Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study).

BACKGROUND: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). METHODS: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. RESULTS: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1-12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. CONCLUSIONS: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. TRIAL REGISTRATION: NCT05218863 (registered 19.01.2022).

Ice structures assembled from cubic water clusters of D2d and S4 symmetry.

The study of self-assembly processes is of key importance for fundamental science and modern technologies. Cubic water clusters of D2d and S4 symmetry show great potential as building blocks for self-assembly. The objective of this paper is to construct possible ice structures formed by hydrogen bonding of these very stable water clusters. A number of such structures are herein presented, including quasi-2D and 3D ices as well as spatial layered and tubular ices. The energetics and structure of many configurations differing in the arrangement of hydrogen atoms in hydrogen bonds have been studied. It was established that the proton disorder of all such ices is of island type. The residual entropy of these ices is equal to ln(3)/4 in dimensionless form. For layered structures formed by the stacking of multiple bilayers, the determining role of the van der Waals interactions is shown. Note that, for all considered ices, the lowest-energy configurations are formed only by clusters of D2d symmetry.

Optimizing Fluid Management Guided by Volumetric Parameters in Patients with Sepsis and ARDS.

We compared two de-escalation strategies guided by either extravascular lung water or global end-diastolic volume-oriented algorithms in patients with sepsis and ARDS. Sixty patients with sepsis and ARDS were randomized to receive de-escalation fluid therapy, guided either by the extravascular lung water index (EVLWI, n = 30) or the global end-diastolic volume index (GEDVI, n = 30). In cases of GEDVI > 650 mL/m2 or EVLWI > 10 mL/kg, diuretics and/or controlled ultrafiltration were administered to achieve the cumulative 48-h fluid balance in the range of 0 to -3000 mL. During 48 h of goal-directed de-escalation therapy, we observed a decrease in the SOFA score (p < 0.05). Extravascular lung water decreased only in the EVLWI-oriented group (p < 0.001). In parallel, PaO2/FiO2 increased by 30% in the EVLWI group and by 15% in the GEDVI group (p < 0.05). The patients with direct ARDS demonstrated better responses to dehydration therapy concerning arterial oxygenation and lung fluid balance. In sepsis-induced ARDS, both fluid management strategies, based either on GEDVI or EVLWI, improved arterial oxygenation and attenuated organ dysfunction. The de-escalation therapy was more efficient for direct ARDS.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

The Validation of Cardiac Index and Stroke-Volume Variation Measured by the Pulse-Wave Transit Time-Analysis Versus Conventional Pulse-Contour Analysis After Off-Pump Coronary Artery Bypass Grafting: Observational Study.

OBJECTIVE: To compare the reliability of cardiac index (CI) and stroke-volume variation (SVV) measured by the pulse-wave transit-time (PWTT) method using estimated continuous cardiac output (esCCO) technique with conventional pulse-contour analysis after off-pump coronary artery bypass grafting (OPCAB). DESIGN: A single-center, prospective, observational study. SETTING: At a 1,000-bed university hospital. PARTICIPANTS: A total of 21 patients were enrolled after elective OPCAB. INTERVENTIONS: The study authors performed a method comparison study with simultaneous measurement of CI and SVV based on the esCCO technique (CIesCCO and esSVV, correspondingly) and pulse-contour analysis (CIPCA and SVVPCA, correspondingly). As a secondary analysis, they also assessed the trending ability of CIesCCO versus CIPCA. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 178 measurement pairs for CI, and 174 pairs for SVV during the 10 study stages. The mean bias between CIesCCO and CIPCA was 0.06 L min/m2, with limits of agreement of ± 0.92 L min/m2 and a percentage error (PE) of 35.3%. The analysis of the trending ability of CI measured by PWTT revealed a concordance rate of 70%. The mean bias between esSVV and SVVPCA was -6.1%, with limits of agreement of ± 15.5% and a PE of 137%. CONCLUSIONS: The overall performance of CIesCCO and esSVV versus CIPCA and SVVPCA is not clinically acceptable. A further improvement of the PWTT algorithm may be required for an accurate and precise assessment of CI and SVV.

Hydrogen bond arrangements in (H2O)20, 24, 28 clathrate hydrate cages: Optimization and many-body analysis.

We provide a detailed study of hydrogen bonding arrangements, relative stability, residual entropy, and an analysis of the many-body effects in the (H2O)20 (D-cage), (H2O)24 (T-cage), and (H2O)28 (H-cage) hollow cages making up structures I (sI) and II (sII) of clathrate hydrate lattices. Based on the enumeration of the possible hydrogen bonding networks for a fixed oxygen atom scaffold, the residual entropy (S0) of these three gas phase cages was estimated at 0.754 82, 0.754 44, and 0.754 17 · Nkb, where N is the number of molecules and kb is Boltzmann's constant. A previously identified descriptor of enhanced stability based on the relative arrangement and connectivity of nearest-neighbor fragments on the polyhedral water cluster [strong-weak-effective-bond model] also applies to the larger hollow cages. The three cages contain a maximum of 7, 9, and 11 such preferable arrangements of trans nearest dimer pairs with one "free" OH bond on the donor molecule (t1d dimers). The Many-Body Expansion (MBE) up to the 4-body suggests that the many-body terms vary nearly linearly with the cluster binding energy. Using a hierarchical approach of screening the relative stability of networks starting from optimizations with the TIP4P, TTM2.1-F, and MB-pol classical potentials, subsequently refining at more accurate levels of electronic structure theory (DFT and MP2), and finally correcting for zero-point energy, we were able to identify a group of four low-lying isomers of the (H2O)24 T-cage, two of which are antisymmetric and the other two form a pair of antipode configurations.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.

The Glycocalyx Shedding Influences Hemodynamic and Metabolic Response to Fluid Load in Septic Shock.

OBJECTIVE: Sepsis-associated endothelial dysfunction and degradation result in release of inflammatory mediators, compromise endothelial permeability, and impair alveolar fluid clearance leading to pulmonary edema. Excessive fluid therapy in septic shock damage the endothelial glycocalyx which will increase capillary leakage. The aim of our study was to assess the relationship of endothelial glycocalyx shedding with hemodynamic and metabolic response to fluid load in patients with septic shock. METHODS: Eighteen adult patients were included in prospective observational study. To predict the response to infusion, we performed fluid load test by using crystalloids 7 mL kg-1 for 10 minutes. The plasma concentrations of endothelial glycocalyx components including heparan sulfate proteoglycan and syndecan 1 were measured at baseline, 2, 24 hours after fluid load test. RESULTS: We observed associations of syndecan 1 with extravascular lung water index (rho = 0.48, P =.04) at baseline and of heparan sulfate proteoglycan with extravascular lung water index (rho= -0.56, P = .03) and pulse pressure variation (rho = 0.53, P = .04) at 24 hours after fluid load test. The plasma concentration of syndecan 1 correlated with lactate at baseline (rho = 0.51, P = .02) and at 24 hours after fluid load test (rho = 0.76, P = .009). At 2 hours after fluid load test, the concentration of syndecan 1 correlated with global end-diastolic volume index (rho= 0.93, P = .001) in normovolemic patients. CONCLUSIONS: The shedding of endothelial glycocalyx after fluid load test in septic shock is associated with hemodynamic and metabolic responses and related with the severity of pulmonary edema.

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update.

Background: Accidental hypothermia (AH) is an unintended decrease in body core temperature (BCT) to below 35°C. We present an update on physiological/pathophysiological changes associated with AH and rewarming from hypothermic cardiac arrest (HCA). Temperature Regulation and Metabolism: Triggered by falling skin temperature, Thyrotropin-Releasing Hormone (TRH) from hypothalamus induces release of Thyroid-Stimulating Hormone (TSH) and Prolactin from pituitary gland anterior lobe that stimulate thyroid generation of triiodothyronine and thyroxine (T4). The latter act together with noradrenaline to induce heat production by binding to adrenergic ß3-receptors in fat cells. Exposed to cold, noradrenaline prompts degradation of triglycerides from brown adipose tissue (BAT) into free fatty acids that uncouple metabolism to heat production, rather than generating adenosine triphosphate. If BAT is lacking, AH occurs more readily. Cardiac Output: Assuming a 7% drop in metabolism per °C, a BCT decrease of 10°C can reduce metabolism by 70% paralleled by a corresponding decline in CO. Consequently, it is possible to maintain adequate oxygen delivery provided correctly performed cardiopulmonary resuscitation (CPR), which might result in approximately 30% of CO generated at normal BCT. Liver and Coagulation: AH promotes coagulation disturbances following trauma and acidosis by reducing coagulation and platelet functions. Mean prothrombin and partial thromboplastin times might increase by 40-60% in moderate hypothermia. Rewarming might release tissue factor from damaged tissues, that triggers disseminated intravascular coagulation. Hypothermia might inhibit platelet aggregation and coagulation. Kidneys: Renal blood flow decreases due to vasoconstriction of afferent arterioles, electrolyte and fluid disturbances and increasing blood viscosity. Severely deranged renal function occurs particularly in the presence of rhabdomyolysis induced by severe AH combined with trauma. Conclusion: Metabolism drops 7% per °C fall in BCT, reducing CO correspondingly. Therefore, it is possible to maintain adequate oxygen delivery after 10°C drop in BCT provided correctly performed CPR. Hypothermia may facilitate rhabdomyolysis in traumatized patients. Victims suspected of HCA should be rewarmed before being pronounced dead. Rewarming avalanche victims of HCA with serum potassium > 12 mmol/L and a burial time >30 min with no air pocket, most probably be futile.

Invasive and Non-invasive Dynamic Parameters to Predict Fluid Responsiveness After Off-pump Coronary Surgery.

OBJECTIVE: This study aimed to assess the predictive value of invasive and non-invasive dynamic parameters for evaluation of fluid responsiveness after off-pump coronary artery bypass grafting. METHODS: Thirty-two adult patients after off-pump coronary surgery were enrolled into a single-center pilot prospective observational study. After arrival to the intensive care unit, all patients received standard fluid challenge test to assess fluid responsiveness. The patients with an increase in cardiac index ≥ 15% after the test were defined as fluid responders. We measured pulse pressure variation using 2 monitoring systems (PPVPiCCO and PPVNK), stroke volume variation, heart-lung interaction index, and plethysmogram variability index before and after standard fluid challenge test. RESULTS: After intensive care unit admission, the absolute values of stroke volume variation, PPVPiCCO, PPVNK, and heart-lung interaction index were significantly higher among fluid responders (P < .05). Response to standard fluid challenge test was predicted by dynamic assessment of PPVPiCCO (area under the curve 0.84), PPVNK (area under the curve 0.71), stroke volume variation (area under the curve 0.77), and heart-lung interaction index (area under the curve 0.77) (P < .05). The plethysmogram variability index value did not demonstrate any predictive ability regarding fluid responsiveness (area under the curve 0.5, P =.1). CONCLUSIONS: In patients after off-pump coronary surgery, both invasive parameters such as pulse pressure and stroke volume variations and non-invasive parameter such as heart-lung interaction index are able to predict fluid responsiveness. Thus, these dynamic parameters can be used to guide fluid therapy during the early postoperative period after off-pump coronary surgery.

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

BACKGROUND: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. OBJECTIVE: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. DESIGN: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). INTERVENTION: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. CONTROL: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. SETTING: Recruitment from 108 centers in 22 countries from 2018 to 2021. PATIENTS: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. MEASUREMENTS: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 µmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. METHODS: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Substudy results will be analyzed in 2022. LIMITATIONS: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. CONCLUSIONS: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

CONTEXTE: La plupart des patients qui prennent des médicaments antihypertenseurs continuent de les prendre le matin d'une intervention chirurgicale et pendant la période périopératoire. De plus en plus de preuves suggèrent que cette pratique pourrait entraîner l'hypotension périopératoire et augmenter le risque de complications. Ce protocole décrit une sous-étude sur l'insuffisance rénale aiguë (IRA) découlant de l'essai Perioperative Ischemic Evaluation-3 (POISE-3). Cet essai teste l'effet d'une stratégie d'évitement de l'hypotension périopératoire par rapport à une stratégie d'évitement de l'hypertension chez des patients qui subissent une chirurgie non cardiaque. OBJECTIFS: Cette sous-étude de l'essai POISE-3 vise à déterminer si une stratégie d'évitement de l'hypotension périopératoire réduit le risque d'IRA comparativement à la stratégie d'évitement de l'hypertension. TYPE D'ÉTUDE: Essai clinique randomisé à répartition 1:1 au groupe intervention (stratégie d'évitement de l'hypotension périopératoire) ou au groupe témoin (stratégie d'évitement de l'hypertension). GROUPE INTERVENTION: Si la pression artérielle systolique (PAS) avant l'opération est <130 mmHg, tous les médicaments antihypertenseurs sont suspendus le matin de la chirurgie. Si la PAS est ≥130 mmHg, certains médicaments (excluant les inhibiteurs de l'enzyme de conversion de l'angiotensine [IECA], les antagonistes du récepteur de l'angiotensine [ARA] ou les inhibiteurs de la rénine) peuvent être poursuivis de façon graduelle. Pendant la chirurgie, la pression artérielle moyenne (PAM) du patient est maintenue à ≥80 mmHg. Dans les 48 heures suivant l'intervention chirurgicale, certains médicaments antihypertenseurs (excluant les IECA, les ARA ou les inhibiteurs de la rénine) peuvent être réintroduits par étapes si la PAS est ≥130 mmHg. GROUPE TÉMOIN: Les patients reçoivent leurs médicaments antihypertenseurs habituels avant et après la chirurgie. La PAM du patient est maintenue à ≥60 mmHg de l'induction de l'anesthésie à la fin de l'intervention chirurgicale. CADRE: Recrutement à partir de 108 centres dans 22 pays entre 2018 à 2021. SUJETS: Des patients (~6 800) âgés de 45 ans et plus atteints d'athérosclérose, ou présentant un risque de l'être, devant subir une chirurgie non cardiaque et prenant des médicaments antihypertenseurs sur une base régulière. MESURES: Le principal critère d'évaluation de cette sous-étude est une IRA postopératoire définie par une hausse d'au moins 26,5 µmol/L (≥0,3 mg/dL) de la créatinine sérique dans les 48 heures suivant la randomisation ou d'au moins 50 % dans les 7 jours suivant la randomisation. MÉTHODOLOGIE: L'analyse primaire (par intention de traiter) examinera le risque relatif d'une IRA et l'intervalle de confiance à 95 % dans le groupe intervention par rapport au groupe témoin. Nous répéterons l'analyse primaire en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante (définie par un DFGe prérandomisation <60 ml/min/1,73 m2). RÉSULTATS: Les résultats de cette sous-étude seront analysés en 2022. LIMITES: Il n'est pas possible de procéder à l'insu des patients ou des prestataires de soins pour cette intervention; des mesures objectives seront toutefois utilisées pour évaluer l'IRA. CONCLUSION: Cette sous-étude fournira des estimations généralisables de l'effet d'une stratégie visant à éviter l'hypotension périopératoire sur le risque d'insuffisance rénale aiguë.

Thermal stability of water polyhedra with square faces.

The ability to form numerous crystalline modifications of ice and gas hydrate frameworks is a characteristic feature of water. In fact, this structural variety is much wider due to the proton disorder. Configurations with different arrangements of hydrogen atoms (protons) in hydrogen bonds are not equivalent in their properties. Polyhedral water clusters are convenient objects for studying the effect of proton disorder on the properties of ice-like systems. It was previously established that the stability of water polyhedra is determined by the competition of two factors. The geometric factor gives preference to tetrahedrally coordinated structures with a large number of pentagonal faces. The topological factor takes into account the number of energetically most favorable types of H-bonds. This number increases with the number of square faces. It was found that tetrahedrally coordinated structures are not the most stable. However, these calculations were performed without taking thermal effects into account (Kirov M. V., J Phys Chem A, 124:4463 - 4470, 2020). The purpose of the present article is to study the structural stability of various water polyhedra at different temperatures. In the course of modeling, using the Amoeba force field, the advantage of configurations with a large number of square faces is demonstrated. The structure and energetics of surface defects are studied. Several very stable structures of unusual shape were found, including polyhedra which contain 4-coordinated molecules and polyhedra whose O-H groups are directed to the cluster center. The comparative analysis of cluster stability includes the temperature intervals of melting-like transitions.

Rewarming From Hypothermic Cardiac Arrest Applying Extracorporeal Life Support: A Systematic Review and Meta-Analysis.

Introduction: This systematic review and meta-analysis aims at comparing outcomes of rewarming after accidental hypothermic cardiac arrest (HCA) with cardiopulmonary bypass (CPB) or/and extracorporeal membrane oxygenation (ECMO). Material and Methods: Literature searches were limited to references with an abstract in English, French or German. Additionally, we searched reference lists of included papers. Primary outcome was survival to hospital discharge. We assessed neurological outcome, differences in relative risks (RR) of surviving, as related to the applied rewarming technique, sex, asphyxia, and witnessed or unwitnessed HCA. We calculated hypothermia outcome prediction probability score after extracorporeal life support (HOPE) in patients in whom we found individual data. P < 0.05 considered significant. Results: Twenty-three case observation studies comprising 464 patients were included in a meta-analysis comparing outcomes of rewarming with CPB or/and ECMO. One-hundred-and-seventy-two patients (37%) survived to hospital discharge, 76 of 245 (31%) after CPB and 96 of 219 (44 %) after ECMO; 87 and 75%, respectively, had good neurological outcomes. Overall chance of surviving was 41% higher (P = 0.005) with ECMO as compared with CPB. A man and a woman had 46% (P = 0.043) and 31% (P = 0.115) higher chance, respectively, of surviving with ECMO as compared with CPB. Avalanche victims had the lowest chance of surviving, followed by drowning and people losing consciousness in cold environments. Assessed by logistic regression, asphyxia, unwitnessed HCA, male sex, high initial body temperature, low pH and high serum potassium (s-K+) levels were associated with reduced chance of surviving. In patients displaying individual data, overall mean predictive surviving probability (HOPE score; n = 134) was 33.9 ± 33.6% with no significant difference between ECMO and CPB-treated patients. We also surveyed 80 case reports with 96 victims of HCA, who underwent resuscitation with CPB or ECMO, without including them in the meta-analysis. Conclusions: The chance of surviving was significantly higher after rewarming with ECMO, as compared to CPB, and in patients with witnessed compared to unwitnessed HCA. Avalanche victims had the lowest probability of surviving. Male sex, high initial body temperature, low pH, and high s-K+ were factors associated with low surviving chances.

Intra-abdominal hypertension and hypoxic respiratory failure together predict adverse outcome - A sub-analysis of a prospective cohort.

PURPOSE: To assess whether the combination of intra-abdominal hypertension (IAH, intra-abdominal pressure ≥ 12 mmHg) and hypoxic respiratory failure (HRF, PaO2/FiO2 ratio < 300 mmHg) in patients receiving invasive ventilation is an independent risk factor for 90- and 28-day mortality as well as ICU- and ventilation-free days. METHODS: Mechanically ventilated patients who had blood gas analyses performed and intra-abdominal pressure measured, were included from a prospective cohort. Subgroups were defined by the absence (Group 1) or the presence of either IAH (Group 2) or HRF (Group 3) or both (Group 4). Mixed-effects regression analysis was performed. RESULTS: Ninety-day mortality increased from 16% (Group 1, n = 50) to 30% (Group 2, n = 20) and 27% (Group 3, n = 100) to 49% (Group 4, n = 142), log-rank test p < 0.001. The combination of IAH and HRF was associated with increased 90- and 28-day mortality as well as with fewer ICU- and ventilation-free days. The association with 90-day mortality was no longer present after adjustment for independent variables. However, the association with 28-day mortality, ICU- and ventilation-free days persisted after adjusting for independent variables. CONCLUSIONS: In our sub-analysis, the combination of IAH and HRF was not independently associated with 90-day mortality but independently increased the odds of 28-day mortality, and reduced the number of ICU- and ventilation-free days.

Volumetric Monitoring and Extravascular Lung Water in Perioperative Setting and Critically Ill.

In the new century, our diagnostic armamentarium has been significantly reinforced by the 'three-dimensional' volumetric haemodynamic monitoring currently available at the bedside in many perioperative and intensive care settings. The volumetric approach has improved our insight into the haemodynamic scenarios of many critical illnesses and surgical interventions, including sepsis, circulatory shock, acute respiratory distress syndrome as well as cardiothoracic and transplantation surgery. However, the influence of volumetric haemodynamic monitoring on clinical outcome is still a subject for debates. This review presents physiological background, technical details, aspects of bedside use, limitations and further perspectives of the volumetric approach to the cardiopulmonary monitoring.

Energetics of Water Polyhedra with Square Faces.

In ice and other icelike systems, the structural variety of tetrahedrally coordinated systems increases strongly due to proton disorder. Configurations that differ from each other only by the arrangement of hydrogen atoms (protons) in hydrogen bonds are nonequivalent. Polyhedral water clusters are interesting objects of study since the analysis of the energetics of these tetrahedrally coordinated systems reveals very simple regularities. For water polyhedra of the most regular shape, the simplified physical model of strong and weak effective H bonds (the SWEB model) has been developed. This model allows predicting the classes of the most stable proton configurations. The number of H bonds that are more preferable from the point of view of Coulomb interaction is the only classification criterion for this model. For water polyhedra with square faces, this model becomes less accurate. However, for such clusters, there is another essential topological indicator: the number of molecules that are completely located in the planes of square faces. The results of numerous calculations show that these two topological indices largely determine the energetics of a huge number of proton configurations in water polyhedra with square faces.

Lung Ultrasonography and Cardiac Surgery: A Narrative Review.

Pulmonary complications are common after cardiac surgery and are closely related to postoperative heart failure and adverse outcomes. Lung ultrasonography (LUS) is currently a widely accepted diagnostic approach with well-established methodology, nomenclature, accuracy, and prognostic value in numerous clinical conditions. The advantages of LUS are universally recognized and include bedside applicability, high diagnostic sensitivity and reproducibility, no radiation exposure, and low cost. However, routine perioperative ultrasonography during cardiac surgery generally is limited to echocardiography, diagnosis of pleural effusion, and as a diagnostic tool for postoperative complications in different organs, and few studies have explored the clinical outcomes in relation to LUS among cardiac patients. This narrative review presents the clinical evidence regarding LUS application in intensive care and during the perioperative period for cardiac surgery. Furthermore, this review describes the methodology and the diagnostic and prognostic accuracies of LUS. A summary of ongoing clinical trials evaluating the clinical outcomes related to LUS also is provided. Finally, this review discusses the rationale for upcoming clinical research regarding whether routine use of LUS can modify current intensive care practice and potentially affect the clinical outcomes after cardiac surgery.

Protective ventilation from ICU to operating room: state of art and new horizons.

The prevention of ventilator-associated lung injury (VALI) and postoperative pulmonary complications (PPC) is of paramount importance for improving outcomes both in the operating room and in the intensive care unit (ICU). Protective respiratory support includes a wide spectrum of interventions to decrease pulmonary stress-strain injuries. The motto 'low tidal volume for all' should become routine, both during major surgery and in the ICU, while application of a high positive end-expiratory pressure (PEEP) strategy and of alveolar recruitment maneuvers requires a personalized approach and requires further investigation. Patient self-inflicted lung injury is an important type of VALI, which should be diagnosed and mitigated at the early stage, during restoration of spontaneous breathing. This narrative review highlights the strategies used for protective positive pressure ventilation. The emerging concepts of damaging energy and power, as well as pathways to personalization of the respiratory settings, are discussed in detail. In the future, individualized approaches to protective ventilation may involve multiple respiratory settings extending beyond low tidal volume and PEEP, implemented in parallel with quantifying the risk of VALI and PPC.

Dynamic Tests to Predict Fluid Responsiveness After Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE: To test the hypothesis that a positive end-expiratory pressure test and the mini-fluid challenge predict fluid responsiveness in patients after off-pump coronary artery bypass grafting. DESIGN: Single-center pilot prospective observational study. SETTING: City Hospital #1 of Arkhangelsk, Russian Federation. PARTICIPANTS: Thirty-two adult patients after off-pump coronary artery surgery. INTERVENTIONS: To assess fluid responsiveness, after arrival to the intensive care unit, all patients received a test with increase in positive end-expiratory pressure from 5 to 20 cmH2O for 2 minutes, a mini-fluid challenge test with administration of crystalloids at 1.5 mL/kg during 2 minutes, and standard fluid challenge test using 7 mL/kg during 10 minutes. MEASUREMENTS AND MAIN RESULTS: The patients with an increase in cardiac index by ≥15% after a standard fluid challenge test were defined as fluid responders. According to receiver operating characteristic analysis, a decrease in mean arterial pressure exceeding 5 mmHg in 120 seconds of the positive end-expiratory pressure test identified fluid responsiveness with an area under the curve of 0.73 (p = 0.03). The reduction in pulse pressure and stroke volume variations by more than 2% during mini-fluid challenge test predicted positive response to fluid load with an area under the curve of 0.77 and 0.75, respectively (p < 0.05). CONCLUSION: Both the positive end-expiratory pressure test and the mini-fluid challenge test are feasible after off-pump coronary artery bypass grafting and can be used to predict fluid responsiveness in these patients.