Prospective survey of parenteral nutrition in Switzerland: a three-year nation-wide survey

BACKGROUND AND AIMS: The goals of this national survey were to determine the current PN practices and admixture formulations used in Switzerland. METHODS: During three years, an annual questionnaire was sent to all heads of Swiss hospital pharmacies. RESULTS: 92% of Swiss hospitals with a full-time pharmacist participated. Different PN systems were commonly used for adult patients: 2 commercial formulas in 2 or 3 compartments bags, 2 commercial formulas with/without lipid, 3 formulas compounded by the hospital pharmacy. For hospitalized adults, 83% of PN bags were administered as commercial multicompartment bags. The compounding of individualized PN admixtures takes place primarily in pharmacies of medium to large size hospitals. For pediatric PN, hospital compounding is routine because of individualized PN compositions and absence of commercially available standardized admixtures. Long-term home-PN was mostly delivered by hospital pharmacies (57%) or by private nutrition support home delivery services (37%). Most PN formula compositions complied with European guidelines and represented 2.6+/-2.0% of the hospital drug budget. Multi-disciplinary nutritional support teams were present in 52% of hospitals. CONCLUSION: In Switzerland, most PN for hospitalized adults were administered as commercial multi-compartment bags. The compounding of individualized PN admixtures were still important for pediatric patients and long-term home-PN.     

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?     

Influence of vitamins, trace elements, and iron on lipid peroxidation reactions in all-in-one admixtures for neonatal parenteral nutrition

Background: The purpose of this study was to evaluate the effect of vitamins, trace elements, or iron on lipid peroxidation in all‐in‐one parenteral nutrition (PN) admixtures for preterm neonates. Methods: Malondialdehyde (MDA) concentrations were analyzed over a 24‐hour period (H1‐H24) in lipid‐containing PN solutions that have a composition identical to that used in the routine clinical care of preterm infants. Six different solutions were prepared and evaluated when exposed to ambient light and light‐protected conditions as follows: control (without vitamins [Vit], trace elements [TE], or iron [Fe] [Vit?TE?Fe?]), solution 1 (Vit+TE+Fe?), solution 2 (Vit+TE?Fe?), solution 3 (Vit?TE+Fe?), solution 4 (Vit?TE?Fe+), and solution 5 (Vit+TE+Fe+). Results: MDA concentrations in PN solutions were significantly higher at H24 than at H0 when they contained multivitamins (P < .001), trace elements (P = .002), or iron saccharate (P = .018). MDA concentration was particularly high when all 3 micronutrients were present (P < .001) or when the solutions were exposed to ambient light. In solutions containing iron, MDA concentrations were elevated at H0, and levels did not change whether protected from (P < .001) or exposed to (P < .001) from light. Conclusions: The addition of vitamins and trace elements to PN solutions induces a significant increase in peroxidation products, which are lowered when admixtures are protected from light. Iron should not be included in these solutions, even if solutions are light‐protected. By following these conditions it is possible to use all‐in‐one admixtures in the nutrition management of preterm infants.     

Aluminum Contamination in Parenteral Nutrition Admixtures for Low‐Birth‐Weight Preterm Infants in Mexico

Background: Aluminum contamination from intravenous solutions still represents an unsolved clinical and biochemical problem. Increased aluminum intake constitutes a risk factor for the development to metabolic bone disease, anemia, cholestasis, and neurocognitive alterations. Low‐birth‐weight preterm infants (LBWPIs) are one of the most exposed populations for aluminum toxicity. Methods: To determine the presence of aluminum in components employed in the preparation of parenteral nutrition (PN) admixtures in Mexico and compare with the maximal aluminum recommended intake from the Food and Drug Administration. Results: Cysteine, trace elements, levocarnitine, phosphate, and calcium salts tested positive for aluminum contamination. All components analyzed were contained in glass vials. Total aluminum intake for 2 sample PN admixtures were calculated in basis to cover nutrition requirements of 2 hypothetical LBWPIs. Aluminum contents, stratified in micrograms per kilogram of weight, exceeded maximal aluminum recommendations, particularly for the very LBWPIs. Substituting sodium phosphate for potassium phosphate salts reduced aluminum intake by 52.7%. Calcium gluconate was the leading aluminum contamination source and confers the greatest risk for aluminum overdose, even with the salt substitution of potassium phosphate by sodium phosphate salts. Adding cysteine and trace elements might increase aluminum content in PN admixtures. Conclusion: Cysteine, trace elements, phosphate, and gluconate salts are the main sources of aluminum in PN prepared in Mexico. Substituting sodium phosphate for potassium phosphate salts reduces aluminum intake but does not resolve aluminum contamination risk. Mineral salts contained in plastic vials should be explored as an additional measure to reduce aluminum contamination.     

Parenteral nutrition practices in hospital pharmacies in Switzerland, France, and Belgium

OBJECTIVE: Important changes in administering total parenteral nutrition (PN) admixtures have occurred over the past decade. This study describes hospital pharmacists' practices in France (F), Switzerland (CH), and Belgium (B). METHODS: From the responses received using a standardized questionnaire, (n = 378) we determined the origin, types of container used, and choice of PN formula (standard versus tailor-made) and the type of quality control and the existence of nutrition support teams. RESULTS: The mean response rates were 55.6% (CH), 30.5% (F), and 24.5% (B). Standard formulas were used mainly for adult patients (CH, 86%; F, 79%; B, 86%), whereas approximately 50% of tailor-made PN bags were used for children. Single-compartment or multicompartment bags or glass bottles contained standard formulas. Most standard formulas were provided by industry, apart from (B), where 50% of PN solutions were compounded by hospital pharmacies. Single-compartment bags contained generally tailor-made formulas produced exclusively by hospital pharmacies in (CH) and (B), whereas 33% were provided by industry in (F). Quality controls were mostly visual and occurred in 75% to 95% of hospitals. Nutrition support teams were present in 32% to 45% of hospitals. CONCLUSION: The choice, origin, and type of container used for PN formulas were highly variable among countries. However, the use of standard formulas in bags was predominant in (CH) and (B). The function of nutrition support teams was similar in (F), (CH), and (B).     

药师与临床营养支持

美国肠外肠外营养学会建议由医师、营养师、护师和药师组成一个联合小组,共同完成临床营养支持工作,以确保每位病人接受到最适宜的全方位服务。药师的参与可以提高效用、降低副作用和费用,我们体会可以从以下几方面做些工作：（1）处方的审查和标签：既注意营养组分的量,也关注配成TNA后各组分的实际浓度,使处方配比合理化,协助医师真正实现个体化给药。（2）配制环境及技术：严格执行无菌操作基本原则,从处方设计到配制操作过程都应有质量保证即质量管理活动贯穿于全过程。临时配制最好由经过专门训练的合格人员来承担。不同配伍的、不稳定的或污染的静脉输液会显增加病人的致病率甚至死亡率。药剂科应成立有专人负责的一个小组并建立相应的规章制度和操作规程。（3）PN的配伍和稳定性：关注配制时间、储存周期、营养组分相互作用和包装材料对组分稳定性影响,防止不溶性微粒和乳析现象的发生。尽量避免将药物配伍入PN液中,关注包括Y型管在内的配伍变化。（4）PN混合液的在线过滤：建议使用终端滤器,防止输注过程的危害。0．2μm的滤器可用于一般输液,1．2μm的滤器适于含脂肪乳的PN液。选择膜滤器时不应考虑膜的耐受范围。（5）肝素问题：肝素会降低脂肪乳的稳定性。（6）导管：药师应注意导管对药物的吸附、导管添加剂的游离释出和导管入口处的消毒问题。（7）材料与包装容器的影响：包装材质、热压灭菌过程和不同品牌市售产品对PN液的稳定性和配伍的影响都应注意。（8）药师也应关注肠内营养,协助医师做好患营养支持过渡工作,并注意下胃管给药时的一些稳定性问题。     

A simple equation to estimate the osmolarity of neonatal parenteral nutrition solutions

A predictive equation of osmolarity that correlates closely with the measured osmolality was determined. Taking into account that an osmometer is not available in most clinical settings, the proposed equation appears to provide a quick and simple osmolarity calculation of neonatal parenteral nutrition solutions. OBJECTIVE: We measured the osmolalities of neonatal parenteral nutrition (PN) solutions to determine if these values may be predicted by a simple equation for calculation of their osmolarity values. METHODS: The osmolalities of 101 consecutive different final PN admixtures, prepared for 36 neonates, were measured by the freezing point depression method. The respective intra-assay and interassay coefficients of variation were always <2.1%. Linear multivariate regression analysis was used to determine a predictive equation of osmolarity that correlates closely with the value of measured osmolality. RESULTS: The mean (SD) osmolality of the final PN admixtures was 749.7 (165.4) mOsm/kg. The best-fitted equation, with a coefficient of discrimination R2 = .95 (R2 = .90 for samples between 500 and 1000 mOsm/L) is osmolarity (mOsm/L) = (nitrogen x 0.8) + (glucose x 1.235) + (sodium x 2.25) + (phosphorus x 5.43)-50, with the concentration of components in mmol/L. Adapting the equation in our daily practice, using g/L for glucose and amino acids, mg/L for phosphorus, and mEq/L for sodium, the equation is osmolarity (mOsm/L) = (amino acid x 8) + (glucose x 7) + (sodium x 2) + (phosphorus x 0.2) - 50, with a similar R2. CONCLUSIONS: Taking into account that an osmometer is not available in most clinical settings, the proposed equation appears to provide a quick and simple osmolarity calculation of neonatal PN solutions, thus allowing more accurate decisions to be taken regarding the choice of route and rate of administration of PN solutions.     

Microbiological quality control study of "all-in-one" total parenteral nutrition admixtures

A microbiological quality control study of parenteral nutrition (PN) is presented. The study was carried out in the Pharmacy and Microbiology Services of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from April 1991 to May 1998 and represents more than 25,000 lipid-containing PN admixtures prepared during that 7-year period. A randomized sampling procedure according to the cumulative sum control charts was performed and a 0.45-microm membrane filtration method was used as the microbiological test. Validation showed that the method is sensitive for sterility tests. Bacterial growth was observed on 59 filters (4.58% of the samples). A second control was made for these positive outcomes, and bacterial growth was found in only two cases. The patients' clinical history was reviewed and no relation between the microorganisms of the nutrition and the results obtained from blood cultures was observed. The quality control study revealed a low incidence of contamination in our PN preparation process.     

Calcium and Phosphate Compatibility in Low‐Osmolarity Parenteral Nutrition Admixtures Intended for Peripheral Vein Administration

Background: Precipitation of calcium (Ca) and phosphate (P) salts can lead to potentially lethal outcomes, especially in low‐osmolarity parenteral nutrition (LO‐PN) formulations. Three concentrations of amino acids (AA) and 2 concentrations of calcium gluconate and sodium phosphate injections on the compatibility of Ca and P in LO‐PN admixtures were studied. Methods: Final AA concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n = 2) for a total of 12 base (3 × 2× 2) formulations. Triplicate bags of each were analyzed for subvisible micro‐precipitates using the light obscuration (or extinction) method for particle counts per milliliter (PC) in the size range of 1.8‐50 μm at 7 time intervals over 48 hours stored at 30°C ± 0.2°C. Visual evaluation was performed using a high‐intensity lamp against a black background for detection of macro‐precipitates. The pH of all 36 admixtures was measured at 0 and 48 hours. Any precipitated material was isolated and characterized by polarized light microscopy and infrared spectroscopy. Results: Of the 12 base LO‐PN formulations tested, those containing 1% and 2% AA with 5 mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some resulted in visible dibasic calcium phosphate precipitation. Analyses of variance based on concentrations of AA, Ca, P, and time were highly significant independent variables for increases in the PC of potentially embolic particles, that is, sizes >5 μm (P < .0001). The lowest concentrations of Ca and P, 2.5 and 15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes compared with the other Ca and P combinations. Conclusions: LO‐PN admixtures (AA ≤ 3%; G = 5%) should not contain more than 2.5 mmol/L of Ca from calcium gluconate injection and no more than 15 mmol/L of P from potassium or sodium phosphates injection.     

Compatibility of Intravenous Medications With Parenteral Nutrition

Background and Aim: Hospitalized patients requiring parenteral nutrition (PN) often need to receive intravenous (IV) medications as well. Y‐site administration is occasionally necessary, but physicochemical incompatibilities can occur between the medications and PN. The aim of the present study was to assess the physical compatibility between 25 frequently coadministered IV medications and a commercially available ready‐to‐use total PN. Methods: PN (NuTRIflex Lipid Special; B. Braun Medical AG, Sempach, Switzerland) and medications were mixed in 1:1 (v/v) proportions, and the stability was assessed at the time of mixing and after 1 and 4 hours. The stability of lipid emulsion was observed by microscopic investigation, visual inspection, dynamic laser light scattering, and laser light obscuration. The binary admixtures of PN (without lipid emulsion) and medications were used to detect discoloration, visibly detectable precipitates, and subvisual particles. Results: Two of 25 medications were incompatible with the lipid emulsion (serum albumin 20% and tropisetron), 2 showed signs of degradation (discoloration) over time (esomeprazole and pantoprazole), and 1 precipitated at high concentrations (5‐fluorouracil). The other 20 medications were considered compatible when administered by Y‐site. Conclusion: The present study validated the compatibility of 1 commercially available PN and 20 medications. These results offer new solutions to support the implementation of complex therapeutic schemes in practice, when coadministration via Y‐site cannot be avoided.     

Prediction of parenteral nutrition osmolarity by digital refractometry

Background: Infusion of high‐osmolarity parenteral nutrition (PN) formulations into a peripheral vein will damage the vessel. In this study, the authors developed a refractometric method to predict PN formulation osmolarity for patients receiving PN. Methods: Nutrients in PN formulations were prepared for Brix value and osmolality measurement. Brix value and osmolality measurement of the dextrose, amino acids, and electrolytes were used to evaluate the limiting factor of PN osmolarity prediction. A best‐fit equation was generated to predict PN osmolarity (mOsm/L): 81.05 × Brix value – 116.33 (R ² > 0.99). To validate the PN osmolarity prediction by these 4 equations, a total of 500 PN admixtures were tested. Results: The authors found strong linear relationships between the Brix values and the osmolality measurement of dextrose (R ² = 0.97), amino acids (R ² = 0.99), and electrolytes (R ² > 0.96). When PN‐measured osmolality was between 600 and 900 mOsm/kg, approximately 43%, 29%, 43%, and 0% of the predicted osmolarity obtained by equations 1, 2, 3, and 4 were outside the acceptable 90% to 110% confidence interval range, respectively. When measured osmolality was between 900 and 1,500 mOsm/kg, 31%, 100%, 85%, and 15% of the predicted osmolarity by equations 1, 2, 3, and 4 were outside the acceptable 90% to 110% confidence interval range, respectively. Conclusions: The refractive method permits accurate PN osmolarity prediction and reasonable quality assurance before PN formulation administration.     

Effects of pH, temperature, concentration, and time on particle counts in lipid-containing total parenteral nutrition admixtures

It has been standard practice in the United States to separate lipid emulsion from the other components of total parenteral nutrition (TPN) due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent difficulties. Infusion of all nutrients from one container has many advantages. In this study standard and concentrated admixtures were aseptically prepared using generally accepted guidelines of the nutritional requirements for a 70-kg patient. Treatments of standard and concentrated admixtures consisted of: storing at 4 degrees C without adjusting the pH; increasing the pH to 6.6 and storing at 4 degrees C; increasing the pH to 6.6 and storing at room temperature. Samples were monitored for 3 weeks by means of Coulter Counter analysis, pH determinations, and visual observations. The pH of the admixtures did not change over 3 weeks. Mean counts of particles with sizes between 1.6 and 25.4 mu increased over time for each treatment group. Within treatments, concentrated admixtures had significantly greater particle counts than the corresponding standard admixtures. Within the standard and within the concentrated admixtures, the particle counts were significantly greater for group one than for group three. Particle counts in group two tended to lie between the values of group one and three. Visual signs of emulsion deterioration were greatest in those admixtures in which the pH was not adjusted and occurred earlier in concentrated admixtures.     

Effect of Intralipid, amino acids, container, temperature, and duration of storage on vitamin stability in total parenteral nutrition admixtures

This study was designed to determine the stability of certain vitamins added to total parenteral nutrition (TPN) admixtures with or without Intralipid iv fat emulsion and with each of four amino acid solutions stored in either glass bottles or plastic bags at either ambient room (25 degrees C) or refrigerator (5 degrees C) temperature for a 48-hr period. Riboflavin and folacin were not affected by the experimental conditions. The presence of Intralipid resulted in higher levels of vitamin E due to Intralipid's inherent vitamin E content; no other experimental conditions affected vitamin E. Thiamin levels decreased in admixtures containing the amino acid solution C and stored at 25 degrees C. Vitamin A levels were lower in admixtures stored in plastic but were maintained in admixtures containing Intralipid and stored in glass bottles at either temperature. Vitamin C levels were maintained in admixtures stored at 5 degrees C for all experimental conditions. The greatest vitamin C losses occurred in admixtures containing amino acid solutions C or D stored in plastic bags, or containing D stored in glass bottles at 25 degrees C.     

Influence of lipid type on bis (2-ethylhexyl)phthalate (DEHP) leaching from infusion line sets in parenteral nutrition

Background: Bis(2‐ethylhexyl)phthalate (or DEHP) is widely used in polyvinyl chloride (PVC) tubings for its good plasticizing properties. Because it is not covalently bound to the plastic matrix, it is able to escape from PVC during the infusion of the lipid emulsions used in parenteral nutrition (PN). This creates a vector through which it can enter into contact with the patient via the nutrition admixtures infused. This study was designed to assess the potential role of the type of lipids used in PN admixtures on the quantity of DEHP leached out from PVC‐based tubings. Methods: PVC‐based infusion lines, 6 commercially available lipid emulsions, and their oil base components were left in direct contact, and the amount of DEHP leached was measured by liquid chromatography. Results: After a 24‐hour exposure period, DEHP migration varied significantly (P = .0000152) according to lipid type. The olive oil–based emulsion Clinoleic leached the most DEHP (65.8 µg/mL intravenous fat emulsion), followed by the fish oil–based emulsion Omegaven (37.8 µg/mL). The soybean oil–based emulsions Intralipid, Medialipide, Lipidem, and Structolipid showed comparable performances, with DEHP leaching rates into the emulsion measured at 27.3, 27.8, 23.6, and 19.6 µg/mL, respectively. Results from the same experiments run on pure‐form oils (soybean oil, olive oil, coconut oil, and cod liver oil) confirmed the influence of lipid type on DEHP leaching. Conclusion: The major DEHP leaching caused by olive oil–based emulsions raises cause for concern because DEHP presents distinctive toxic effects, including an increased risk of cholestasis.     

Effect of phototherapy light, sodium bisulfite, and pH on vitamin stability in total parenteral nutrition admixtures

The three sections of this study extend previous research into losses of vitamins A, C, E, thiamin, riboflavin, and folic acid from total parenteral nutrition (TPN) admixtures. First, phototherapy light on TPN admixtures containing one of four amino acid solutions was studied. Experimental conditions included presence or absence of Intralipid iv fat emulsion, plastic bag or glass bottle storage container, and storage time of up to 48 hrs. The second phase studied stability of the same vitamins (except vitamin E) for 48 hrs in admixtures containing the amino acid solution which has no bisulfite, in glass bottles; with or without Intralipid; and with added sodium bisulfite (final concentrations of 0, 1, 2, 3, 4, 5 and 10 mEq/liter). Third, vitamin C and thiamin levels were measured in admixtures containing the amino acid solution with no bisulfite, without Intralipid, stored in glass bottles with various bisulfite concentrations (0, 1, 2, or 3 mEq/liter) and three pH levels (5.5, 6.5, and 6.75 pH). Exposure of TPN admixtures to phototherapy light caused losses of vitamins A, C, and riboflavin. Intralipid inclusion significantly reduced losses of vitamin A and riboflavin, but did not appear to affect vitamin C levels. The smallest vitamin C losses were noted in admixtures containing amino acid solutions A or B. Phototherapy light did not affect thiamin levels. Bisulfite had no affect on vitamin C, riboflavin, or folic acid levels. Vitamin A levels were maintained with bisulfite concentrations less than 3 mEq/liter. At 3 mEq/liter bisulfite, admixtures with Intralipid showed 50% loss of vitamin A.(ABSTRACT TRUNCATED AT 250 WORDS)     

ω‐3 Fatty Acids Prevent Hepatic Steatosis,Independent of PPAR‐α Activity,in a Murine Model of Parenteral Nutrition–Associated Liver Disease

Objectives: ω‐3 Fatty acids (FAs), natural ligands for the peroxisome proliferator‐activated receptor–α (PPAR‐α), attenuate parenteral nutrition–associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω‐3 FAs are still unknown. The aim of this study was to determine the effects of ω‐3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR‐α and microsomal triglyceride transfer protein (MTP) in this experimental setting. Methods: 129S1/SvImJ wild‐type or 129S4/SvJaePparatm/Gonz/J PPAR‐α knockout mice were fed chow and water (controls); oral, fat‐free PN solution only (PN‐O); PN‐O plus intraperitoneal (IP) ω‐6 FA‐predominant supplements (PN–ω‐6); or PN‐O plus IP ω‐3 FA (PN–ω‐3). Control and PN‐O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR‐α messenger RNA were assessed after 19 days. Results: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN‐O and PN–ω‐6 groups accumulated significantly greater amounts of TG when compared with PN–ω‐3 mice. Studies in PPAR‐α null animals showed that PN feeding increases hepatic TG as in wild‐type mice. PPAR‐α null mice in the PN‐O and PN–ω‐6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω‐3 FAs. Conclusions: PN induces TG accumulation (steatosis) in wild‐type and PPAR‐α null mice. In PN‐fed wild‐type and PPAR‐α null mice given IP ω‐3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω‐3 FAs results from PPAR‐α–independent pathways.     

Incidence,Prevention, and Treatment of Parenteral Nutrition–Associated Cholestasis and Intestinal Failure–Associated Liver Disease in Infants and Children

Background: Cholestasis is a significant life‐threatening complication in children on parenteral nutrition (PN). Strategies to prevent/treat PN‐associated cholestasis (PNAC) and intestinal failure–associated liver disease (IFALD) have reached moderate success with little supporting evidence. Aims of this systematic review were (1) to determine the incidence of PNAC/IFALD in children receiving PN for ≥14 days and (2) to review the efficacy of measures to prevent/treat PNAC/IFALD. Methods: Of 4696 abstracts screened, 406 relevant articles were reviewed, and studies on children with PN ≥14 days and cholestasis (conjugated bilirubin ≥ 2 mg/dL) were included. Analyzed parameters were (1) PNAC/IFALD incidence by decade and by PN length and (2) PNAC/IFALD prevention and treatment (prospective studies). Results: Twenty‐three articles (3280 patients) showed an incidence of 28.2% and 49.8% of PNAC and IFALD, respectively, with no evident alteration over the last decades. The incidence of PNAC was directly proportional to the length of PN (from 15.7% for PN ≤1 month up to 60.9% for PN ≥2 months; P < .0001). Ten studies on PNAC met inclusion criteria. High or intermediate‐dose of oral erythromycin and aminoacid‐free PN with enteral whey protein gained significant benefits in preterm neonates (P < .05, P = .003, and P < .001, respectively). None of the studies reviewed met inclusion criteria for treatment. Conclusions: The incidence of PNAC/IFALD in children has no obvious decrease over time. PNAC is directly correlated to the length of PN. Erythromycin and aminoacid‐free PN with enteral whey protein have shown to prevent PNAC in preterm neonates. There is a lack of high‐quality prospective studies, especially on IFALD.     

Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome

Background: Teduglutide was discontinued after being tested for ≥ 24 weeks in patients with parenteral nutrition (PN) ‐dependent short bowel syndrome in a clinical trial for efficacy to reduce PN volume. This study was describes change in body mass index (BMI) and PN volume over 12 months in patients who stopped drug after the clinical trial. Methods: Prescribed PN volume, weight, and complications were reported. Patients with stable (NEUT, n = 15) or decreased (DEC, n = 7) PN volume by 12 months after stopping drug (NEUT/DEC, n = 22) were compared to those who had increased PN volume (INC, n = 15). With drug response defined by ≥20% reduction from pre‐drug PN volume to end of drug therapy, 12 INC and 13 NEUT/DEC patients were drug responders. Results: Eleven of 20 eligible sites reported data for 39 of 53 eligible study participants, with follow‐up data for 37. INC patients had shorter colon and less frequently had colon in continuity than NEUT/DEC. BMI was decreased at 3, 6, and 12 months relative to the first off‐drug visit in INC patients (P = .001), but not in NEUT/DEC patients. Change in BMI off‐drug was predicted by colon and small bowel length, baseline BMI, and on‐drug change in PN volume (adjusted R2 = 0.708). Conclusions: Gastrointestinal anatomy, baseline BMI, and PN volume reduction on‐drug predicted change in BMI off‐drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.     

Economic analysis of home vs hospital-based parenteral nutrition in Ontario, Canada

BACKGROUND: Advances in technology and infrastructure have facilitated transfer of complex services from acute care hospitals to the home. This increases the burden on community resources but may provide net savings to the health care system. We undertook a retrospective cohort study of patients transferred from hospital to home while receiving home parenteral nutrition (PN) to assess their costs of care. METHODS: A detailed review of medical records was undertaken for all patients managed by the Hamilton Health Sciences Home PN Program between 1996 and 2001 whose PN was initiated in hospital. Mean per diem direct medical costs were estimated from the perspective of the provincial Ministry of Health for 3 periods: the last 2 weeks before discharge and the first month after discharge. Costs were compared among time intervals and among patients subgroups defined by age and underlying disease. RESULTS: Twenty-nine eligible subjects were identified. Common indications for PN included malignancy (n = 12), inflammatory bowel disease (n = 6), and intestinal ischemia (n = 4). Mean per diem costs in the last week of hospitalization were higher than those in the first month after discharge (dollars 567 vs dollars 405, p < .0001). Acute care resources accounted for <10% of the overall costs on home PN. The estimated monthly savings per patient maintained on home PN were dollars 4860 (95% confidence interval dollars 2700-dollars 7000). Savings were even greater among patients with underlying malignancy and advanced age. CONCLUSIONS: Home PN is cost saving when compared with hospital-based PN. Neither age nor underlying malignancy should pose a barrier to receipt of home PN.     

The number of granule cells and spine density on Purkinje cells in aged, ethanol-fed rats.

The purpose of this study was to determine whether chronic intake of ethanol by aged F344 rats was associated with a reduction in parallel fiber input to cerebellar Purkinje neurons (PN). Previous results from this laboratory provided direct evidence that synaptic density in PN dendritic arbors was significantly decreased and indirect evidence that terminal dendritic segments of PN were deleted during chronic ethanol treatment. From these results, it was hypothesized that an ethanol-related deletion of PN terminal dendritic segments might result from 1) a reduction in parallel fiber input to PN from cerebellar granule neurons or 2) a reduction in dendritic spines, the postsynaptic sites for parallel fiber input to PN dendrites. Measurements of the total number of cerebellar granule neurons (GN) and the volume of the GN layer, and measurements of the density of spines on PN terminal dendritic segments were made in separate groups of aged, ethanol-treated and control rats. There were no significant ethanol-related changes in these parameters after 40-48 weeks of ethanol treatment.