Commercial Parenteral Nutrition Research Articles

Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies

PurposeAminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids. MethodsGentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure. ResultsGM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage. ConclusionIn conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Y-Site Compatibility Studies of Ketoprofen with Parenteral Nutrition Admixtures for Central and Peripheral Administration.

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.

Could Commercial Formulations Replace Individualized Prescription in Pediatric Home Parenteral Nutrition?

Standard parenteral nutrition (PN) solutions are safe and can meet the nutritional requirements of a significant number of pediatric patients. However, they may not always be adequate for those on long term PN. We aimed to compare the composition of individually tailored prescriptions in a pediatric population on home PN with that of available commercial PN formulations. Retrospective analysis of the individual prescriptions of metabolically stable pediatric patients on home PN over a 1-year period (March 2019 to March 2020). These were compared with commercially available solutions with electrolytes, and replacement was considered adequate if three successive criteria were met: non-protein calorie to volume ratio (maximum variation 15%); non-protein calorie to nitrogen ratio (NPC:N) (maximum variation either 20% for long term use or 35% for possible short term use); electrolyte concentration (maximum increase 20%). Twenty-four patients were included (67% male; median age 7.5 years). The most common diagnosis was short bowel syndrome (58%). Replacement with a standard formulation was considered appropriate for possible short term use (maximum variation of 35% in NPC:N) in 16 (67%) patients and for long term use (maximum variation of 20% in NPC:N), the number of patients decreased to 10 (42%). Standard PN solutions can be adequate for a significant proportion of pediatric patients on home PN. Their use in the short term may also be appropriate in holiday periods or in settings of limited resources or restricted access to hospital facilities, such as those imposed by the COVID-19 pandemic.

Stability and Compatibility Aspects of Drugs: The Case of Selected Cephalosporins.

Intravenous drug incompatibilities are a common cause of medical errors, contributing to ineffective therapy and even life-threatening events. The co-administration of drugs must always be supported by studies confirming compatibility and thus guarantee the therapy’s safety. Particular attention should be paid to the possible incompatibilities or degradation of intravenous cephalosporins in different infusion regimens since the administration of drugs with inadequate quality may cause treatment failure. Therefore, an appropriate stability test should be performed. The study aimed to present various aspects of the stability and compatibility of five cephalosporins: cefepime (CFE), cefuroxime (CFU), ceftriaxone (CFX), ceftazidime (CFZ), and cefazoline (CFL). The degradation studies in parenteral infusion fluids and PN admixtures were conducted for CFE and CFU. The interactions between CFX or CFZ and PN admixtures, as well as the compatibility of CFL with five commercial parenteral nutrition (PN) admixtures, were investigated. The content of CFX and CFZ in PN admixture after 24 h was >90%. CFL administered simultaneously with PN admixture by the same infusion set using Y-site was compatible only with Nutriflex Lipid Special. CFE and CFU were stable in all tested infusion fluids for a minimum of 48 h and decomposed in PN admixtures during storage.

Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures.

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM–PN admixture samples. Physicochemical properties of MPM–PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM–PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM–Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM–Kabiven, MPM–Nutriflex Lipid Special, and MPM–Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM–Olimel), significant differences in zeta potential (MPM–Olimel, MPM–Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM–Kabiven, MPM–Olimel, and MPM–Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios.

Parenteral Nutrition–Associated Liver Disease in Adult Inpatients Receiving Commercial Premixed Parenteral Nutrition for More Than 2 Weeks

AbstractBackgroundLong‐term use of parenteral nutrition (PN) may elicit complications, including PN‐associated liver disease (PNALD), which may yield critical outcomes. This study intended to investigate the development of complications associated with commercial premixed PN in adult patients.MethodsAdult patients who received nutrition support with commercial PN without enteral intake for >14 consecutive admission days were included in the analysis.ResultsSeventy‐two adults, from 2001 to 2016, were reviewed. Mean length of hospital stay was 43.0 days. A mean of 27.3 days of PN was given. Mean energy supplied by PN was 29 kcal/kg/d. Ten patients (13.8%) developed PNALD. Length of stay was significantly longer (P = .034), and duration of PN administration was significantly longer (P = .022) in patients who developed PNALD. The proportion of PN products with soybean oil–based lipids was significantly higher, and fish oil– or medium‐chain triglyceride–containing combination lipids were significantly lower in the patient group with PNALD (P = .02). Multivariate logistic regression analysis showed that longer duration of days receiving PN support was an independent risk factor for PNALD (odds ratio, 1.052; P = .029).Conclusion: The incidence of PNALD in hospitalized adult patients who received daily PN support with commercial premixed 3‐in‐1 products for >2 weeks was 13.8%. Longer duration of days receiving PN support was an independent risk factor for PNALD.

Practice of parenteral nutrition in hospitalized adult patients in Korea: A retrospective multicenter cross-sectional study.

There have been no studies on the characteristics of parenteral nutrition (PN) supply for adult inpatients in South Korea. The aim of this retrospective multicenter cross sectional study was to investigate the current practice and characteristics of PN support in hospitalized adult patients in South Korea for the first time. This study was conducted retrospectively for the adult patients who were hospitalized and received PN in nine hospitals on August 1st, 2017 to October 30th, 2017. We evaluated the type of PN formulation, PN administration period, administration route, calories supplied, amount of protein supplied, and laboratory results. Among the 11,580 inpatient admissions on that day, 1,439 patients received PN (12.4%). The majority of enrolled patients (96.5%) used the commercial PN, of which 86.2% were multi-chamber. 71.2% of them received PN peripherally. The average in hospital PN duration was 17.8 ± 52.6 days. Patients received only 65.4 ± 25.4% calories of their target calories. The in-hospital mortality of enrolled patients was 22%. In South Korea, commercial PN was usually administered to hospitalized adult patients and in-hospital mortality in adult patients using PN was higher in South Korea compared to other countries. This study provides the characteristics and the PN support status of hospitalized adult patients receiving PN in South Korea.

MON-PO561: Standardized Commercial Parenteral Nutrition with Extra Nitrogen Formulations Prescription in a Tertiary Hospital

MON-PO561: Standardized Commercial Parenteral Nutrition with Extra Nitrogen Formulations Prescription in a Tertiary Hospital

Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans.

Background: We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. Methods: In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. Results: In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. Conclusions: These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin.

Probability‐Based Compatibility Curves for Calcium and Phosphates in Parenteral Nutrition Formulations

The information content of the calcium phosphate compatibility curves for adult parenteral nutrition (PN) solutions may benefit from a more sophisticated statistical treatment. Binary logistic regression analyses were evaluated as part of an alternate method for generating formulation compatibility curves. A commercial PN solution was challenged with a systematic array of calcium and phosphate concentrations. These formulations were then characterized for particulates by visual inspection, light obscuration, and filtration followed by optical microscopy. Logistic regression analyses of the data were compared with traditional treatments for generating compatibility curves. Assay-dependent differences were observed in the compatibility curves and associated probability contours; the microscopic method of precipitate detection generated the most robust results. Calcium and phosphate compatibility data generated from small-volume glass containers reasonably predicted the observed compatibility of clinically relevant flexible containers. The published methods for creating calcium and phosphate compatibility curves via connecting the highest passing or lowest failing calcium concentrations should be augmented or replaced by probability contours of the entire experimental design to determine zones of formulation incompatibilities. We recommend researchers evaluate their data with logistic regression analysis to help build a more comprehensive probabilistic database of compatibility information.

Compounding vs Standardized Commercial Parenteral Nutrition Product

Standardized commercial parenteral nutrition (PN) formulations have advantages and disadvantages as compared with PN formulations compounded using an automated compounding device. These advantages and disadvantages are discussed along with the supporting available research.

Lysine requirement in parenterally fed postsurgical human neonates

The lysine requirement of human neonates receiving parenteral nutrition (PN) has not been determined experimentally. The objective was to determine the parenteral lysine requirement for human neonates by using the minimally invasive indicator amino acid oxidation technique with l-[1-(13)C] phenylalanine as the indicator amino acid. Eleven postsurgical neonates were randomly assigned to 15 lysine intakes ranging from 50 to 260 mg . kg(-1) . d(-1). Breath and urine samples were collected at baseline and at plateau for (13)CO(2) (F(13)CO(2)) and amino acid enrichment, respectively. The mean lysine requirement was determined by applying a 2-phase linear regression crossover analysis to the measured rates of F(13)CO(2) release and l-[1-(13)C]phenylalanine oxidation. The mean parenteral lysine requirement determined by F(13)CO(2) release oxidation was 104.9 mg . kg(-1) . d(-1) (upper and lower CIs: 120.6 and 89.1 mg . kg(-1) . d(-1), respectively). The mean lysine parenteral requirement determined by phenylalanine oxidation was 117.6 mg . kg(-1) . d(-1) (upper and lower CIs: 157.5 and 77.6 mg . kg(-1) . d(-1), respectively). Graded intakes of lysine had no effect on phenylalanine flux. We recommend a mean lysine requirement for the postsurgical PN-fed neonate of 104.9 mg . kg(-1) . d(-1), which is 32-43% of the lysine concentration presently found in commercial PN solutions (246-330 mg . kg(-1) . d(-1)). This trial was registered at clinicaltrials.gov as NCT00779753.

Threonine requirement of parenterally fed postsurgical human neonates

BackgroundThe threonine requirement of human neonates who receive parenteral nutrition (PN) has not been determined experimentally. ObjectiveThe objective was to determine the parenteral threonine requirement for human neonates by using the minimally invasive indicator amino acid oxidation technique with l-[1-13C]phenylalanine as the indicator amino acid. DesignNine postsurgical neonates were randomly assigned to 16 threonine intakes ranging from 10 to 100 mg · kg−1 · d−1. Breath and urine samples were collected at baseline and at plateau for 13CO2 and amino acid enrichment, respectively. The mean threonine requirement was determined by applying a 2-phase linear regression crossover analysis to the measured rates of 13CO2 release (F13CO2) and l-[1-13C]phenylalanine oxidation. ResultsThe mean threonine parenteral requirement determined by using phenylalanine oxidation was 37.6 mg · kg−1 · d−1 (upper and lower confidence limits, respectively: 29.9 and 45.2 mg · kg−1 · d−1) and by using F13CO2 oxidation was 32.8 mg · kg−1 · d−1 (upper and lower confidence limits, respectively: 29.7 and 35.9 mg · kg−1 · d−1). Graded intakes of threonine had no effect on phenylalanine flux. ConclusionThis is the first study to report on the threonine requirement for human neonates receiving PN. We found that the threonine requirement for postsurgical PN-fed neonates is 22–32% of the content of threonine that is presently found in commercial PN solutions (111–165 mg · kg−1 · d−1).

Use of N‐Acetyl Cysteine for the Treatment of Parenteral Nutrition–induced Liver Disease in Children Receiving Home Parenteral Nutrition

Use of <i>N</i>‐Acetyl Cysteine for the Treatment of Parenteral Nutrition–induced Liver Disease in Children Receiving Home Parenteral Nutrition

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

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.

Effects of branched-chain amino acids on placental amino acid transfer and insulin and glucagon release in the ovine fetus

Objective: Competition for placental amino acid transporters can affect the fetal supply of amino acids. Specifically, the branched-chain amino acids—isoleucine, leucine, and valine—may inhibit the transfer of other amino acids. This study was undertaken to determine the effect of branched-chain amino acids on the umbilical uptake of amino acids. Study Design: Six late-gestation ewes were infused sequentially for 2 hours with 3 different mixtures of amino acids: (1) one that was comparable to commercial parenteral nutrition preparations, (2) the same solution without branched-chain amino acids, and (3) branched-chain amino acids alone. Maternal and fetal blood samples were collected simultaneously for the determination of uterine and umbilical uptake values of amino acids, and for concentrations of arterial insulin, glucagon, glucose, and lactate before (control) and during (experimental) infusion. Results: Umbilical uptake of branched-chain amino acids increased significantly when they were present in the infusates. The fetal uptake of several other amino acids could be increased by increasing their maternal concentrations. Inhibition of umbilical uptake by branched-chain amino acids could be shown for threonine and methionine. The infusion of branched-chain amino acids alone did not affect maternal and fetal insulin or glucagon concentrations. Conclusions: In late-gestation sheep, an increase in maternal plasma concentration of branched-chain amino acids led to increased branched-chain amino acid umbilical uptake, but branched-chain amino acids can also inhibit the transport of some amino acids to the fetus. Changes in fetal plasma concentration and uptake of branched-chain amino acid appear to have no significant effect on fetal insulin or glucagon. (Am J Obstet Gynecol 2001;185:487-95.)

HPLC-based method using sample pre-column clean-up for the determination of methanethiol and ethanethiol in parenteral amino acid solutions.

A method has been developed for the chromatographic determination of methanethiol (MT) and ethanethiol (ET) as contaminants in amino acid parenteral nutrition (PN) solutions. The clean-up of the samples before chromatographic analysis was investigated by solid-phase extraction (SPE) on pre-columns filled with polyethylene powder (PE), aluminium oxide (AlOx), silica (SiOx), or polyurethane foam (PUF) as adsorbents. The thiols were more efficiently separated from the matrices by SPE on PUF pre-columns. Simultaneous derivatization and elution with DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) enabled further discrimination between MT and ET by reversed-phase HPLC with spectrophotometric detection. The retention times for the derivatized MT and ET species were 12.5 and 23.0 min, respectively. Recoveries from spiked PN samples were calculated to be approximately 90%, and the MT and ET content of commercial PN solutions was determined using the methodology described. Detection limits of 15 and 10 microg L(-1) were calculated for MT and ET, respectively.

Voltammetric determination of volatile free sulfide and alkylthiols as contaminants in parenteral amino acid solutions

A method for the simultaneous voltammetric determination of free sulfide and volatile alkythiols (methanethiol/ethanethiol) existing as contaminant in parenteral nutrition (PN) solutions was developed. The volatile sulfides (dihydrogensulfide and alkylthiols) formed in the formulations were distilled over 45 min at 47°C in a purpose-made Conway cell. The analytes were quantified by differential pulse cathodic stripping voltametry (DPCSV) at the hanging mercury-drop electrode and determined, simultaneously as dihydrogensulfide and alkylthiols using a 60 s preconcentration time at −300 mV (versus Ag/AgCl, Cl − 3.0 mol l −1). The voltammetric signals were directly linear proportional to the sulfides concentrations in the PN solutions in the range 3–20 μmol l −1 and detection limits of about 2 μmol l −1 were calculated. Recoveries of sulfides from PN solutions in the range 90–110% were calculated using the method and nine commercial PN formulations were analyzed. Methanethiol and ethanethiol were quantified from their composite signals, and the mutual influence of the analytes on the DPCSV measurements is discussed.

Contribution of branched-chain amino acids to uteroplacental ammonia production in sheep.

The uteroplacental tissues are a principal site of ammonia production for the conceptus. The goal of this study was to examine the effect of the composition of maternal amino acid (AA) infusate on uteroplacental ammonia production. Seven pregnant ewes (126 +/- 1. 4 days gestation) were infused through the maternal femoral vein (duration 3.5 h, rate 240 ml per hour) with three solutions of AAs. The first infusate was comparable to commercial parenteral nutrition preparations, the second infusate contained the same solution without branched-chain AAs (BCAAs), and the third infusate contained only BCAAs. Blood samples were simultaneously collected from the maternal artery, uterine vein, fetal artery, and umbilical vein to determine plasma AA concentrations and whole blood ammonia concentrations, before (control) and 2 h after (experimental) the start of infusion. Uterine and umbilical blood flows were measured using the ethanol steady-state diffusion method. Results showed that fetal arterial and venous ammonia concentrations increased significantly after infusions with all AAs or only BCAAs, but not without BCAAs. Uteroplacental ammonia production increased in response to each of the three infusates. However, this increase was much greater when the BCAAs were present in infusates. We conclude that there is a significant contribution of BCAAs to the uteroplacental ammonia production. Maternal AA infusions containing BCAAs can result in increased fetal blood ammonia concentrations.

Glutamine in parenteral nutrition: more food for thought

See article on page 82 Until recently glutamine had not been included in commercial parenteral nutrition solutions. This is because of concerns about its spontaneous degradation, which results in the...