Energetics of proton configurations in water polyhedra and hydrate frameworks: topology vs. geometry.

The water frameworks of clathrate hydrates are characterized by a small deviation from tetrahedral geometry. The faces of the hydrate cages are most often pentagonal because the square and hexagonal faces produce appreciable strains on the hydrogen bonds. However, taking into account the specific arrangement of hydrogen atoms (protons) in the hydrogen bonds complicates the picture. The pentagonal rings are inferior to square and hexagonal rings in the number of stronger types of bonds corresponding to energetically more favorable mutual orientations of H-bonded molecules. The proton configurations with a large number of energetically preferable bonds can be computed during combinatorial optimization on the base of simplified topological models. A more accurate topological model for polyhedral water clusters allows us to find a class of proton configurations that are optimal in the number of energetically favorable H-bonds, taking into account the interaction between the second and third neighbors in the network. These topological models give preference to water polyhedra and clathrate hydrate structures without pentagonal faces. We show that the geometric stability factor (tetrahedrality) is decisive for proton-disordered systems. At that time, the topological factor (maximum number of preferred H-bond types) is often dominant when searching for the lowest-energy proton configurations. The energy minimization is carried out using different molecular interaction potentials and the Tinker molecular modeling package.

In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study.

AIMS: Previous research suggests that patients undergoing upper gastrointestinal surgery are at high risk of poor postoperative outcomes. The aim of our study was to describe patient outcomes after elective upper gastrointestinal surgery at a global level. METHODS: Prospective analysis of data collected during an international seven-day cohort study of 474 hospitals in 27 countries. Patients undergoing elective upper gastrointestinal surgery were recruited. Outcome measures were in-hospital complications and mortality at 30-days. Results are presented as n(%) and odds ratios with 95% confidence intervals. RESULTS: 2139 patients were included, of whom 498 (23.2%) developed one or more postoperative complications, with 30 deaths (1.4%). Patients with complications had longer median hospital stay 11 (6-18) days vs. 5 (2-10) days. Infectious complications were most frequent, affecting 368 (17.2%) patients. 328 (15.3%) patients were admitted to critical care postoperatively, of whom 161 (49.1%) developed a complication with 14 deaths (4.3%). In a multivariable logistic regression model we identified age (OR 1.02 [1.01-1.03]), American Society of Anesthesiologists physical status III (OR 2.12 [1.44-3.16]) and IV (OR 3.23 [1.72-6.09]), surgery for cancer (OR 1.63 [1.27-2.11]), open procedure (OR 1.40 [1.10-1.78]), intermediate surgery (OR 1.75 [1.12-2.81]) and major surgery (OR 2.65 [1.72-4.23]) as independent risk factors for postoperative complications. Patients undergoing major surgery for upper gastrointestinal cancer experienced twice the rate of complications compared to those undergoing other procedures (224/578 patients [38.8%] versus 274/1561 patients [17.6%]). CONCLUSIONS: Complications and death are common after upper gastrointestinal surgery. Patients undergoing major surgery for cancer are at greatest risk.

Classification of hydrogen bond flips in small water polyhedra applied to concerted proton tunneling.

Recently a new mechanism of proton tunneling in a prism-like water hexamer was revealed [Richardson et al., Science, 2016, 351, 1310]. The tunneling motion involves the concerted breaking of two hydrogen bonds and rotations of two nearest water molecules. Eventually, this structural transformation means flipping one of the hydrogen bonds without the creation of defects in the hydrogen bond network. On the surface of polyhedral water clusters, there are five essentially different types of hydrogen bonds, and only two of them can be changed in this manner. In this article, the topological classification of such transformations for five small water polyhedra: triangular, pentagonal, and hexagonal prisms as well as cube and polyhedron 4454, consisting of four square and four pentagonal faces, is presented. Our classification includes the enumeration of all possible one-bond-flips with consideration of the types of hydrogen bonds on the polyhedral surface. Attention is paid to the most stable proton configurations which can be studied in experiments. It was established that a number of one-bond-flip transitions between the low energy configurations are possible in clusters in the shape of triangular and pentagonal prisms.

[CONTINUOUS HEMOGLOBIN MONITORING USING PULSE CO-OXIMETRY IN CARDIAC SURGERY.]

THE AIM: To assess the accuracy ofcontinuous hemoglobin monitoring using pulse co-oximetry and revealfactors affecting the results of the measurements during early postoperative period in cardiac surgery. MATERIALS AND METHODS: 27 patients undergoing off-pump CABG and 16patients after elective complex (repair or replacement of two or more valves) or combined (valve and coronary artery) cardiac surgery requiring CPB were enrolled into a prospective observational study. Both groups received continuous hemoglobin monitoring using pulse co-oximetry (SpHb). During early postoperative period SpHb was compared with hemoglobin concentration in the arterial blood (Hbart). RESULTS: Wefoundpositive correlation between SpHb and Hb in both groups (rho =0,29, p < 0,05 u rho=0,34; p<0.005 respectively). The Bland-Altman analysis showed a bias ? limits of agreement (?I.96 SD) between the continuously measured hemoglobin and reference arterial blood hemoglobin concentration of -6,0 ? 41,0 g/l in the off-pump group and 7,7 k 31,0 g/l in the CPB group. CONCLUSIONS: Hemoglobin measurement using pulse co-oximetry does not provide acceptable accuracy during early postoperative period in cardiac surgery. Applicability of this technology is influenced by vascular tone, systemic and regional tissue hypoperfusion.

POSTOPERATIVE PULMONARY COMPLICATIONS AND ACUTE RESPIRATORY DISTRESS SYNDROME -BETTER PREVENT THEN TREAT.

In parallel with increasing number, duration and extensiveness of surgical interventions, postoperative pulmonary complications (PPC) and acute respiratory distress syndrome (ARDS) remain the major challenges for anesthesiologists and surgical ICU physicians. PPC and ARDS have multiple risk factors that should be recognized early and modifed within the appropriate "time window ". Today we possess reliable models (ARISCAT LIPS, EALI etc.) to predict the risk of non-infectious (hypoxemia, atelectases, pleuritis) and infectious PPC (postoperative pneumonia). The bundle of primaty and secondary prevention strategies is available and can be implemented both in the perioperative settings and in the ICU in patients at risk of PPC and ARDS. The prophylactic approach is realized as a bundle of strategies presented in "Checklist for Lung Injury Prevention" (CLIP). The bundle of preventive protective ventilation comprises low tidal volume (6-8 ml/kg predicted body weight), control of respiratory plateau and driving pressures, moderate positive end- expiratory pressure (PEEPS cm H20), and minimal safe level of inspired oxygen fraction. Pharmacological prevention ofARDS has shown quite satisfactory experimental results and needs further clinicql investigations.

[MONITORING OF CEREBRAL OXYGENATION AND COGNITIVE FUNCTION IN CAROTID ENDARTERECTOMY: THE ROLE OF TRANSIENT BYPASS OF CAROTID ARTERY].

UNLABELLED: BACKGROUND AND OBJECTVE: Carotid endarterectomy (CEE) is an effective surgical technique to prevent cerebral ischemia and stroke, but can be associated with intervention-related complications. The surgical shunting of the intervention area may reduce the risk of the intraoperative ipsilateral cerebral ischemia following the carotid artery clamping but is controversial. The goal of this study was to compare the cerebral tissue oxygen saturation (SctO2) and early changes of cognitive functions in CEE in the settings of transient vascular bypass and without this method. METHODS: 45 adult patients were randomized to either the bypass group (the Bypass group, n = 24) or the Controls / No Bypass (the Control group, n = 21). All patients were monitored for invasive arterial pressure, SpO, EtCO,, and cerebral oxygenation (SctO2, Fore-Sight, CASMED, USA) over the contra- and ipsilateral frontal head areas. The cognitive functions were assessed using series of Montreal Cognitive Assessment score (MoCA) before the intervention, and on 6 and 36 hrs after the CEE. RESULTS: We did not find intergroup differences in the surgery duration, degree of stenosis and baseline cognitive function. The values of SctO2 reduced significantly only above contralateral side; these changes were attenuated in the shunt group. There were no intergroup differences in postoperative cognitive function. CONCLUSION: Empiric transient vascular bypass during carotid endarterectomy did not result in significant changes of the ipsilateral cerebral oxygenation, hyperperfusion and cognitive function, but attenuated the decrease of SctO2 over the contralateral hemisphere.

[VOLEMIC STATUS AND THE PHASIC APPROACH TO THE TREATMENT OF CRITICAL STATES--NEW OPPORTUNITES AND PROSPECTS].

Current guidelines suggest that an early and aggressive fluid therapy is the best rescue approach to restore and preserve cardiac index, organ function and decrease the risk of multiple organ failure in shock of various origin. However, escala- tion of fluid resuscitation is a double-edged sword often associated with reperfusion, glicocalyx injury, capillary leakage, delayed weight gain and heperhydration. The body of evidences demons trates that an excessive fluid load in ICUpatient with global increased permeability syndrome, and, particularly, in ARDS and acute kidney injury can be devastating, particularly when guided with central venous pressure. This important therapeutical conflict highlights the importance of the emerging concept of "phasic "fluid management and physiologic monitoring. The type and volume of the fluid should be thoroughly selected in accordance with the phase of shock, risk of impending organ dysfunction and individual co-morbidity. The phasic approach, along with individualized early and delayed goal-directed protocols might fasten the resolution of organ dysfunction, reduce the duration of shock and mechanical ventilation and improve the outcomes.

[THE EFFICACY AND SAFETY OF DEXMEDETOMIDINE FOR SEDATION OF PATIENTS DURING PROLONGED MECHANICAL VENTILATION IN INTENSIVE CARE UNITS (RUSSIAN MULTICENTER STUDY RESULTS)].

A multicenter prospective study investigated the efficacy and safety dexmedetomidine of sedation in 103 patients during long-term (> 12 h) mechanical ventilation and in cases of delirium. Protocol of sedation included intravenous infusions of dexmedetomidine 1.4/kg/h and administering of analgesic drugs, and if necessary--sedative drugs (propofol, midazolam). Group 1 included 69 patients in whom dexmedetomidine sedation was performed for prolonged mechanical ventilation. Group 2 consisted of 34 patients in whom dexmedetomidine was used due to development of delirious state. Dexmedetomi- dine was used as an infusion of 0.7 mg/kg for 1 hour with further correction of dosage. We recorded a level of sedation by RASS, the need for the appointment of other drugs with sedative effects, the duration of mechanical ventilation, length of ICU stay. The infusion of dexmedetomidine can provide a target level of sedation for RASS from 0 to -3 at 80-90% of patients with surgical and therapeutic profile who underwent prolonged mechanical ventilation. The frequency of adverse events appeared due to the development of bradycardia, hypotension. In the use of dexmedetomidine bolus injection should be avoided.

[Monitoring of intra-abdominal pressure and abdominal perfusion pressure in urgent abdominal surgery].

GOALS OF THE STUDY: To evaluate the changes in intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) during perioperative period in urgent abdominal surgery and to assess the relationship of these parameters with gas exchange and tissue perfusion. MATERIALS AND METHODS: Twenty-four patients undergoing emergency abdominal surgery were enrolled into a prospective observational study. We recorded IAP APP, mean arterial pressure, arterial and venous blood gases after induction of anesthesia, at the end of surgery, and 6, 12, 48 and 72 h postoperatively. LAP was measured by nasogastric tube using CiMON monitor (Pulsion Medical Systems, Germany). In addition, we studied the relationship of IAP and APP with blood gases parameters. RESULTS: We observed perioperative increase of IAP (> 12 mm Hg) in 75% of enrolled patients, tendency to postoperative rise of IAP and transient increase of arterial lactate at 6 h after surgery. APP remained within normal values. We found positive correlation of APP with PaO2/FiO2 and ScvO2 at 72 hours after surgery. CONCLUSION: Transient perioperative increase of IAP was observed in 75% patients undergoing urgent abdominal surgery; however in parallel with intensive care the abdominal perfusion pressure remained within normal values. Abdominal perfusion is related with arterial oxygenation and central venous saturation.

Validation of cardiac output monitoring based on uncalibrated pulse contour analysis vs transpulmonary thermodilution during off-pump coronary artery bypass grafting.

BACKGROUND: Cardiac output monitoring, as a part of a goal-directed haemodynamic management, has been shown to improve perioperative outcome in high-risk patients undergoing major surgical interventions. However, thorough validation of cardiac output monitoring devices in different clinical conditions is warranted. The aim of our study was to compare the reliability of a novel system for cardiac index (CI) monitoring based on uncalibrated pulse contour analysis (UPCA) with transpulmonary thermodilution (TPTD) during off-pump coronary artery bypass grafting (OPCAB). METHODS: Twenty patients undergoing elective OPCAB were enrolled into the study. CI measured by means of UPCA (CIUPCA) was validated against CI determined with TPTD technique (CITPTD). Parallel measurements of CI were performed at nine stages during the surgery and after operation. We assessed the accuracy and the precision of individual values and the agreement of trends of changes in CI. RESULTS: Totally, 180 pairs of data were collected. There was a significant correlation between CIUPCA and CITPTD (ρ=0.836, P<0.01). According to a Bland-Altman analysis, the mean bias between the methods was -0.14 litre min(-1) m(-2) with limits of agreement of ±0.82 litre min(-1) m(-2) and a percentage error of 31%. A polar plot trend analysis revealed acceptable angular bias (-0.54°), increased radial limits of agreement (±52.7°), and decreased polar concordance rate (74%). CONCLUSIONS: In OPCAB, UPCA provides accurate and precise CI measurements compared with TPTD. However, the ability of this method to follow trends in cardiac output is poor. CLINICAL TRIAL REGISTRATION: NCT01773720 (ClinicalTrials.gov).

[Choice of optimal perfusion flow rate during surgical correction of combined acquired heart diseases].

Cardiac output during the use of cardiopulmonary bypass (CPB) is defined by perfusion flow rate, which is calculated by multiplying the perfusion index (PI) on the body surface area. To date, there is no clear definition of an optimal PI and flow rate of perfusion. 60 patients operated with CPB were enrolled in the prospective study to determine the relations between different modes of perfusion and oxygen transport during surgical correction of combined valvular heart disease. Calculation of the CPB flow rate was based on PI 2.5 and 3.0 l/min/m2. Results of the study demonstrate that perfusion based on PI 2.5 l/min/m2 provides more stable oxygen transport parameters and reduces the time of ICU stay in comparison with the flow rate based on PI 3.0 l/min/m2.

[Comparison of sevoflurane and propofol anesthesia for aortocoronary bypass surgery without artificial circulation].

UNLABELLED: The purpose of the study was to compare the effectiveness of sevoflurane and propofol during combined anesthesia with epidural component during aortocoronary bypass surgery without artificial circulation. MATERIALS AND METHODS: The study included 24 patients with ischemic heart disease. All patients underwent aortocoronary bypass surgery on the working heart (from 1 to 5 bypasses) under combined anesthesia (propofol or sevoflurane with epidural anesthesia with the use of ropicavaine and fentanyl). Induction of anesthesia was carried out by midasolam 0.06 mg/kg, propofol 1-1.5 mg/kg, fentanyl 2.5 mcg/kg, myorelaxation was reached by pipecuronium bromide 0.1 mg/kg. Patients were randomized into propofol group (n = 12) and sevoflurane group (n = 12). Both groups received low flow anesthesia (1l/min) with the use of Drager Primus anesthesia workstation. Anesthesia in the first group was maintained by propofol 3-5 mg/kg/h, in the second group by sevoflurane 0.5-3 vol.%. In both groups additional fentanyl was administered in the dose of 1.2 -1.5 mcg/kg/h. RESULTS: In the postoperative period the increase of the stroke volume and decrease of blood plasma lactate were noticed in the sevoflurane group. The postoperative pain, 6 hours after the aortocoronary bypass surgery in the control group was evidently higher according to Visual Analogue Scale. CONCLUSION: Use of sevorane as a component of combined anesthesia during aortocoronary bypass surgery allows to improve the performance of the myocardium, reduce the severity of hypoperfusion in the perioperative period and reduce the severity of pain after the surgery compared to propofol anesthesia.

[Central venous blood oxygen saturation and venous to arterial PCO2 difference after combined heart valve surgery].

The aim of our study was to investigate the relationship between central venous oxygen saturation (ScvO2) and venous-to-arterial difference in PCO2 (Pv-aCO2) and their role in the assessment of balance between oxygen delivery and consumption after combined valve surgery. The prospective observation study included 38 adult patients with acquired valvular hear diseases, requiring surgical correction of two or more valves using cardiopulmonary bypass. All patients were divided into 2 groups according to the central value of central venous oxygen saturation (ScvO2): low ScvO2 (ScvO2 < 70%) and high ScvO2 (ScvO2 > 70%). In both groups blood gases, Pv-aCO2, lactate concentration, hemodynamic parameters, cardiac index, oxygen delivery and oxygen consumption were assessed. During the postoperative period there was a decrease of ScvO2 < 70% in 26% of patients which was accompanied by increased Pv-aCO2 > 5 mmHg and by risen oxygen consumption. We observed a moderate correlation between ScvO2 and Pv-aCO2 during the early postoperative period: at the end of surgery, 6 and 12 hours after it (rho = -0.53; -0.62 and -0.43 respectively, n = 38, p < 0.01). The changes in ScvO2 and Pv-aCO2 regressed after 24 hours in ICU. Thus, decreased ScvO2 and increased Pv-aCO2 after combined valve surgery are related and reflect the rise in oxygen consumption.

Complications related to less-invasive haemodynamic monitoring.

BACKGROUND: The aim of this study was to evaluate the type and incidence of complications during insertion, maintenance, and withdrawal of central arterial catheters used for transpulmonary thermodilution haemodynamic monitoring (PiCCO™). METHODS: We conducted a prospective, observational, multicentre study in 14 European intensive care units (six countries). A total of 514 consecutive patients in whom haemodynamic monitoring by PiCCO™ was indicated were studied. RESULTS: Five hundred and fourteen PiCCO catheters (475 in femoral, 26 in radial, nine in axillary, and four in brachial arteries) were inserted. Arterial access was obtained on the first attempt in 86.4% of the patients. Minor problems such as oozing after insertion (3.3%) or removal of the catheter (3.5%) were observed, but no episodes of serious bleeding (more than 50 ml) were recorded. Small local haematomas were observed after insertion (4.5%) and after removal (1.2%) of the catheter. These complications were not more frequent in patients with coagulation abnormalities. The incidence of site inflammation and catheter-related infection was 2% and 0.78%, respectively. Other complications such as ischaemia (0.4%), pulse loss (0.4%), or femoral artery thrombosis (0.2%) were rare, transient, and all resolved with catheter removal or embolectomy, respectively. CONCLUSIONS: In this series of patients, central arterial catheters used for PiCCO™ monitoring were demonstrated to be a safe alternative for advanced haemodynamic monitoring.

The effects of methylene blue on ovine post-pneumonectomy pulmonary oedema.

BACKGROUND: We recently reported that post-pneumonectomy pulmonary oedema (PPO) occurs after ventilating the remaining lung with excessive tidal volumes. Studies in small animals have indicated that nitric oxide (NO) release increases in hyper-inflated lungs, but confirmatory evidence from larger animals is still lacking. We hypothesized that PPO could be prevented by methylene blue (MB), an inhibitor of NO synthase. METHODS: Sheep were subjected to a right-sided pneumonectomy (PE) and randomly assigned to a protectively ventilated group ((PROTV group, n=7) with tidal volumes of 6 ml/kg at 20 inflations/min and a positive end-expiratory pressure (PEEP) of 2 cmH(2)O, and two groups undergoing 'injurious ventilation' (INJV) with tidal volumes of 12 ml/kg and zero end-expiratory pressure (ZEEP), a control group (INJV group, n=7) and a treatment group subjected to MB 1 h after PE (INJV+MB group, n=7). Haemodynamic variables, lung mechanics, blood gases and plasma nitrites and nitrates (NOx) were determined. RESULTS: PE reduced pulmonary blood volume, extravascular lung water (EVLWI) and quasistatic lung compliance in all groups, in parallel with a rise in peak airway pressure (P<0.05). In the INJV group, pulmonary arterial pressure, EVLWI and pulmonary vascular permeability index increased and arterial oxygenation decreased towards cessation of the experiments. These changes were not antagonized by MB. Plasma NOx increased in all the groups compared with baseline, but with no intergroup difference. CONCLUSION: MB did not reduce PPO and accumulation of NOx in sheep subjected to ventilation with excessive tidal volumes and ZEEP.

Radiographic lung density assessed by computed tomography is associated with extravascular lung water content.

BACKGROUND: We hypothesized that in acute lung injury (ALI), the volume of pulmonary tissue with aqueous density, as determined by spiral computed tomography (CT), is associated with extravascular lung water content. Our aim was to compare tissue volume index, as assessed by CT, before and after oleic acid-induced ALI, with extravascular lung water indexes (EVLWI), determined with single transpulmonary thermodilution (EVLWI(STD)), thermal-dye dilution (EVLWI(TDD)), and postmortem gravimetry (EVLWI(G)). METHODS: Seven instrumented sheep received an intravenous infusion of oleic acid 0.08 ml/kg (OA group) and four animals had vehicle only (Control group). The day before, and immediately after the experiment, sheep were anesthetized to undergo quantitative CT examinations during a short breath hold. Hemodynamics, oxygenation, EVLWI(STD), and EVLW(TDD) were registered. Linear regression analysis was used to assess the relationships between EVLWI(STD), EVLW(TDD), EVLWI(G), and lung tissue volume index (TVI(CT)) determined with CT. RESULTS: In the OA group, total lung volume increased compared with Controls. Poorly and non-aerated lung volumes increased a 3.6- and 4.9-fold, respectively, and TVI(CT) almost doubled. EVLWI(STD), EVLWI(TDD), and TVI(CT) were associated significantly with EVLWI(G) (r=0.85, 0.90, and 0.88, respectively; P<0.001). TVI(CT) deviated from the reference EVLWI(G) values to the greatest extent with a mean bias +/- 2SD of 4.0 +/- 6.0 ml/kg. CONCLUSIONS: In ovine oleic acid-induced ALI, lung tissue volume, as assessed by quantitative CT, is in close agreement with EVLWI, as determined by indicator dilution methods and postmortem gravimetry, but overestimates lung fluid content.

[Use of microstream capnography and alveolar recruitment during off-pump coronary artery bypass grafting].

The aim of the study was to investigate changes in EtCO2 and its correlation with PaCO2, and cardiac function during off-pump coronary artery bypass grafting (OPCAB) and to evaluate whether the recruitment maneuver was effective in improving gas exchange after OPCAB. Twenty adult patients scheduled for elective OPCAB were enrolled in a prospective randomized study. Anesthesia was maintained with midazolam, propofol, and fentanyl. After OPCAB the patients were randomized to a control group receiving conventional ventilation (n=10) or to a RM group (n=10) having ventilation and RM. RM was performed at min 15 after transfer to an ICU, by increasing airway pressure to 40 cm H2O for 40 sec subsequently adjusting PEEP to a level of 2 cm H2O above the lower inflection point of the pressure-volume curve. The measurements included hemodynamics, microstream capnography, respiratory parameters, and blood gasses. The baseline EtCO2 correlated with PaCO2 and cardiac index in both group (r = 0.7 and 0.81, respectively; p < 0.05). In the control group, OPCAB was followed by a rise in PaCO2 and worsening of arterial oxygenation (p < 0.05). After recruitment, EtCO, increased transiently whereas PaO2/FiO2 return to the baseline level. There was a moderate correlation between EtCO2 and PaCO2 before and after RM (r = 0.7 and 0.8, respectively; p < 0.05). The Bland-Altman analysis has shown that the difference between PaCO2 an EtCO2 was 1.9 +/- 11.4 mm Hg (M +/- 2SD). Thus, during OPCAB, EtCO2 measured by microstream capnography cor related well with PaCO2 and cardiac function. The use of RM after OPCAB increases CO2 elimination and improve arterial oxygenation.