A.S.P.E.N. Clinical Guidelines

Background: Parenteral nutrition (PN) is a high‐alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to guide safe use and optimize clinical outcome, several issues are better addressed through evidence‐based policies, procedures, and practices. This document provides evidence‐based guidance for clinical practices involving PN prescribing, order review, and preparation. Method: A systematic review of the best available evidence was used by an expert work group to answer a series of questions about PN prescribing, order review, compounding, labeling, and dispensing. Concepts from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) format were applied as appropriate. The specific clinical guideline recommendations were developed using consensus prior to review and approval by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. The following questions were addressed: (1) Does education of prescribers improve PN ordering? (2) What is the maximum safe osmolarity of PN admixtures intended for peripheral vein administration? (3) What are the appropriate calcium intake and calcium‐phosphate ratios in PN for optimal neonatal bone mineralization? (4) What are the clinical advantages or disadvantages of commercially available premade (“premixed”) multichambered PN formulations compared with traditional/customized PN formulations? (5) What are the clinical (infection, catheter occlusion) advantages or disadvantages of 2‐in‐1 compared with 3‐in‐1 PN admixtures? (6) What macronutrient dosing limits are expected to provide for the most stable 3‐in‐1 admixtures? (7) What are the most appropriate recommendations for optimizing calcium (gluconate) and (Na‐ or K‐) phosphate compatibility in PN admixtures? (8) What micronutrient contamination is present in parenteral stock solutions currently used to compound PN admixtures? (9) Is it safe to use the PN admixture as a vehicle for non‐nutrient medication delivery? (10) Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis? (11) What methods of repackaging intravenous fat emulsion (IVFE) into smaller patient‐specific volumes are safe? (12) What beyond‐use date should be used for (a) IVFE dispensed for separate infusion in the original container and (b) repackaged IVFE?     

A.S.P.E.N. Clinical Guidelines

Background: Due to the high prevalence of obesity in adults, nutrition support clinicians are encountering greater numbers of obese patients who require nutrition support during hospitalization. The purpose of this clinical guideline is to serve as a framework for the nutrition support care of adult patients with obesity. Method: A systematic review of the best available evidence to answer a series of questions regarding management of nutrition support in patients with obesity was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process, that includes consideration of the strength of the evidence together with the risks and benefits to the patient, was used to develop the clinical guideline recommendations prior to multiple levels of external and internal review and approval by the A.S.P.E.N. Board of Directors. Questions: (1) Do clinical outcomes vary across levels of obesity in critically ill or hospitalized non?intensive care unit (ICU) patients? (2) How should energy requirements be determined in obese critically ill or hospitalized non‐ICU patients? (3) Are clinical outcomes improved with hypocaloric, high protein diets in hospitalized patients? (4) In obese patients who have had a malabsorptive or restrictive surgical procedure, what micronutrients should be evaluated?     

A.S.P.E.N. Clinical Guidelines

Background: Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. Method: A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. Questions: (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?     

A.S.P.E.N. Parenteral Nutrition Safety Consensus Recommendations

Parenteral nutrition (PN) serves as an important therapeutic modality that is used in adults, children, and infants for a variety of indications. The appropriate use of this complex therapy aims to maximize clinical benefit while minimizing the potential risks for adverse events. Complications can occur as a result of the therapy and as the result of the PN process. These consensus recommendations are based on practices that are generally accepted to minimize errors with PN therapy, categorized in the areas of PN prescribing, order review and verification, compounding, and administration. These recommendations should be used in conjunction with other A.S.P.E.N. publications, and researchers should consider studying the questions brought forth in this document.     

Proceedings of the 2014 A.S.P.E.N. Research Workshop

The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high‐resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross‐reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.‐sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease.     

Proceedings From FDA/A.S.P.E.N. Public Workshop

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited. While soybean‐based IVFEs have comprised the dominant fat in U.S. markets, a number of other novel IVFEs may prove to optimize the care of children and adults in both hospitalized and home settings. The October 2013 U.S. Food and Drug Administration (FDA)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Public Workshop brought together scientists, researchers, and clinical experts to present updated clinical perspectives of IVFEs, including historical development, current state of usage throughout the world, and considerations for the regulatory approval of new IVFEs in the United States.     

Expediting Transition to Home Parenteral Nutrition With Fast‐Track Cycling

Background. Delivery of home parenteral nutrition (PN) is typically cycled over 12 hours. Discharge to home on PN is often delayed due to potential adverse events (AEs) associated with cycling PN. The purpose was to determine whether patients requiring long‐term PN can be cycled from 24 hours to 12 hours in 1 day instead of 2 days without increasing the risk of PN‐related AEs. Methods. Hospitalized patients receiving PN at goal calories infused over 24 hours without severe electrolyte or blood glucose abnormalities were eligible. Patients were randomly assigned to a 1‐step “fast‐track” protocol or 2‐step “standard” protocol. AEs were defined as hypoglycemia or hyperglycemia, new‐onset or worsening dyspnea, tachycardia, tachypnea, lower extremity or sacral edema, pulmonary edema, or abdominal ascites and were graded as minor or major. Results. In the 63 patients studied, the most prevalent PN‐related AE was hyperglycemia, occurring in 24.2% and 30.0% of patients in the fast‐track and standard groups, respectively. Overall, there was no significant difference in the prevalence of PN‐related minor AEs between fast‐track and standard groups (33.3% and 53.3%, P = .5). No major PN‐related AEs occurred in the fast‐track group, while 1 major PN‐related AE (pulmonary edema) occurred in the standard group. Conclusions. Fast‐track cycling is as safe as standard cycling in patients without diabetes mellitus or major organ dysfunction requiring long‐term PN. Fast‐track cycling could potentially expedite hospital discharge, resulting in decreased healthcare costs and improved patient satisfaction.     

A.S.P.E.N. Clinical Guidelines

Background: Hyperglycemia is a frequent occurrence in adult hospitalized patients who receive nutrition support. Both hyperglycemia and hypoglycemia (resulting from attempts to correct hyperglycemia) are associated with adverse outcomes in diabetic as well as nondiabetic patients. This American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Clinical Guideline summarizes the most current evidence and provides guidelines for the desired blood glucose goal range in hospitalized patients receiving nutrition support, the definition of hypoglycemia, and the rationale for use of diabetes‐specific enteral formulas in hospitalized patients. Method: A systematic review of the best available evidence to answer a series of questions regarding glucose control in adults receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. Results/Conclusions: 1. What is the desired blood glucose goal range in adult hospitalized patients receiving nutrition support? We recommend a target blood glucose goal range of 140–180 mg/dL (7.8–10 mmol/L). (Strong) 2. How is hypoglycemia defined in adult hospitalized patients receiving nutrition support? We recommend that hypoglycemia be defined as a blood glucose concentration of <70 mg/dL (<3.9 mmol/L). (Strong) 3. Should diabetes‐specific enteral formulas be used for adult hospitalized patients with hyperglycemia? We cannot make a recommendation at this time.     

Vitamin D deficiency in patients receiving home parenteral nutrition

Background: In addition to its role in bone metabolism, vitamin D has important immunomodulatory and antineoplastic effects. Patients on home parenteral nutrition (HPN) receive most of their vitamin D from intravenous (IV) supplementation. Vitamin D deficiency is common in the general population, and the adequacy of vitamin D supplementation in HPN patients is unclear. The purpose of this study is to determine the vitamin D status of patients on HPN. Methods: Consecutive patients seen in a regional home nutrition program had their oral and IV vitamin D intakes determined. Plasma 25‐hydroxyvitamin D levels were measured in all patients. Intake of calcium, magnesium, and phosphate were also determined. Results: The mean 25‐hydroxyvitamin D level in 22 patients receiving HPN for a mean of 33.5 months (range, 1–177) was 42 nmol/L. Vitamin D deficiency was present in 15 (68%) patients and vitamin D insufficiency in 6 (27%) patients. The mean dietary vitamin D intake was 79.5 IU per day, while the mean IV supplementation was 166 IU per day. Conclusions: In this study of a regional Canadian HPN program, there was a high prevalence of vitamin D deficiency/insufficiency affecting virtually all patients. All patients receiving HPN should be supplemented with vitamin D and have their 25‐hydroxyvitamin D levels monitored. Further studies are required to determine optimal methods and dosing of vitamin D replacement using oral supplements or ultraviolet light therapy.     

Challenging the 48‐Hour Rule‐Out for Central Line–Associated Bloodstream Infections in the Pediatric Intestinal Failure Population

Introduction: While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line–associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. Methods: A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. Results: Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C‐reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. Conclusion: Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.     

Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean Oil Lipid Emulsion in Children Receiving Parenteral Nutrition

Background: Soybean oil lipid emulsion may compromise immune function and promote hepatic damage due to its composition of long‐chain fatty acids, phytosterols, high proportion of ω‐6 fatty acids, and low α‐tocopherol levels. Combination lipid emulsions have been developed using medium‐chain triglyceride oil, fish oil, and/or olive oil, which provide adequate essential fatty acids, a smaller concentration of ω‐6 fatty acids, and lower levels of phytosterols. The purpose of this systematic review is to determine if combination lipid emulsions have a more favorable impact on bilirubin levels, triglyceride levels, and incidence of infection compared with soybean oil lipid emulsions in children receiving parenteral nutrition. Methods: This study comprises a systematic review of published studies. Data were sufficient and homogeneous to conduct a meta‐analysis for total bilirubin and infection. Results: Nine studies met the inclusion criteria. Meta‐analysis showed that combination lipid emulsion decreased total bilirubin by a mean difference of 2.09 mg/dL (95% confidence interval, –4.42 to 0.24) compared with soybean oil lipid emulsion, although the result was not statistically significant (P = .08). Meta‐analysis revealed no statistically significant difference in incidence of infection between the combination lipid emulsion and the soybean oil lipid emulsion groups (P = .846). None of the 4 studies that included triglyceride as an outcome detected a significant difference in triglyceride levels between the combination lipid emulsion and soybean oil lipid emulsion groups. Conclusion: There is inadequate evidence that combination lipid emulsions offer any benefit regarding bilirubin levels, triglyceride levels, or incidence of infection compared with soybean oil lipid emulsions.     

A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most devastating diseases in the neonatal population, with extremely low birth weight and extremely preterm infants at greatest risk. METHOD: A systematic review of the best available evidence to answer a series of questions regarding nutrition support of neonates at risk of NEC was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. RESULTS/ CONCLUSIONS: (1) When and how should feeds be started in infants at high risk for NEC? We suggest that minimal enteral nutrition be initiated within the first 2 days of life and advanced by 30 mL/kg/d in infants ≥ 1, 000 g. (Weak) (2) Does the provision of mother's milk reduce the risk of developing NEC? We suggest the exclusive use of mother's milk rather than bovine-based products or formula in infants at risk for NEC. (Weak) (3) Do probiotics reduce the risk of developing NEC? There are insufficient data to recommend the use of probiotics in infants at risk for NEC. (Further research needed.) (4) Do nutrients either prevent or predispose to the development of NEC? We do not recommend glutamine supplementation for infants at risk for NEC (Strong). There is insufficient evidence to recommend arginine and/or long chain polyunsaturated fatty acid supplementation for infants at risk for NEC. (Further research needed.) (5) When should feeds be reintroduced to infants with NEC? There are insufficient data to make a recommendation regarding time to reintroduce feedings to infants after NEC. (Further research needed.).     

Teduglutide‐Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome

Background: Teduglutide, a glucagon‐like peptide‐2 (GLP‐2) analogue, is available for long‐term use by parenteral nutrition (PN)–dependent adults to promote intestinal adaptation but is not approved for use in pediatric patients. The objective of this study was to assess teduglutide‐stimulated induced intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation in a neonatal piglet model of short bowel syndrome (SBS). Materials and Methods: Neonatal piglets (48 hours old; n = 72) underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment groups, in a 2 × 2 factorial design, with PN or PEN (80% standard PN/20% standard enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received nutrient infusions for 4 hours, 48 hours, or 7 days. Results: Teduglutide improved (P < .05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon; apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). These effects were complemented and synergistically enhanced by PEN in both site and timing of action. Structural adaptations preceded functional adaptations, but crypt depth remained a strong indicator of adaptation, regardless of time. Conclusions: The combination of teduglutide and PEN enhances intestinal adaptation beyond that of either therapy alone.     

Physical Compatibility of Calcium Chloride and Sodium Glycerophosphate in Pediatric Parenteral Nutrition Solutions

Background: Calcium and phosphate precipitation is an ongoing concern when compounding pediatric parenteral nutrition (PN) solutions. Considerable effort has been expended in producing graphs, tables, and equations to guide the practitioner in prescribing PN that will remain stable. Calcium gluconate is preferred over calcium chloride when compounding PN because of its superior compatibility with inorganic phosphates. PN solutions containing calcium gluconate carry a higher aluminum load than equivalent solutions compounded with calcium chloride, leading to increased potential for aluminum toxicity. This study tested the solubility of calcium chloride in PN solutions compounded with an organic phosphate component, sodium glycerophosphate (NaGP), in place of sodium phosphate. Methods: Five PN solutions were compounded by adding calcium chloride at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteine, and lipids. The physical stability was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals using U.S. Pharmacopeia <788> standards. Results: Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Calcium chloride was found to be physically compatible with NaGP in PN at the tested concentrations. Conclusion: Utilization of NaGP in PN solutions would eliminate the need for precipitation curves and allow for the use of calcium chloride. Compounding with NaGP and calcium chloride allows the practitioner a mechanism for reducing the aluminum load in PN.     

Long-Term Use of Mixed-Oil Lipid Emulsion in Soybean Oil–Intolerant Home Parenteral Nutrition Patients

Background: Although home parenteral nutrition (HPN) is lifesaving for patients with chronic intestinal failure (IF), long-term use can be associated with complications such as infections, metabolic abnormalities, and IF–associated liver disease (IFALD). The key to treatment of many of these complications is prevention. Guidelines recommend avoidance of overfeeding, use of oral/enteral nutrition if possible, cyclic PN, and maintaining dose of soybean oil (SO) intravenous lipid emulsion (ILE) <1 g/kg/day as preventive strategies for IFALD. Additionally, with development of IFALD, ω-6/ω-3 polyunsaturated fatty acid ratio should be decreased in ILE. The newly available mixed-oil (MO) ILE offers such an opportunity; however, there is a paucity of long-term data available. Methods: The current study reports our long-term experience with MO ILE use in HPN patients. Results: Seventeen patients (8 female and 9 male) with an average age of 47 ± 12 years and median HPN duration of 4.6 years (1.1–32.1 years) have utilized MO ILE for >12 months after being transitioned from SO ILE because of intolerance. Use of MO ILE allowed an increase in ILE energy from 8% ± 8% to 22% ± 8% while reducing dextrose energy from 66% ± 8% to 54% ± 5%, maintaining stability in alkaline phosphatase and triglyceride levels, and achieving improvement in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and α-tocopherol levels. Conclusion: In this HPN cohort with SO ILE intolerance, MO ILE was well tolerated and allowed an improvement in macronutrient composition while improving some liver parameters over a 12-month period.     

Pharmaceutical and Clinical Aspects of Lipid Injectable Emulsions

The first clinically successful lipid injectable emulsion was marketed in 1961, consisting of soybean oil triglycerides in sterile water for injection. Since that time, numerous products have entered the market, with the main difference being changes in the oil composition with triglycerides of plant and marine oil origin. With this change, the fatty acid profiles are unique, coming from medium‐ and long‐chain triglycerides. The fatty acids can be saturated or unsaturated, having different pharmaceutical and metabolic activities that affect the safety and efficacy of these unique pharmaceutical dosage forms.     

Hypothyroidism and Iodine Deficiency in an Infant Requiring Total Parenteral Nutrition

While iodine deficiency remains a relatively rare cause of thyroid dysfunction in the United States, little is known about iodine status and deficiency in children requiring parenteral nutrition (PN). This population may be at an elevated risk of thyroid dysregulation and neurodevelopmental sequelae due to low concentrations in typical PN formulations. Furthermore, with the widespread practice of switching from iodine‐based antiseptics to chlorhexadine, previous inadvertent sources of iodine are being eliminated as well.