Parenteral Solutions Research Articles

Hydrogen sulfide in parenteral amino-acid solutions

We have previously reported appreciable concentrations of hydrogen sulfide (H 2S) in paediatric amino-acid solutions, apparently formed from cysteine during the production process. Since manufacturers assured us of their aim to reduce the contents of the potentially toxic H 2S in these solutions, we determined whether lower amounts have been achieved 2 years after our first report. Median H 20S content of 13 paediatric amino-acid solutions was 22.8 μg/I (range: not detectable to > 280 μg/l which is comparable to the amounts previously found. Median H2S content of 8 special solutions for renal and hepatic disorders was 15.8 μg/I (range not detectable to > 280 μg/I). We conclude that manufacturers should make further efforts to reduce H2S amounts in parenteral amino-acid solutions.

Blood Substitutes

Blood Substitutes

Stability and compatibility of 2.5 mg/ml methotrexate solution in plastic syringes over 7 days

The physico-chemical stability and the compatibility between a 2.5-mg/ml methotrexate solution and plastic syringes were studied over a 7 day period at + 4 and 25°C. During this study, pH was determined and MTX degradation products were assayed by HPLC. The compatibility study consisted of the titration of reducing substances, TLC of extracted additives, assay of extracted ions by AAS, resistivity measurement, dynamometric test and UV, visible and IR absorption spectrophotometry. Stability and compatibility studies showed that 2.5 mg/ml methotrexate parenteral solution remained chemically stable in a plastic syringe over a period of 7 days under the tested conditions.

Capsules and suppositories of methadone for patients on high-dose opioids for cancer pain: clinical and economic considerations

The dose ratio, analgesic efficacy, toxicity and cost of methadone for cancer pain were evaluated in a retrospective review of 50 consecutive patients treated on a Palliative Care Unit. Patients were switched from hydromorphone 267.7 ± 178.8 mg sc per day to custom-made capsules (24) or suppositories (26) of methadone for reasons of uncontrolled pain (24), toxicity (8), both (15) or other (2). The change in opioid occurred over 2.5 ±3.6 days, with another 4.4±3.7 days required to reach stable methadone dose. The ratio of stable methadone dose to final hydromorphone dose was 1.07±0.9 (oral) and 1.88±1.27 (rectal) ( p=0.01). Visual analogue scores for pain intensity (0–100 mm) declined from 50.8±22 to 40±20 ( p= 0.01). The most frequent toxicities were constipation (46), sedation (42) and nausea (18). Six patients developed respiratory depression. Total cost of treatment was Canadian $116.77 ± 157.17 for methadone capsules and Canadian $105.34± 146.35 for methadone suppositories, vs Canadian $3450.51 ±5098.58 ( p=0.0001) for hydromorphone parenteral solution and Canadian $1801.21 ±2661.52 ( p=0.0001) for hydromorphone powder. It is concluded that methadone is an effective and inexpensive alternative in patients receiving high-dose opioids for cancer pain, at dose ratios much lower than recommended in the literature. The incidence of serious toxicities suggests that methadone should only be initiated in an adequately monitored setting by pain management experts.

理論式による多剤配合時のｐＨ予測方法

A method for predicting pH changes in multiple admixtures was designed on the basis of the acid-base equilibrium theory. The pH's of transfusions mixed with the various injections were estimated by solving a general theoretical equation for proton concentrations in the multicomponents-blended aquaous solution obtained using a dichotomy as the algorithm. Eighty-two transfusions and parenteral solution mixture combinations were examined for the efficacy of the predicted equation. As a result, the estimated pH was in good agreement with the measured pH in all examinations, and a good corelation existed between the measured and calculated values of pH. Furthermore, the incompatibility of the parenteral admixture can be easily predicted using the present estimation-program for pH changes without any preliminary pH titration tests. These results suggest that this prediction method will be a useful tool for constructing and handling database incompatibility.

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.

Technician checking of pharmacists computerized order entry for parenteral nutrient solutions.

Technician checking of pharmacists computerized order entry for parenteral nutrient solutions.

Optimization of the determination of amino acids in parenteral solutions by high-performance liquid chromatography with precolumn derivatization using 9-fluorenylmethyl chloroformate

An automatic precolumn derivatization procedure is presented for the determination of amino acids in parenteral solutions by reversed-phase high-performance liquid chromatography. The fluorenylmethyl chloroformate was used as the reagent for derivatization. The optimum conditions for the derivatization reaction, separation and detection were investigated from reproducibility and linearity data. This method has the advantage of automatic precolumn derivatization, a shorter analysis time with optimum separation and high reproducibility of retention times and peak areas for all amino acids with both UV and fluorescence detection.

Taurine in Pediatric Nutrition

The past 20 years have seen the status of taurine change from an end product of methionine and cysteine metabolism and substance conjugated to bile acids to that of an important, and sometimes essential, nutrient. It is now added to most synthetic human infant formulas and pediatric parenteral solutions throughout the world. This article describes the research that led to this end.

Effects of different types of isocaloric parenteral nutrients on food intake and metabolic concomitants

Whether spontaneous food intake (SFI) is controlled by infused nutrient type or its caloric content, irrespective of nutrient type, was investigated. Rats were infused for 4 days with isocaloric solutions of different nutrient type but sharing the same intermediary metabolic oxidative pathway, providing 25% of daily caloric needs. One parenteral solution was a glucose, fat and amino acid mix (TPN-25%); the other provided ketone bodies (TRO-3.5%). Effects of parenteral infusions on SFI and metabolic concomitants were compared and contrasted to that in a group of orally fed rats. Both infusions reduced SFI by 50%. Rats receiving TRI-3.5% had lower blood glucose and insulin concentrations, but increased hepatic glycogen content compared to TPN-25% or orally fed rats. No differences in hepatic triglycerides occurred between the three groups. However, serum free fatty acids were significantly lower in TRI-3.5% and in TPN-25% groups vs. fed rats. Data indicate food intake suppression is mediated by caloric content rather than nutrient type, suggesting that a mediator of SFI regulation could be at the citric acid cycle level.

Abnormal trace elements in a patient on total parenteral nutrition with normal renal function

Objective: To describe trace metal changes in a 74-year-old male patient with mesenteric fibrosis and a small bowel fistula who was maintained on total parenteral nutrition in the hospital and at home. Methods: Trace elements which included chromium and selenium were monitored over a 14-month period as part of his nutrient follow-up. Results: Serum chromium reached levels >21-fold the upper reference range, and serum selenium, in contrast, was <0.5 the lower reference range. Plasma aluminum was also measured, and found to be nearly twice the upper reference range, although the patient had normal renal function. We measured the aluminum content of the parenteral nutrients and additives, and found that replacement of calcium gluconate by calcium chloride helped to reduce the aluminum content in the final parenteral solution by 34%. Aluminum and chromium contaminants found in parenteral solutions need to be reduced or removed to avoid toxic accumulation. Conclusion: This study illustrates the importance of adequately adjusting essential trace elements, and monitoring contaminants in parenteral fluids in an individual on total parenteral nutrition.

Electrochemical Behavior and Polarographic Assay of Nitroxynil

Abstract Nitroxynil is an anthelmintic veterinary drug used in prophylaxis and treatment of hepatic distomatosis. A simple method for its identification and determination in pharmaceutical parenteral solutions is described. The method is based on electrochemical reduction of the nitro group at the dropping mercury electrode. The ac and dc polarographic and cyclic voltammetric responses of the drug are reported. Accuracy and precision of the method are good, and sample preparation is easy.

Study of hypocaloric peripheral parenteral nutrition in postoperative patients (Europan project)

The objective of this study is to ascertain whether or not the supply of a low-calorieamino acids (AA) parenteral solution is useful in postoperative patients, by assessing a series of parameters that indicate nutritional status. 75 postoperative patients who met at least 2 of the 3 criteria: 1) albumin less than 3 g/dl; 2)prealbumin less than 21 mg/dl; 3) body weight less than 95% of ideal weight, were studied. Patients were divided into 4 groups: control group, 15 patients receiving conventional infusion therapy; group I, 20 patients receiving glucose + AA; group II, 20 patients receiving glycerol + AA; and group III, 20 patients receiving sorbitol-xylitol + AA. The most significant findings were a prompt recovery of short half-life proteins (prealbumin and retinol binding protein), a less negative nitrogen balance, a greater decrease in urinary 3-methylhistidine and a marked increase in most AAs when hypocaloric peripheral parenteral nutrition (HPPN) was used. As regards complications, suture dehiscence occurred in a greater percentage of controlpatients than in the active therapy groups (13.3% versus 5%) and, in contrast, a greater number of cases of infusion phlebitis was observed in the HPPN groups. Clinical data were not statistically significant. We conclude that HPPN is a valid means for providing nutritional support but, at present,there are few randomized, controlled studies that show that its use is clearly beneficial.

Aluminum in parenteral solutions revisited—again

It has been a dozen years since aluminum was first shown to contaminate parenteral nutrition solutions and to be a contributing factor in the pathogenesis of metabolic bone disease in parenteral nutrition patients as well as in uremic patients. However, there are no regulations in place to effectively reduce aluminum contamination of various parenterally administered nutrients, drugs, and biologic products. The purpose of this review is fourfold: 1) to summarize our knowledge of the adverse effects of aluminum on bone formation and mineralization in parenteral nutrition patients; 2) to discuss the possible role of aluminum in the osteopenic bone disease of preterm infants; 3) to show how lack of regulations covering aluminum content of parenteral solutions can lead to vulnerability of new groups of patients to aluminum toxicity, the example being given here is that of burn patients; and 4) to trace the development of efforts at regulating the aluminum contamination of large- and small-volume parenteral drug products and to point out what still needs to be done in this regard.

Stability of propofol with parenteral nutrient solutions during simulated Y-site injection.

The stability of propofol in three parenteral nutrient (PN) solutions was studied. Nine combinations of three PN solutions (with amino acid concentrations of 1.5, 2.5, and 5.0%) and three propofol concentrations (0.5, 2.0, and 3.0 mg/mL) were prepared in triplicate and stored at 22 degrees C under fluorescent light. Duplicate samples were visually inspected for color changes, precipitation, or gas formation, and the pH of the samples was determined. These samples were evaluated for propofol content by high-performance liquid chromatography at zero, one, three, and five hours. The stability of the vehicle for propofol injection (similar in composition to fat emulsion) was evaluated by visual inspection, pH determination, and particle-size measurements at zero, one, three, and five hours. The concentration of propofol in all of the propofol-PN combinations remained greater than 90% of the initial concentration except for the combination of propofol 0.5 mg/mL and the 1.5% amino acid PN solution, which contained only 72% of the initial propofol concentration five hours after the start of the study. Visual examination revealed no evidence of color change, precipitation, gas formation, creaming, or streaking in any of the propofol-PN solution combinations. No substantial changes in pH occurred. The particle size of the vehicle for propofol remained relatively constant throughout the study period. Propofol 2 and 3 mg/mL was stable for five hours during simulated Y-site injection with PN solutions containing 1.5, 2.5, and 5% amino acids. Propofol 0.5 mg/mL was stable during simulated Y-site injection with the same PN nutrition solutions for five hours, except for the solution containing 1.5% amino acid.

Controle de esterilidade de soluções parenterais de grande volume utilizadas na rede hospitalar da cidade de São Paulo

This surveillance intend to show up the conditions of sterility fromcomercially prepared great volume parenteral solutions used in hospitais to keep and restorethe volume and composition of the body fluids to normal. An amount of 582 samplesmanufactured at industries and at hospital pharmacies were analise from 1989 to 1993. Theresults had shown 9,62% of the total samples didn't meet the requirements of sterility andwithin the same batch different samples gave different results concerning sterility.

Determination of atropine and obidoxime in automatic injection devices used as antidotes against nerve agent intoxication

A capillary gas-liquid chromatographic (GLC) and an ion-pair high performance liquid chromatographic (HPLC) method were developed for the assay of atropine sulphate and obidoxime chloride from a parenteral solution in commercial automatic injection devices. The injectors are aimed for the emergency treatment of poisoning by nerve agents. The two-step GLC method consists of extraction of atropine as a free base prior to GLC analysis using scopolamine as an internal standard. Obidoxime is determined directly in a diluted sample solution by reversed-phase HPLC using sodium 1-heptanesulphonate as a counter ion in the mobile phase. The relative standard deviation (R.S.D.) was 1.81% for the GLC procedure with injectors containing only atropine and 2.37% for the GLC of atropine in atropine-obidoxime injectors. The R.S.D. for the HPLC procedure of obidoxime in atropine-obidoxime injectors was 0.82%. The corresponding R.S.D.s for the sampling of atropine-obidoxime injectors were 0.36% and 0.27%. The coefficient of determination ( r 2) was 1.000 for both methods. The recoveries at the target concentration averaged 101.0% and 98.7% with a standard error of the mean of 0.30 for both methods. The retention times for atropine and obidoxime were 6.27 and 4.29 min, respectively.

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.

Growth retardation in children receiving long-term total parenteral nutrition: effects of ornithine α-ketoglutarate

We evaluated the effect of ornithine ketoglutarate (OKG) in reversing abnormal growth in six prepubertal children receiving total parenteral nutrition (TPN) for 5-10 y. They were 1-4 SDs below their expected 50th percentile for height. The energy and nitrogen intakes were unchanged from 8 mo before the beginning of the study until its completion. Two consecutive periods of 5 mo each were studied. OKG (15 g) was added to the parenteral solution during the first period (OKG+) but not during the second period (OKG-). Height velocity (HV) increased (P < 0.05) from a median of 3.8 cm/y to 6.45 cm/y (range 1.8-6.7) during the OKG+ period, and decreased (P < 0.05) to a median of 3.65 cm/y in the OKG- period. Plasma concentrations of insulin-like growth factor 1 (IGF1), glutamine, and glutamate increased (P < 0.05) during the OKG+ period. Variations of IGF1 concentrations correlated with HV variations (r = 0.82, P < 0.005) during both periods. This study demonstrates that OKG is associated with statural growth acceleration and increased IGF1 concentrations.

Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates

A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition-either the standard solution or a solution containing 25 μg of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days [p = 0.014]). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms. (J PEDIATR 1994;125:259-63)