This prospective, randomized clinical study suggests an immunomodulatory role for the volatile anesthetic sevoflurane in patients undergoing OLV for thoracic surgery with significant reduction of inflammatory mediators and a significantly better clinical outcome (defined by postoperative adverse events) during sevoflurane anesthesia.

Background Mortality in acute respiratory failure remains high despite the use of lung-protective ventilation. Recent studies have shown an association between baseline ventilation parameters (driving pressure or mechanical power) and outcomes for patients with acute respiratory distress syndrome. Strategies focused on limiting these parameters have been proposed to further improve outcomes. However, it remains unknown whether driving pressure and mechanical power should be limited over the entire duration of mechanical ventilation and in all patients with acute respiratory failure. We aimed to estimate the association between exposure to different intensities of mechanical ventilation over time and intensive care unit (ICU) mortality in patients with acute respiratory failure.Methods In this registry-based, prospective cohort study, we obtained data from the Toronto Intensive Care Observational Registry, which includes all patients receiving mechanical ventilation for 4 h or more in nine ICUs that are affiliated with the University of Toronto (Toronto, ON, Canada). We included all adult (≥18 years) patients who received invasive mechanical ventilation between April 11, 2014, and June 5, 2019. Patients were excluded if they received treatment with extracorporeal life support. The primary outcome was ICU mortality. Bayesian joint models were used to estimate the strength of associations, accounting for informative censoring due to death during follow-up.Findings Of 13 939 patients recorded in the registry, 13 408 (96•2%) were eligible for descriptive analysis. The primary analysis comprised 7876 (58•7%) patients with complete baseline characteristics, and a secondary analysis included all 13 408 patients after multiple imputation in the joint model analysis. 2409 (18•0%) of 13 408 patients died in the ICU. After adjustment for baseline characteristics, including age and severity of illness, a significant increase in the hazard of death was found to be associated with each daily increment in driving pressure (hazard ratio 1•064, 95% credible interval 1•057-1•071) or mechanical power (hazard ratio 1•060, 95% credible interval 1•053-1•066). These associations persisted over the duration of mechanical ventilation.Interpretation Cumulative exposure to higher intensities of mechanical ventilation was harmful, even for short durations. Limiting exposure to driving pressure or mechanical power should be evaluated in further studies as promising ventilation strategies to reduce mortality in patients with acute respiratory failure.

BackgroundExcessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔPocc) could be used as a highly feasible non-invasive technique to screen for these conditions.MethodsRespiratory muscle pressure (Pmus), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔPocc were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔPL,dyn and Pmus from ΔPocc was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China).ResultsFifty-two daily recordings were collected in 16 patients. In this sample, Pmus and ΔPL were frequently excessively high: Pmus exceeded 10 cm H2O on 84% of study days and ΔPL,dyn exceeded 15 cm H2O on 53% of study days. ΔPocc measurements accurately detected Pmus > 10 cm H2O (AUROC 0.92, 95% CI 0.83–0.97) and ΔPL,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86–0.99). In the external validation cohort (n = 12), estimating Pmus and ΔPL,dyn from ΔPocc measurements detected excessively high Pmus and ΔPL,dyn with similar accuracy (AUROC ≥ 0.94).ConclusionsMeasuring ΔPocc enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.

Postconditioning with sevoflurane attenuates lung damage and preserves lung function in an in vivo model of acute lung injury.

No abstract

Injection of functional nanomagnets in human blood enables selective removal of disease‐causing metals, overdosed drugs, and proteins at the (sub‐)nanomolar level. This direct in vivo extraction provides a powerful alternative to classical pharmaceutical treatments as disease‐causing agents are removed from the organism rather than treating symptoms from exposure. A number of clinically relevant assays demonstrate blood compatibility of the functional nanomagnets.

Objective To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. Design Observational study. Setting 30 countries across five continents, 3 January 2020 to 29 August 2021. Participants 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. Interventions ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. Main outcome measure The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. Results 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO 2 /FiO 2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference –7.1%, 95% confidence interval –8.2% to –6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO 2 /FiO 2 <80 mm Hg or with driving pressures >15 cmH 2 O during the first 10 days of mechanical ventilation. Conclusions ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Background. After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal transection. We found that in patients undergoing portal vein ligation and parenchymal transection, portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response. We postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growth. Methods. A rat model of rapid (portal vein ligation and parenchymal transection) and slow regeneration (portal vein ligation) was established. Portal vein flow and pressure data were collected. Liver regeneration was assessed in rats using computed tomography, proliferation with Ki-67, and hypoxia with pimonidazole and HIF-1a staining. Results. The rat model confirmed acceleration of regeneration in portal vein ligation and parenchymal transection as well as the portal vein hyperflow seen in patients. Additionally, tissue hypoxia was observed after portal vein ligation and parenchymal transection, while little hypoxia staining was detected after portal vein ligation. To determine if hypoxia is a consequence or an inciting stimulus of rapid liver regeneration, we used a prolylhydroxylase blocker to activate hypoxia signaling pathways in the slow model. This clearly accelerated slow to rapid liver regeneration. Inversely, abrogation of hypoxia led to a blunting of rapid growth to slow growth. The topical application of prolyl-hydroxylase inhibitors on livers in rats induced spontaneous areas of regeneration. Conclusion. This study shows that pharmacologically induced hypoxic signaling accelerates liver regeneration similar to portal vein ligation and parenchymal transection. Hypoxia is likely an accelerator of liver regeneration. Also, prolyl-hydroxylase inhibitors may be used to enhance liver regeneration pharmaceutically. Background. After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal transection. We found that in patients undergoing portal vein ligation and parenchymal transection, portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response. We postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growth. Methods. A rat model of rapid (portal vein ligation and parenchymal transection) and slow regeneration (portal vein ligation) was established. Portal vein flow and pressure data were collected. Liver regeneration was assessed in rats using computed tomography, proliferation with Ki-6...