Comparative characteristics of the main sanogenetic mechanisms in large laboratory animals (pigs) with acute blood loss and after infusion of an isotonic colloidal solution based on dextran and an isotonic solution based on polyglucin in conditions of general external cooling

The experiment was carried out on male pigs, which in the operating room were simulated with acute blood loss (air temperature 23oC). Then the animals were placed in a climatic chamber (minus 50 ° C) for 10 minutes. Then the temperature in the climatic chamber was raised to minus 10 ° C and the introduction of the test solutions to the animals began. It was found that in both groups there were similar indicators of blood pressure. The heart rate and respiratory rate in animals in the group with the experimental solution based on polyglucin derivatives were lower than in the group with the solution based on dextran. Key words: external general cooling, pigs, blood pressure, heart rate, respiratory rate, infusion solution.

Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing

Aim/Background In this study, the prolonged physical and chemical stability of the anticancer agent cabazitaxel, commercially available as Jevtana®, was examined. Both concentrate-solvent mixture and infusion solution were examined with the aim to extend the use of multidose left-over cabazitaxel and infusion solutions and with that reduce financial and environmental waste. Methods A validated stability-indicating high-pressure liquid chromatography (HPLC) method with ultraviolet (UV) and photodiode array (PDA) detection was used to examine the purity and any degradation of cabazitaxel. The concentrate-solvent mixture and infusion solution samples that were tested had been stored out of the range of the criteria stated in the summary of product characteristics (SmPC). The concentrate-solvent mixtures were stored at 3–5°C, 18–21°C, and 40 °C, whereas the infusion solution was stored at 3–5°C. All samples were tested at t = 0, t = 1 week and t = 2 weeks. Results All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. However, the concentrate-solvent mixtures stored at 18-21°C and 40 °C showed a degradation product forming in all the samples lowering the purity of the samples from 100% to 99.91% and 98.20% respectively, whereas all samples stored at 3–5°C remained at 100%. Conclusion Concentrate-solvent mixture and infusion solution of cabazitaxel, Jevtana®, can be used up to 2 weeks after preparation if stored at 3–5°C and prepared under aseptic conditions.

Incompatibility of remimazolam besylate with Ringer’s acetate infusion resulting in total occlusion of an intravenous catheter

Remimazolam besylate is an ultra-short-acting benzodiazepine derivative recently approved in Japan for general anaesthesia. However, less attention has been paid to the compatibility of remimazolam with infusion solutions, and the mechanism underlying the incompatibility remains unknown. The patient was a 65-year-old man who underwent a high tibial osteotomy. After the induction of general anaesthesia using remimazolam solution (5 mg/mL), we noticed precipitate completely blocking the lumen of the intravenous tube connected to a Ringer’s acetate Physio140 drip. The mixture of remimazolam solution (5 mg/mL) with Physio140 solution immediately resulted in the formation of substantial precipitate. Nuclear magnetic resonance analysis revealed that the precipitate was remimazolam. Ultraviolet spectrophotometry revealed that the mixture of remimazolam solution with higher ratios of Physio140 resulted in significantly lower solubility, concomitant with an increase in pH. It would be important to consider the remimazolam concentration and infusion solution pH to avoid the production of precipitates.

The influence of solution choice on fluid resuscitation in patients with septic shock

The aim. Compare the hemodynamic effects and safety of infusion of the balanced crystalloid solution, sorbitol-based solution, and standard solution (0.9 % sodium chloride). Materials and methods. A prospective randomized clinical trial was carried out, the study included 68 adult patients, who had the active surgical infection, and were in a state of septic shock. A corresponding solution with a volume of 500 ml was used for resuscitation. Hemodynamic and other clinical and laboratory parameters were monitored. Results. There was no significant difference in mean arterial pressure (MAP) between the 3 groups before the 45th minute (p>0.05), from the 50th minute to 2 hours they were found only between the NS and Sorb groups (p <0.05). No statistically significant difference in heart rate (HR) was obtained in any measurement (p> 0.05). Cardiac output (CO) and oxygen delivery (DO2) did not differ until 35 min (p> 0.05) and up to 40 min (p> 0.05); after 40 min and 45 min, a significant difference was also found between the Sorb and NS groups (p <0.05). After infusion of a sorbitol-containing solution and a balanced polyionic solution, the acid-base state of the blood significantly improved. The applied dose of the sorbitol-containing solution was safe for renal function and blood clotting in septic shock in this study. But the applied balanced polyionic solution may be associated with a decrease in the number of platelets. Daily changes by APACHE II scores in each group were not statistically significant. The difference in 7-day and 28-day mortality between groups was not statistically significant (p>0.05). Conclusions. In our study, the balanced polyionic solution with 1.9 % sodium lactate and 6 % sorbitol was the most effective and safe infusion solution for the treatment of septic shock, it can be used as a supplement to balanced crystalloid solutions. When using a balanced polyionic solution (Ringer's acetate) with 0.07 % L-malonic acid, the platelet count should be monitored more often

Physicochemical stability of human insulin 1 I.U./mL infusion solution in 50 mL polypropylene syringes

Objectives The objective of this study was to investigate the physicochemical stability of human insulin 1 I.U./mL injection solutions (Insuman® Rapid) diluted with 0.9% NaCl solution in 50 mL disposable three-piece polypropylene syringes and stored refrigerated or at room temperature. Methods 1 I.U./mL test solutions were prepared with Insuman® Rapid and 0.9% sodium chloride infusion solution in 50 mL Original-Perfusor® syringes and BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or 48 h at 20–25 °C/diffuse room light in order to determine chemical stability. Additional test solutions were stored 28 days at 2–8 °C/dark followed by 24 h at 20–25 °C/diffuse room light to measure pH and particle counts. Human insulin concentrations were analysed by reversed-phase high-performance liquid chromatography at predefined time points. Test solutions were regularly inspected; subvisible particles and pH values were measured. Results Insuman® Rapid 1 I.U./mL injection solutions, stored at 2–8 °C/dark for 90 days showed a decrease of insulin content over time, regardless of the syringe type used. When kept at 20–25 °C/diffuse room light for 48 h, a slight decrease of the HI concentration was observed in both syringe types. No evidence of colour change, relevant particle formation or major pH-change was observed throughout the observation period in any test solution. Conclusions Insuman® Rapid 1 I.U./mL injection solutions can be prepared by dilution with 0.9% NaCl infusion solution in disposable 50 mL three-piece polypropylene syringes as suitable primary containers. Physicochemical stability has been demonstrated for at least 21 days stored at 2–8 °C/dark followed by 48 h at 20–25 °C/diffuse room light.

Use of locally prepared peritoneal dialysis (PD) fluid for acute PD in children and infants in Africa

Background: In less well-resourced countries, the high cost of commercially available peritoneal dialysis (PD) fluid limits its use. The major concerns regarding bedside-prepared PD fluid is peritonitis as well as electrolyte disorders. The aim of this study was to review our experience with the use of PD fluids prepared at the bedside using the intravenous infusion solution Balsol (Fresenius Kabi). Methods: This was a retrospective review of all patients who received PD for acute kidney injury (AKI) using a bedside-prepared PD solution adapted from the intravenous solution Balsol in our intensive care unit. Results: In total, 49 cases of acute PD were performed. Of the 49 children, 21 (43%) were male. The ages of the patients ranged from newborn to 10.2 years (median 0.33 years). The weight of children ranged from 1.3 kg to 50 kg (median 4.1 kg). The type of PD catheters used: Cook catheters, 41 patients; Kimal peel-away, 10 patients; and surgical inserted Tenckhoff type of catheter, 2 patients. The duration of PD was 1–17 days (median 3 days) Complications included peritonitis in 2 of 49 patients and blocked catheter in 6 of 49 patients. There were no electrolyte disturbances as a result of the PD. Overall survival was 43% of patients. Conclusions: Locally prepared PD solutions at the bedside adapted from intravenous solutions can be used safely and effectively. This has important relevance for centres in less well-resourced countries, where commercially produced PD fluid is not available for the management of AKI.

INFLUENCE OF THE USE OF GRAVITY SETS IN A PRESSURE VOLUMETRIC INFUSION PUMP WITH AN IMPACT ON THE ACCURACY OF INFUSION SOLUTION FLOWS

The subject of the work was the experimental verification of the negative influence of gravity sets in a pressure volumetric infusion pump with an impact on the accuracy of infusion solution dosing. The quality criterion for gravity sets was the accuracy of the flow versus the reference set by the volumetric infusion pump. The solution consisted of 14-hour measurements with two types of gravity sets, Intrafix® Primeline sets were used as universal sets and Standardline IS‑103 gravity sets. The insulin pump flow rate was set at 300 ml/h and 50 ml/h, and the actual flow rate of the infusion solution was recorded every hour using a graduated cylinder. Used gravity sets were also processed by mechanical tests, unused sets were subjected to these tests and the obtained data were compared with each other. Experiments carried out showed that at the set flow rate of 300 ml/h, the flow error with the universal set was -3% and at a set flow rate of 50 ml/h the error was +2.3%. Flow accuracy using gravity sets was worse, a flow error of -7.2% was detected for a flow rate of 50 ml/h and a flow error of -7.7% was measured for 300 ml/h. The volumetric pump used declares a tolerated inaccuracy of ± 3% when used with standard infusion sets. Based on the data, it can be concluded that the replacement of set types has an influence on the dosage of infusion solutions.

Эффективность реамберина в коррекции процессов перекисного окисления липидов в плазме крови больных эпилепсией детей

The antioxidant activity of reamberin was studied in children with epilepsy: 10 patients with epilepsy received intravenous reamberin (Research and Technological Pharmaceutical Firm POLYSAN, Saint Petersburg, Russia) 200 ml of 1,5 % infusion solution at a rate of 40-80 drops/min (2-4 ml/min) once daily for 5 days; 15 patients with epilepsy received only valporic acid (a control group). The efficacy of the medication was evaluated by the levels of lipid hydroperoxides, conjugated dienes, and malondialdehyde and by the activity of the main components of the antioxidant system (ceruloplasmin, vitamin E, catalase) in the blood of epileptic children. The administration of reamberin to patients with epilepsy significantly reduced the plasma levels of lipid hydroperoxides by 15 %, conjugated dienes by 15 %, and malondialdehyde by 24 % compared to the patients in the control group. An analysis of the effect of succinate-containing medications on the activity of the antioxidant system components revealed that the blood concentrations of ceruloplasmin and catalase were 37 % and 24 %, respectively, higher than those in the control group. Thus, the inclusion of reamberin into the treatment of children with epilepsy should be considered pathogenically justified, clinically reasonable, and promising.

VALIDATION RESEARCHES OF THE PRODUCTION PROCESS OF THE GLUCOSE MEDICINE INFUSION SOLUTION

The purpose of the work is to carry out validation researches of the technological process of production of glucose solution for infusions using the bracketing approach for batches of different volumes and fullness the filling of containers. The object of the research is the manufacturing process for the manufacture of glucose infusion solution 50 mg / ml. Data collection was carried out on the basis of series production protocols, protocols for analysis of of raw materials and supplies, intermediate and finished products, series packaging protocols, other protocol and registration documentation of the drug production process. Validation studies were carried out at all stages of the technological process with the determination of critical parameters, confirming the quality of the product under the investigated parameters and the reproducibility of the results when the initial parameters were changed, such asy: preparation of raw materials, solution preparation, filtration of solution, filling and capping of vials, sterilization, inspection, packaging. The technological scheme for the production of the drug Glucose solution for infusion of 50 mg / ml was determined. Validation studies and data collection were carried out on 3 industrial series, determined by the bracketing method: 2000 l with a dosage of 200 ml of medicine per bottle (min. series size, min. dosage), 5000 l and a filling volume of 400 ml (min. series size for bottles of 400 ml), 10000 l with packaging in bottles of 500 ml (max. series size, max. dosage). The obtained research results indicate the reproducibility and normativity of the quality indicators of intermediate and finished products in accordance with the regulatory documentation and declared acceptance criteria for all investigated release forms of 200 ml, 400 ml and 500 ml in glass bottles. The results of validation examinations of the technological process for preparing a solution for glucose infusion solution of 50 mg / ml is representative of the intermediate parameters of drug production and are determined to be satisfactory to ensure stable quality indicators. The results of validation researches were obtained using a scientifically based approach to the selection of limit values, risk analysis and determination of critical parameters. The results of the study are of practical importance for organizing the validation of the technological process for the production of medicines with several dosages, volumes of production series, various sizes of container filling, in order to reduce the number of tests to save resources and time.

Influence of different qualitative composition of infusion solutions on cerebral hemodynamics in patients with acute ischemic stroke

The aim: Investigate the effect of 0.9% NaCl, HES 130, HAES-LX-5% and mannitol 15% on cerebral hemodynamics in patients with AIS. Materials and methods: The study included 100 patients with AIS. As the investigated solutions were used: isosmolar 0.9% NaCl, hyperosmolar mannitol 15%, colloid-isoosmolar HES 130, colloid-hyperosmolar HAES-LX-5%. The control group received only 0.9% NaCl compared: 0.9% NaCl+HES 130, 0.9% NaCl+HAES-LX-5%, 0.9% NaCl+mannitol 15%. Evaluation of cerebral hemodynamic (indexes of cerebral blood flow) was performed using doppler ultrasound of cerebral arteries. Results: The dynamics of specific volume velocity of blood flow per 100 grams of brain substance indicates that in the group of 0.9% NaCl and 0.9% NaCl+mannitol is the tendency to decrease the blood flow of the brain during 7 days of treatment, respectively: 2.8% and 7.5%. In patients with HES 130 solution cerebral blood flow increases by 14.2%, whereas when applied HAES-LX-5% during 7 days, it increases by 43.2% (p=0.004). Conclusions: The analysis of the data of treatment the patients with AIS showed the best effect (p=0.004) of improvement of the cerebral circulation in the use of the polyfunctional infusion solution HAES-LX-5% unlike the 0.9% NaCl group and group of 0.9% NaCl+mannitol where was a decrease of the dynamics of cerebral blood flow, which could lead to hypoperfusion of the brain.