Aim. To assess whether plasma mitochondrial DNA (mtDNA) levels in the early postoperative period can predict the development of systemic inflammatory response syndrome (SIRS) and multiple organ failure in patients undergoing cardiac surgery.Methods. This pilot, prospective, observational, cohort study included 85 patients undergoing cardiac surgery. Plasma mtDNA levels were determined immediately after the surgery, and the development of SIRS, acute kidney injury, acute heart failure, and adult respiratory distress syndrome was assessed.Results. The mtDNA levels showed good potential for predicting the development of SIRS within 1-2 days after the surgery (area under the curve = 0.74). Regarding the cut-off point, a mtDNA level of >0.54 ng/mL predicted the development of SIRS in the early postoperative period with a sensitivity of 73.7% and a specificity of 66%. The odds ratio for the development of acute kidney injury with/without SIRS was 3.4 [confidence interval (CI) = 1.27–9.08; p = 0.0149]; acute heart failure, 5.7 (CI = 2.20–14.84; p = 0.0003); and adult respiratory distress syndrome, 3.6 (CI = 1.01–11.10; p = 0.047).Conclusion. The plasma mtDNA levels in the early postoperative period can be used as a predictive marker for the development of SIRS and multiple organ failure in patients undergoing cardiac surgery. Moreover, SIRS is associated with the development of acute kidney injury, acute heart failure, and adult respiratory distress syndrome.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Received 25 March 2019. Revised 3 April 2019. Accepted 8 April 2019.

The purpose of the study: to assess the significance of the nDNA plasma level in patients after cardiac surgery to predict the development of acute heart failure (AHF), acute kidney injury (AKI) and SIRS. Material and methods. The present prospective observational pilot cohort study of nDNA plasma level and the development of complications. Results. The nDNA plasma level was maximal 12 h after surgery. The level of nDNA > 20.5 ng/ml 12 h after surgery can predict risk of SIRS (sensitivity/specificity - 56/75 %); > 17.9 ng/ml - risk of AKI (79/69 %) and the AHF (62/58 %). Conclusion. The nDNA plasma level may be a predictor of early complications after cardiac surgery.

Delirium in the intensive care ward is actively being discussed by anesthesiologists for a long period of time. However at present there are fairly scarce evidences on the efficiency of various techniques of prevention and management of this disorder. Goal of the research: to assess the impact of inhalation sedation on the intensity and duration of sepsis-associated delirium in the intensive care ward of the surgical hospital. Methods. The one-centered, prospective, randomized comparative study was conducted in order to assess the efficiency of inhalation sedation in the patients with sepsis-associated delirium. Propofol was used for the intravenous sedation in the control group. 187 adult patients, admitted to the intensive care ward of Vorokhobov City Clinical Hospital no. 67, were included into the study. Results. Inhalation sedation reduced the delirium duration compared to intravenous use of propofol: delirium was fully managed on the 5th day in the group where sevorane was used [4; 7], while in the group where propofol was used delirium lasted for 7 days [6; 8] (p = 0.03). The study did not detect any effect of inhalation sedation on the intensity of oxidative stress (level of oxidized peptides in the blood plasma of the patients) and degree of neuronal damage (differences between groups are not significant, p = 0.37). No differences were recorded in the value of procalcitonin and SOFA score at any stage of the study. Conclusion. The frequency of delirium in the mixed population of sepsis patients makes 27.9%. Use of inhalation sedation with sevoflurane compared to intravenous administration of propofol reduces the duration of delirium therapy from 7 to 5 days.

Ischemia, reperfusion, oxidative stress, system inflammatory response – all these events are the cause or important link in the pathogenesis of numerous serious complications of cardiac surgeries. The damaging action of each of the above has been numerously proved by experiments and clinical practice and it seems that these events can be considered to be only very negative ones. However controlled ischemia initiates development of the phenomenon so-called as ischemic pre-conditioning, when the targeted organ develops enhanced resistance to the consequent damaging ischemia. Reperfusion is an inevitable and necessary stage of rehabilitation after previous ischemia. What about oxidative stress? Damaging potential of the active forms of oxygen is a fact, however minimal concentrations of the active oxygen forms are intercellular regulators and it means they are absolutely necessary for normal cellular vital activity. Besides numerous studies have proved noticeable intensification of the oxidative stress during artificial circulation (AC), however stuides failed to demonstrate reduction in the number of complications and peri-operative mortality when performing coronary artery bypass on the beating heart compared to the surgeries performed under AC. What is the true contribution of the oxidative stress into the development of post-operative complications? There have been found no evidences of the clinical efficiency of any of existing antioxidants as per mortality reduction criteria or decrease of hospital stay duration. Unfortunately we do not have unambiguous answers to the set up questions. There is no doubt only about the fact that critical actuality dictates the urgent need for further studying of the oxidative stress role in the pathogenesis of ischemic and reprefusional lesions in cardiac surgery.

Basing on the existing data about the positive impact of inhalation induction and anesthetic support (IIAS) and levosimendan it is planned to study and compare within framework of the coming study the impact of IIAS and pre-operative preparation through administration of levosimendan on the rates of myocardial contractility during intra and early post-operative periods, the need in inotropic agents, and 30-day and 1 year mortality of the patients with lower ejection fraction of left ventricular during surgery on infrarenal part of aorta.

Pre-surgery infusion with levosimendan with the rate of 0.05–0.1 mkg*kg-1 min-1 to the elder patients (60–75 years old) with lower ejection fraction of the left ventricle (less than 50%) results in its increase by 16.7% (p < 0.01), cardiac index – by 10.3% (p >< 0.01) and reduction of NT-proBNP level in blood by 24.1% (p >< 0.1) in 24 hours after the medication infusion start. The changes persist for at least 24 hours after the surgery. Key words: levosimendan, cardiac failure, peri-operative period, pre-surgery preparation, cardiac surgery, reduction of NT-proBNP level.>< 0.01), cardiac index – by 10.3% (p< 0.01) and reduction of NT-proBNP level in blood by 24.1% (p < 0.1) in 24 hours after the medication infusion start. The changes persist for at least 24 hours after the surgery. Key words: levosimendan, cardiac failure, peri-operative period, pre-surgery preparation, cardiac surgery, reduction of NT-proBNP level.>< 0.1) in 24 hours after the medication infusion start. The changes persist for at least 24 hours after the surgery.

The purpose of the study was to determine the efficacy of a synthetic leu-enkephalin stabilized analogue to prevent damage of endothelial cells monolayer in vitro caused by serum samples from septic shock patients.Materials and methods. The experiments were performed using the EaHy.926 endothelial cells monolayer. We studied the in vitro effect of synthetic leu-enkephalin analogue on the cell damage caused by serum samples from five septic shock patients. The status of endothelial intercellular junctions was estimated by immunofluorescence microscopy and western blot with antibodies against adherens junction protein, VE-cadherin, and against the tight junctions protein, claudin. Cell viability was determined by staining with propidium iodide.Results. Preconditioning with a synthetic leu-enkephalin analogue (10, 50 and 100 μg/ml) of endothelial cells in vitro prevented the destruction of both tight and adherens junction and partially prevented endothelial cell death.Conclusion. Preconditioning with a synthetic leu-enkephalin analogue partially prevents endothelial cell damage caused by exposure to septic patients’ sera in vitro. These data ensure the need for clinical trials on the effectiveness of a synthetic leu-enkephalin analogue for prevention of sepsis-associated endothelial dysfunction in clinics.

Background. Currently, the incidence of complications and perioperative mortality in cardiac surgery is still higher than in general surgery. This is partly associated with the development of oxidative stress, which is regarded as excessive accumulation of reactive oxygen species and nitrogen species. There are nowadays few studies demonstrating an increase of nitrotyrosine plasma level in patients during cardiac surgery. The relationship of these changes with post-operative complications and adverse outcomes has not been studied yet. Aim. Investigation the dynamics of the nitrotyrosine plasma level in patients after cardiac surgery and the assessment of its prognostic significance in terms of the development of early postoperative complications.Methods. The prospective observational cohort study involved 28 adult patients admitted at the cardiac intensive care unit of Moscow Regional Research and Clinical Institute (Moscow, Russian Federation). The relationship of the oxidative stress severity measured by intraoperative nitrotyrosine plasma levels and the development of acute kidney injury, cardiac failure and systemic inflammatory response syndrome was studied. Results. There was no significant perioperative dynamics of nitrotyrosine plasma levels when studying this oxidative stress marker in patients undergoing cardiac surgery. The level of nitrotyrosine plasma by the end of surgery was 12.1 [9.9; 13.0] nmol/mg of protein, which was 5% higher (p>0.5) than the initial level of 11.6 [9.3; 12.2] nmol/mg of protein, and returned to 11.5 [10.9; 12.4] after the 1st postoperative day. The same perioperative dynamics occurred in the subgroups with different surgery techniques: valve surgery, сoronary artery bypass grafting with cardiopulmonary bypass and off-pump сoronary artery bypass grafting.Conclusion. The negative result achieved in the given study might suggest that there are no significant changes of the perioperative nitrotyrosine plasma level in patients undergoing cardiac surgery, as well as that there is no significant correlation between the nitrotyrosine plasma level of and the incidence of postoperative complications.Received 26 December 2016. Accepted 4 May 2017.Funding: The study was carried out within the state-funded research project “Oxidant stress in cardiac surgery: new markers-predictors of complication development and pathogenetically substantiated therapy” granted to Moscow Regional Research and Clinical Institute.Conflict of interest: The authors declare no conflict of interest.Author contributionsConceptualization, study design: V.V. Likhvantsev.Data collection and analysis: T.S. Zabelina, Yu.V. Skripkin, O.N. Ulitkina. Drafting the article: O.A. Grebenchikov, Zh.S. Philippovskaya.Critical revision of the article: O.A. Grebenchikov.Final approval of the version to be published: V.V. Likhvantsev.

Delirium in the intensive care ward is actively being discussed by anesthesiologists for a long period of time. However at present there are fairly scarce evidences on the efficiency of various techniques of prevention and management of this disorder. Goal of the research: to assess the impact of inhalation sedation on the intensity and duration of sepsis-associated delirium in the intensive care ward of the surgical hospital. Methods. The one-centered, prospective, randomized comparative study was conducted in order to assess the efficiency of inhalation sedation in the patients with sepsis-associated delirium. Propofol was used for the intravenous sedation in the control group. 187 adult patients, admitted to the intensive care ward of Vorokhobov City Clinical Hospital no. 67, were included into the study. Results. Inhalation sedation reduced the delirium duration compared to intravenous use of propofol: delirium was fully managed on the 5th day in the group where sevorane was used [4; 7], while in the group where propofol was used delirium lasted for 7 days [6; 8] (p = 0.03). The study did not detect any effect of inhalation sedation on the intensity of oxidative stress (level of oxidized peptides in the blood plasma of the patients) and degree of neuronal damage (differences between groups are not significant, p = 0.37). No differences were recorded in the value of procalcitonin and SOFA score at any stage of the study. Conclusion. The frequency of delirium in the mixed population of sepsis patients makes 27.9%. Use of inhalation sedation with sevoflurane compared to intravenous administration of propofol reduces the duration of delirium therapy from 7 to 5 days.

Concurrent cardiac failure is an universally accepted risk factor in surgical patients undergoiing cardiac or non-cardiac surgery.The aim of this study was to search for and identify factors or markers, which would permit to predict early (up to 30 days) or late (up to 1 year) adverse outcomes in patients with acute heart failure (AHF) in the vascular surgery.Materials and Methods. A randomized, multicenter, prospective — retrospective study was performed. 89 patients who had signed the Informed Consent Form were randomized. Throughout the four stages of the study, the cardiac index (CI) and the left ventricle ejection fraction (LVEF) values were recorded. At the same stages, blood was sampled to be tested for the NT-proBNP level. The TnT level was tested only at the 3rd stage of the study. The required stay in the intensive care unit (ICU) and in the in-patient hospital, the incidence of infarctions and strokes during the early postoperative period (up to 30 days), the 30&day and one-year mortality rates were recorded.Results. Different AHF prevention methods were used in patients included into this study in the postoperative period. Predictors of adverse events were studied in a combined population. The incidence of acute myocardial infarction (AMI) was 12% and that of stroke was 2%. The in-hospital mortality rate in the combined group was 2%; the one-year mortality was 10%. Patients stayed in the intensive care unit for 3 (2—4) days; the hospital stay was 11 (10—13) days; the composite adverse outcome of the surgical treatment was registered in 15% of patients. As a result, the Troponin T level was the only significant prognostic factor during the first 24 hours of the postoperative period. A study of the prognostic significance of different parameters in relation to their effect on the one-year mortality rate demonstrated a similar result. Vasoactive Inotropes Score (VIS) turned out to be the most significant criterion for prediction of possible treatment duration.Conclusion. The study results confirmed the predictive value of early determination of TnT levels after reparative vascular surgeries in patients with decreased left ventricular ejection fraction. The diagnostic value of the VIS calculation needs further confirmation.

OBJECTIVETo measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery.SETTINGCardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital.DESIGNProspective observational study.PARTICIPANTSFifty adult patients undergoing cardiac surgery.INTERVENTIONSNuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated.MEASUREMENTS AND MAIN RESULTSCardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors.CONCLUSIONSThe authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury.

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta‐analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double‐blind, placebo‐controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30‐day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30‐day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], ‐5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, ‐2 hours; 95% CI, ‐5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, ‐12 hours; 95% CI, ‐21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, ‐1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low‐dose levosimendan in addition to standard care did not result in lower 30‐day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.)

Congestive heart failure is consistently associated with adverse outcomes, and is characterized by a twofold increase in mortality in noncardiac surgery. In this regard, developing the methods aimed to prevent and treatacute heart failure (AHF) in the intraoperative period remain a challenging problem. Objective. To evaluate the efficacy of preoperative levosimendan infusion in reduction both mortality and duration of treatment of elderly patients with reduced left ventricular ejection fraction in noncardiac surgery. Material and Methods . Design: Multicenter blind randomized placebocontrolled study. Patients: 81 patients operated on abdominal organs. The main endpoint of the study: The length of stay in the Intensive Care Unit (ICU) and at the hospital were chosen as the primary endpoints. The secondary endpoints of the study were 30 day and annual mortality, the rate of acute myocardial infarction and stroke. Results. Levosimendan infusion at a rate of 0,05 μg/kg/min — 0,1 μg/kg/min to patients with low left ven tricular ejection fraction just before the surgery reduced the length of stay in ICU for 2 days and required hospital stay for 3 days. NTproBNP showed the best ratio of sensitivity/specificity in predicting 30day mortality in cumulative group: AUC=0,86 (90,77 to 0,93), P<0,0001. From other indicators the most informative were the Inotropes scoring, no change or decrease of a left ventricular ejection fraction, and cardiac index. Conclusion. To reduce perioperative mortality, the intravenous infusion of levosimendan at a rate of 0,05—0,1 μg/kg/min in elderly patients with low left ventricular ejection fraction is recommened as a preoperative preparation the day before the alleged noncardiac surgery.

Ischemia, reperfusion, oxidative stress, system inflammatory response – all these events are the cause or important link in the pathogenesis of numerous serious complications of cardiac surgeries. The damaging action of each of the above has been numerously proved by experiments and clinical practice and it seems that these events can be considered to be only very negative ones. However controlled ischemia initiates development of the phenomenon so-called as ischemic pre-conditioning, when the targeted organ develops enhanced resistance to the consequent damaging ischemia. Reperfusion is an inevitable and necessary stage of rehabilitation after previous ischemia. What about oxidative stress? Damaging potential of the active forms of oxygen is a fact, however minimal concentrations of the active oxygen forms are intercellular regulators and it means they are absolutely necessary for normal cellular vital activity. Besides numerous studies have proved noticeable intensification of the oxidative stress during artificial circulation (AC), however stuides failed to demonstrate reduction in the number of complications and peri-operative mortality when performing coronary artery bypass on the beating heart compared to the surgeries performed under AC. What is the true contribution of the oxidative stress into the development of post-operative complications? There have been found no evidences of the clinical efficiency of any of existing antioxidants as per mortality reduction criteria or decrease of hospital stay duration. Unfortunately we do not have unambiguous answers to the set up questions. There is no doubt only about the fact that critical actuality dictates the urgent need for further studying of the oxidative stress role in the pathogenesis of ischemic and reprefusional lesions in cardiac surgery.

BACKGROUND:Chronic heart failure (CHF) significantly worsens the prognosis of surgical treatment in noncardiac surgery, doubling mortality in compared with patients with coronary artery disease. Modern anesthesiology has at least two methods that potentially can improve the results in noncardiac surgery: anesthetic cardioprotection and the prevention of CHF decompensation with levosimendan.THE AIM:to study the efficacy of anesthetic cardioprotection andpreoperative preparation with levosimendan for the prevention of CHF decompensation in patients with reduced left ventricular ejectionfraction in noncardiac surgery.ENDPOINTS:the primary endpoint of the trial is the need and the maximum dose of inotropic drugs in the perioperative period; secondary point: the length of stay in the ICU, composite outcome, the dynamics of SI, FI, the content ofNT-proBNP and TnT Materials and methods: A randomized study was performed in three groups of patients during reconstructive operations on infrarenal part of aorta: control (traditional methodfor prevention of decompensation of CHF were used) - 31 patients; the group with the anesthetic cardioprotectivei - 31 patients; the group with a preoperative preparing with levosimendan - 30 patients.RESULTS:The incidence of heart failure (estimated by need to use inotropic drugs - IS) was 83% of control group patients and 75% of the patients of the group "VIMA" (p = 0,65). The number ofpatients needing the use of dobutamine in LS-group was significantly below, 50% (p = 0,02 relative to control group and p = 0,08 compared to the group VIMA). IS in the control group was 8 [6, 9] μg xkg⁻¹ - xmin⁻¹ ; group VIMA 8 [3; 9] mg xkg ⁻¹ xmin⁻¹ , whereas in the LS group only 2 [0; 7] mg ⁻¹ xkg⁻¹ xmin⁻¹ . Differences between groups credible, given the Bonferroni correction (p = 0,0015). In our study, was not identified significant differences in 30-day mortality: in the control group it was 3,4%; in the group VIMA of 3,1%; in the group of LS - 0% (p > 0,017); however, a composite outcome (number of adverse events (heart attack+stroke+mortality) were slightly better in the LS group - 17%, against 34% in the control group (p = 0,043).CONCLUSION:Preoperative preparation with levosimendan in patients with reduced fraction left ventricle ejection when performing reconstructive operations on the descending aorta reduces the incidence of episodes of decompensation of heart failure compared with the control group to 39,8% (p < 0,05). The use of this technique improves the composite outcome of operations on the infrarenal aorta. The study has not shown the influence of anesthetic cardioprotection in terms of hospitalization and composite outcome of surgical treatment.

Basing on the existing data about the positive impact of inhalation induction and anesthetic support (IIAS) and levosimendan it is planned to study and compare within framework of the coming study the impact of IIAS and pre-operative preparation through administration of levosimendan on the rates of myocardial contractility during intra and early post-operative periods, the need in inotropic agents, and 30-day and 1 year mortality of the patients with lower ejection fraction of left ventricular during surgery on infrarenal part of aorta.

The article is devoted to the existence of the problem of intraoperative provide patients with concomitant diabetes mellitus: a disease is not diagnosed in time, it increases the probability of death in the performance of surgery by 50%, where as the timely prevention and preparation reduces the chance of developing specific complications to the level of patients with the general population. The paper discusses the recommendations developed by the British Association ofEndocrinologists 2011 and Russia in 2015, as well as the Association ofAnaesthetists of Great Britain and Ireland (2015), provides practical recommendations for the preoperative preparation, anesthetic and resuscitation provide patients with concomitant diabetes mellitus.