Introduction: The reliability of statistical analysis and its results is becoming a focal point in scientific discourse, overshadowing concerns about statistical significance. Systematic reviews and meta-analyses are characterized by a range of serious statistical and methodological limitations, including insufficient statistical power, clinical and statistical heterogeneity, systematic errors, potential low quality of included examinations, limited data availability, and publication bias. In this context, “Trial Sequential Analysis” (TSA) emerges as a promising methodological tool used in combination with meta-analyses to enhance the precision and robustness of scientific conclusions. Objective: The study is aimed to demonstrating potential scenarios for the using TSA and its role in improving the reliability of scientific conclusions through meta-analyses published in Russian journals on anesthesiology-resuscitation, as well as the authors’ own meta-analyses.Methods: This study is a systematic review without a detailed description of the case studies. The search for meta-analyses was conducted using the keywords “meta-analysis”, “mortality”, “delirium”, “sedation”. Two researchers independently reviewed the titles and abstracts of the selected meta-analyses and extracted data. TSA was conducted for all meta-analyses using “TSA software” (Copenhagen, Denmark). Results: 6 studies were considered, and 7 TSA evaluations were performed. Six out of the seven TSA evaluations confirmed the conclusions of the pertinent meta-analyses. In one TSA, the cumulative Z-line did not reach the required sample size, highlighting the need for additional studies to definitively confirm the result. In two TSAs, the sample size in the meta-analysis was insufficient to draw definitive conclusions. The application of TSA in these cases could provide more substantiated and cautious conclusions.Conclusion: This study explores various scenarios for the application of TSA in meta-analyses published in both Russian and international journals in the fields of anesthesiology and resuscitation. The significance of TSA for enhancing the validity and clinical relevance of research findings was substantiated. Received 3 February 2024. Revised 18 March 2024. Accepted 20 March 2024. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: M.Ya. YadgarovData collection and analysis: M.Ya. Yadgarov, L.B. Berikashvili, P.A. PolyakovStatistical analysis: M.Ya. Yadgarov, P.A. PolyakovDrafting the article: M.Ya. Yadgarov, L.B. Berikashvili, K.K. Kadantseva, A.V. Smirnova, I.V. Kuznetsov, A.A. YakovlevCritical revision of the article: V.V. LikhvantsevFinal approval of the version to be published: M.Ya. Yadgarov, L.B. Berikashvili, P.A. Polyakov, K.K. Kadantseva, A.V. Smirnova, I.V. Kuznetsov, A.A. Yakovlev, V.V. Likhvantsev

Актуальность. Достоверность статистического анализа и его результатов выходит на первый план научного дискурса, оттесняя вопросы статистической значимости. Систематические обзоры и метаанализы характеризуются серьезными статистическими и методологическими ограничениями, среди которых недостаточная статистическая мощность, клиническая и статистическая неоднородность, систематические ошибки, возможное низкое качество включенных исследований, ограниченная доступность данных в исследованиях и публикационное смещение. В этом контексте последовательный анализ исследований — перспективный методологический инструмент, применяемый в качестве дополнения к метаанализам с целью повышения точности и устойчивости научных выводов. Цель. Продемонстрировать сценарии использования последовательного анализа исследований и его роль в улучшении достоверности научных выводов на примере метаанализов в российских журналах по анестезио­логии-реаниматологии, а также метаанализов авторов. Методы. Выполнили систематический обзор без подробного описания исследований. Осуществили поиск метаанализов по ключевым словам: метаанализ, летальность, делирий, седация. Два исследователя провели независимую проверку названий и аннотаций отобранных метаанализов, а также извлекли данные. Для всех метаанализов выполнили последовательный анализ исследований с использованием программного обеспечения TSA software (Копенгаген, Дания). Результаты. Рассмотрели 6 исследований и осуществили 7 последовательных анализов исследований. Шесть из семи оценок подтвердили выводы соответствующих метаанализов. В одном последовательном анализе кумулятивная Z-линия не достигла необходимого размера выборки, что подчеркивает необходимость в дополнительных исследованиях для окончательного подтверждения результата. В двух последовательных анализах размер выборки был недостаточен для формирования окончательных выводов. Последовательный анализ исследований в этих случаях мог бы обеспечить более обоснованные и осторожные выводы. Заключение. Использование последовательного анализа исследований для повышения достоверности и клинической релевантности научных выводов обосновано. Поступила в редакцию 3 февраля 2024 г. Исправлена 18 марта 2024 г. Принята к печати 20 марта 2024 г. Финансирование Исследование не имело спонсорской поддержки. Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: М.Я. Ядгаров Сбор и анализ данных: М.Я. Ядгаров, Л.Б. Берикашвили, П.А. Поляков Статистическая обработка данных: М.Я. Ядгаров, П.А. Поляков Написание статьи: М.Я. Ядгаров, Л.Б. Берикашвили, К.К. Каданцева, А.В. Смирнова, И.В. Кузнецов, А.А. Яковлев Исправление статьи: В.В. Лихванцев Утверждение окончательного варианта статьи: все авторы

Metastatic processes remain the main cause of deaths in oncology. Methods of anesthesia, in particular regional anesthesia, are considered as potential modulators of the immune response and metastatic spread. The ambiguity of the available data on the effect of regional and general anesthesia on metastatic spread is partly due to the fact that general anesthetic in combined anesthesia is quite often not taken into account, and this, in turn, masks the possible influence of regional anesthesia. The purpose of this meta-analysis was to make a comparative assessment of the effect of general anesthesia and general anesthesia in combination with regional anesthesia on the relapse-free and overall survival of cancer patients after surgery. Materials and methods. We analyzed 8 randomized controlled trials involving 1822 patients and comparing the groups of cancer patients who were operated either under general anesthesia (total intravenous (TIVA) or inhalation (IA)), or general anesthesia in combination with regional anesthesia (TIVA+RA or IA+RA, respectively). Trial using combinations of inhaled and intravenous anesthetics was excluded from the analysis for a more accurate assessment of the effect of regional anesthesia. The study complies with the recommendations of the Cochrane Community and PRISMA standards. The protocol was registered on the INPLASY platform. We used PubMed, Google Scholar and CENTRAL databases. We used a subgroup analysis and GRADE tool to assess the quality of evidence. Results. There were no statistically significant differences in relapse-free and overall survival when comparing different anesthesia methods. For a relapse-free survival, comparing TIVA vs TIVA+RA resulted in no significant difference : OR=1.20 [95% CI 0.92-1.55]; when IA vs IA+RA were compared, OR=1.10 [95% CI 0.94-1.29]. Similar results were obtained for overall survival. Conclusion. Based on the meta-analysis results, regional anesthesia had no effect on relapse-free and overall survival in oncosurgery patients.

The aim of the study. To study the achievability and contingency to maintain an effective plasma lithium concentration in the perioperative period in patients undergoing carotid endarterectomy (CEAE) with oral intake of lithium carbonate pills. Materials and methods. It was a prospective study, as a preparatory stage of the multicenter «BINOS» (NCT05126238) RCT. The sample included 15 patients undergoing elective CEAE. In the course of this study, patients were administered oral lithium carbonate, 900 mg per day during 4 perioperative days: two days before the procedure, in the day of surgery and in the 1st postoperative day. Plasma lithium concentration was monitored every 24 hours during all 4 days from the onset of treatment. Results. Increased plasma lithium concentrations were found in blood samples taken at 48 hours (0.68 mmol/l [0.53–0.84, P = 0.004) and 72 hours (0.68 mmol/l [0.62–0.90, P < 0.001), as compared with the initial values (0.14 mmol/l [0.11–0.17).While during the period between 48 and 72 hours from the onset of treatment the plasma lithium concentration remained in the therapeutic range (0.4–1.2 mmol/l) in 100% of patients. Conclusion. Oral intake of lithium carbonate pills at a dose of 900 mg/day during 2 preoperative days provided an effective and safe plasma lithium concentration in 100% of patients enrolled in the study.

ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить влияние протоколизированно-персонифицированного подхода к управлению гемодинамикой (ППУГ) на 30-дневную летальность и продолжительность пребывания в палате интенсивной терапии (ПИТ) и стационаре пациентов пожилого и старческого возраста, перенесших обширную операцию на органах брюшной полости, определить предикторы летального исхода. МАТЕРИАЛ И МЕТОДЫ Проведено ретроспективно-проспективное клиническое исследование эффективности применения ППУГ в периоперационном периоде хирургических вмешательств на органах брюшной полости у пациентов пожилого и старческого возраста. Исследовано влияние немодифицируемых (пол, возраст, наличие и характер сопутствующих заболеваний) и модифицируемых (сердечный индекс (СИ), уровень NT-proBNP, продолжительность операции, длительность анестезии) факторов на 30-дневную летальность и длительность пребывания в ПИТ и стационаре. РЕЗУЛЬТАТЫ Критериям включения/исключения соответствовали 90 пациентов, пролеченных с применением ППУГ (основная группа), которые ретроспективно сопоставлены с 89 пациентами группы исторического контроля со стандартным ведением в послеоперационном периоде. Статистически значимая взаимосвязь между применением ППУГ и 30-дневной летальностью не выявлена (p=0,813). Длительность пребывания в ПИТ пациентов основной группы (2 (1,0—8,3) сут) меньше по сравнению с длительностью пребывания в ПИТ пациентов контрольной группы (6 (2,0—16,5) сут) (p<0,001), так же как и в стационаре — 12 (10—20) сут и 18 (12—26) сут соответственно (p<0,001). В результате многофакторного регрессионного анализа обеих групп выявлено два независимых предиктора летального исхода: возраст ≥72 года (ОШ корр. 12,37; 95% ДИ 3,38—45,36; p<0,001) и СИ при поступлении ≤2,1 л/мин/м2 (ОШ корр. 4,80; 95% ДИ 1,28—18,06; p=0,02). ЗАКЛЮЧЕНИЕ Старший возраст (≥72 лет) и меньшая величина сердечного индекса при поступлении (≤2,1 л/мин/м2) независимо связаны с бóльшим риском летального исхода. Применение протоколизированно-персонифицированного подхода к управлению гемодинамикой у пациентов, перенесших обширную операцию на органах брюшной полости, не связано с изменением 30-дневной летальности, но независимо ассоциировано с меньшей длительностью пребывания в палате интенсивной терапии и стационаре.

The history of the study of postoperative neurocognitive disorders (PND) looks as a long and thorny path of more than 400 years. Despite all accumulated data on PND risk factors and outcomes, there’s still no complete understanding of the etiology and pathogenesis of this complication. Moreover, current anesthesiologyresuscitation practice still faces challenges and has pending questions in diagnosis and classification of postoperative neurocognitive disorders. The purpose of the review. To contemplate the evolution in the perceptions of the international medical community (IMC) regarding diagnostic approaches and algorithms in PND management. The review covers the history of development of such PND concepts as postoperative delirium, postoperative cognitive dysfunction, emergence agitation and emergence delirium. Also, the pre-existing and current international classifications of postoperative neurocognitive disorders are discussed in chronological order, supplemented by the analysis of their strengths and weaknesses. The paper also delves into current viewpoints concerning the etiology of particular postoperative neurocognitive disorders, and PND potential relevance for postoperative outcomes. Conclusion. Current algorithms and modalities used for PND diagnosis, are novel but yet not ultimate for IMC in the context of continuous progress in medical practice. Early postoperative neurocognitive disorders remain the most poorly studied phenomena with no approved definitions and diagnostic modalities to identify. It is probably the time for IMC to undertake a joint effort to find answers to current unresolved questions regarding postoperative neurocognitive disorders.

The objective: to develop a predictive model for assessing the risk of death in patients with COVID-19 admitted to the intensive care unit (ICU). Subjects and Methods. This was a single-center retrospective cohort study of hospital mortality in patients admitted to ICU of V.P. Demikhov City Clinical Hospital from March 6 to June 3, 2020. Results. Case histories of 403 patients were analyzed. In-hospital 30-day mortality among patients treated in ICU was 44.9% (181/403 patients). A multivariate analysis showed that significant predictors of death in patients with COVID-19 were the age of 60 years or more (adj. OR 3.84; 95% CI 1.56‒9.44, p = 0.003), COPD (adj. OR 2.35; 95% CI 1.12‒4.95, p = 0.024), peripheral artery diseases (adj. OR: 5.08; 95% CI 1.87‒13.76, p = 0.001) and CKD stage 3b and higher (adj. OR 4.58; 95% CI 2.36‒8.90, p < 0.001), LDH 300 IU/l or more (adj. OR 3.05; 95% CI 1.23‒7.58, p = 0.016), and CRP 200 mg/l or more (adj. OR 3.65; 95% CI 1.95‒6.85, p < 0.001). Predictive model quality: AUC = 0.811 [0.733‒0.874], p < 0.001. Conclusions. A nomogram to assess the risk of death in patients with COVID-19 has been developed. It includes the assessment of age, history of COPD, CKD stage 3b and higher, peripheral artery diseases, and monitoring of LDH and CRP.

Introduction and aim. Recent evidence suggests that inhalation anesthesia (IA) is associated with higher cancer mortality than total intravenous anesthesia (TIVA), possibly due to a modulation of the immune response.The aim of this study was to determine the impact of anesthesia techniques on selected parameters of patient immunity considering the evidence of relationship between the anesthesia methods and immune status and, consequently, the incidence of cancer recurrence.Methods. We performed a meta-analysis of clinical studies published in PubMed, Google Scholar, and Cochrane databases, aimed at assessing the impact of anesthesia on the postoperative immune status of patients undergoing breast cancer (BC) surgery. Five randomized and three observational studies were included (a total of 637 patients, of which 320 (50.2%) in the TIVA group). Data on leukocyte counts, matrix metalloproteinases (MMP) 9 and 3, interleukins (IL) 6 and 10 levels, and neutrophil-lymphocyte index (NLI) values were retrieved.Results. Patients after breast cancer surgery who underwent TIVA had significantly lower white blood cell counts (standardized mean difference (SMD)=–0.32; 95% CI: –0.58 to –0.06; I2=58%, P=0.020) and MMP-9 (SMD=–0.35; 95% CI: –0.67 to –0.03; P=0.030; I2=0%) in the postoperative period compared with patients receiving IA. No significant differences in the levels of MMP-3, IL-6, IL-10, and NLI values were found between the two groups.Conclusion. The patients who underwent breast cancer surgery under TIVA had lower blood leukocyte counts and levels of MMP-9, which is involved in the remodeling of extracellular matrix, compared with those operated on under IA, suggesting that the anesthesia method may have an impact on the immunity of breast cancer patients.

The objective: to evaluate the prognostic value of Nomogram M for major adverse cardiac events (MACE) and major adverse cardiac and cerebral events (MACCE) after elective cardiac surgery with cardiopulmonary bypass.Subjects and Methods. This is a retrospective cohort study of the Nomogram M prognostic value for MACE and MACCE after elective cardiac surgery with cardiopulmonary bypass. 158 patients were enrolled in the study. The prognostic value was estimated using ROC-analysis.Results. The frequency of MACE and MACCE during hospitalization made 5.7% (9 of 158 patients) and 6.3% (10 of 158 patients), respectively. AUC Nomogram M for MACE was 0.888 [0.825; 0.950] (p < 0.001). Cut-off value made 12.5 points (sensitivity – 88.89%, specificity – 83.89%). Odd ratio was 41.67 [95% CI 4.98; 348.61] (p < 0.001).AUC Nomogram M for MACCE was 0.893 [0.834; 0.951] (p < 0.001). Cut-off value made 12.5 points (sensitivity – 90.00%, specificity – 84.46%). Odd ratio was 48.91 [95% CI 5.91; 404.78] (p < 0.001)Conclusion. Nomogram M has a good prognostic value for the occurrence of MACE and MACCE after elective cardiac surgery with cardiopulmonary bypass. For MACE sensitivity made 88.89%, and specificity – 83.89%. For MACCE sensitivity was 90.00%, specificity – 84.46%.

Актуальность. Вазоактивная-инотропная шкала зарекомендовала себя в качестве хорошего предиктора неблагоприятного течения послеоперационного периода. Тем не менее данная шкала не включена в современные прогностические модели. Цель исследования. Модифицировать номограмму, созданную по итогам исследования E-CABG registry, и оценить эффективность модификации для прогнозирования вероятности наступления летального исхода после плановых кардиальных операций в условиях искусственного кровообращения. Материалы и методы. Проведен анализ пред- и интраоперационных данных 158 пациентов, перенесших плановую операцию на сердце в условиях искусственного кровообращения. На основании полученных результатов значение SYNTAX исходной номограммы было заменено на значение VIS. Прогностическая способность новой модели была оценена в ROC-анализе. Результаты. 30-дневная летальность в группе пациентов составила 5,06 % (умерло 8 из 158 пациентов). По результатам ROC-анализа модифицированная номограмма имеет AUC = 0,897 (0,844–0,951) (p < 0,001). Точка отсечения составила 12,75 балла (чувствительность — 87,5 %, специфичность — 86,7 %). Заключение. Модифицированная номограмма, включающая в себя значение вазоактивной-инотропной шкалы, обладает отличной способностью прогнозирования 30-дневной летальности.

Comparative studies on the efficacy and safety of Inhalation Anesthesia (IA) and Total IntraVenous Anesthesia (TIVA) have been performed for many years, and the results were various. The aim of this study was to evaluate new data on the clinical efficacy of anesthetic preconditioning, the difference between inhalation and intravenous anesthesia on cardiac protection and clinically relevant outcomes in cancer surgery. Materials and methods . We carried out a systematic review and meta-analysis on searches and analysis of the literature over the past five years in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results. Out of the 759 articles which were initially identified, we selected 3 studies regarding the clinical significance of anesthetic cardioprotection and 10 studies comparing IA and TIVA in patients undergoing surgery for malignant diseases. Two meta-analyses and one multi-regional clinical trial (MRCT) suggest that further studies of the effectiveness of anesthetic cardioprotection is futile. A meta-analysis of 9 retrospective cohort studies and 1 MRCT showed a detrimental effect of IA on 3-year survival in surgical oncology (Hazard Ratio (HR): 1.73 (1.36; 1.96) Heterogeneity: Q = 8.336, df = 3, I 2 ; f 2 = 64.01, overall effect analysis: Z = 2.386 (P<0.017)). Analysis of 5-year mortality did not reveal any differences, although it did not remove any doubts about the possible negative effect of the use of IA in surgical oncology. Conclusion . Due to the futility of the previous efforts, the authors suggest not starting new studies aimed at finding evidence of the effectiveness of anesthetic cardioprotection on clinically relevant outcomes. However, since cohort studies indicate a possible beneficial effect of the use of TIVA in surgical oncology, the authors suggest conducting a serious comparative MRCT in this setting.

The objective: to investigate the efficacy and safety of terlipressin when it is used as an additional vasopressor in septic shock.Subjects: A single-center, observational, retrospective-prospective study of the efficacy and safety of combined therapy of septic shock with norepinephrine and terlipressin versus monotherapy with norepinephrine was conducted.Results. The use of terlipressin made it possible to reduce the average daily need for noradrenaline in patients with septic shock from 0.68 μg · kg-1 · min-1 in the control group to 0.55 μg · kg-1 · min-1 in the study group (p = 0.015) and reduce the duration of vasopressor support from 8 days [6.0-11.0] to 6 days [5.0-8.0] in the study group (p = 0.023). The use of terlipressin did not reduce the need for mechanical ventilation, but it did reduce the duration of ventilation. The number of days free from mechanical ventilation in patients in the control group was 6.0 [1.0-18.0], in the study group - 16.0 [2.0-22.0], (p = 0.039).Conclusion. The use of terlipressin as a supplement to norepinephrine is an effective and relatively safe treatment for hypotension in refractory septic shock.

Aim of the study was to evaluate the feasibility of using a modified nomogram (the M nomogram) to predict the occurrence of new postoperative hemodynamically significant arrhythmias after elective cardiac surgery with cardiopulmonary bypass within 30 days post operation.Materials and methods. This was a retrospective cohort study. The prognostic value of the model using ROC-analysis of the modified nomogram was estimated based on the medical records of 144 patients who underwent elective cardiac surgery with cardiopulmonary bypass.Results. The incidence of new postoperative hemodynamically significant arrhythmias was 13.9% (20 of 144 patients). For the modified nomogram, the AUC was 0.777 [95% CI: 0.661–0.892] (P<0.001); at a cutoff of 12 points, the sensitivity was 60.0% and specificity was 89.52%. The odds ratio was 10.26 (95% CI: 3.63–29.06) (P<0.001). Conclusion. The modified nomogram has an acceptable prognostic value for the occurrence of new hemodynamically significant arrhythmias after elective cardiac operations with cardiopulmonary bypass based on AUC 0.777 [0.661–0.892] (P<0.001), and is currently the best model for predicting the outcome.

Introduction. The Vasoactive-Inotropic Score has been shown as a good predictor of adverse events in postoperative period. Nevertheless, the score is not included in modern predictive models. Objectives. To modify the nomogram that was created as a result of the E-CABG registry trial, and to evaluate the efficacy of the modification to predict 30-day mortality after elective cardiac surgery with cardiopulmonary bypass. Materials and methods. Pre- and intraoperative data of 158 patients who underwent elective cardiac surgery with cardiopulmonary bypass was analyzed. Based on the obtained results, the SYNTAX value in the original nomogram was replaced with the VIS value. The predictive model was evaluated in ROC-analysis. Results. The frequency of 30-day mortality in group was 5,06 %. According to the results of ROC-analysis the modified nomogram has AUC = 0,897 (0.844– 0.951) (p < 0.001). The cut-off value was 12.75 points (sensitivity — 87.5 %; specificity — 86.7 %). Conclusions. The modified nomogram has an excellent predictive ability for 30-day mortality.

The aim of the study: to examine the anti-inflammatory effect of lithium chloride by exposing the human neutrophils to serum of patients with septic shock in vitro.Material and methods. The study was carried out on neutrophils extracted from the blood of 6 healthy donors, which were activated with serum from patients with septic shock. The neutrophil activity was evaluated with fluorescent antibodies to the CD11b and CD66b markers of degranulation. The level of human neutrophil apoptosis and necrosis was assessed 22 hours after extraction; quantitative assessment was made using annexin V and propidium iodide with flow cytofluorimetry. Intact and activated neutrophils were treated with 0.3, 3.0 and 9.0 mmol lithium chloride solution.Results. The level of CD11b expression on the surface of intact neutrophils (healthy donors) was 3434.50 [3311.0-3799.0] arbitrary fluorescence units (AFU). Incubation of neutrophils with serum of patients with septic shock increased CD11b expression 2.5 times to 8589.0 [7279.0-11258.0] AFU (P=0.005) vs intact leukocytes, and increased CD66b expression 2.7 times up to 27 600.0 [22 999.0-28 989.0] AFU ((P=0.005) vs intact neutrophils. Lithium chloride in concentrations of 0.3, 3.0 and 9.0 mmol in a dose-dependent manner reduced the level of expression of CD11b and CD66b molecules on the surface of activated neutrophils. Septic serum reduced spontaneous neutrophil apoptosis, and 3.0 mmol and higher lithium chloride solution induced spontaneous neutrophil apoptosis.Conclusion. Lithium chloride reduces the activation of neutrophils preactivated by serum of patients with septic shock, reduces expression of CD11b and CD66b molecules on the neutrophil surface, inhibiting the process of their activation (degranulation). Lithium chloride in concentration of 3.0 mmol and higher is able to induce spontaneous apoptosis of neutrophils activated by serum of patients with septic shock.

Abstract The review presents the main aspects of the cardioprotective properties of the xenon inhalation anesthetic. Based on the analysis of publications, the article discusses modern views on the mechanisms of the protective action of xenon, realized using pre- and post-conditioning mechanisms, shows major molecular targets and their effects. The article presents the results of experimental studies in vivo and in vitro, which showed the protective effect of xenon on the myocardium and the results of recent randomized clinical trials. The analysis of studies demonstrates the ability of xenon to increase myocardial resistance to ischemia and reperfusion and opens up good prospects for its use in clinical practice in patients with a high risk of cardiac complications.