Total Parenteral Nutrient Solutions Research Articles

Physical compatibility of various drugs with neonatal total parenteral nutrient solution during simulated Y-site administration

The physical compatibility of various drugs with neonatal total parenteral nutrient (TPN) solution during simulated Y-site administration was evaluated. Study drugs were selected based on the lack of compatibility data with them and neonatal TPN solution and the frequency of use in a local neonatal unit. These drugs included amiodarone, caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, midazolam, pentobarbital, phenobarbital, and rifampin. Equal volumes of neonatal TPN solution or sterile water for injection were combined with study drugs or sterile water for injection at concentrations used clinically in neonates. Each test was performed in triplicate. The samples were examined via turbidimetric analysis and visually against light and dark backgrounds immediately after mixing and at 0.25, 0.5, 1, 2, and 3 hours after mixing. Analysis of variance was used to determine statistically significant differences between the test and control solutions. Many of the drugs studied exhibited no visual or turbidimetric evidence of incompatibility when combined with neonatal TPN solution for up to three hours in a simulated Y-site injection. Pentobarbital, phenobarbital, and rifampin formed visible precipitation immediately after mixing with the neonatal TPN solution. Caffeine citrate, clindamycin, enalaprilat, epinephrine, fluconazole, fosphenytoin sodium, hydrocortisone, metoclopramide, and midazolam exhibited no visual or turbidimetric evidence of incompatibility when combined with a neonatal TPN solution for up to three hours in a simulated Y-site injection. Amiodarone, pentobarbital, phenobarbital, and rifampin were not compatible with the neonatal TPN solution and should not be coadministered via Y-site injection.

Quality risk management for prepared sterile products in hospital pharmacy

BackgroundA hospital pharmacy (HP) prepares compounded sterile preparations (CSPs) following the current good manufacturing practice (cGMP) requirements. A quality risk management (QRM) is needed for the assessment, control, communication and...

Factors affecting the sterility of work areas in barrier isolators and a biological safety cabinet.

Factors affecting the sterility of the work area in barrier isolators and a biological safety cabinet (BSC) were studied. A study in a mother-and-child tertiary care teaching hospital in Canada examined the effects of a range of variables on the sterility of work areas in four barrier isolators and a standard BSC. The variables consisted of type of equipment (barrier isolator or BSC), day of the week (Monday through Thursday), time of day (0800-1000, 1000-1200, 1200-1400, and 1400-1600), sampling site (16 surfaces and 5 air sedimentation zones), type of product prepared (antimicrobial, total parenteral nutrient solution, etc.), cleaning procedure (before or after primary cleaning), and level of product preparation activity (none to intense). A total of 657 surface and air sedimentation samples, 327 plated onto Trypticase soy agar (TSA) and 330 onto Sabouraud dextrose agar (SAB-D), were taken during a 20-day period. Thirty-three (5%) of the samples yielded microbial growth when cultured (24 on TSA and 9 on SAB-D). A total of 74 isolates were identified, including Bacillus, Staphylococcus, Penicillium, Micrococcus, Corynebacterium, and Mucor species. Single-variable analysis showed that sampling site, sample type, the time of day samples were taken, and the types of equipment contributed significantly to microbial growth in the samples taken. Several variables were associated with microbial growth in samples from the work areas of barrier isolators and a BSC. More study is needed to compare BSCs and barrier isolators with respect to sterility.

Stability of Morphine Hydrochloride in a Total Parenteral Nutrient Solution.

The chemical stability of morphine hydrochloride in a total parenteral nutrient solution wasevaluated using a HPLC-ultraviolet detection system. This method is sensitive enough to measure morphine hydrochloride at concentrations as low as 0.2 nmol and produces highly reproducible results and requires 5.5 min per sample for separation and quantitation. Solutions of morphine hydrochloride in a total parenteral nutrient solution are chemically stable for 1 month when stored at 4°C and room temperature (20°C) with protection and no protection from environmental light. No loss of morphine hydrochloride due to adsorption in the polyethylene chloride (PEC) bags was found.

Extent of trace-element contamination from simulated compounding of total parenteral nutrient solutions.

The extent and sources of trace-element contamination during simulated manual and automated compounding of total parenteral nutrient (TPN) solutions were studied. Four experimental groups were prepared: (1) sterile water for injection as received from the manufacturer, (2) TPN bags manually filled with sterile water for injection, (3) TPN bags automatically filled with sterile water for injection, and (4) sterile water for injection manually added directly to sample vials (i.e., bypassing the TPN bag). After the bags had been stored for 16 hours at 4 degrees C, samples were analyzed for 66 trace elements by inductively coupled plasma-mass spectrometry. Of the 66 trace elements analyzed for, 3 (zinc, boron, and aluminum) were present as contaminants in each of the experimental groups. Very low background concentrations of zinc, boron, and aluminum were found to contaminate the sterile water as received from the manufacturer. Simulated compounding (manual or automated) in TPN bags did not contribute additional boron or aluminum but did result in a mean total zinc concentration of 35.4 micrograms/L; of this, 12.4 micrograms/L came from the compounding equipment, 9.1 micrograms/L from the TPN bag, and 13.9 micrograms/L from the sterile water for injection. Although the amount of zinc contributed by compounding was significantly higher than the background level, the amount was inconsequential compared with that needed to satisfy physiological requirements. Simulated compounding of TPN solutions either manually or with an automated system contributed minimal trace-element contamination.

The solubility of calcium and phosphate in two specialty amino acid solutions.

The purpose of this study was to determine precipitation limits and construct curves for calcium and phosphorus in parenteral nutrition solutions compounded with specialty amino acid solutions. The effect of temperature, concentration of amino acids, and pH on the solubility of calcium and phosphate was studied for two specialized amino acid solutions: NephrAmine and HepatAmine. Ten amino acid solutions were manufactured with NephrAmine and 12 with HepatAmine at amino acid concentrations of 0.8%, 1.5%, and 2%. The final dextrose concentration was 10%. Some of the solutions were tested with the additive cysteine hydrochloride, 40 mg cysteine/g of protein, and some were buffered with sodium bicarbonate or hydrochloric acid to model the pH of a combined fat emulsion and total parenteral nutrient (TPN) solution. Calcium gluconate and potassium phosphate were added to test samples of each TPN solution. A range of calcium concentrations of 2.5 to 40 mEq/L and phosphate concentrations of 2.5 to 40 mmol/L were tested. After storage at room temperature (25 degrees C) for 18 hours, solutions were inspected for precipitation. At the end of the 18-hour period, the solutions were held in a water bath at 37 degrees C for 30 minutes and inspected for precipitation and microcrystallization. Solubility curves were plotted to represent Ca-PO4 solubility limits before visual or microscopic precipitation. These curves depend on the variables of time, temperature, concentration, and pH. These data and graphs will help the clinical pharmacist estimate Ca-PO4 solubility limits and prevent precipitation of TPN solutions formulated with NephrAmine or Hepatamine.

Offsite intravenous admixture center shared by health-system facilities.

The creation of an offsite i.v. admixture center shared by four affiliated health care facilities is described. The i.v. admixture center was developed to consolidate the admixture services of four Carilion Health System (Roanoke, Virginia)-affiliated facilities: Roanoke Memorial Hospital (RMH), RMH's Cancer and Rehabilitation Center, Community Hospital of Roanoke Valley (CHRV), and the Roanoke Memorial Home Health Parenteral Therapy Program. The proposed advantages of a shared i.v. admixture service included providing full i.v. services for CHRV, increasing the ability to prepare home i.v. admixtures on a daily basis, increasing space for preparing i.v. admixtures, avoiding adding admixture staff members at any of the facilities, reducing supply duplication and admixture waste, and standardizing and improving quality. The Carilion Admixture Center was built in Carilion's materials management building at a total cost for construction and new equipment of $80,000; it opened in April 1992. The facility is responsible for providing piggyback admixtures, premixed piggyback solutions, injectable antineoplastic agents, total parenteral nutrient solutions, prefilled syringes for pediatric patients, large-volume solutions containing additives, and all admixtures required for the home health care patients. The facility was certified as a Class 20,000 environment. Start-up problems included computer glitches and a heavier-than-anticipated workload during the first year of operation. Nearly 700,000 i.v. admixtures were compounded at the center between October 1992 and September 1994. There were 95 reports of missing doses during the day shift at RMH between November 1992 and January 1993; only 6% were due to errors at the admixture center. The estimated total cost avoidance for salaries, benefits, and nonbillable supplies for October 1992 through September 1994 was $437,000. Intravenous admixture services provided by three hospital facilities and one home health agency were successfully consolidated into one shared offsite center.

Stability and Activity of Intravenous Immunoglobulin with Neonatal Dextrose and Total Parenteral Nutrient Solutions

To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. In vitro compatibility study. Samples were taken at time = 0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.

Specific Gravity-based Determination of Dextrose Content of Total Parenteral Nutrient Solutions for Neonates

Specific Gravity-based Determination of Dextrose Content of Total Parenteral Nutrient Solutions for Neonates

Visual Compatibility of Ciprofloxacin with Selected Components of total Parenteral Nutrient Solutions During Simulated Y-site Injection

Visual Compatibility of Ciprofloxacin with Selected Components of total Parenteral Nutrient Solutions During Simulated Y-site Injection

Investigational drug information through a hospitalwide computer system

A hospitalwide computer system that combines protocol-specific information on investigational drugs with order entry is described. A large university teaching hospital had in place a computerized clinical information system. Among other uses, physicians used the system for direct entry of total parenteral nutrient solution orders and associated laboratory tests; labels are produced automatically. Personnel from the pharmacy and information services departments met to discuss how to apply the computer system to investigational drug information. The application they designed has three components: protocol information, order entry, and patient monitoring. Protocol information, including all the standard drug data plus regulatory and investigator information, is displayed as a report on the user's terminal. The order-entry pathway allows the research pharmacist to predesign medication labels that are specific to each study and include all required information. This saves time, ensures accurate labeling, and provides a means for generating patient charges. The patient-monitoring component provides information to the research pharmacist in a daily report to assist in locating subject patients and to monitor compliance with protocols. The system has improved the access of health-care professionals to investigational drug information and decreased the time pharmacists spend dispensing these agents. The system has been well received, although up to three weeks is needed to bring the information online. A hospitalwide information system is effective in disseminating information on investigational drugs and facilitating order entry.

Biological activity of recombinant interleukin-2 in intravenous admixtures containing antibiotic, morphine sulfate, or total parenteral nutrient solution

The biological activity of recombinant interleukin-2 in intravenous admixtures containing gentamicin sulfate, tobramycin sulfate, amikacin sulfate, ticarcillin disodium, piperacillin sodium, morphine sulfate, or total parenteral nutrient (TPN) solution was investigated. Recombinant interleukin-2 in a formulation containing human serum albumin was diluted to a therapeutic dose and mixed with the other drugs in test tubes to simulate mixing distal to the Y-site of an i.v. administration set. All test tubes were visually observed for precipitates. Triplicate test samples of recombinant interleukin-2 and interleukin-2 with drug were added to microplate wells containing lymphocyte tissue culture media (an interleukin-2-dependent murine cytotoxic T cell line, CTLL-2) using serial dilutions. The microplates were incubated then pulsed with mouse lymphocyte media containing tritiated thymidine (3H-thymidine). The amount of 3H-thymidine incorporated into lymphocyte DNA was measured using a beta counter. The average counts per minute (cpm) of a sample was analyzed as a function of the logarithm of sample dilution; one interleukin-2 unit was defined as 50% of the maximum cpm measured in the samples. At minimum dilutions, ticarcillin disodium reduced the effect of interleukin-2 on CTLL-2 growth; the other antibiotics and morphine sulfate had no effect. Interleukin-2 mixed with TPN solutions showed slightly enhanced growth of the CTLL-2 line compared with the interleukin-2 standard. Mixtures of multiple antibiotics, morphine, and TPN solutions with and without 20% fat emulsion had no effect on interleukin-2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Reducing waste of intravenous solutions

A program to minimize the waste of i.v. drug solutions is outlined, and the results of audits to determine the effectiveness of the program are presented. The program for reducing i.v. solution waste at a 500-bed acute-care center involves measures to compound admixtures for individual shifts, recycle solutions, remove unused solutions from nursing units, use a standardized administration schedule and automatic stop orders, standardize total parenteral nutrient (TPN) solutions, use commercially prepared products when possible, verify telephone orders, and prepare labile products just before use. From January 1987 to January 1990, six 30-day audits were performed to determine the number of i.v. admixtures discarded. The audits showed the hospital's average rate of waste to be 3.27%, well below other published values. The medical and surgical intensive-care units, pediatrics wards, and general medicine units accounted for most of the waste, which was largely attributable to dosage changes and stat-type drugs ordered but never used. Poor communication between the pharmacy and the nursing units also contributed to sterile product waste. Although the audits showed that waste was already at a low level, they pointed out areas for further improvement. A computer linkup that gives physicians the formulas for i.v. solutions is being set up, the list of standardized TPN solution formulas is being expanded to include condition-specific solutions, and clinical pharmacists are establishing better communication with the nursing units. By using several methods to reduce the waste of i.v. solutions, a pharmacy department has limited the rate of waste to only 3.27%.

Visual compatibility of ganciclovir sodium and total parenteral nutrient solution during simulated Y-site injection

Visual compatibility of ganciclovir sodium and total parenteral nutrient solution during simulated Y-site injection

In vitro evaluation of the stability of ranitidine hydrochloride in total parenteral nutrient mixtures

The stability of ranitidine hydrochloride in various total parenteral nutrient (TPN) solutions was studied, as well as the effect of ranitidine on the stability of lipid emulsion and amino acids in these solutions. Ranitidine hydrochloride 25 mg/mL was added to each of the following mixtures to make final concentrations of approximately 50 and 100 mg/L: (1) TPN solution containing 4.5% amino acids, 22.7% dextrose, and electrolytes; (2) 10% lipid emulsion; (3) TPN solution containing 3.7% amino acids, 18.5% dextrose, 3.7% lipid emulsion, and electrolytes (all-in-one mixture); and (4) 0.9% sodium chloride injection. Mixtures were tested at room temperature and at 4 degrees C and were either protected from or exposed to fluorescent light. Sampling was done at 0, 12, 24, 36, and 48 hours, and the ranitidine concentration was determined by high-performance liquid chromatography. Samples were also analyzed for lipid particle size distribution and for amino acid content. At 48 hours, the all-in-one mixtures retained 86.0% to 91.4% of the initial ranitidine concentration. With one exception (ranitidine 50 mg/L in 0.9% sodium chloride injection, stored at room temperature and not protected from light), all other solutions retained at least 90% of the initial concentration at 48 hours. No visible changes in color and minimal changes in pH values were noted. There were no important changes in lipid particle-size distribution; 96% of all particles counted from any mixture were smaller than 1.44 microns in diameter at 48 hours. Ranitidine did not have an effect on amino acid concentrations in these mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of Imipenem and Cilastatin Sodium in Total Parenteral Nutrient Solution

The chemical stability and compatibility of imipenem-cilastatin sodium (Primaxin) in two different total parenteral nutrient (TPN) solutions was determined. TPN solutions consisted of 4.25% and 5% amino acids with 25% and 35% dextrose, respectively. Imipenem-cilastatin sodium was constituted with 10 ml of sterile water and admixed with 90 ml of TPN solution for a final concentration of 5 mg/ml of each drug. The final solutions were assayed at times 0 (immediately after admixture), 15 min, 30 min, 1, 4, 8, and 24 hr by a stability-indicating high-performance liquid chromatographic assay. Concurrently, test TPN solutions were monitored for pH changes, color changes, and precipitate formation. The potential effect of imipenem-cilastatin sodium on the stability of amino acids and other TPN additives was not evaluated. Imipenem and cilastatin sodium was stable (greater than or equal to 90% recovered) in each TPN solution at 15 min. A significant (greater than or equal to 10%) and steady decrease of imipenem recovery occurred at subsequent sampling times. Cilastatin appeared more stable than imipenem in both TPN solutions. A physical color change from colorless to dark orange appeared in each TPN solution over the 24-hr study period. Imipenem-cilastatin sodium is stable for 15 min in the TPN solutions studied; however, until the stability of the amino acids can be determined, the antibiotic should be administered through a separate line or Y-site while the TPN infusion is interrupted.

Effect of retrograde aminophylline administration on calcium and phosphate solubility in neonatal total parenteral nutrient solutions

The effect of retrograde administration of aminophylline injection on calcium and phosphate solubility in neonatal total parenteral nutrient (TPN) solutions was studied. Neonatal TPN solutions containing two amino acids solutions in three concentrations (Travasol 1% and 2% and TrophAmine 2%) were formulated. Calcium and phosphate salts were added to achieve calcium concentrations of 10, 15, 20, 25, 30, or 40 meq/L and phosphorus concentrations of 10, 15, 20, 25, 30, or 40 mmol/L. Samples were inspected visually after 18-24 hours; solutions free of precipitation were then infused through two parallel syringe-pump systems designed to simulate clinical conditions for TPN solution administration to a 1-kg neonate. To one system, a 7.5-mg aminophylline dose was added as a manual retrograde injection; sterile water for injection was added as a manual retrograde injection to the other system. The solutions were inspected throughout a one-hour infusion period for precipitate formation in the i.v. apparatus, and the pH of the effluents was determined. Concurrent aminophylline administration resulted in visible precipitate in all but a few of the solutions tested. The solution containing Travasol 2%, calcium 10 meq/L, and phosphorus 10 mmol/L remained clear, as did the solutions containing TrophAmine 2% and the following concentrations of calcium and phosphorus: calcium 10 meq/L and phosphorus 10, 15, or 20 mmol/L; calcium 15 meq/L and phosphorus 10 or 15 mmol/L; and calcium 20 meq/L and phosphorus 10 or 15 mmol/L. An average increase in pH of 0.63 unit was noted in all solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of famotidine 20 and 40 mg/L and amino acids in total parenteral nutrient solutions

The stability of famotidine in total parenteral nutrient (TPN) solutions and the concentrations of amino acids in the presence of famotidine were determined. Two famotidine concentrations (20 mg/L and 40 mg/L) and two amino acid concentrations (20 g/L and 42.5 g/L) were studied under the following storage conditions: refrigerated for 24 hours and then kept at room temperature (20-22 degrees C) for 24 hours, at room temperature for 48 hours, or refrigerated for seven days. Control TPN solutions were studied under the same storage conditions. TPN solutions also contained dextrose 25%, electrolytes, trace elements, and vitamins. Famotidine concentration was determined at 0, 24, and 48 hours and at seven days by high-performance liquid chromatography. Amino acid concentration was determined in the TPN solutions containing 42.5 g/L of amino acids without famotidine and with famotidine 40 mg/L under both 48-hour storage conditions. At 24 hours, all solutions retained at least 95% of the initial famotidine concentration. Seven of the eight famotidine solutions retained more than 95% of the initial famotidine concentration at 48 hours. All samples refrigerated for seven days retained more than 95% of the initial famotidine concentration. The concentration of amino acids in TPN solutions containing 42.5 g/L of amino acids was not affected by the addition of famotidine 40 mg/L under either 48-hour storage condition. Famotidine in concentrations of 20 mg/L and 40 mg/L is stable under the studied 48-hour storage conditions in TPN solutions containing amino acid concentrations of either 20 g/L or 42.5 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term stability of famotidine 20 mg/L in a total parenteral nutrient solution

Long-term stability of famotidine 20 mg/L in a total parenteral nutrient solution

Stability of vancomycin hydrochloride in total parenteral nutrient solutions

Stability of vancomycin hydrochloride in total parenteral nutrient solutions