Infusion Of Solution Research Articles

The first data on international multicenter clinical study RheoSTAT-CP0620 on the efficacy and safety of Rheosorbilact® infusion in therapy of sepsis

Sepsis stays a common and life-threatening pathological condition; hospital mortality in patients with sepsis exceeds 30 %. Fluid resuscitation is an important component of sepsis treatment. The purpose of this work was to evaluate the efficacy and safety of the multicomponent infusion solution Rheosorbilact in the treatment of patients with sepsis. The international multicenter randomized study RheoSTAT-CP0620 included 180 patients aged 18 to 60 years diagnosed with sepsis. Patients received Rheosorbilact therapy in dosage according to the package insert. A change in the SOFA score on day 3 of treatment was considered to be the primary endpoint. Changes in APACHE II, SAPS II, and MODS scores, as well as changes in endogenous intoxication markers on day 3 of treatment, were considered the secondary endpoints. The safety of the drug was assessed by analysis of adverse events and vital signs after 3 days of therapy. On day 3 of Rheosorbilact treatment, statistically significant changes in SOFA (by 2.01±1.37 points), APACHE II (by 4.24±3.76 points), SAPS II (by 3.40±5.30 points), and MODS (by 1.37±1.37 points) scales were recorded. In addition, there was a statistically significant improvement in markers of endogenous intoxication (urea, creatinine and total bilirubin concentrations, leukocyte counts, and calculated intoxication indices) on day 3 of treatment. The majority of adverse events (71.74 %) were mild. None of the adverse events were related to the study drug and did not result in the patient’s withdrawal from the study. According to the results of RheoSTAT-CP0620, Rheosorbilact is an effective and safe drug for the treatment of patients with sepsis. It is advisable to include Rheosorbilact in routine treatment algorithms for patients with sepsis.

In situ green analytical methods for the rapid and sensitive determination of a newly launched orphan anticancer drug; Tigecycline in infusion bags: comparative study

BackgroundTigecycline (TIG), an antimicrobial agent indicated for complex bacterial infections, is now approved by FDA as an orphan chemotherapeutic agent for the treatment of acute myeloid leukemia due to its inhibitory effects on pathways of activating, signaling and abnormal mitochondrial function in cancer cells. TIG is mainly administered as intravenous infusion through centralized unit of oncology centers. This necessitates the continuous analytical quality control of the prepared solution in order to identify and quantify TIG for safe intravenous administration to patients. Moreover, the clinical staff exposure risk to toxic drugs during daily handling must be considered. Such concerns require a fast, cost-effective and green analytical procedure for sensitive determination of TIG directly in infusion bags. In this work, we propose a simple, rapid and green capillary zone electrophoretic (CZE) method for the sensitive assay of TIG directly in infusion bags, in addition to three simple and green spectrophotometric methods.ResultsTIG solutions corresponding to clinical ranges were detected in 5%glucose. Validation of all the proposed methods was according to ICH guidelines. Greenness assessment was performed depending on Green Analytical Procedure Index (GAPI) and the Eco-scale approach which showed that the proposed methods are better eco-friendly methods than reported ones. It also revealed the superiority of our proposed methods in terms of simplicity and sensitivity for TIG determination in infusion bags. Quantification limits obtained were significantly lower than the administered range of TIG in infusion bags and lower than its maximum serum concentration (Cmax). This promotes the application of the proposed methods for the pharmacokinetics and bioavailability studies of TIG in various biological fluids.ConclusionsThis work reports, for the first time, CZE method for the direct and rapid determination of TIG and its separation from other components in intravenous infusion solution. The developed CZE method has several advantages over current chromatographic methods such as higher efficiency of separation within short analysis time, consumption of fewer quantities of chemicals and offering better resolution than HPLC. Moreover, three green spectrophotometric methods are also proposed for TIG determination that offer many advantages such as accuracy, precision, simplicity, specificity and facility of quantification and separation of the selected drug in infusion bags and pharmaceutical preparations without any techniques for extraction.

Hypoglycaemia associated with variable rate intravenous insulin infusion and concurrent administration of balanced electrolyte solution: A single hospital experience

Hypoglycaemia associated with variable rate intravenous insulin infusion and concurrent administration of balanced electrolyte solution: A single hospital experience

MO662: Effects of Blood Contact with Haemodialysis Membrane on the Kidney in a Rat Extracorporeal Perfusion Model

Abstract BACKGROUND AND AIMS A microcirculatory disturbance was found to occur during hemodialysis in an organ such as the brain or heart, which was recently considered to lead to functional impairment of these organs. Decrease in blood volume due to water removal during hemodialysis and the reaction of blood vessels with activated leukocytes and platelets that have come in contact with the dialysis membrane may cause the microcirculatory disturbance of the organs. Residual renal function decline after initiation of hemodialysis is well-known, but the mechanism has not yet been fully understood. In the present study, we focused on the effects of leucocytes and platelets activated by contact with the dialysis membrane and aimed to clarify the effects of blood contact with the dialysis membrane on the kidney. METHOD Male Sprague–Dawley rats weighing 397.4 ± 38.6 g were used for the experiment. We compared three experimental groups; the sham group, in which only puncture and infusion of Ringer's lactate solution were performed; the extracorporeal perfusion alone group, in which extracorporeal perfusion was performed only through a blood circuit; and the dialyzer group, in which extracorporeal perfusion was performed through a blood circuit and dialyzer. Blood was withdrawn from the femoral artery and returned to the femoral vein. The blood flow rate was 0.5–1.0 mL/min, the perfusion time was 4-h and no water removal was performed. During the perfusion experiment, arterial pressure and percutaneous arterial oxygen saturation (SpO2) were measured and at the end of perfusion, serum interleukin-6 (IL-6), a marker of inflammation and urinary kidney injury molecule-1 (KIM-1), a marker of kidney injury, were measured. After completing the perfusion experiment, kidneys were removed and morphology was evaluated by a hematoxylin and eosin (HE) staining. RESULTS AND DISCUSSION Arterial pressure during perfusion showed a significant upward trend during the first 2-h in the extracorporeal alone and dialyzer groups, while SpO2 showed a significant downward trend in these groups. Serum IL-6 levels were significantly higher in the extracorporeal perfusion alone group (P < .05, n = 8) and the dialyzer group (P < .01, n = 6) than in the sham group (n = 7). Urinary KIM-1 level in the dialyzer group was significantly higher than that in normal rats (P < .01, n = 7). Glomerular congestion was observed in the kidney only in the dialyzer group from the HE staining. There was a significant correlation between the increase in arterial pressure and the decrease in SpO2, suggesting that peripheral circulatory disturbance due to peripheral vasoconstriction occurred in the extracorporeal perfusion alone and the dialyzer groups. In addition, extracorporeal perfusion through the dialyzer caused high levels of IL-6 in serum and KIM-1 in urine, suggesting that systemic inflammatory and kidney injury have occurred. These reactions may contribute to the progression of residual renal dysfunction due to dialysis treatment, especially for the patients after the initiation of hemodialysis. CONCLUSION Extracorporeal perfusion and blood contact with a dialyzer caused systemic inflammation and the microcirculatory disturbance of kidneys, resulting in glomerular congestion and kidney injury in a rat extracorporeal perfusion model.

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

A Qualitative Study on the Benefits of Tumescence in Cadaveric Dissection with Faculty & First‐year Medical Students at SHSU‐COM

Hands‐on cadaver dissection is considered essential to the optimal education of future physicians, and the quality of students’ dissections has been directly related to their performance on national board exams. Some centers, however, have reduced or even eliminated cadaver dissections due to time constraints and safety concerns. To address such concerns while optimizing the benefits of hands‐on learning, we introduced tumescence into our first‐year anatomy lab. This involved the manual infusion of cadaver wetting solution into subcutaneous and interstitial tissue planes using a syringe and a blunt‐tipped canula. This technique was utilized by our students and faculty during the Clinical Anatomy course. A qualitative survey of students and faculty regarding the benefit, if any, of the tumescence was subsequently carried out and a thematic analysis of the responses was performed. The most frequent theme which surfaced in the survey was an increased ease and efficiency of dissection with the use of tumescence. In addition, the themes of separation, spaces, and planes, were common, reflecting in the respondents, an increased appreciation of tissue planes and relationships. The survey lent support to the conclusion that cadaver tumescence can improve the quality and speed of dissections safely, while increasing the appreciation of natural tissue planes.

Vascular rinsing and chilling carcasses improves meat quality and food safety: a review.

Rinse & Chill® technology (RCT) entails rinsing the vasculature using a chilled isotonic solution (3°C; 98.5% water and a blend of dextrose, maltose, and sodium phosphates) to rinse out the residual blood from the carcass. Infusion of pre-chilled solutions into intact animal carcasses immediately upon exsanguination is advantageous in terms of lowering the internal muscle temperature and accelerating chilling. This technology is primarily used for purposes of effective blood removal, favorable pH decline, and efficient carcass chilling, all of which improve meat quality and safety. Although RCT solution contains some substrates, the pre-rigor muscle is still physiologically active at the time of early postmortem and vascular rinsing. Consequently, these substrates are fully metabolized by the muscle, leaving no detectable residues in meat. The technology has been commercially approved and in continuous use since 2000 in the United States and since 1997 in Australia. As of January 2022, 23 plants have implemented RCT among the 5 countries (Australia, US, Canada, New Zealand, and Japan) that have evaluated and approved RCT. All plants are operating under sound Sanitation Standard Operation Procedures (SSOP) and a sound Hazard Analysis Critical Control Point (HACCP) program. No food safety issues have been reported associated with the use of this technology. RCT has been adapted by the meat industry to improve product safety and meat quality while improving economic performance. Therefore, this review summarizes highlights of how RCT technically works on a variety of animal types (beef, bison, pork, and lamb).

Glucose infusion suppresses acute restraint stress-induced peripheral and central sympathetic responses in rats.

Acute restraint stress (RS) induces sympathetic activation such as elevating plasma catecholamines, resulting in increase in blood glucose. We aimed to investigate whether glucose infusion affects the RS-induced sympathetic responses. Plasma catecholamines were measured by high-performance liquid chromatography with electrochemical detection. Blood glucose levels were measured with a glucometer and a glucose assay kit. Cardiac parameters were measured by echocardiographic and hemodynamic analysis. Prostanoid levels in the paraventricular nucleus of hypothalamus (PVN) microdialysates were measured by liquid chromatography-ion trap tandem mass spectrometry analysis. RS significantly increased plasma noradrenaline and adrenaline. Intravenous infusion of a 5% glucose solution significantly attenuated the RS-induced elevation of plasma adrenaline but did not alter the plasma noradrenaline. Glucose administration during RS suppressed the progression of cardiac impairment by attenuating the decline rates in left ventricular diastolic, end-diastolic volume, stroke volume, fractional shortening, and ejection fraction. Both Intravenous and intracerebroventricular infusion of glucose solution significantly attenuated the RS-induced elevation of thromboxane B2 (TxB2) (a metabolite of TxA2) levels in the PVN but did not alter prostaglandin E2 levels in the PVN. Our results demonstrate that glucose infusion suppresses RS-induced elevation of plasma adrenaline and left ventricular dysfunction. In the brain, glucose infusion suppresses RS-induced production of TxA2 in the PVN.

Ravulizumab (Ultomiris)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses ravulizumab (Ultomiris), 10 mg/mL concentrate for solution for infusion.
 Indication: For the treatment of adult patients with paroxysmal nocturnal hemoglobinuria.

Stability of Hydrocortisone Sodium Succinate in Intensive Care Units: Focus on Practical Points

Background: Although single daily 24 hours preparation of hydrocortisone solution infusion is widely used in intensive care clinical practice, most manufacturers limit its infusion time to only four hours. The data on efficacy of this practice are scarce. Objective: To determine the physical and chemical stability of hydrocortisone solution used in intensive care units (ICU). Materials and Methods: Powder form of 100 mg hydrocortisone was reconstituted first with sterile water for injection (SWI) and then added to normal saline solution (NSS) to obtain 1 and 2 mg/mL solutions, or first reconstituted with NSS then added to bag of NSS to obtain 1 mg/mL solution. The solutions were then stored in three different conditions, refrigerator (4±2℃), ICU (25±3℃), and hospital room (30±2℃) temperatures for 48 hours. The physical and chemical stabilities were assessed at an initial time, 4, 8, 12, 24, and 48 hours. Results: Hydrocortisone reconstituted in SWI showed an acceptable labeled amount range (100.28±3.83%), similar to reconstitution in NSS (96.05±1.00%). Hydrocortisone solutions of 1 and 2 mg/mL stored at 4±2℃, 25±3℃, and 30±2℃ showed similar percent label amount, and the statistical tests were not significantly different among the three ranges of temperatures (p>0.05). Conclusion: Hydrocortisone reconstituted using SWI followed by NSS to obtain final concentrations of 1 to 2 mg/mL or using only NSS to obtain a final concentration of 1 mg/mL, provided an acceptable range of % hydrocortisone remaining up to 48 hours when stored at 4±2℃, 25±3℃, and 30±2℃. Keywords: Hydrocortisone; Intensive care units; Normal saline solution; Stability; Sterile water for injection

Efficacy and safety of rapid intermittent bolus compared with slow continuous infusion in patients with severe hypernatremia (SALSA II trial): a study protocol for a randomized controlled trial.

BackgroundHypernatremia is a common electrolyte disorder in children and elderly people and has high short-term mortality. However, no high-quality studies have examined the correction rate of hypernatremia and the amount of fluid required for correction. Therefore, in this study, we will compare the efficacy and safety of rapid intermittent bolus (RIB) and slow continuous infusion (SCI) of electrolyte-free solution in hypernatremia treatment. MethodsThis is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental groups. A total of 166 participants with severe hypernatremia will be enrolled and divided into two randomized groups; both the RIB and SCI groups will be managed with electrolyte-free water. We plan to infuse the same amount of fluid to both groups, for 1 hour in the RIB group and continuously in the SCI group. The primary outcome is a rapid decrease in serum sodium levels within 24 hours. The secondary outcomes will further compare the efficacy and safety of the two treatment protocols.ConclusionThis is the first randomized controlled trial to evaluate the efficacy and safety of RIB correction compared with SCI in adult patients with severe hypernatremia.

Neuroprotective effects of strength training in a neuroinflammatory animal model

BackgroundThe preventive role of muscular strength on diminishing neuroinflammation is yet unknown. In this study, the role of the prophylactic muscular strength exercise was investigated in order to verify whether it would diminish cognitive alterations and modify the antioxidant intracellular scenery in an animal neuroinflammatory model in of the CA1 region of the hippocampus.MethodsThe animals received muscular strength training (SE) three times a week for eight weeks. Subsequently, the stereotaxic surgery was performed with an intra-hippocampal infusion of either saline solution (SAL) or lipopolysaccharide (LPS). Next, we performed the behavioral tests: object recognition and social recognition. Then, the animals were euthanized, and their hippocampus and prefrontal cortex were collected. In another moment, we performed the dosage of the antioxidant activity and histological analysis.ResultsThe results showed that the muscular strength exercises could show a beneficial prophylactic effect in the cognitive deficiencies caused by acute neuroinflammation. Regarding oxidative stress, there was an increase in catalase enzyme activity (CAT) in the group (SE + LPS) compared to the control groups (p < 0.05). As for the cognitive alterations, there were found in the (SE + LPS) group, diminishing the mnemonic hazard of the discriminative and social memories compared to the control groups (p < 0.05).ConclusionWe concluded, therefore, that the exercise performed prophylactically presents a protective effect capable of minimizing such mnemonic deficits and increasing catalase enzyme activity in rats that suffered a local neuroinflammatory process in the hippocampus.

Effects of ileal glucose infusion on enteropancreatic hormone secretion in humans: relationship to glucose absorption

BackgroundsThe distal small intestine plays an important role in regulating the secretion of entero-pancreatic hormones that are critical to the control of glucose metabolism and appetite, but the quantitative contribution of a specific segment to these effects is unknown. PurposesTo determine the effects of 30 cm of the ileum exposed to glucose on the secretion of ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) insulin, C-peptide and glucagon, in relation to glucose absorption in non-diabetic subjects. Basic procedures10 non-diabetic subjects with a loop ileostomy after early-stage rectal cancer resection were studied on 2 days in a double-blind, randomized and crossover fashion, when a catheter was inserted retrogradely 30 cm from the ileostomy for infusion of a glucose solution containing 30 g glucose and 3 g 3-O-methylglucose (as a marker of active glucose absorption), or 0.9% saline, over 60 min. Ghrelin, GIP, GLP-1, insulin, C-peptide, glucagon and ileal glucose absorption (from concentrations of 3-O-methylglucose in serum and glucose in ileostomy effluent) were measured over 180 min. Main findings12.0 ± 1.2 g glucose was absorbed over 180 min. Compared to saline, ileal glucose resulted in minimal increases in blood glucose and plasma insulin and C-peptide, but substantial increases in plasma GLP-1, without affecting ghrelin, GIP or glucagon. The magnitude of the GLP-1 response to glucose was strongly related to the increase in serum 3-O-methylglucose. Principal conclusionsStimulation of the terminal ileum by glucose, even over a short length (30 cm), induces substantial GLP-1 release, coupled primarily to active glucose absorption.Clinical registration:NCT05030376 (ClinicalTrials.gov).

Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway

BackgroundThe aim of this study was to investigate the effect of tumor necrosis factor receptor-related factor 6 (TRAF6) in acute pancreatitis (AP)-induced intestinal barrier injury via the Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signal pathway. MethodsRat models of acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) were established by intraperitoneal injection of caerulein and retrograde infusion of sodium taurocholate solution into the biliopancreatic duct, respectively. Separate groups of model rats were pretreated with the TRAF6 inhibitor, MG-132. Rats were sacrificed at 12 h after the last injection for inducing AP. Histopathological changes, inflammatory response, intestinal barrier function, and protein expression levels were assessed by pathological score, ELISA, TUNEL, qRT-PCR, immunohistochemistry and western blotting. ResultsRat models of AEP and ANP were successfully established as evidenced by the pathological changes in the pancreas and intestine. Pre-treatment with MG-132 significantly alleviated pancreatic and intestinal pathological scores, reduced serum levels of amylase, IL-1β, and IL-6, and ameliorated apoptosis of mucosal cells. MG-132 reduced intestinal barrier injury, including serum levels of diamine oxidase and lipopolysaccharide, and intestinal expressions of ZO-1 and occludin. Moreover, it significantly suppressed the activation of the intestinal TLR4/NF-κB signaling pathway. ConclusionsTRAF6 inhibitor alleviated pancreatic and intestinal injury in AEP and ANP. This effect may be mediated through inhibition of the TLR4/NF-κB signaling pathway, which in turn regulates the inflammatory response and intestinal barrier injury.

Evaluation of cerebral hemodynamics by transcranial Doppler ultrasonography and its correlation with intracranial pressure in an animal model of intracranial hypertension.

Transcranial Doppler has been tested in the evaluation of cerebral hemodynamics as a non-invasive assessment of intracranial pressure (ICP), but there is controversy in the literature about its actual benefit and usefulness in this situation. To investigate cerebral blood flow assessed by Doppler technique and correlate with the variations of the ICP in the acute phase of intracranial hypertension in an animal model. An experimental animal model of intracranial hypertension was used. The experiment consisted of two groups of animals in which intracranial balloons were implanted and inflated with 4 mL (A) and 7 mL (B) for controlled simulation of different volumes of hematoma. The values of ICP and Doppler parameters (systolic [FVs], diastolic [FVd], and mean [FVm] cerebral blood flow velocities and pulsatility index [PI]) were collected during the entire procedure (before and during hematoma simulations and venous hypertonic saline infusion intervention). Comparisons between Doppler parameters and ICP monitoring were performed. Twenty pigs were studied, 10 in group A and 10 in group B. A significant correlation between PI and ICP was obtained, especially shortly after abrupt elevation of ICP. There was no correlation between ICP and FVs, FVd or FVm separately. There was also no significant change in ICP after intravenous infusion of hypertonic saline solution. These results demonstrate the potential of PI as a parameter for the evaluation of patients with suspected ICP elevation.

Effect of a single meloxicam administration on newborn Holstein-Friesian dystocia calves: Field results from the first 10 days of life.

Background and Aim:Calves have increased morbidity and mortality rates after dystocia. One cause is pain during birth, which reduces their colostrum intake. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may break this causality. This study aimed to determine the consequences of a single administration of the NSAID meloxicam to dystocia calves after birth.Materials and Methods:Fifty Holstein–Friesian calves born with dystocia from four dairy cattle farms were included in this study. The animals were randomized into two groups. The animals in Group I (n=25, treatment group) received subcutaneous 0.5 mg meloxicam/kg body weight 2-8 h after birth. The animals in Group II (n=25, control group) received a control substance (Amynin®, bovine infusion solution, Merial) with the same volume. The newborn calves were clinically examined on the 1st and 10th days of life. The information regarding the days in between was gathered by questioning the farmer.Results:There was a significant difference (p=0.04) only in calves with thin, mushy fecal consistency on the 10th day in the treatment group compared with the control group. Moreover, meloxicam had no effect on dystocia calves.Conclusion:Since NSAID administration did not produce a significant clinical effect, its necessity is questionable. Further studies should examine how modifying its application time would have an effect. The primary indicators of well-being, such as pain indicators in the blood, were not measured; however, these should be considered in subsequent studies.

A Clinical Case of an Unspecified Paralytic Ileus Patient Treated with Korean Medicine

Objectives: This study examined a clinical case of a paralytic ileus patient diagnosed with Soeumin.Methods: The patient was treated with herbal medicine (Hyangsayangwi-tang, Baekhaogunja-tang, Palmulgunja-tang), infusion solution treatments, acupuncture, moxibustion, and rehabilitative therapy. Their effects were evaluated using the visual analog scale (VAS).Results: After receiving Korean medical treatment for 38 days, the VAS score for dyspepsia was reduced from 8 to 2, the VAS score for nausea and vomiting was reduced from 8 to 2, and the VAS score for abdominal pain was reduced from 7 to less than 1.Conclusions: Korean medicine could be effective in relieving the symptoms of paralytic Ileus.

Establishment of a New Cryopreservation Solution for Chimeric Antigen Receptor T Cells.

Preservation and transportation are essential for the clinical application of chimeric antigen receptor T (CAR-T) cells. This study aimed to optimize a cryopreservation solution for CAR-T cells and evaluate the antitumor efficiency of CAR-T cells using this optimized solution in vitro and in vivo. First, the stability of the cryopreservation solution for CAR-T infusion was detected by the L27 (37) orthogonal experiment. Subsequently, osmolality and pH were analyzed for the preservation reagent. Additionally, apoptosis and CAR expression of CAR-T cells were measured by flow cytometry, and the cytotoxicity was determined by calcein-AM staining. The results showed that cryopreservation solutions used in this study demonstrated high chemical stability, which induced only 2% CAR-T cells apoptosis in optimal solutions, which were slightly lower than other commercial solutions. Moreover, the CAR expression was not significantly affected by preservation with these solutions. There were no significant differences in the cytotoxicity between fresh and thawed CAR-T cells cryopreserved in the cryopreservation solutions in vivo and in vitro. This study developed a new cryopreservation solution for CAR-T cells, and it was safe and also had negligible effects on the CAR-T cells antitumor activity.

Clinical parameters associated with the development of mortality in patients after non-cardial surgical interventions

Background.Cardiac arrhythmias remain a clinically significant problem in the conditions of the general surgical department, since they make a significant contribution to the risk of fatal complications. The aim of the study. To study the clinical, instrumental and laboratory characteristics of patients depending on the development or absence of a fatal outcome after non-cardial abdominal surgical interventions, as well as to evaluate the effect of early atrial fibrillation on mortality. Methods. The methodology was carried out according to the type of "case-control" study. 83 lethal "cases" were selected and 143 "controls" were selected. A total of 226 medical histories are included in the analysis. Results.The group with mortality was significantly older than the group without mortality: 75 (64;82) years versus 61 (44;72) years, respectively (p&lt;0.001). Differences in the groups were observed in the severity of concomitant pathology: in the group with mortality, CHF was significantly more pronounced (p&lt;0.001), diabetes mellitus was more common – 34% vs. 10% (p&lt;0.001) and the frequency of COPD was higher – 8.4% vs. 1.4% (p=0.031). However, there were no statistically significant differences in the frequency of myocardial infarction (p=0.121). Statistically significant differences in perioperative parameters included differences in intraoperative infusion of solutions with a volume of more than 3 liters (p=0.003) and in postoperative infusion of solutions with a volume of 1-3 liters and 3-5 liters (p=0.001 and p&lt;0.001). In the group with a fatal outcome, infusion in large volumes significantly prevailed. Also, the group with a fatal outcome was statistically significantly different in the frequency of relaporotomies (p&lt;0.001).; by the frequency of systemic inflammatory reaction syndrome (p&lt;0.001), by the frequency of bleeding (p=0.031), by the frequency of AFP (p&lt;0.001), thromboembolic complications (p&lt;0.001) and the frequency of pneumonia (p&lt;0.001). All of the above events were more often observed in the group of patients with a fatal outcome. Statistically significant independent factors increasing the risk of mortality in our sample were: history of cardiac arrhythmias (OR 3.4 at 95% CI 1.7-6.9), CHF 2-3 FC (OR 6.8 at 95% CI 3.7-12.6), DM (OR 4.9 at 95% CI 2.3-9.6), COPD (OR 6.5 at 95% CI 1.3-32), intraoperative infusion of more than 3 liters (OR 2.9 at 95% CI 1.46-5.7), postoperative infusion of 3-5 liters (OR 2.9 at 95% CI 1.6-5.0), thromboembolic complications (OR 37.9 at 95% CI 8.7-164). Conclusions.Statistically significant independent factors that increase the risk of mortality are: a history of cardiac arrhythmias, heart failure, chronic obstructive pulmonary disease, large infusion of solutions during and after surgery, diabetes mellitus, the development of thromboembolic complications. The development of postoperative atrial fibrillation increases the chances of a fatal outcome by 15 times: the odds ratio was 14.8 with 95% CI from 7.4 to 29.4.

EFFECTIVENESS AND SAFETY OF FAVIPIRAVIR INFUSION IN PATIENTS HOSPITALIZED WITH COVID-19

Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important.The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients.Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol.Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability.Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.