The aim of this review is to assess the impact of frailty on outcomes in critical illness among older and very old patients, and to summarize current approaches to their management in the intensive care unit (ICU). Materials and Methods. The review included 66 publications from PubMed, Google Scholar, the Cochrane Library, and eLIBRARY.RU. The search was conducted using the keywords «frailty», «older patient in intensive care», «treatment of elderly and senescent patients», «critical conditions in older age», «immunosenescence», «cognitive impairment», and «sarcopenia». Results . We reviewed the processes encompassed by the concept of frailty or «senile asthenia» (SA); tools for assessing SA severity; identified the factors of physiological aging that affect the course of the underlying disease in elderly and senile patients in the ICU; and highlighted the specific features of their treatment approach. Conclusion . A number of physiological aging factors significantly influence the management strategy for the studied ICU patient cohort, including changes in hormonal regulation, immunosenescence, sarcopenia, and altered cognitive function. Comorbidities, medication use patterns, and mobility status should also be taken into account. Frailty leads to higher mortality among older and very old ICU patients compared with patients without SA. For management of frail patients a unified approach is recommended combining a multidisciplinary team and family caregivers to maintain patient’s motivation and adherence to the prescribed treatment.
Conventional respiratory indices have limited accuracy for predicting weaning outcomes in critically ill surgical patients. Diaphragmatic ultrasound has emerged as a promising bedside tool for evaluating respiratory muscle function during liberation from mechanical ventilation. Aim . To evaluate the predictive value of ultrasound-derived diaphragmatic function indices for weaning outcomes in surgical intensive care unit (ICU) patients and to compare their performance with conventional respiratory parameters. Methods . This prospective observational study included mechanically ventilated adult patients undergoing spontaneous breathing trials (SBT) in a surgical ICU. Diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were assessed by bedside ultrasound immediately before SBT initiation. Diaphragmatic rapid shallow breathing indices based on DE (DE-RSBI) and DTF (DTF-RSBI) were also calculated. Conventional respiratory parameters, including respiratory rate (RR), rapid shallow breathing index (RSBI), and PaO₂/FiO₂ ratio (P/F), were recorded simultaneously. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis and DeLong comparison tests. Multivariable logistic regression was performed to identify independent predictors of successful weaning. Results . DE demonstrated the highest predictive performance for successful weaning, with an AUC of 0.793, followed by DTF (0.740) and DTF-RSBI (0.711). In contrast, RR and conventional RSBI showed limited discriminative ability, with AUC values close to 0.5. DeLong analysis demonstrated significantly greater AUC values for both DE and DTF compared with the P/F ratio and RSBI. The optimal cutoff values were >1.26 cm for DE and >16.3% for DTF. In multivariable analysis, lower APACHE II score, higher P/F ratio, and greater DE remained independently associated with successful weaning. Each 1 mm increase in DE was associated with a 66.6% increase in the odds of successful weaning (adjusted OR 1.67, 95% CI 1.31–2.12; p < 0.001). Conclusion . Ultrasound-derived diaphragmatic indices, particularly diaphragmatic excursion, demonstrated superior predictive performance compared with conventional respiratory parameters and may provide valuable adjunctive information during weaning assessment in surgical ICU patients.
Objective . To substantiate the concept of perioperative infectious risk by analyzing current approaches to classifying complications, methods for predicting them, and the key factors influencing surgical outcomes. Materials and Methods. We conducted an analytical review based on expert judgement and a systematic search of publications from the preceding 10 years in PubMed and Lens.org. The analysis included data on the epidemiology of infectious complications, classification systems (CDC, Clavien-Dindo, Accordion), prognostic scores (ASA, SOFA, ACS-NSQIP, SORT), laboratory markers (CRP, IL-6, procalcitonin, neutrophil-tolymphocyte ratio), and machine learning models (PERISCOPE AI, Random Forest, SVM, ensemble methods). Results . The risk of infectious complications was shown to be determined by the cumulative effect of modifiable and nonmodifiable factors related to both the patient and the healthcare facility. Laboratory markers demonstrated high prognostic value: IL-6 levels above 432 pg/mL and CRP 150 mg/L on postoperative day 3 were statistically significantly associated with adverse outcomes. Advanced prognostic tools provided high accuracy: the AUROC for ACS-NSQIP reached 0.80, and for PERISCOPE AI, 0.82–0.91. The use of scoring systems and machine learning made it possible to identify high-risk patients before clinical symptoms appeared. Conclusion . Risk of perioperative infections is multifactorial and requires an integrated approach to risk stratification, incorporating clinical data, risk assessment scales, laboratory markers, and AI models. The use of structured prognostic tools enables early identification of complications, optimize prevention, and reduce mortality.
Aspiration-related complications remain one of the most significant causes of early postoperative pneumonia, and microaspiration often occurs without symptoms and is not recognized at an early stage. The sensitivity of chest X-ray and CT (computed tomography) for the earliest changes is limited, creating a diagnostic «gap» in which lung ultrasound (LUS) may play a key role. Patient case presentation . A 62-year-old patient with class III obesity (body mass index [BMI] 46.5 kg/m²), ASA class III, and a significant oncologic history experienced a prolonged (8-hour) neurosurgical procedure in the prone position. In the early postoperative period, after reintubation, she developed severe hypoxemia in the absence of specific changes on chest radiography or chest CT, while laboratory inflammatory markers were consistent with a nonspecific postoperative response. Lung ultrasound revealed a pattern atypical for atelectasis: multiple small (up to 1.5 cm²) subpleural consolidations scattered predominantly in the right lung, including nondependent areas, in the environment of preserved aeration of the surrounding tissue and a low lung ultrasound score. Diagnostic assessment and interventions. The initial impression of atelectasis was revised in favor of early aspiration pneumonia, despite a «negative» CT scan. On serial ultrasound, there was a rapid increase in the number and size of subpleural consolidations, a rise in the total ultrasound score from 7 to 17, and the appearance of a right-sided pleural effusion, which prompted repeat CT and escalation of respiratory and antibiotic therapy. The repeat CT confirmed multiple areas of consolidation and hydrothorax; aspiration pneumonia was ultimately confirmed by bronchoscopy and bronchoalveolar lavage culture, which grew polymicrobial oral flora. Conclusion . In the presented case, the specific lung ultrasound pattern and its progression preceded radiographic changes and made it possible to promptly suspect postoperative microaspiration as the cause of severe respiratory failure. Routine use of standardized lung ultrasound screening in high-risk patients may become a promising tool for the very early diagnosis of microaspiration, expediting the initiation of antimicrobial therapy.
Presence and decompensation of comorbid conditions can directly affect levels of wakefulness and cosciousness in patients with chronic disorders of consciousness (DoC). Identifying and thorough assessment of comorbid conditions and concurrent diseases is a decisive step in diagnosing signs of consciousness, monitoring changes over time, and making prognoses in patients with DoC. Objective . To assess the incidence and severity of comorbid conditions in patients with chronic DoC using the Comorbidities Coma Scale (CoCoS). Materials and Methods. At the Russian Center of Neurology and Neurosciences, we conducted a retrospective review of the medical records of 52 patients with chronic DoC of various etiologies (31 men, 21 women; traumatic etiology, n = 18; non-traumatic etiology, n = 34). To determine the type of DoC, all patients were independently assessed twice by two investigators using the Coma Recovery Scale–Revised (CRS-R). To account for the severity and nature of brain injury, we analyzed etiology (traumatic/non-traumatic), time since injury, and the baseline CRS-R score as an integrated measure of neurological deficit. Comorbid status was assessed using the CoCoS scale. Results . Different types of stomas as life-sustaining medical devices (tracheostomy, gastrostomy, and suprapubic cystostomy) in 100%, and joint disorders in 98% were identified as predominant comorbid conditions in patients with chronic DoC. Less common comorbid conditions included urinary tract infections (71.15%), kidney diseases (57.69%), pressure ulcers (53.85%), infectious respiratory diseases (46.15%), malnutrition (38.46%), anemia (30.77%), fractures of bones and skull (28.85%), hydrocephalus (13.46%), and paroxysmal autonomic activity (13.25%). Сomorbidity of moderate severity was identified in one patient (1.96%); all others were classified as mild. When stratified by etiology, no significant differences in the total CoCoS score were found between the traumatic and non-traumatic groups (p > 0.05). No correlation was observed between CRS-R and CoCoS scores in the overall sample (p = 0.051, R = 0.227); similar results were obtained in the subgroup analyses (traumatic: p = 0.43, R = 0.19; non-traumatic: p = 0.28, R = 0.21). Conclusion . The analysis revealed a high prevalence of medical devices used to support vital functions and prevent joint contractures, reflecting apparent dependence of patients with chronic DoC on technical support and care. In most cases, the comorbidity burden was mild, indicating a relatively compensated somatic status. The absence of a significant correlation between the level of consciousness and comorbidity burden suggests that, in cases of mild comorbidity, somatic disorders are not the determining factor masking conscious activity. These findings underscore the need for an interdisciplinary approach to the management of such patients and the mandatory quantitative assessment of structural brain damage, otherwise it is impossible to distinguish the contribution of primary brain injury from that of concomitant pathology into development of chronic DoC.
Objective of the study : to investigate the neuroprotective potential of hypothermia under conditions of hypoxia and interleukin-6, which simulates systemic inflammation in vitro. Materials and methods. We established an in vitro model of a neurovascular unit (NVU) consisting of neurons, astrocytes, and endothelial cells. The NVU was cultured under anoxic conditions with the addition of serum containing either the maximum or minimum concentration of interleukin-6 (IL-6). Serum samples were obtained from a collection of serum samples from 78 pediatric patients aged 1 month to 6.5 years (13 [9–23] months) with body weights ranging from 3.3 to 21.5 kg (8.7 [6.9–11.0] kg), who underwent surgical correction of congenital septal heart defects under cardiopulmonary bypass. An intact NVU model was used as the control group. Cells were incubated for 15 minutes at different temperatures (20, 24, 28, and 37°C), followed by immunocytochemical assessment of the following NVU damage markers expression: claudin-5, occludin-1, and receptors for interleukin-1 (IL-1) and IL-6. Results . We found that, during incubation under anoxic conditions, a decrease in the fluorescence intensity of claudin-5 occurred at all temperature conditions, and hypothermia had no protective effect. For occludin-1, a temperature of 24°C counteracted the effect of anoxia only when exposed to serum with the minimum IL-6 concentration (p = 0.442). Exposure to serum with the maximum IL-6 concentration resulted in a significant decrease in the fluorescence intensity of this marker compared to the control group (p = 0.092). Hypothermia at 20°C did not restore the expression levels of IL-1 receptors to those of the control group; however, it had a protective effect on the expression of IL-6 receptors and neutralized the effects of anoxia (p = 0.044), but only in the absence of serum. Conclusion . Exposure to serum containing varying concentrations of IL-6 results in a more pronounced effect on the expression of NVU damage markers than hypoxia. Hypothermia within the temperature range studied generally did not provide the expected protective effect: the expression of claudin-5, IL-1 and IL-6 receptors was not comparable to that of the control group, even without the addition of serum.
Maintaining oral hygiene in patients receiving respiratory support is critically important for preventing healthcare-associated infections. The aim of the study was to evaluate the clinical effect of octenidine dihydrochloride mouthwash added to local oral hygiene care protocol for patients receiving respiratory support. Materials and Methods. This prospective cohort study included 299 patients receiving respiratory support in the ICU setting during 2023–2026 years; after propensity score matching (PSM), 208 (104 pairs) patients were included in the final analysis. Oral hygiene protocol included twice-daily tooth brushing and oral rinsing at a frequency determined by the Intensive Care Oral Care Frequency Assessment Scale (ICOCFAS). Octenidine dihydrochloride 0.1% solution was used as the rinse in the study group, and distilled water — in the control group. A dentist assessed oral health using the Challacombe Scale of Clinical Oral Dryness (CSCOD), Plaque Index (PI), and Modified Gingival Index (MGI) at predefined time points. Results . During days 1–3, the study group showed a decrease in the median MGI and PI values compared with the control group (p < 0.001). By day 7, the favorable changes in the MGI and PI in the study group had boosted, and between-group differences remained significant (p < 0.001). The effect of the intervention did not depend on the clinical outcome: the «group × outcome» interaction was not statistically significant for ∆MGI 1–3 and ∆MGI 1–7 (p = 0.269 and p = 0.141, respectively). Changes in xerostomia (CSCOD) did not differ significantly between the groups (p = 0.119). Conclusion . The use of 0.1% octenidine dihydrochloride mouthwash as a part of the oral hygiene protocol in patients receiving respiratory support results in rapid resolution of gingival inflammation (MGI) and effective removal of dental plaque (PI). However, the persisting rigidness of xerostomia (CSCOD) regardless of the hygiene care protocol warrants searching for additional correction strategies.
Objective: to compare the nutritional and metabolic effects of two amino acids-containing solutions, differed in amino acid profiles and sorbitol presence, when employed as a part of standardized combined post-operative nutritional support in patients undergoing surgery for abdominal cancer.Materials and Methods. A prospective randomized study was conducted in two specialized hospitals. The study included 120 nutritionally stable patients aged 18–80 with stage I–III colorectal tumors and ASA class II–III anesthetic risk (mean BMI 25.3–27.6 kg/m²), who underwent elective abdominal surgeries and required parenteral administration of protein-carbohydrate nutrition solution (PCNS) for at least 5 days. Patients were randomly assigned into two groups for receiving PCNS formulations Amiparcenin or Aminoven formulated at 10-percent concentration (60 patients, each group). Both regimens involved administering an amino acid solution at 10 ml/kg/day in combination with a 10% dextrose solution at 10 ml/kg/day, alongside with early enteral feeding. The amino acid and nutritional profiles were assessed before initiation of nutritional support (T0), on the 2nd (T1), and 5th (T2) postoperative days. Key indicators included the sum of branched-chain amino acids (BCAA_sum), the sum of aromatic amino acids (AAA_sum), the ratio of BCAA/AAA, the integral indicator of amino acids in the urea cycle (UreaCycle_sum), and index ratios of ornithine to citrulline, arginine to ornithine, and arginine to citrulline. Additionally, total protein, albumin, nitrogen balance, bioimpedance indicator of active cellular mass (BIA ACM), creatinine, liver function markers, and electrolyte profiles were analyzed. To evaluate clinical equivalence, a two one-sided tests (TOST) analysis was employed with pre-defined limits of clinically acceptable difference (∆) for each parameter.Results. By day 5, both groups showed statistically significant changes in total protein and albumin levels, reflecting the transition from the early catabolic phase and the impact of nutritional support; no intergroup differences were observed for these parameters, and the TOST analysis confirmed their equivalence within the predefined limits of ∆. The branched-chain amino acids (BCAA_sum) level increased from T0 to T1 and then stabilized at T2 in both groups; the factors «group» and the «group×period» interaction were not significant (p = 0.285 and p = 0.362, respectively), however, the equivalence of absolute BCAA_sum values at T2 with a narrow ∆ = 10 µmol/L was not confirmed (p-TOST> 0.05). For AAA_sum, differences were documented based on the «group» factor (p = 0.035) and the interaction «period×group» (p = 0.0099), with alignment of absolute values at T2. The ratio of BCAA/AAA and the index indicators of the urea cycle (Orn/Cit, Arg/Orn, Arg/Cit) remained stable, with no intergroup differences, and met the equivalence criteria throughout all observation periods. According to bio-impedance analysis, the Amiparcenin group showed a more significant increase in active cell mass (p by Friedman = 0.00001; intergroup p at T1 = 0.0048, at T2 = 0.00014), while the Aminoven group did not show significant dynamics; moreover, the TOST analysis with a wide ∆ showed formal equivalence in BIA ACM. Creatinine, urea, transaminases, and electrolyte levels remained comparable between the groups and were within clinically acceptable ranges; equivalence for these parameters was confirmed.Conclusion. In the early postoperative period, Amiparcenin and Aminoven 10% solutions provide comparable amino acid and nutritional supply, and biochemical effects as a part of standardized combined nutritional support in patients with abdominal cancers. The studied regimens met equivalence criteria for most essential amino acid indicators (including BCAA/AAA), markers of inflammation, protein metabolism, liver and kidney function, and electrolyte balance. The differences found in absolute values of BCAA_sum, AAA_sum, UreaCycle_sum, and malondialdehyde (MDA) do not translate into clinically significant shifts during the first 5 days post-surgery.
Traumatic brain injury (TBI) remains one of the leading causes of disability, and current approaches to neuroprotection have limited efficacy. The inert gas krypton is considered a promising neuroprotective agent; however, data on its effects in TBI and on components of the neurovascular unit (NVU) are limited.Objective. To evaluate the neuroprotective potential of krypton in rats with traumatic brain injury (TBI) in vivo and in NVU cell cultures subjected to oxygen-glucose deprivation (OGD) in vitro.Materials and Methods. The study included 48 Wistar rats divided into 3 groups: SO (sham operated), TBI (N₂/O₂ 70/30 %), and TBI + iKr (Kr/O₂ 70/30 %). A model of controlled open brain contusion injury was used. On day 14, we assessed neurological deficits (limb placing test, LPT), the extent of brain injury (T2-weighted MRI slices), morphological changes (hematoxylin-eosin staining), and the expression of GFAP and Caspase-3 (fluorescent immunohistochemistry, IHC). IL-1β, IL-6, and TNF-α mRNA levels in the injury zone were determined by PCR. In vitro studies investigated the effect of krypton preconditioning (Kr/O₂ 79/21 %, 24 h) on the survival of neuronal (SH-SY5Y), glial (C6), and vascular endothelial (Ea.Hy926) cells during OGD (4–6 h).Results. A significant neurological deficit of 2.5 (2; 5.25) scores was determined by the TBI modeling accompanied by a large volume of brain damage of 33 (28; 39) mm³. Krypton inhalation led to a reduction in the lesion volume to 18 (15; 26) mm³ and accelerated the recovery of sensorimotor functions: starting on day 7, the indicators in the TBI + iKr group were statistically significantly better than in the TBI group, and by day 14, they approached the values of the SO (control) group. In the TBI + iKr group, IL-1β and TNF-α levels in the affected hemisphere were nearly 50% lower than in the TBI group, while remaining higher than in the SO group; changes in IL-6 levels were insignificant. Histologically, less significant cerebral edema, spongiosis, and neuronal degeneration were observed in the TBI + iKr group. Immunohistochemical analysis revealed a trend toward more pronounced reactive gliosis (GFAP) with no differences in Caspase-3. In vitro, krypton preconditioning under OGD conditions did not improve the survival of neuronal, glial, and endothelial cells.Conclusion. Krypton exerted significant neuroprotective effect in experimental TBI in rats, reducing neurological deficits, the extent of structural damage, and the severity of the inflammatory response. The absence of a protective effect in NVU cellular models underscores the essential role of systemic and intercellular interactions in the neuroprotective action of krypton and warrants further research into its mechanisms of action and dosing optimization.
Modulation of sphingosine-1-phosphate receptors exerts various neuroprotective effects under conditions of cerebral ischemia. In this study, we investigated the relationship between the lipid composition of brain tissue, lipid signaling, and the content of the proinflammatory cytokine TNFα, as well as the expression of its receptor, TNFR1. Objective. In a rat model of acute cerebral ischemia, to evaluate the effects of FTY720 on the lipid composition of brain tissue, ceramide concentration, and the expression of key enzymes involved in its synthesis, as well as on the contents of TNF-α and its receptor TNFR1.Materials and Methods. The study was conducted on 37 male white non-linear rats weighing 180–230 g. Acute cerebral ischemia was induced by a combined procedure involving irreversible ligation of the left common carotid artery and reversible ligation of the right common carotid artery. The animals were divided into three groups: sham-operated, rats with acute cerebral ischemia, and rats with ischemia following prior administration of FTY720 (fingolimod). On the third day of observation, neurological deficits in surviving animals were assessed using the Garcia scale. The sphingolipid and phospholipid composition of brain tissue was examined using thin-layer chromatography. Ceramide concentration, the expression of enzymes involved in its biosynthetic, TNFα, and TNFR1 concentrations were evaluated using immunofluorescent microscopy.Results. Pretreatment with fingolimod was associated with better survival rates: 31% in the FTY720 group vs. 20% in the Ischemia group (p = 0.043). Functional impairments on the Garcia scale were significantly less severe in the FTY720 group than in the Ischemia group: 14 [13.5; 15] vs. 11 [10; 12.5] scores (Me [Q1; Q3]), p < 0.01). FTY720 group also demonstrated a decrease in ceramide concentration in the brain tissue compared to the Ischemia group (p = 0.0005), along with downregulated expression of aSMase (p = 0.0012), nSMase (p = 0.0003) enzymes involved in its synthesis, of SPT (p = 0.0002), and CerS (p = 0.0001), a decrease in pro-inflammatory cytokine TNFα (p = 0.0003) concentration and normalized expression of its receptor TNFR1.Conclusion. Preservation of phospholipid composition and reduction in the excessive production of ceramide and pro-inflammatory cytokines in the brain tissue are associated with less severe neurological deficits and improved survival rates in rats during the acute phase of cerebral ischemia.
COVID-19 remains one of the most significant causes of hospital admissions and deaths, frequently associated with septic complications. Reliable and simple prognostic tools are required to identify patients at high risk of developing sepsis and death early on.Aim of the study. To evaluate the prognostic ability of the REMS, NEWS, NEWS2, qSOFA, and SIRS criteria in predicting sepsis, septic shock, and mortality in patients with COVID-19.Materials and methods. A retrospective study was performed on 870 patients with confirmed COVID-19 who were hospitalized in anesthesiology and intensive care units. REMS, NEWS, NEWS2, qSOFA, and SIRS scores were calculated for each patient upon admission. The predictive ability of the scales was evaluated using ROC analysis, temporal associations were assessed using the Cox proportional hazards model, and the cumulative risk of outcome was assessed using the Kaplan–Meier method.Results. The REMS scale demonstrated satisfactory predictive ability for mortality and septic shock (AUC = 0.780 and 0.724, respectively) and unsatisfactory for sepsis (AUC = 0.677), p 0.0001. The NEWS, NEWS2, qSOFA, and SIRS scales showed unsatisfactory results for all outcomes. The Kaplan–Meier analysis showed that patients with high REMS scores developed sepsis or septic shock earlier and had shorter survival (p 0.0001). The Cox model identified REMS as the scale with the highest risk ratio (RR 1.215; 95% CI 1.178–1.254) and concordance index (C = 0.656).Conclusion. The REMS, NEWS, NEWS2, qSOFA, and SIRS rapid scales have a statistically significant prognostic value, but only the REMS provides a satisfactory accuracy in predicting septic shock and death in patients with COVID-19. The study was limited by its single-center and retrospective design.
Passive euthanasia and the withdrawal of life-sustaining treatment (LST) in modern Russian practice are normatively indistinguishable, leading to ethical, legal, and clinical-practical conflicts for intensive care physicians and increasing the moral distress among healthcare staff.The purpose of this research is to clarify the distinctions between active and passive euthanasia and the cessation of futile life-sustaining treatment, as well as to demonstrate why these distinctions are not taken into account in Russian legislation and professional discourse.Materials and Methods. The study included foreign and Russian bioethical and legal texts. A qualitative analysis of the historiography was conducted, supplemented by a structural-thematic analysis of the philosophical dilemmas associated with the end of life.Results. The analysis identified three key lines of demarcation: 1) between active killing and allowing death through the refusal of intervention; 2) between passive euthanasia and the ethical cessation of LST; 3) between the physician's intention to hasten death and the intention to remove medical obstacles to the natural process of dying while being willing to continue assistance if the patient survives. It was shown that the Russian legal norm, which effectively criminalizes any forms of cessation of medical treatment, has developed against the backdrop of insufficient reflection on these distinctions and leads to a discrepancy between normative language and actual clinical practice, where doctors are forced to document treatment provision but often omit or alter it in practice.Conclusion. The integration into the Russian context of more nuanced criteria for assessing intention, causality, and futility of treatment, developed in Western bioethics, combined with consideration of local sociocultural contexts and religious traditions, is a necessary condition for developing a coherent end-of-life regulation model that reduces moral distress for physicians and enhances patient trust in medical decisions.
Thermal injuries caused by external cold exposure remain one of the most significant multidisciplinary challenges in critical care medicine. In cases of refractory circulatory arrest resulting from hypothermia, the use of circulatory support methods, particularly the veno-arterial extracorporeal membrane oxygenation (VA ECMO) system, becomes specially grounded and desirable.Objective. To demonstrate the successful use of veno-arterial ECMO in a patient with severe accidental hypothermia complicated by refractory circulatory arrest during the prehospital phase.Materials and Methods. We present the clinical case of a 42-year-old patient with severe generalized hypothermia (temperature 20.0°C), marked hemodynamic instability, and subsequent development of refractory ventricular fibrillation. Given the ineffectiveness of standard resuscitation measures during the prehospital phase, we initiated VA ECMO followed by extracorporeal rewarming and comprehensive intensive care.Results. Following initiation of VA ECMO and controlled warming, restoration of cardiac rhythm and cardiorespiratory function was achieved. Weaning from VA ECMO was performed on the third day, and from respiratory support within the first two days of the hospital stay. On the 22nd day, the patient was discharged in a stable somatic condition without significant neurological deficits. Conclusion. Early prehospital initiation of VA ECMO as a part of comprehensive intensive care may represent an effective treatment option for severe accidental hypothermia complicated by refractory circulatory arrest.
The aim of the study. To compare the effectiveness of thrombolytic therapy in patients with ischemic stroke with forteplase and alteplase in clinical practice. Materials and methods. A single-center retrospective cohort study was conducted using data from the reperfusion interventions registry at the Arkhangelsk regional vascular center. The primary endpoint was patients’ functional recovery at discharge from the hospital. The incidence of type 2 intracranial hemorrhages according to the Heidelberg bleeding classification, mortality, and the duration of hospital stay were analyzed as the secondary endpoints. Descriptive statistics were used. Simple and multivariate multiple linear and logistic regression models were constructed to assess the relationship of forteplase use with functional recovery and length of hospital stay. Results. The study involved 213 patients with the mean age of 68 (60; 76) years, including 111 (52.1%) men. Forteplase was used in 91 (42.7%) patients. Modified Rankin scale scores of 0–2 were documented in 52 (57.14%) and 51 (41.8%) patients in the forteplase and alteplase groups, respectively, p = 0.019. After correction for potential confounders, no relationship was found between achieving good functional recovery and the use of forteplase: adjusted odds ratio was 1.04 [95% CI 0.54–2.01], p = 0.91. The incidence of type 2 parenchymal hemorrhages was 3.3% in the forteplase group vs 0.8% in the alteplase group, p = 0.315, and the mortality rates were 6.59% vs 11.48%, respectively, p = 0.247. The use of forteplase did not affect the length of hospital stay in a multivariate analysis: B = –0.54 [95% CI –3.74–2.66], p = 0.741. Conclusion. Thrombolysis with forteplase is an effective and safe method of treatment in the acute period of ischemic stroke. Rates of achieving good functional recovery, incidence of intracranial hemorrhage, and length of hospital stay were comparable in groups treated with forteplase and alteplase after correction for significant confounders.
Objective. The aim of this review is to summarize the pathological mechanisms associated with the toxicity of phenothiazines in overdose. Materials and methods. A database search was conducted on PubMed, Google Scholar and eLibrary were used to identify original research articles, clinical reports, review articles, editorials, commentaries, and brief communications. Additional sources not identified through the search of these databases were analyzed after reviewing the reference lists of the selected articles. Articles were selected based on the relevance of the title and abstract to the purpose of this review. Results. This review analyzes the mechanisms of action of phenothiazines in the context of their long-term clinical use and in overdose, as well as the mechanisms of action of proposed potential areas of application of phenothiazines. Clinical manifestations of phenothiazine poisoning are predominantly characterized by antagonism of dopamine D₁–D₄ receptors, histamine H₁ receptors, α₁–α₂ α-adrenergic receptors and muscarinic acetylcholine receptors M₁–M₂. In addition, phenothiazines are able to increase the permeability of the blood-brain barrier through apoptosis, increase global methylation, effectively enhance chemotherapy of some tumors and provide neuroprotection by reducing GFAP production (PKC-δ/NOX/MnSOD pathway). Conclusions. Given the potential for new applications of phenothiazines, further study of the effects of phenothiazines on the central nervous system in overdose, with a focus on repeat overdose episodes, is important at the morphological level to identify the underlying morphological substrate. Further study of the mechanisms associated with phenothiazine use is needed to develop more effective therapeutic strategies to improve patient outcome, not only in psychiatry but also in other disciplines.
Necrotizing pulmonary infections (NPI) emerge as severe complications of community-acquired pneumonia (CAP), and immune system cells are involved in their pathogenesis. Highly informative biomarkers are required to determine high-risk patients to prevent life-threatening complications of NPI. Previously, we have shown that variations in immune cell numbers can be employed as prognostic biomarkers in NPI. We proposed that genetic variants encoding receptors detected on the surface of neutrophils, monocytes, and macrophages migrating to lung tissues during inflammation may predict the unfavorable course of NPI. One of these candidate genes could be the OLR1 gene, which encodes LOX-1 receptors that bind oxidized low-density lipoproteins oxLDL on the surface of immune and other cells. The aim of the study. To find out the OLR1 gene single nucleotide polymorphism contribution to the clinical course of NPIs (pleural empyema) and variability in the number of immune cells in patients with post-CAP NPI. Materials and methods. The study included patients of the Moscow City Hospital (aged 18–87 years, n = 216) with NPIs developed after CAP. Categorical data were described by indicating absolute values, which were compared using four-field contingency tables and the χ² test with Yates' correction for sample continuity and Fisher's exact test (FET). Results. NPIs were the most common complication of CAP. In patients with NPI and the minor allele G OLR1 rs11053646, which encodes the LOX-1 167N variant, the course of the disease was less likely to be complicated by a fistula (p = 0.0015; exact Fisher test (EFT); OR = 3.55, 95% CI: 1.55–8.13; RR = 2.37, 95% CI: 1.24–4.50; n = 216). However, the significance of this association was influenced by previous COVID-19 documented in patient's medical history based on PCR test results. For patients who had been infected with COVID-19, this association persisted (p = 0.0058; EFT; OR = 7.27, 95% CI: 1.54–34.3; RR = 4.28, 95% CI:1.31–16.23; n = 81), whereas in patients with no PCR test confirmed COVID-19, this association was not statistically significant (p = 0.1065, EFT, n = 135). Thus, only post-COVID-10 carriers of the minor allele G OLR1 rs11053646 were protected from a severe course of NPIs complicated with fistula development. A study in a limited subgroup of patients showed a trend for a fistula development to associate with increased OxLDL plasma concentration of more than 100 ng/ml (p = 0.045; n = 19). Conclusion. Post-COVID-19 сarriers of major OLR1 rs11053646 CC genotype exhibit increased risk for the unfavorable course of NPI (pleural empyema) complicated with fistula. The presence of alternative G allele of OLR1 rs11053646 in patient genotype associates with favorable course of NPIs.
Aim of the study. To study the effect of helium-oxygen mixture on predictors of postoperative pulmonary complications in cancer patients with chronic obstructive pulmonary disease (COPD). Materials and methods. A single-center prospective clinical study with historical control included 208 patients, among them 104 patients received helium-oxygen mixture inhalations (70% helium and 30% oxygen) in the preoperative period (He group) and 104 patients were the historical control group (Ctrl group). Given the risk of bias associated with confounders, we conducted a one-to-one matching analysis based on pseudorandomization to adjust for the unbalanced baseline characteristics of the groups. We used logistic regression to develop the pseudo-randomization estimates. We used the nearest neighbor matching 1:1 with a caliper of 0.1 to achieve better similarity among matched pairs. After pseudo-randomization, we included 87 patients in each group, ensuring adequate balance across all covariates. A multivariate logistic regression analysis was performed to identify factors associated with the risk of postoperative pulmonary complications. Results. In the He group, there was a statistically significant improvement in a number of functional parameters compared to the Ctrl group. FEV1, FVC, mod. Tiffno index values in the He group increased significantly ( р = 0,0009; р = 0,0115; р = 014, respectively), gas exchange parameters (PaO₂, PaCO₂, pH, SpO₂) improved ( р = 0.0006; р = 0.004; р = 0.0097; р = 0.001, respectively). Hypoxia tolerance tests also showed significantly greater values in the He group (Stange test, р = 0.016; Sabrazes (Gench) post-exhalation breath-holding test, р = 0.024). Analysis of postoperative parameters showed significant advantage of the He group over the control group in terms of critically important clinical outcomes. At the final stage of stepwise selection, three independent predictors were included in the risk model for postoperative pulmonary complications: SpO₂, the breath-holding test, and the duration of postoperative mechanical ventilation. The quality of the model was high, with a correctly classified case rate of 92.2%, a Hosmer–Lemeshow goodness-of-fit statistic of р = 0.933, and a total model significance of p <0.000. Conclusion. We performed the first clinical study that showed the importance of preoperative preparation using a helium-oxygen mixture in cancer patients with chronic obstructive pulmonary disease and identified predictors of pulmonary complications after thoracic surgery.
Cardiac arrest remains one of the leading causes of death worldwide. Even with successful resuscitation, patient outcomes are often poor due to post-resuscitation syndrome, which includes cerebral hypoxia, myocardial dysfunction, microcirculatory disorders, coagulation abnormalities, and systemic inflammation. Argon, an inert noble gas, has neuroprotective and cardioprotective properties, making it a promising candidate for early post-resuscitation therapy. The aim of the study was to evaluate the organoprotective properties of an argon-oxygen mixture when inhaled in the early post-resuscitation period for 2 hours after asphyxial circulatory arrest in rats. Materials and methods. A prospective randomized controlled experimental study was conducted on male Wistar rats ( n = 43) using an asphyxial circulatory arrest model. The animals were divided into three groups: sham-operated (SO, n = 12), circulatory arrest with resuscitation (CAR, n = 13), and circulatory arrest with resuscitation and two-hour inhalation of a 70%/30% argon-oxygen mixture in the post-resuscitation period (CAR + iAr, n = 18). Hemodynamics, microcirculation, blood gas composition, coagulation (low-frequency piezothromboelastography), neurological status, and biomarkers of organ damage were evaluated. Beclin-1 and caspase-3 expression was analyzed immunohistochemically. Results. Argon inhalation did not have a significant effect on systemic hemodynamics, but it was accompanied by improved tissue oxygenation and metabolism: a decrease in blood lactate ( p = 0.043), an increase in the p/F oxygenation index ( p = 0.001), and stabilization of microcirculation variability (Kv, σ). Statistically significantly increased expression of the Beclin-1 protein in the lungs, myocardium, and hippocampus reflected activation of autophagy. In the CAR + iAr group, there was an improvement in neurological status compared to CAR ( p = 0.02), a decrease in serum neuron-specific enolase ( p = 0.011), and a decrease in the number of caspase-3-positive cells ( p = 0.011), indicating a reduction in apoptosis and damage to the nervous tissue. Argon had a moderate anticoagulant and antiplatelet effect (coagulation drive intensity — CDI, and maximum clot firmness-MCF reduction), while maintaining normal processes of clot retraction and lysis. The electrophysiological parameters of the heart (QRS, QTc) varied within the physiological range, indicating the absence of pro-arrhythmic effects in argon. Conclusion. Early inhalation of argon-oxygen mixture after circulatory arrest has a multisystem protective effect: improves oxygenation and microcirculation, promotes activation of autophagy mechanisms in vital organs, reduces the severity of neuronal damage, and modulates blood clotting in some measure. Argon can be considered a promising therapeutic agent for post-resuscitation syndrome. Further clarification is needed to assess argon’s molecular mechanisms of action and long-term outcomes after its use.
Bronchial asthma remains one of the most common chronic respiratory diseases characterized by episodes of severe airway obstruction. In cases of refractory status asthmaticus complicated by critical hypercapnia and decompensated respiratory acidosis, conventional methods of respiratory support, including mechanical ventilation, are often insufficient. The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) is considered a promising method for stabilizing gas exchange and minimizing ventilator-induced damage. Objective: to share clinical experience in successful use of VV-ECMO in patients with refractory status asthmaticus complicated by severe hypercapnia and decompensated respiratory acidosis, resistant to correction by conventional respiratory support and lung-protective ventilation. Materials and methods. VV-ECMO was used as an extracorporeal alternative for lung gas exchange function in two female-patients with refractory status asthmaticus complicated by severe hypercapnia and decompensated respiratory acidosis. Results. VV-ECMO reduced the risk of developing ventilator-induced lung injury (VILI) allowing maintenance of lung-protective mechanical ventilation, and therefore, enabling accelerated respiratory rehabilitation. In both presented cases, early initiation of VV-ECMO improved gas exchange parameters and mitigated ventilator-associated complications, thereby confirming the relevance of its’ use in patients with severe exacerbations of bronchial asthma complicated by uncontrolled hypercapnia. Conclusion. Presented experience highlights the importance and feasibility of further VV-ECMO exploration as an intensified approach for management of severe BA exacerbations accompanied by critical hypercapnia and respiratory failure. This might require larger-scale randomized trials to identify optimal indications and protocols for VV-ECMO use.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a viable modality for supporting circulation in patients with severe ventricular arrhythmia and high risk of acute hemodynamic instability during radiofrequency ablation (RFA) procedure. Objectives: ( a) To demonstrate the feasibility and effectiveness of VA-ECMO as a mechanical circulatory support during radiofrequency ablation in patients with sustained-recurrent ventricular tachyarrhythmia, which allows to achieve control of arrhythmia and improves survival in this high-risk cohort; (b) to determine the patient-selection criteria for VA-ECMO. Case reports. We analyzed 5 cases of sustained -recurrent ventricular tachycardia in patients (all men, mean age 59 years) who were hospitalized in the intensive care unit. All patients had multiple episodes of ventricular tachycardia despite continuous conservative therapy. Four patients underwent radiofrequency ablation of the arrhythmogenic substrate with VA-ECMO support, resulting in complete elimination of tachyarrhythmia. The patients were successfully weaned from ECMO and subsequently discharged. In the fifth patient with left ventricular ejection fraction of 17–20% due to dilated cardiomyopathy the invasive procedure was excluded due to the terminal stage of heart failure, extremely high perioperative risk, and anticipated RFA failure. After patient's condition stabilized, he was referred to a tertiary center for orthotopic heart transplantation (OHT). Results. All patients who underwent ECMO-assisted RFA achieved complete control of arrhythmia without recurrence during the entire follow-up period. Successful weaning from ECMO and discharge from the hospital confirmed the effectiveness of this strategy. One case demonstrated the limitations of the method, i. e. in a patient with terminal myocardial damage RFA was considered palliative. Conclusion. ECMO support during ablation procedure allows the use of RFA in patients with severe structural myocardial pathology and high risk of hemodynamic instability. Scrupulous selection of patients with localized arrhythmogenic substrate and the potential for restoring myocardial function after RFA are the key components for procedural success.
