Andrey G. Yavorovskiy

INTRODUCTION: Endothelial dysfunction plays a key role in the pathogenesis of ischemia-reperfusion injury. OBJECTIVES: To evaluate the effect of intraoperative inhaled nitric oxide (iNO) on endothelial function, endothelial damage markers, and clinical outcomes in patients with cardiovascular pathology undergoing laparoscopic surgery. MATERIALS AND METHODS: A pilot prospective randomized open-label study was conducted. Forty patients with cardiovascular pathology (Revised Cardiac Risk Index > 2) scheduled for elective laparoscopic surgery lasting > 120 min were enrolled. Patients were randomized into two groups: main group — inhalation of NO at 40 ppm throughout surgery (AIT-NO-01 “Tianox”, RFNC-VNIIEF, Russia); control group — standard anesthesia. The dynamics of endothelial dysfunction markers (NOtotal, endothelin-1, von Willebrand factor, vascular cell adhesion molecule-1, inducible NO-synthase (iNOS)), length of hospital stay, and organ damage markers (intestinal fatty acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP), and creatinine) were analysed. RESULTS: Groups were comparable at baseline. At 12 hours after surgery, the NO group had higher levels of NOtotal (14 [11; 20] vs 8 [6; 9] nmol/ml; p < 0.001) and von Willebrand factor (154 [94; 403] vs 83 [56; 202] %; p = 0.023) and a lower level of endothelin-1 (5.79 [4.35; 12.64] vs 13.4 [5.71; 21.27] fmol/ml; p = 0.041). The iNO group had lower levels of I-FABP, LBP, creatinine, vascular cell adhesion molecule-1 (0.93 ± 0.18 vs 1.30 ± 0.49 scores) (p = 0.043), and iNOS (1.33 ± 0.49 vs 1.86 ± 0.38 scores) (p = 0.015). Hospital stay was shorter in the iNO group: 11 (8; 13) vs 14 (10.5; 21.0) days (p = 0.01). CONCLUSIONS: Intraoperative inhaled nitric oxide administration to patients with cardiovascular disease undergoing laparoscopic surgery may be associated with improved endothelial function, a favorable profile of intestinal and renal injury biomarkers, and a reduced length of hospital stay. Results require confirmation in larger randomized trials.

INTRODUCTION: Organ toxicity of anticancer treatment remains a significant problem in comorbid patients. Xenon has organoprotective properties, but its clinical use during chemotherapy has been insufficiently studied. OBJECTIVE: To assess changes in organ damage markers, as well as the safety and tolerability of inhaled subanesthetic xenon in patients receiving systemic anticancer therapy. MATERIALS AND METHODS: A prospective randomized controlled study was conducted. Forty-four women with breast, ovarian, or uterine corpus cancer were randomized; 41 completed the intervention stage and were analyzed: 20 in the xenon group and 21 in the control group. The xenon group received three 30-minute inhalations of an oxygen-xenon mixture containing 27–34 % xenon on Days 1, 3, and 5 from chemotherapy initiation; controls received oxygen-nitrogen inhalations. The primary outcome was change in high-sensitivity cardiac troponin T from baseline to Day 15. Secondary outcomes included N-terminal pro-B-type natriuretic peptide (NT-proBNP), S100B protein, syndecan-1, echocardiographic parameters, kidney and liver function tests; safety was assessed by adverse events. RESULTS: Change in high-sensitivity cardiac troponin T from baseline to Day 15 was 8.94 [4.50; 13.30] pg/mL in the control group and 1.01 [−0.09; 1.98] pg/mL in the xenon group (p < 0.001). In the baseline-adjusted model, the between-group difference at Day 15 was β = −7.90 (95% CI: −12.85; −2.94; p = 0.003). The adjusted between-group difference in left ventricular ejection fraction change was +4.66 % (95% CI: 2.4; 6.9; p < 0.001). Significant within-group changes in NT-proBNP and S100B were observed in the control group, whereas no significant changes were observed in the xenon group. CONCLUSIONS: Three 30-minute inhalations of an oxygen-xenon mixture containing 27–34 % xenon were well tolerated and were associated with preliminary differences in changes in markers of subclinical organ damage. These findings require confirmation in larger studies with longer follow-up.

The objective was to analyze current evidence on pharmacogenetic factors influencing interindividual variability in the response to agents used for general anesthesia, as well as to assess their potential role in the development of individual susceptibility to postoperative neurocognitive disorders. Materials and methods. A review was conducted using the principles of a structured search in PubMed/MEDLINE, Google Scholar, Scopus, and Web of Science. Data from PharmGKB/ClinPGx and CPIC were also considered. Publications addressing general anesthesia, propofol, fentanyl, sevoflurane, pharmacogenetic markers, and postoperative cognitive outcomes were analyzed. Results. The most extensively studied pharmacogenetic associations for propofol involve polymorphisms of the CYP2B6 and UGT1A9 genes; for fentanyl, OPRM1, ABCB1, and CYP3A4; and for sevoflurane, RYR1, CACNA1S, GRIN2B, MTRR, and APOE. These polymorphisms are associated with interindividual differences in drug clearance, dose requirements, sensitivity to sedative and analgesic effects, hemodynamic response, and the rate of postoperative recovery. Pharmacogenetic variability may potentially modify the risk of excessive or insufficient depth of anesthesia, inadequate analgesia, and cerebral hypoperfusion. Through these mechanisms, pharmacogenetic factors may influence stress response, neuroinflammation, and other key pathways involved in the pathogenesis of postoperative neurocognitive disorders. Conclusion. Although direct evidence linking individual polymorphisms to cognitive outcomes remains limited, the available data support the consideration of pharmacogenetic factors as a significant component of comprehensive risk assessment for postoperative neurocognitive impairment. Their greatest practical value lies not in isolated use for selecting anesthetic management strategies, but in integration with clinical, geriatric, neuropsychological, and perioperative parameters for personalized risk stratification and prevention of adverse neurocognitive outcomes.

Regional anesthesia has gained recognition in recent years as a promising field in anesthesiology, allowing a substantial reduction in perioperative opioid consumption and, consequently, decreasing the incidence of opioid‑related complications. The main limitation of this approach is the relatively short duration of nerve blockade. Considerable attention has been paid to pharmacological methods for prolonging sensory block, which can be achieved using adjuvants – drugs that enhance the effect of local anesthetics. This area is highly popular in contemporary international research. At present, five key groups of adjuvants have been described: α‑adrenergic agonists (epinephrine), α2‑agonists (dexmedetomidine, clonidine), glucocorticoids (dexamethasone), opioid analgesics (morphine, tramadol, fentanyl), and other agents (ketamine, magnesium sulfate, nonsteroidal anti‑inflammatory drugs [NSAIDs], pregabalin). The objective of this review is to analyze and systematize available data on the use of adjuvants for prolongation of regional nerve blocks.

Introduction: The passive leg raising (PLR) test is a non-invasive diagnostic tool for assessing fluid responsiveness, a pivotal aspect in hypotension management. Despite its growing application, a unified comparative assessment of prognostic accuracy for various PLR test parameters is currently lacking. Objective: Our study aimed to evaluate the efficacy of different PLR test indicators in predicting fluid responsiveness. Methods: We conducted a network meta-analysis, analyzing prospectivestudies that explored diagnostic accuracy of PLR test for fluid responsiveness. Electronic databases were searched until March 2024; this search was supplemented by snowballing methods. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of evidence. Results: Sixteen prospective cohort studies involving 784 patients were included. The network meta-analysis revealed that cardiac output parameters measured during the PLR test have the highest prognostic significance for assessing fluid responsiveness compared to other parameters (SUCRA score = 88.3). Utilizing arterial blood flow indicators results in a moderate prognostic value for the PLR test (SUCRA score = 72.0). The use of such conventional parameters as arterial blood pressure and inferior vena cava diameter reduces prognostic accuracy to unsatisfactory levels (SUCRA score < 50). The superiority of PLR test prognostic capability when using cardiac output parameters over arterial blood pressure indicators is supported by high-quality evidence. Conclusion: Our network meta-analysis demonstrated that using PLR test with cardiac output parameters ensures maximum sensitivity and specificity. Consequently, the use of more straightforward and easily obtainableparameters (arterial blood pressure, inferior vena cava diameter) is not recommended for assessing fluid responsiveness. Received 9 October 2025. Revised 14 October 2025. Accepted 18 February 2026. FundingThe study did not have sponsorship. Conflict of interestThe authors declare no conflict of interest. Contribution of the authorsConception and study design: V.V. Likhvantsev, L.B. Berikashvili Data collection and analysis: I.V. Kuznetsov, P.V. Ryzhkov, M.Ya. Yadgarov, L.B. Berikashvili Statistical analysis: M.Ya. YadgarovDrafting the article: I.V. Kuznetsov, L.B. Berikashvili, M.Ya. Yadgarov, A.G. Yavorovskiy, A.A. Yakovlev Critical revision of the article: V.V. Likhvantsev Final approval of the version to be published: all authors

Introduction: The passive leg raising (PLR) test is a non-invasive diagnostic tool for assessing fluid responsiveness, a pivotal aspect in hypotension management. Despite its growing application, a unified comparative assessment of prognostic accuracy for various PLR test parameters is currently lacking. Objective: Our study aimed to evaluate the efficacy of different PLR test indicators in predicting fluid responsiveness. Methods: We conducted a network meta-analysis, analyzing prospectivestudies that explored diagnostic accuracy of PLR test for fluid responsiveness. Electronic databases were searched until March 2024; this search was supplemented by snowballing methods. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of evidence. Results: Sixteen prospective cohort studies involving 784 patients were included. The network meta-analysis revealed that cardiac output parameters measured during the PLR test have the highest prognostic significance for assessing fluid responsiveness compared to other parameters (SUCRA score = 88.3). Utilizing arterial blood flow indicators results in a moderate prognostic value for the PLR test (SUCRA score = 72.0). The use of such conventional parameters as arterial blood pressure and inferior vena cava diameter reduces prognostic accuracy to unsatisfactory levels (SUCRA score < 50). The superiority of PLR test prognostic capability when using cardiac output parameters over arterial blood pressure indicators is supported by high-quality evidence. Conclusion: Our network meta-analysis demonstrated that using PLR test with cardiac output parameters ensures maximum sensitivity and specificity. Consequently, the use of more straightforward and easily obtainableparameters (arterial blood pressure, inferior vena cava diameter) is not recommended for assessing fluid responsiveness. Received 9 October 2025. Revised 14 October 2025. Accepted 18 February 2026. FundingThe study did not have sponsorship. Conflict of interestThe authors declare no conflict of interest. Contribution of the authorsConception and study design: V.V. Likhvantsev, L.B. Berikashvili Data collection and analysis: I.V. Kuznetsov, P.V. Ryzhkov, M.Ya. Yadgarov, L.B. Berikashvili Statistical analysis: M.Ya. YadgarovDrafting the article: I.V. Kuznetsov, L.B. Berikashvili, M.Ya. Yadgarov, A.G. Yavorovskiy, A.A. Yakovlev Critical revision of the article: V.V. Likhvantsev Final approval of the version to be published: all authors

Introduction . Patients with cardiovascular disease undergoing laparoscopic surgery are at high risk of developing various postoperative complications. A significant portion of these complications are due to splanchnic organ hypoperfusion caused by pneumoperitoneum and associated chronic pathological conditions. Despite the demonstrated organ-protective effect of inhaled nitric oxide (iNO) in cardiac surgery, its use in laparoscopic procedures has not been studied. The objective was to determine whether intraoperative nitric oxide inhalation at a dose of 40 ppm affects cardiac, endothelial, and hemostatic parameters in patients with cardiovascular disease (CVD) requiring laparoscopic abdominal surgery. Materials and methods . A pilot randomized study was conducted involving 40 patients with CVD undergoing lengthy laparoscopic procedures. In the main group (n = 20), iNO was delivered using an AIT-NO-01 device (Tianox, Russia) at a concentration of 40 ppm with monitoring of nitrogen dioxide (NO ₂ ) and methemoglobin levels. In the control group (n = 20), no additional anesthetic interventions were provided. Results . iNO at a dose of 40 ppm was well tolerated, with no adverse events recorded; NO ₂ concentrations remained below 2 ppm. iNO had a significant effect on glycoprotein 5 concentrations (–4.80 ± 9.02 vs. +0.36 ± 7.05, p = 0.054) and reduced endothelin-1 levels by approximately 70% (+1.05 ± 3.86 vs. +3.47 ± 4.69 pg/ml, p = 0.082), indicating increased endothelial activity. NT-proBNP variability in the iNO group was 86% lower than in the control group. The decrease in end-diastolic volume was 7.9 times greater in the study group (–12.7 vs. –1.6 mL, p = 0.268). In both groups, a statistically significant increase in potassium levels relative to baseline was noted after 24 hours (control: p = 0.019; iNO: p = 0.002). Conclusion . The use of iNO at a dose of 40 ppm in laparoscopic abdominal surgery appears safe. Complex effects on coagulation factors, the endothelium, cardiac load, and electrolytes were revealed, which justifies conducting large-scale randomized trials to confirm the organ-protective effects.

Acute cholecystitis represents a significant problem in contemporary abdominal surgery. The gold standard for treating this pathology is laparoscopic cholecystectomy. Postoperative pain substantially impedes rehabilitation and impairs the quality of patient recovery. Optimization of perioperative anesthesiology strategies remains a priority task for anesthesiologists and surgeons. This narrative review systematically synthesizes data from randomized controlled trials, meta-analyses, and systematic reviews on anesthesiology support for laparoscopic cholecystectomy, with a focus on regional anesthesia techniques. Contemporary studies indicate that peripheral nerve blocks are associated with reduced opioid requirements, accelerated postoperative recovery, and enhanced patient treatment satisfaction. Particular attention is paid to transversus abdominis plane block and erector spinae plane block, which demonstrate the strongest evidence base. Despite the substantial body of accumulated data, the selection of optimal anesthesia methodology remains subject to scientific debate, underscoring the need for additional research of high methodological quality.

Objective. To evaluate nephroprotective effect of balanced amino acid infusion in patients with intact kidney function undergoing cardiac surgery with cardiopulmonary bypass (CPB). Material and methods. The study included 128 patients divided into two groups: the intervention group (n=64) and the control group (n=64). In the intervention group, a balanced amino acid solution (Aminoven 10%, Fresenius Kabi, Austria) was administered at a dose of 2 g/kg/day immediately after anesthesia induction and for the first 24 hours postoperatively. The control group received placebo infusion (a balanced crystalloid solution — Sterofundin, 20 ml/kg/day, B. Braun, Germany) under identical conditions. Statistical analysis of data was performed in Python 3.12 environment. Results. There were significant differences in estimated glomerular filtration rates (eGFR) (92 [84.1; 100.3] vs. 82.6 [72.4; 92.1], p=0.0011) and creatinine clearance (106.1 [94.8; 118.3] vs. 94.1 [82.9; 105.6], p=0.001). There was less incidence of acute kidney injury (AKI) in the intervention group (12.5% vs. 23.4%) (although this difference was not significance (p=0.166)), as well as shorter duration of injury (3 [3; 3] vs. 5 [4; 5.75] days, p=0.002). Additionally, AKI was less severe in the intervention group and required lower doses of loop diuretics. Analysis of blood urea levels confirmed safety of amino acid infusion. Conclusion. Infusion of a balanced amino acid mixture has a positive impact on kidney function parameters, incidence and duration of AKI in patients with intact kidney function. This intervention is safe and does not affect nitrogen balance.

BACKGROUND: Acute kidney injury is one of the most common complications after cardiac surgery with cardiopulmonary bypass, with the least favorable prognosis. Despite a variety of pharmacological and non-pharmacological interventions, there is no universally effective strategy for preventing acute kidney injury. One promising nephroprotective approach is activating renal functional reserve via amino acid infusion. AIM: The work aimed to assess the nephroprotective potential of perioperative intravenous infusion of a balanced amino acid solution in patients after cardiac surgery with cardiopulmonary bypass. METHODS: A randomized, double-blind, placebo-controlled, single-center study with pooled post hoc analysis included 260 patients aged 18–75 years who underwent elective cardiac surgery with cardiopulmonary bypass. The treatment group (n=130) received a 10% amino acid solution (2 g/kg/day for 24 hours); the control group (n=130) received an equal amount of balanced crystalloid solution. The primary endpoint was the estimated glomerular filtration rate according to the CKD-EPI equation. Secondary endpoints included the incidence, severity, and duration of acute kidney injury; urine output; diuretic use; duration of renal replacement therapy; and length of ICU/hospital stay. The statistical analysis included the Mann–Whitney U test, z-test, and Holm–Bonferroni correction. RESULTS: Amino acid infusion significantly improved renal function, with a median glomerular filtration rate of 79 [61; 93] vs 72 [55; 86] mL/min/1.73 m2 (pHolm 0.0005). The incidence of acute kidney injury decreased from 29.2% to 18.5% (pHolm 0.042); the incidence of severe acute kidney injury from 17.7% to 6.2% (pHolm 0.0123); and the duration of acute kidney injury from 5 [4; 6] to 3 [3; 4] days (pHolm 0.0024). Serum creatinine and urea levels were lower, and urine output was higher in the treatment group. CONCLUSION: Perioperative amino acid infusion safely reduces the incidence and severity of acute kidney injury and improves renal function parameters after cardiac surgery with cardiopulmonary bypass, supporting its use as an early nephroprotective strategy.