral and Enteral Nutrition’s A.S.P.E.N. Safe Practices for PN provides standard nutrient ranges for adult and pediatric patients.1 Standard ranges for protein and energy requirements are age-specific and incorporate dosing weight, adjusted for obesity and metabolic demand. Standard ranges for electrolytes are age-specific and based on normal organ function and normal losses, but may also be limited by compatibility restraints. Include a dosing weight on all PN orders to allow the compounding pharmacist to properly assess that all prescribed ingredients are within an acceptable nutrient range. If any component falls outside an acceptable range, the compounding pharmacist should verify that it is warranted by a specific clinical situation. This is an important safety check to minimize prescriber error and requires a pharmacist who is knowledgeable in PN therapy. Standard operating procedure that incorporates a clinical review of the PN prescription prior to compounding should be established, and when verification of an outlying nutrient dose is required it should be documented in the medical record.
Standardizing PN Labels
A standardized PN order form and label are recommended in the A.S.P.E.N. guidelines to minimize prescriber error.1 A 2003 survey of PN labeling practices in the United States identified significant variations in the way PN ingredients were being labeled by volume and concentration.2 This lack of standardization can lead to misinterpretation of the order, particularly when patients are transferred between healthcare settings. It is recommended that the PN label be standardized to include the amount per day, and that there is a limit of one PN bag per day. The label should also include dosing weight, route of administration (or at least specification when a central vein is required), administration date and time, beyond-use date and time, and any overfill volume. The format used for the PN label should always be consistent with that used for the PN order to facilitate verification by the nurse before the bag is administered. Likewise, when converting from paper order forms to CPOE, the PN label format should be adapted to mirror the format used for CPOE.
Improving Compounding Safety
Because PN compounding involves pooling multiple sterile commercial products for a specific patient, it is a medium-risk level compounded sterile preparation (CSP) per USP Chapter <797>. As such, it is an ideal candidate for automated compounding, which delivers an improved level of safety and accuracy compared to manual methods. Utilizing automated dose warning limits can help to ensure that an inadvertent catastrophic amount is not delivered. In addition to concern for dosage accuracy, there is concern for microbial contamination of PN formulations during the compounding process. The 2011 Alabama outbreak of Serratia marcescens bacteremia in patients receiving PN is thought to be due to contaminated PN from a single outsourced compounding pharmacy that used a nonsterile form of amino acids contaminated with tap water.3 Per USP <797>, the use of a non-sterile ingredient for PN compounding increases the level of risk from medium to high. It is the responsibility of the pharmacist overseeing the compounding process to ensure that appropriate standards are in place for producing a safe CSP based on level of risk. When outsourcing PN, measures of the facility’s compliance with USP <797> are needed to assess the quality of the compounding process. If this is not available or until state boards of pharmacy do a better job of regulating and overseeing compliance with USP <797>, an institution that outsources PN may be warranted to hire an independent surveyor.
An alternative to compounding PN for a specific patient is to utilize commercially available premixed PN preparations, which are available in multiple macronutrient combinations with the dextrose and amino acids contained in separate chambers. The chamber seal must be opened prior to use in order to allow mixture of contents. The bags are available with or without electrolytes, and IV fat emulsion may be added to the mixed contents prior to use or given separately. Vitamins and trace elements are not included in the premixed preparation and thus, must be added prior to use. Because there are fewer ingredients to add, premixed PN is less complex to prepare, which may decrease the risk of compounding and calculation errors and lessen the risk of contamination. Premixed PN preparations do have some limitations, however. For example, they are designed to meet standard nutrient requirements in non-critical patients, and as such may not meet the needs of patients with high protein requirements or those requiring other nutrients outside a standard range. These premixed preparations are available in 1 L- or 2 L-sized bags, which may not match a patient’s 24-hour requirements, resulting in wastage or the need for more than one bag per day. In addition, they are not well suited for floor stock or storage in an automated dispensing cabinet since additives are required (at a minimum, vitamins and trace elements) and there is a safety issue if the seal is not opened prior to use. The complexity of the PN patient population will determine the suitability of premixed PN preparations for your facility. For institutions without sufficient volume to justify an automated compounder or those lacking PN expertise, premixed PN offers a safer alternative to manual PN compounding. These products also can provide a solution for managing shortages of individual PN ingredients.
Recently, almost all components of a PN formulation have been impacted by product shortages, forcing many pharmacists to replace their standard injectable solution with a different product.4 This can increase the risk of a compounding error if the automated compounder software is not changed to reflect the new product. In addition to possible safety issues with outsourcing, critical shortages of PN nutrients can result in significant harm and may require dose conservation, rationing, and alternative therapeutic measures.5 Practice recommendations for dealing with PN product shortages are available on the A.S.P.E.N. website (www.nutritioncare.org).
Parenteral nutrition is a complex product that presents unique prescribing and compounding challenges. Using a carefully developed, patient-specific nutrition care plan combined with selective compounding options, pharmacists can provide safe and effective PN to patients.
References are available online at: pppmag.com/pnsupp
Vanessa J. Kumpf, PharmD, BCNSP, is a nutrition support pharmacy specialist at Vanderbilt Medical Center in Nashville, Tennessee, and an affiliate associate professor in the Department of Pharmacy, University of Tennessee Health Science Center.
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