Intraoperative Vasoactive Medications and Perioperative Outcomes in Liver Transplantation: A Systematic Review and Network Meta-analyses.

We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.

Liquid-Liquid Phase Separation of the Intrinsically Disordered Domain of the Fused in Sarcoma Protein Results in Substantial Slowing of Hydration Dynamics.

Formation of liquid condensates plays a critical role in biology via localization of different components or via altered hydrodynamic transport, yet the hydrogen-bonding environment within condensates, pivotal for solvation, has remained elusive. We explore the hydrogen-bond dynamics within condensates formed by the low-complexity domain of the fused in sarcoma protein. Probing the hydrogen-bond dynamics sensed by condensate proteins using two-dimensional infrared spectroscopy of the protein amide I vibrations, we find that frequency-frequency correlations of the amide I vibration decay on a picosecond time scale. Interestingly, these dynamics are markedly slower for proteins in the condensate than in a homogeneous protein solution, indicative of different hydration dynamics. All-atom molecular dynamics simulations confirm that lifetimes of hydrogen-bonds between water and the protein are longer in the condensates than in the protein in solution. Altered hydrogen-bonding dynamics may contribute to unique solvation and reaction dynamics in such condensates.

Synthesis of 3-Alkyl Oxazolidines, Derived from 2-Hydroxymethyl Piperidine, as Analytical Standards for the Analysis of Volatile Aldehydes in the Workplace.

Hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-15 for the quantitative analysis of various aldehydes were obtained in good yield via the condensation reaction of 2-hydroxymethylpiperidine (2-HMP) with aldehydes under mild conditions. When acrolein was used, the bicyclic 17 was obtained. This novel compound has suitable physical characteristics for an analytical standard. The hexahydro-3-vinyl-3H-oxazolo[3,4-a]pyridine 16 can be obtained at higher temperatures using an excess of acrolein (3 equiv). Following the same procedure as for 16, but with an excess of 2-HMP (2 equiv), a diastereomeric mixture of 18/19, which are both bisadducts of 2-HMP with acrolein, was obtained. The latter mixture can be easily converted into pure 18. Mechanistically, a thorough 1H-NMR study did not show any evidence that the condensation reaction proceeded via an enamine. The reaction probably proceeded through an elusive hemiaminal and fleeting iminium ion, which underwent subsequent cyclization to give hexahydro-3-alkyl-3H-oxazolo[3,4-a]pyridines 4-16. The reaction pathways for the preparation of 4-18 are described.

Effects of an open lung extubation strategy compared with a conventional extubation strategy on postoperative pulmonary complications after general anesthesia: a single-centre pilot randomized controlled trial.

PURPOSE: Postoperative pulmonary complications (PPCs) are a common cause of morbidity. Postoperative atelectasis is thought to be a significant risk factor in their development. Recent imaging studies suggest that patients' extubation may result in similar postoperative atelectasis regardless of the intraoperative mechanical ventilation strategy used. In this pilot trial, we hypothesized that a study investigating the effects of an open lung extubation strategy compared with a conventional one on PPCs would be feasible. METHODS: We conducted a pilot, single-centre, double-blinded randomized controlled trial. Adult patients at moderate to high risk of PPCs and scheduled for elective surgery were eligible. Patients were randomized to an open lung extubation strategy (semirecumbent position, fraction of inspired oxygen [FIO2] 50%, pressure support ventilation, unchanged positive end-expiratory pressure) or to a conventional extubation strategy (dorsal decubitus position, FIO2 100%, manual bag ventilation). The primary feasibility outcome was global protocol adherence while the primary exploratory efficacy outcome was PPCs. RESULTS: We randomized 35 patients to the conventional extubation group and 34 to the open lung extubation group. We observed a global protocol adherence of 96% (95% confidence interval, 88 to 99), which was not different between groups. Eight PPCs occurred (two in the conventional extubation group vs six in the open lung extubation group). Less postoperative supplemental oxygen and better lung aeration were observed in the open lung extubation group. CONCLUSIONS: In this single-centre pilot trial, we observed excellent feasibility. A multicentre pilot trial comparing the effect of an open lung extubation strategy with that of a conventional extubation strategy on the occurrence of PPCs is feasible. STUDY REGISTRATION DATE: ClinicalTrials.gov (NCT04993001); registered 6 August 2021.

RéSUMé: OBJECTIF: Les complications pulmonaires postopératoires (CPP) sont une cause fréquente de morbidité. L'atélectasie postopératoire est considérée comme un facteur de risque important de CPP. Des études d'imagerie récentes suggèrent que l'extubation des patient·es peut entraîner une atélectasie postopératoire semblable, quelle que soit la stratégie de ventilation mécanique peropératoire utilisée. Dans cet essai pilote, nous avons émis l'hypothèse qu'une étude examinant les effets sur les CPP d'une stratégie d'extubation à poumon ouvert par rapport à une stratégie d'extubation conventionnelle serait réalisable. MéTHODE: Nous avons mené une étude randomisée contrôlée pilote, monocentrique et à double insu. Les patient·es adultes présentant un risque modéré à élevé de CPP et devant bénéficier d'une chirurgie non urgente étaient éligibles. Les patient·es ont été randomisé·es à une prise en charge par une stratégie d'extubation à poumon ouvert (position semi-couchée, fraction d'oxygène inspiré [FIO2] 50 %, ventilation par aide inspiratoire, pression positive télé-expiratoire inchangée) ou à une stratégie d'extubation conventionnelle (décubitus dorsal, FIO2 100 %, ventilation manuelle par masque). Le principal critère de faisabilité était l'adhésion au protocole global, tandis que les CPP constituaient le principal critère d'efficacité exploratoire. RéSULTATS: Nous avons randomisé 35 patient·es dans le groupe d'extubation conventionnelle et 34 dans le groupe d'extubation à poumon ouvert. Nous avons observé une adhésion globale au protocole de 96 % (intervalle de confiance à 95 %, 88 à 99), qui n'était pas différente entre les groupes. Huit CPP sont survenues (deux dans le groupe d'extubation conventionnelle vs six dans le groupe d'extubation à poumon ouvert). Nous avons observé des besoins moins importants en oxygène supplémentaire postopératoire et une meilleure aération pulmonaire dans le groupe extubé à poumon ouvert. CONCLUSION: Dans cet essai pilote monocentrique, nous avons observé une excellente faisabilité. Une étude pilote multicentrique comparant l'effet d'une stratégie d'extubation à poumon ouvert à celui d'une stratégie d'extubation conventionnelle sur la survenue de CPP est réalisable. DATE D'ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04993001); enregistrée le 6 août 2021.

Emerging Applications of Extracardiac Ultrasound in Critically Ill Cardiac Patients.

Point-of-care ultrasound has evolved as an invaluable diagnostic modality and procedural guidance tool in the care of critically ill cardiac patients. Beyond focused cardiac ultrasound, additional extracardiac ultrasound modalities may provide important information at the bedside. In addition to new uses of existing modalities, such as pulsed-wave Doppler ultrasound, the development of new applications is fostered by the implementation of additional features in mid-range ultrasound machines commonly acquired for intensive care units, such as tissue elastography, speckle tracking, and contrast-enhanced ultrasound quantification software. This review explores several areas in which ultrasound imaging technology may transform care in the future. First, we review how lung ultrasound in mechanically ventilated patients can enable the personalization of ventilator parameters and help to liberate them from mechanical ventilation. Second, we review the role of venous Doppler in the assessment of organ congestion and how tissue elastography may complement this application. Finally, we explore how contrast-enhanced ultrasound could be used to assess changes in organ perfusion.

Induced asymmetries in membranes.

Lipid asymmetry in plasma membrane of eukaryotes is ubiquitous. The first measurements reported compositional asymmetry: phosphatidylethanolamine and phosphatidylserine are mostly on the cytoplasmic leafet, while phosphatidylcholine and sphingomyelin are mostly on the exoplasmic leaflet. More recent experiments using lipidomics have evidenced the presence of saturation asymmetry between the two leaflets. A question that naturally arises is why such an asymmetry? To complicate matters, it is still largely unknown in which leaflet cholesterol lies. Here, we use chemical potentials to mimic flippase proteins responsible for maintenance of compositional asymmetry in silico. We show that saturation asymmetry naturally arises as a byproduct of phospholipid number asymmetry and sphingomyelin contents, thereby showing that some reported asymmetries may naturally result from others and do not necessarily require being externally driven. We also show that plasmalogen lipids' tendency to be highly unsaturated is also natural. Additionally, we tackle the problem of cholesterol and show that, while it is influenced by all asymmetries, the resulting cholesterol asymmetry tends to be fairly mild.

On kinetics and extreme values in systems with random interactions.

Biological environments such as the cytoplasm are comprised of many different molecules, which makes explicit modeling intractable. In the spirit of Wigner, one may be tempted to assume interactions to derive from a random distribution. Via this approximation, the system can be efficiently treated in the mean-field, and general statements about expected behavior of such systems can be made. Here, I study systems of particles interacting via random potentials, outside of mean-field approximations. These systems exhibit a phase transition temperature, under which part of the components precipitate. The nature of this transition appears to be non-universal, and to depend intimately on the underlying distribution of interactions. Above the phase transition temperature, the system can be efficiently treated using a Bethe approximation, which shows a dependence on extreme value statistics. Relaxation timescales of this system tend to be slow, but can be made arbitrarily fast by increasing the number of neighbors of each particle.

The Crucial Role of Solvation Forces in the Steric Stabilization of Nanoplatelets.

The steric stability of inorganic colloidal particles in an apolar solvent is usually described in terms of the balance between three contributions: the van der Waals attraction, the free energy of mixing, and the ligand compression. However, in the case of nanoparticles, the discrete nature of the ligand shell and the solvent has to be taken into account. Cadmium selenide nanoplatelets are a special case. They combine a weak van der Waals attraction and a large facet to particle size ratio. We use coarse grained molecular dynamics simulations of nanoplatelets in octane to demonstrate that solvation forces are strong enough to induce the formation of nanoplatelet stacks and by that have a crucial impact on the steric stability. In particular, we demonstrate that for sufficiently large nanoplatelets, solvation forces are proportional to the interacting facet area, and their strength is intrinsically tied to the softness of the ligand shell.

Regional pleural strain measurements during mechanical ventilation using ultrasound elastography: A randomized, crossover, proof of concept physiologic study.

Background: Mechanical ventilation is a common therapy in operating rooms and intensive care units. When ill-adapted, it can lead to ventilator-induced lung injury (VILI), which is associated with poor outcomes. Excessive regional pulmonary strain is thought to be a major mechanism responsible for VILI. Scarce bedside methods exist to measure regional pulmonary strain. We propose a novel way to measure regional pleural strain using ultrasound elastography. The objective of this study was to assess the feasibility and reliability of pleural strain measurement by ultrasound elastography and to determine if elastography parameters would correlate with varying tidal volumes. Methods: A single-blind randomized crossover proof of concept study was conducted July to October 2017 at a tertiary care referral center. Ten patients requiring general anesthesia for elective surgery were recruited. After induction, patients received tidal volumes of 6, 8, 10, and 12 mL.kg-1 in random order, while pleural ultrasound cineloops were acquired at 4 standardized locations. Ultrasound radiofrequency speckle tracking allowed computing various pleural translation, strain and shear components. We screened 6 elastography parameters (lateral translation, lateral absolute translation, lateral strain, lateral absolute strain, lateral absolute shear and Von Mises Strain) to identify those with the best dose-response with tidal volumes using linear mixed effect models. Goodness-of-fit was assessed by the coefficient of determination. Intraobserver, interobserver and test-retest reliability were calculated using intraclass correlation coefficients. Results: Analysis was possible in 90.7% of ultrasound cineloops. Lateral absolute shear, lateral absolute strain and Von Mises strain varied significantly with tidal volume and offered the best dose-responses and data modeling fits. Point estimates for intraobserver reliability measures were excellent for all 3 parameters (0.94, 0.94, and 0.93, respectively). Point estimates for interobserver (0.84, 0.83, and 0.77, respectively) and test-retest (0.85, 0.82, and 0.76, respectively) reliability measures were good. Conclusion: Strain imaging is feasible and reproducible. Future studies will have to investigate the clinical relevance of this novel imaging modality. Clinical trial registration: www.Clinicaltrials.gov, identifier NCT03092557.

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

Importance: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. Objective: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, Setting, and Participants: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions: Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main Outcomes and Measures: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001). Conclusions and Relevance: Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02462590.

Computer simulations of lipid regulation by molecular semigrand canonical ensembles.

The plasma membrane is the interface between cells and exterior media. Although its existence has been known for a long time, organization of its constituent lipids remain a challenge. Recently, we have proposed that lipid populations may be controlled by chemical potentials of different lipid species, resulting in semigrand canonical thermodynamic ensembles. However, the currently available molecular dynamics software packages do not facilitate the control of chemical potentials at the molecular level. Here, we propose a variation of existing algorithms that efficiently characterizes and controls the chemical nature of each lipid. Additionally, we allow coupling with collective variables and show that it can be used to dynamically create asymmetric membranes. This algorithm is openly available as a plugin for the HOOMD-Blue molecular dynamics engine.

Finite-size transitions in complex membranes.

The lipid-raft hypothesis postulates that cell membranes possess some degree of lateral organization. The hypothesis has attracted much attention while remaining controversial, with an underlying mechanism that remains elusive. One idea that supports rafts relies on the membrane lying near a critical point. Although supported by experimental evidence, holding a many-component membrane at criticality requires a delicate tuning of all components-a daunting task. Here, we propose a coherent framework to reconcile critical behavior and lipid regulation. Using a lattice model, we show that lipid regulation of a complex membrane, i.e., allowing composition to fluctuate based on relative chemical potentials, can lead to critical behavior. The results are robust against specific values of the chemical potentials. Instead of a conventional transition point, criticality is observed over a large temperature range. This surprising behavior arises from finite-size effects, causing nonequivalent time and space averages. The instantaneous lipid distribution effectively develops a translational symmetry, which we relate to long-wavelength Goldstone modes. The framework is robust and reproduces important experimental trends; membrane-demixing temperature closely follows cell-growth temperature. It also ensures criticality of fixed-composition extracts, such as giant plasma membrane vesicles. Our clear picture provides a strong argument in favor of the critical-membrane hypothesis, without the need for specific sensing mechanisms.

Postoperative outcomes in surgical COVID-19 patients: a multicenter cohort study.

BACKGROUND: Data on postoperative outcomes of the COVID-19 patient population is limited. We described COVID-19 patients who underwent a surgery and the pandemic impact on surgical activities. METHODS: We conducted a multicenter cohort study between March 13 and June 192,020. We included all COVID-19 patients who underwent surgery in nine centres of the Province of Québec, the Canadian province most afflicted by the pandemic. We also included concomitant suspected COVID-19 (subsequently confirmed not to have COVID-19) patients and patients who had recovered from it. We collected data on baseline characteristics, postoperative complications and postoperative mortality. Our primary outcome was 30-day mortality. We also collected data on overall surgical activities during this first wave and during the same period in 2019. RESULTS: We included 44 COVID-19 patients, 18 suspected patients, and 18 patients who had recovered from COVID-19 at time of surgery. Among the 44 COVID-19 patients, 31 surgeries (71%) were urgent and 16 (36%) were major. In these patients, pulmonary complications were frequent (25%) and 30-day mortality was high (15.9%). This mortality was higher in patients with symptoms (23.1%) compared to those without symptoms (5.6%), although not statistically significant (p = 0.118). Of the total 22,616 cases performed among participating centres during the study period, only 0.19% had COVID-19 at the time of surgery. Fewer procedures were performed during the study period compared to the same period in 2019 (44,486 cases). CONCLUSION: In this Canadian cohort study, postoperative 30-day mortality in COVID-19 patients undergoing surgery was high (15.9%). Although few surgeries were performed on COVID-19 patients, the pandemic impact on surgical activity volume was important. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04458337 .

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis.

Introduction: In patients with cystic fibrosis (CF), the monitoring of respiratory muscle activity using electromyography can provide information on the demand-to-capacity ratio of the respiratory system and act as a clinical marker of disease activity, but this technique is not adapted to routine clinical care. Ultrasonography of the diaphragm could provide an alternative, simpler and more widely available alternative allowing the real-time assessment of the diaphragm contractile reserve (DCR), but its relationship with recognized markers of disease severity and clinical outcomes are currently unknown. Methods: Stable patients with CF were prospectively recruited. Diaphragm ultrasound was performed and compared to forced expiratory volume in 1 s (FEV1), residual volume (RV), handgrip strength, fat-free mass index (FFMI), serum vitamin levels, dyspnea levels and rate of acute exacerbation (AE). Diaphragm activity was reported as DCR (the ratio of tidal-to-maximal thickening fractions, representing the remaining diaphragm contractility available after tidal inspiration) and TFmax (representing maximal diaphragm contractile strength). Inter-observer reliability of the measurement of DCR was evaluated using intra-class correlation analysis. Results: 110 patients were included [61 males, median (interquartile range), age 31 (27-38) years, FEV1 66 (46-82)% predicted]. DCR was significantly correlated to FEV1 (rho = 0.46, p < 0.001), RV (rho = -0.46, p < 0.001), FFMI (rho = 0.41, p < 0.001), and handgrip strength (rho = 0.22, p = 0.02), but TFmax was not. In a multiple linear regression analysis, both RV and FFMI were independent predictors of DCR. DCR, but not TFmax, was statistically lower in patients with > 2 exacerbations/year (56 ± 25 vs. 71 ± 17%, p = 0.001) and significantly lower with higher dyspnea levels. A ROC analysis showed that DCR performed better than FEV1 (mean difference in AUROC 0.09, p = 0.04), RV (mean difference in AUROC 0.11, p = 0.03), and TFmax at identifying patients with an mMRC score > 2. Inter-observer reliability of DCR was high (ICC = 0.89, 95% CI 0.84-0.92, p < 0.001). Conclusion: In patients with CF, DCR is a reliable and non-invasive marker of disease severity that is related to respiratory and extra-pulmonary manifestations of the disease and to clinical outcomes. Future studies investigating the use of DCR as a longitudinal marker of disease progression, response to interventions or target for therapy would further validate its translation into clinical practice.

Regulating Lipid Composition Rationalizes Acyl Tail Saturation Homeostasis in Ectotherms.

Cell membranes mainly consist of lipid bilayers with an actively regulated composition. The underlying processes are still poorly understood, in particular, how the hundreds of components are controlled. Cholesterol has been found to correlate with phospholipid saturation for reasons that remain unclear. To better understand the link between cell membrane regulation and chemical composition, we establish a computational framework based on chemical reaction networks, resulting in multiple semigrand canonical ensembles. By running computer simulations, we show that regulating the chemical potential of lipid species is sufficient to reproduce the experimentally observed increase in acyl tail saturation with added cholesterol. Our model proposes a different picture of lipid regulation in which components can be regulated passively instead of actively. In this picture, phospholipid acyl tail composition naturally adapts to added molecules such as cholesterol or proteins. A comparison between regulated membranes with commonly studied ternary model membranes shows stark differences: for instance, correlation lengths and viscosities observed are independent of lipid chemical affinity.

A proposed lung ultrasound and phenotypic algorithm for the care of COVID-19 patients with acute respiratory failure.

Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure.

RéSUMé: Les complications pulmonaires du coronavirus (COVID-19) constituent ses manifestations cliniques les plus fréquentes. De récentes observations cliniques ont fait émerger deux phénotypes : le phénotype à élastance faible ou type L (low), et le phénotype à élastance élevée, ou type H (high). La présentation clinique, la physiopathologie, les mécanismes pulmonaires, ainsi que les observations radiologiques et échographiques de ces deux différents phénotypes sont différents. L'approche thérapeutique variera par conséquent selon le phénotype des patients atteints de COVID-19 souffrant d'insuffisance respiratoire.

Effects of positive end-expiratory pressure/recruitment manoeuvres compared with zero end-expiratory pressure on atelectasis during open gynaecological surgery as assessed by ultrasonography: a randomised controlled trial.

BACKGROUND: During general anaesthesia, most patients develop atelectasis, which promotes postoperative pulmonary complications. RCTs that investigated perioperative lung protection have failed to reduce postoperative pulmonary complications consistently. Ultrasound imaging could help confirm the effects of different protective ventilatory strategies, but this has not been tested in trials. The objective of this study was to use ultrasonography to evaluate whether lung-protective ventilation measures reduce perioperative atelectasis. METHODS: We conducted a prospective, randomised patient- and assessor-blinded controlled trial in women undergoing open gynaecological surgery. Subjects were randomised to either lung protection or zero end-expiratory pressure (ZEEP; with no recruitment manoeuvres [RMs]). Lung protection entailed PEEP (7 cm H2O) and RMs every 30 min. Lung ultrasonography was undertaken at five predefined time points. The primary outcome was the difference in lung ultrasonography score (LUS) between groups before emergence; a lower LUS indicates better lung aeration. RESULTS: We recruited 45 women (34-85 yr old). Women randomised to lung protection had lower mean (standard deviation) LUS before emergence (6.1 [3.7]), compared with women randomised to ZEEP (11.7 [3.9]; 95% confidence interval for the difference between group means [-7.9 to -3.2]; P<0.0001). This difference did not persist after extubation, with similar mean LUSs in women who had received intraoperative lung protection (7.0 [4.1]), compared with women randomised to receive ZEEP (7.7 [3.1]). CONCLUSIONS: As assessed by lung ultrasonography, intraoperative PEEP/RMs decreased aeration loss during general anaesthesia. However, similar degrees of aeration loss were observed after tracheal extubation regardless of intraoperative ventilatory strategy. CLINICAL TRIAL REGISTRATION: NCT02055807.

Effects of Intraoperative Fluid Balance During Liver Transplantation on Postoperative Acute Kidney Injury: An Observational Cohort Study.

BACKGROUND: Liver transplant recipients suffer many postoperative complications. Few studies evaluated the effects of fluid management on these complications. We conducted an observational cohort study to evaluate the association between intraoperative fluid balance and postoperative acute kidney injury (AKI) and other postoperative complications. METHODS: We included consecutive adult liver transplant recipients who had their surgery between July 2008 and December 2017. Our exposure was intraoperative fluid balance, and our primary outcome was the grade of AKI at 48 hours after surgery. Our secondary outcomes were the grade of AKI at 7 days, the need for postoperative renal replacement therapy, postoperative red blood cell transfusions, time to first extubation, time to discharge from the intensive care unit (ICU), and 1-year survival. Every analysis was adjusted for potential confounders. RESULTS: We included 532 transplantations in 492 patients. We observed no effect of fluid balance on either 48-hour AKI, 7-day AKI, or on the need for postoperative renal replacement therapy after adjustments for confounders. A higher fluid balance increased the time to ICU discharge, and increased the risk of dying (hazard ratio = 1.21 [1.04,1.40]). CONCLUSIONS: We observed no association between intraoperative fluid balance and postoperative AKI. Fluid balance was associated with longer time to ICU discharge and lower survival. This study provides insight that might inform the design of a clinical trial on fluid management strategies in this population.