Neurotoxicity of anaesthetics have become one of the most discussed problems in paediatric anaesthesiology. The experimental studies on animal models have shown that the anaesthetics used in general anaesthesia should have an influence on neurodegenerative processes, neuroapoptosis and the irregulated death of the neuronal cells. Because of this fact, scientists are trying to discover the possibilities of how to minimize the adverse effects of anaesthesia and revise the other alternatives of prevention of anaesthesia-induced maladaptive behavioural disorders.

The history of studying the organoprotective properties of argon (Ar) began in 1998 when a group of Russian researchers investigated the effect of hypoxic gas mixtures on mammalian organisms. Over several decades, evidence of the cardio-, neuro-, and nephroprotective effects of argon in various diseases and conditions in experimental models in vivo and in vitro have been accumulated. However, the lack of clinical studies to date has prompted us to carry out a systematic review analyzing the results of preclinical studies revealing organoprotective properties of argon, which could provide a rationale for its future clinical studies.

The aim of this review is to describe the mechanisms of organoprotective properties of argon determined in preclinical studies.

Material and methods. The search yielded 266 articles. The search algorithm was developed in accordance with the requirements and reporting guidelines for systematic reviews and meta-analysis (PRISMA) in the PubMed and Google Scholar databases. The methodology included using search queries, keywords (including MeSH), and logical operators. The keywords used for the search in the PubMed and Google Scholar databases were «argon», «ar», «protection», and «mechanism». The review included in vivo and in vitro studies.

Results. The following mechanisms of argon action were identified: activation of N-terminal c-Jun kinase

(JNK), p38(ERK1/2), and ERK1/2 in models of airway epithelial cells, neuronal and astroglial cell cultures, as well as in models of retinal ischemia and reperfusion injury in rats and a rabbit model of ischemia-reperfusion myocardium. Significant neuroprotective effects of argon and its influence on apoptosis were shown using small rodent models.

Conclusion. The results of preclinical studies of argon have proved both its safety and organoprotective properties in in vitro and in vivo models. Analysis of the data provides a rationale for the initiation of clinical studies of argon, which could significantly improve outcomes in patients after cerebrovascular accidents, particularly post ischemic stroke.

Inotropes and vasopressors are frequently required in critically ill patients and in patients undergoing major surgery. Several molecules are currently available, including catecholamines, phosphodiesterase-3 inhibitors, vasopressin and its analogues, and calcium sensitizers.

We will review current evidence on inotropes use in perioperative and critically ill patients, with focus on most recent randomized controlled trials (RCTs).

Despite being widely used in anesthesia and intensive care, evidences on safety and efficacy of inotropes are scarce. Data from observational studies suggest that inotropes administration may increase mortality in cardiac surgery, acute heart failure, and cardiogenic shock patients. However, randomized controlled trials did not confirm these findings in acute care settings.

Epinephrine has been associated with increased mortality especially in cardiogenic shock, but randomized trials failed to show evidence of increased mortality associated with epinephrine use. Norepinephrine has been traditionally considered contraindicated in patients with ventricular dysfunction, but recent trials suggested hemodynamic effects similar to epinephrine in patients with cardiogenic shock. Dopamine has no additional advantages over norepinephrine and increases the risk of tachyarrhythmias and may increase mortality in cardiogenic shock. Phosphodiesterase-3 (PDE-3) inhibitors are equivalent to catecholamines in terms of major outcomes. Levosimendan is the most investigated inotrope of the last 30 years, but despite promising early studies, high-quality multicenter RCTs repeatedly failed to show any superiority over available agents. There is no highquality RCT clearly demonstrating superiority of one agent over another. In summary, current evidence suggest that the choice of inotrope is unlikely to affect outcome, as long as the target hemodynamic goals are achieved.

Finally, in recent years, mechanical circulatory support (MCS) has become increasingly popular. Thanks to improvement in technology, the safety and biocompatibility of devices are constantly growing. MCS devices have theoretical advantages over inotropes, but their use is limited by costs, availability, and invasiveness.

Conclusion. Future studies should investigate safety, efficacy, and cost-effectiveness of primary MCS versus primary inotropes in patients with acute cardiovascular failure.

Polytrauma is a highly relevant problem from both scientific and clinical perspectives due to its high mortality rate (>20% in young and middle-aged individuals and >45% in the elderly). The lack of consensus in the definition of polytrauma complicates data collection and comparison of available datasets. In addition, selection of the most appropriate management strategy determining the quality of medical care and magnitude of invested resources can be challenging.

Aim of the review. To revisit the current definition of polytrauma and define the perspective directions for the diagnosis and management of patients with polytrauma.

Material and methods. Based on the data of 93 selected publications, we studied the mortality trends in the trauma and main causes of lethal outcomes, analyzed the polytrauma severity scales and determined their potential flaws, examined the guidelines for choosing the orthosurgical strategy according to the severity of the patient’s condition.

Results. The pattern of mortality trends in trauma directly depends on the adequacy of severity assessment and the quality of medical care. The Berlin definition of polytrauma in combination with a mCGS/PTGS scale most accurately classifies polytrauma into four severity groups. For the «stable» patients, the use of primary definitive osteosynthesis with internal fixation (early total care, or ETC) is the gold standard of treatment. For the «borderline» and «unstable» groups, no definitive unified strategy has been adopted. Meanwhile, in «critical» patients, priority is given to general stabilization followed by delayed major surgery (damage control orthopaedics, or DCO), which increases survival.

Conclusion. The use of artificial intelligence and machine learning, which have been employed for more specific goals (predicting mortality and several common complications), seems reasonable for planning the management strategy in the «controversial» groups. The use of a clinical decision support system based on a unified patient registry could improve the quality of care for polytrauma, even by less experienced physicians.

Coronavirus infection caused by the SARS-CoV-2 virus is a multifaceted disease due to generalized vascular endothelial damage. Endothelial damage also underlies COVID-associated coagulopathy.

The paper presents a case of coagulopathy causing myocardial infarction in a 43-year-old patient with no history of coronary disease. We have reviewed the available literature for the pathophysiological rationale of the assumed possibility of coronary thrombosis resulting from coagulopathy with the intact intima of the coronary arteries.

Conclusion. The present observation of coronary thrombosis with radiographically intact coronary artery intima confirms the important role of coronavirus infection in triggering endothelial dysfunction. Currently, the most effective strategy for this type of coronary lesions is the use of anticoagulants and antiplatelet agents along with ECG, echocardiography and troponin level monitoring.

Aim. To compare respiratory mechanics and gas exchange in patients with acute respiratory distress syndrome (ARDS) with and without COVID-19.

Material and methods. We examined 96 patients, who were divided into two groups. The main group included 48 patients with COVID-19-associated ARDS. The control group included 48 patients with ARDS not associated with COVID-19. Most characteristic patients were selected for the following baseline parameters: age, sex, SAPS II score, disease severity, plateau pressure (Pplateau), oxygenation index (PaO₂/FiO₂), and arterial-alveolar oxygen gradient (A-aO₂). Respiratory mechanics and gas exchange parameters assessed immediately after ARDS diagnosis and on days 1, 3 and 7 of treatment included arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) pressure, tidal volume (Vt), respiratory rate (RR), respiratory minute volume (RMV), positive end expiratory pressure (PEEP), and Pplateau.

Results. Patients in the main group had higher Vt (9.7 vs. 5.1 ml/kg, P<0.001), RR (38 vs. 30 min-1, P<0.001), and RMV (27.7 vs. 10.5 l/min, P<0.001). Control group patients showed hypercapnia (PaCO₂ 43 vs. 38 mmHg, P<0.001), lower respiratory compliance (30 vs. 48 ml/cm H₂O, P<0.001) and ventilation ratio (VR) (1.5 vs. 2.0, P<0.01). Lower PEEP values were required for patients in the main group. However, despite the higher rate of tracheal intubation in the control group (50% vs 16.7%) in the initial period of intensive care, the proportion of patients receiving invasive lung ventilation was significantly higher in the main group (33.3% vs.14.6%) by day 7.

Conclusion. The initial phase (the first 7 days) of ARDS associated with COVID-19 is characterized by higher values of Vt, RR and RMV, as well as lung compliance vs «typical» ARDS with almost identical PaO₂/FiO₂ values.

Aim of the study. To explore the structural and functional changes of neurons, glial cells, and synaptic terminals in layers I, III, and V of the sensorimotor cortex (SMC) of the rat brain after bilateral common carotid artery ligation (CCAL).

Material and methods. Incomplete cerebral ischemia was simulated by irreversible bilateral CCAL (2-vessel model of global ischemia without hypotension) on white rats (n=36). Comparative evaluation of the studied SMC structures was performed in the control group (intact rats, n=6) on days 1, 3, 7, 14, and 30 (n=30) after CCAL. Nissl, hematoxylin-eosin staining, and immunohistochemical reactions for NSE, MAP-2, p38, GFAP, and IBA1 were used. Numerical density of pyramidal neurons, astrocytes, oligodendrocytes, microglial cells, and relative area of p38-positive material (synaptic terminals) were determined. Statistical hypotheses were tested using nonparametric methods with Statistica 8.0 software.

Results. After CCAL, the number of degenerative neurons in rat brain SMCs increased. The peak of numerical density of unshrunken neurons was detected after day 1. Later, the numerical density of hyperchromic unshrunken neurons decreased, while that of shrunken neurons increased. These parameters did not reach the control values. The changes in SMC neurons were accompanied by an increase in the numerical density of microglial cells after day 1 and its subsequent decrease. Immunohistochemistry for IBA1 revealed signs of microglial cell activation such as change in shape and loss of processes. Maximum increase in the SMC density of oligodendrocytes was observed on day 7, and that of astrocytes on day 14 after CCAL. The maximum number of NSE-positive neurons occurred on day 1 after CCAL. There was a significant decrease in the number of NSEpositive neurons in SMC layer III on days 3, 7, and 14, and an increase in the number of NSE-positive neurons on day 30. The number of NSE-positive neurons in layer V of the SMC progressively decreased throughout the whole study period. The evolution of changes in the proportion of p38-positive material (synaptic terminal area) differed significantly between the layers of SMC. In the layers I and III, this parameter first decreased (days 1 and 3) and then increased (days 7, 14, and 30). In layer V of SMC, the activation of the protein expression was observed in the acute phase (days 1 and 3), then it decreased on days 7 and 14, and increased again on day 30. The changes found in the numerical density of neurons, glial cells and synaptic terminals were associated with dehydration and overhydration of SMC. We found strong to medium significant associations between the relative area of terminals and neuropil swelling and edema zones.

Conclusion. After CCAL, layers I, III, and V of the SMC of white rats revealed destructive and compensatory changes in neurons, glial cells, and inter-neuronal communication structures. Taken together, all these changes indicate a significant layer-by-layer variability of the neural tissue response to CCAL. Layer III (secondary projection complex) of the SMC was affected to a greater extent. Reorganization of neuronal-glial and interneuronal interrelations occurred along with a prominent neuropil overhydration.

The aim of the study was to assess regional cerebral oxygenation (rScO₂) in patients with acute respiratory distress syndrome (ARDS) associated with COVID-19.

Material and methods. The cross-sectional study was conducted. Twenty-eight patients with severe COVID-19 who were admitted in the intensive care unit were enrolled. Regional cerebral oxygenation was assessed using near-infrared spectroscopy, laboratory markers of cerebral damage, clinical and laboratory characteristics.

Results. Median age of patients was 65 years, of whom 50% were men. Three (11%) patients had severe

ARDS, 8 (29%) patients had moderate ARDS, and 17 (60%) patients had mild ARDS. Mechanical ventilation was performed in 20 (71%) patients, vasopressors were used in 14 (50%) patients. The median levels of cerebral saturation were normal and did not differ between the left (rScO₂l) and right (rScO₂r) hemispheres (68 (58–75) and 69 (59–76), respectively). The level of S-100 protein was increased (0.133 (0.061–0.318) µg/l) in contrast to the normal level of neuron-specific enolase (12.5 (8.0–16.5) µg/l). A correlation was found only between rScO₂ and hemoglobin level (rho=0.437, P=0.02) and between rScO₂ and lymphocyte count (rho=–0.449, P=0.016). An increase in S-100 negatively correlated with a decrease in Glasgow Coma Scale score (rho=–0.478, P=0.028).

Conclusion. Near-infrared spectroscopy did not reveal a decrease in rScO₂ among patients with ARDS associated with COVID-19. The S-100 protein is a useful marker for the assessment of impaired consciousness. Further study of the causes of cerebral dysfunction in patients with severe COVID-19 and methods for its early identification is warranted.

Study aim. To evaluate the efficacy of hemoadsorption in patients with severe COVID-19 on mechanical lung ventilation (MLV) and noninvasive respiratory support.

Material and methods. We retrospectively analysed longitudinal clinical and laboratory parameters of 49 patients with severe coronavirus infection who were treated in the First Intensive care unit of Grodno University Hospital from September 2020 to November 2021 and underwent hemoadsorption using the Hemo-Proteasosorb sorbent. All patients were divided into two groups: Hemo-Proteasosorb + MLV (22 patients who underwent hemoadsorption while being on MLV) and Hemo-Proteasosorb without MLV (27 patients who had hemoadsorption while receiving the low- and high-flow oxygen therapy or noninvasive lung ventilation).

Results. In the Hemo-Proteasosorb + MLV group a decrease in procalcitonin (PCT) (from 0.27 [0.12–2.08] down to 0.14 [0.05–1.77], P=0.027), C-reactive protein (CRP) (from 135.4 [10.6–303.0] down to 64.3 [1.2–147.0], P=0.003), fibrinogen (from 11.7  [4.9–19.49] to 8.2  [3.7–14.7], P=0.00004), and D-dimer (from 1432.0 [443.0–6390.0] to 1087.0 [415.0–3247.0], P=0.006) was seen on day 3 after the hemoadsorption session. The Hemo-Proteasosorb without MLV group also demonstrated a reduction in the levels of CRP (from 4 [10.6–303.0] to 64.3 [1.2–147.0], P=0.003), fibrinogen (from 11.7 [4.9–19.49] to 8.2 [3.7–14.7], P=0.00004), D-dimer (from 1432.0 [443.0–6390.0] to 1087.0 [415.0–3247.0], P=0.006) on day 3 after the hemoadsorption session. The Hemo-Proteasosorb without MLV group also showed a decrease in PCT (from 0.29 [0.14–21.25] to 0.14 [0.04–11.91], P=0.002), CRP (from 132.6 [30.7–183.0] to 28.55 [5.3–182.0], P=0.0002), fibrinogen (from 10.2 [4.41–15.5] to 6.5 [2.8–11.9], P=0.00005), D-dimer (from 1445.0 [365.0–4830.0] to 1049.0 [301.0–3302.0], P=0.005), while an increase in SpO₂/FiO₂ (from 238 [88–461] up to 320 [98–471], P=0.011) was registered. On days 5–7, positive changes in SpO₂/FiO₂ index (238 [88–461] vs 320 [96–471], P=0.0020) were observed in the Hemo-Proteasosorb without MLV group, as well as a trend toward further reduction in the levels of CRP (132.6 [30.7–183.0] vs 23.85 [2.2–200.0], P=0.0001) and fibrinogen (10.2 [4.41–15.5] to 5.11 [2.3–11.5], P=0.0017). The patients were assessed using the NEWS2 score at all the stages of the study. On days 2–3 of the study, a reduction in the mean NEWS2 score was noted in the Hemo-Proteasosorb + MLV group (8.0  [4.0–11.0] vs 6.0 [2.0–10.0], P=0.0002), whereas on days 5–7 its increase was seen vs stage 2 of the study with its values still lower than those prior to hemoadsorption (8.0 [4.0–11.0] vs 7.0 [2.0–9.0], P=0.011). On day 3 of treatment, in the Haemo-Proteasorb without MLV group we observed a decreased mean NEWS2 score (7.0 [3.0–9.0] vs 5.0 [1.0–9.0], P=0.00002), on days 5–7, this trend was still present (7.0 [3.0–9.0] vs 3.0 [1.0–8.0], P=0.00002).

Conclusion. Hemoadsorption was beneficial for patients with severe COVID-19 during both oxygen therapy and mechanical ventilation due to decreased levels of inflammatory markers, hypercoagulation, and reduced NEWS2 scores.