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A.S.P.E.N. Statement on Parenteral Nutrition Standardization

Correspondence: Peggi Guenter, A.S.P.E.N. Electronic mail may be sent to peggig{at}aspen.nutr.org.

In response to questions regarding use of standardized parenteral nutrition (PN) formulations, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) developed a Task Force to address some of these issues. A.S.P.E.N. envisions standardized PN as a broader issue rather than simply using a standardized, commercially available PN product. A standardized process for PN must be explored in order to improve patient safety and clinical appropriateness, and to maximize resource efficiency. A standardized process may include use of standardized PN formulations (including standardized, commercial PN products) but also includes aspects of ordering, labeling, screening, compounding, and administration of PN. A safe PN system must exist which minimizes procedural incidents and maximizes the ability to meet individual patient requirements. Using clinicians with nutrition support therapy expertise will contribute to that safe PN system. The purpose of this statement is to present the published literature associated with standardized PN formulations, to provide recommendations, and to identify areas in need of future research.

The following recommendations on the issue of parenteral nutrition (PN) standardization express the position of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.):

Recommendations

1. A standardized process for PN management is advocated in order to reduce variation and promote uniformity among clinicians and between health care facilities. A standardized process may include use of standardized PN formulations (including standardized, commercial PN products) but also includes aspects of ordering, labeling, screening, and administration of PN.
   
2. The evidence on patient safety does not support the general use of standardized PN formulations across health care organizations.
   
3. The evidence suggests advantages in efficiency, economy, and clinical appropriateness with the use of standardized PN formulations compared with individualized PN formulations in select patient populations.
   
4. When an organization implements standardized PN formulations (including standardized, commercial PN products), a mechanism should be established to provide, compound, or make available customized PN formulations for individuals who have complex requirements secondary to disease or underlying illness, or when otherwise warranted by routine monitoring of electrolytes, organ function, growth, and development.
   
5. Use of the standardized process includes using clinicians with expertise in the area of nutrition support.
   
6. PN compounding practices should adhere to recommendations promulgated by national professional organizations. These include the following: A.S.P.E.N. Safe Practices for Parenteral Nutrition, Section V, Sterile Compounding of Parenteral Nutrition Formulations¹; American Society of Health-System Pharmacists (ASHP) Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition Admixtures²; ASHP Guidelines on Outsourcing Pharmaceutical Services³; and USP General Information Chapter <797>: Pharmaceutical Compounding– Sterile Preparations.⁴
   

Background
The purpose of this statement is to review the published literature associated with standardized PN formulations, to provide recommendations, and to identify areas in need of future research. A process of literature review and classification similar to that of A.S.P.E.N. guidelines development was used.

The term standardized is often misinterpreted. A standardized PN formulation is a PN formulation intended to meet the daily maintenance requirements of a specific patient population (eg, age-, stress-, or disease state–specific) and differentiated by route of administration (central vs peripheral vein). A standardized, commercial PN product is a standardized PN formulation available from a manufacturer and requiring fewer compounding steps before administration. Current examples of these products are concentrated amino acids (± electrolytes) plus concentrated dextrose containers or multichamber bags of these products, often called premixed solutions.

Standardizing the macronutrient and micronutrient content of PN has been of interest since the therapy was developed. PN is a complex formulation with unique physical and chemical characteristics that create challenges in assuring that sterile, stable, and compatible formulations are prescribed, prepared, and administered. Standardizing the content of PN may improve the clinician's prescribing of a complete, balanced formulation, thereby avoiding nutrient omission and subsequent deficiency symptoms or nutrient excess and toxicity symptoms. A standardized PN formulation eases the burden on the pharmacist in assuring a stable, compatible admixture because these criteria would be considered in the development of the formulation. There are also cost and workload issues to consider when standardized PN formulations are available in batches rather than as individual admixtures.

The concern among PN prescribers is the inability to individualize the nutrient mix with the use of standardized PN formulations. Therefore, the frequency by which the standardized formulation needs to be modified may be a barrier to the implementation of a standardized PN formulation system. Limited data exist demonstrating cost savings and improved workload in preparing PN when a standardized PN formulation system is used. The important question is how many or in what percentage of patients can a standardized PN formulation be prescribed? Patients for whom standardized PN may be difficult to use include the following: those with renal, hepatic, or other organ compromise; individuals at risk for refeeding syndrome; those with glucose intolerance; neonatal and pediatric patients; adults with abnormal body composition, large gastrointestinal fluid losses, and critical illness; and home PN patients demonstrating large-volume fluid and electrolyte losses.

Current PN practice includes a variety of prescribing and compounding methods, including individualized PN formulations based on the patient's clinical condition. According to a survey performed in 2003 by A.S.P.E.N.,⁵ significant variation existed for ordering and compounding PN. PN base components were most often ordered as a percentage of final concentration after admixture (eg, dextrose 20%), a practice inconsistent with safe practice guidelines of ordering total amount per day (eg, 200 g/d). In addition, there was no consistent method for ordering PN electrolytes. Eightyeight percent of respondents reported using a standardized PN order form, and there was a significant difference found between the use of standard PN order forms and how often PN orders required clarification. PN orders written with the use of standard order forms seldom required clarification, whereas PN orders not using standard order forms required frequent clarification (p = .015). Approximately 45% of responders to the survey reported adverse events that required intervention directly related to PN. Of these events, 25% caused temporary or permanent harm, and 4.8% resulted in a near-death event or death.

A.S.P.E.N. envisions standardized PN as a broader issue rather than simply using a standardized, commercially available PN product. A standardized process for PN must be explored in order to improve patient safety and clinical appropriateness, and to maximize resource efficiency. A standardized process may include use of standardized PN formulations (including standardized, commercial PN products) but also includes aspects of ordering, labeling, screening, compounding, and administration of PN. A safe PN system must exist that minimizes procedural incidents and maximizes the ability to meet individual patient requirements. Using clinicians with nutrition support therapy expertise will contribute to that safe PN system.

The Joint Commission's National Patient Safety Goal 3B⁶ recommends standardizing and limiting the number of drug concentrations used by the organization. In its frequently asked questions,⁷ updated January 2007 in conjunction with A.S.P.E.N., the Joint Commission notes that this recommendation may apply to PN, but this therapy is a multicomponent formulation and therefore much more complicated than single drug solutions for which the goal was originally intended. As such, standard PN formulations should be evaluated for how they might be used in each health care setting. In addition, Joint Commission standards⁸ recommend the use of drug formulations in their most ready-to-use form. This has brought about a discussion regarding the use of standardized, commercially available PN products that have been used extensively in foreign countries and to some extent in the United States.

Review of Literature
A literature review was conducted to explore the issue of standardized formulations. Search terms included parenteral nutrition, standardized, customized, individualized, tailored (all types of PN formulations and outcomes). References of searched publications were reviewed for additional evidence. Internal A.S.P.E.N. reviewers were requested to provide any missing literature according to these criteria: controlled trials to include standardized vs nonstandardized PN groups; peer-reviewed, English-language journals (abstracts not included); and expert-opinion articles from professional groups only. The publications were categorized by levels of evidence as follows:

1. Large randomized trials or systematic reviews with clear-cut results
   
2. Small or large randomized trials or systematic reviews with uncertain results due to flaws in study design
   
3. Nonrandomized, contemporaneous controls
   
4. Nonrandomized, historical controls
   
5. Case series, uncontrolled studies, surveys, and expert opinion
   

Findings
Table I lists the pertinent findings of these publications. The available evidence comparing standardized to individualized PN formulations in relation to patient safety is significantly limited in both quantity and quality. Currently, no large randomized trials exist comparing the use of standardized PN formulations to individualized PN with respect to all outcomes. Two prospective trials by Cade et al⁹ and Pichard et al¹⁰ have been conducted with adult and neonatal patients, comparing standardized to individualized PN, none of which evaluated the important patient safety outcome of PN error rates. In these studies, only that by Cade et al⁹ included a safety outcome, daily electrolyte serum concentrations, which were not different between the neonatal groups. Five nonrandomized studies (3 contemporaneous controlled [Dice et al,¹¹ Hayes et al,¹² and Krohn et al¹³] and 2 historical controlled [Yeung et al¹⁴ and Lenclen et al¹⁵]) have been conducted evaluating the use of standardized and individualized PN in neonatal, pediatric, and adult populations. As in the previous studies, PN error rates were not reported. The Dice et al¹¹ study demonstrated increased weight gain and nutrient intakes, with an individualized vs standardized program of peripheral PN; however, a confounding variable of pharmacist-monitoring was an additional intervention in the individualized group. The Hayes et al¹² study demonstrated significantly less electrolyte abnormalities with the standardized PN; however, patient acuity as a potential confounding factor was not controlled. The evidence to date does not demonstrate improved safety (as demonstrated by decreased PN incident/error rates) with the use of standardized PN formulations.

The literature comparing standardized to nonstandardized PN formulations with regard to other factors, including efficiency, cost, and clinical appropriateness, does lend support for the potential use of standardized PN formulations for selected patients. In both the randomized trial conducted by Pichard et al¹⁰ and the nonrandomized case control study by Yeung et al,¹⁴ total costs were the lowest for the standardized PN formulations. In the Yeung et al¹⁴ and Lenclen et al¹⁵ nonrandomized studies (neonatal population), nutrient intakes were significantly greater in the standardized PN group compared with the individualized PN group. Potential advantages with regard to cost savings and clinical efficiency may be realized with the use of standardized PN; however, additional research is needed across all patient populations, as well as with varied patient acuity.

Standardized Process for PN
Although there is an absence of safety evidence supporting standardized PN formulations for general use, A.S.P.E.N. advocates a standardized process for the delivery of PN. As shown in Table II, a standardized process addresses PN ordering, labeling, determination of nutrient requirements, screening of the PN order, administration, and monitoring. The reader is encouraged to read A.S.P.E.N.'s Safe Practices for Parenteral Nutrition¹ for a more in-depth review of this topic.

PN Formulation Issues
Numerous considerations exist when evaluating a PN formulation and system. Table III summarizes these issues as they relate to a specific PN process for each type of PN formulation being considered. Whether the PN formulation is individualized for each patient or whether a standardized or commercial PN formulation is used will be dependent on each organization. This will ultimately be influenced by the number and type of patients requiring PN within a specific institution, as well as the overall available resources, including knowledgeable staff, available to the organization. Although it is beyond the scope of this statement to define knowledgeable staff and although no literature exists specifically studying standardized PN formulations and nutrition support teams, there is research on nutrition support teams and clinicians improving the safety of PN. These knowledgeable nutrition support clinicians and teams have demonstrated improvements in PN catheter infection rates, metabolic complications, inappropriate use of PN, and substantial cost savings.^23–35 A.S.P.E.N. guidelines and standards provide clinicians with best practices for PN therapy.^22,36–44

Future Research
Future research is based on unanswered questions or gaps in the literature after an assessment of the current body of knowledge and identification of the issues that deserve further investigation. These questions should be answered by the highest level of research possible. The following research recommendations are based on the above literature review of standardized PN.

1. Determine the effect of standardized PN formulations and standardized, commercial PN products on patient safety. Patient safety parameters should include frequency of procedural safety incidents (prescribing, calculation, compounding, compatibility, and administration incidents) and infection-control outcomes.
   
2. Evaluate the ergonomic and economic effects of standardized, commercial PN products available in the United States vs other modes of PN delivery.
   
3. Randomized, controlled studies are needed to evaluate the clinical outcome differences between standardized (including standardized, commercial PN products) and individualized PN formulations in defined patient populations. Clinical outcomes should include morbidity and mortality; ability for formulas to meet nutritional requirements, and changes in nutrition assessment parameters or laboratory values.
   
4. Evaluate the effect of nutrition support clinicians (including board-certified nutrition support clinicians) or nutrition support services/teams on clinical outcome and patient safety differences between standardized (including standardized, commercial PN products) and individualized PN formulations.
   

	CONCLUSION

Top CONCLUSION

 
A variety of clinical practices exist to order, compound, and deliver PN. While a variety of available current practice guidelines exist allowing individualized patient PN prescribing, patient requirements should be balanced with standardized processes to enhance patient safety and reduce both ordering and compounding errors. An extensive literature search was conducted on the use of standardized PN formulations. Although sufficient evidence does not exist to suggest all patients should receive standardized formulations according to safety issues, A.S.P.E.N. recommends the use of standardized processes using clinicians with expertise in nutrition support therapy for improving PN. Future research should be conducted to answer the clinical questions about standardized formulations and safety issues.

Received for publication June 12, 2007. Accepted for publication June 12, 2007.

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Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 5, 441-448 (2007)
DOI: 10.1177/0148607107031005441


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