Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia-reperfusion injury (IRI)-Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. METHODS: Medical data of 105 patients undergoing SPKT between 1998-2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included "IRI- associated posttransplant clinical outcome" as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for "pancreatic IRI" and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. RESULTS: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17-0.84; p = 0.029). CONCLUSIONS: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

The Influence of Positive End-Expiratory Pressure on Leakage and Oxygenation Using a Laryngeal Mask Airway: A Randomized Trial.

BACKGROUND: The value of positive end-expiratory pressure (PEEP) in maintaining oxygenation during ventilation with a laryngeal mask airway (LMA) mask is unclear. To clarify the potential benefit or harm to PEEP application during positive pressure ventilation with a ProSeal LMA® mask, we compared the effect of PEEP versus zero end-expiratory pressure (ZEEP) on gas leakage and oxygenation. We hypothesized that a PEEP of 8 mbar (8.2 cm H 2 O) would be associated with an increased incidence of gas leakage compared to ZEEP. METHODS: We designed a prospective, controlled, randomized, single-blinded, multicenter clinical trial. Patients >18 years of age with an American Society of Anesthesiologists (ASA) physical status I/II without increased risk of aspiration were enrolled if they were scheduled for elective surgery under general anesthesia with an LMA mask. Patients were randomized to a control group managed with ZEEP or an intervention group managed with a PEEP of 8 mbar. Both groups received positive pressure ventilation. The primary end point was the occurrence of gas leakage. The Student t test and χ 2 test were used for statistical analysis. RESULTS: A total of 174 patients were enrolled in the ZEEP group, and 208 were enrolled in the PEEP group. The incidence of gas leakage did not differ between the 2 groups (ZEEP: 23/174, 13.2%; PEEP: 42/208, 20.2%; P = .071; odds ratio [OR], 1.611; 95% confidence interval [CI], 0.954-2.891). However, more patients required reseating of the LMA mask in the PEEP group (ZEEP: 5/174, 2.9%; PEEP: 18/208, 8.7%; P = .018; OR, 3.202; 95% CI, 1.164-8.812). The need for endotracheal intubation did not differ between groups (ZEEP: 2/174, 1.1%; PEEP: 7/208, 3.4%; P = .190; OR, 2.995; 95% CI, 0.614-14.608). After positive pressure ventilation for 25 minutes, the mean peripheral oxygen saturation (Sp o2 ) was higher in the PEEP than in the ZEEP group (98.5 [1.9]% vs 98.0 [1.4]%; P = .01). Peak inspiratory pressure (PIP; 16 [2] vs 12 [4] mbar; P < .001) and dynamic compliance (57 [14] vs 49 [14] mL/mbar; P < .001) were both higher in the PEEP group than in the ZEEP group. CONCLUSIONS: Use of PEEP did not affect the overall incidence of gas leakage. However, PEEP did result in a higher incidence of attempts to reseat the LMA mask compared to ZEEP, whereas the incidence of rescue intubation did not differ between groups. We concluded that a PEEP of 8 mbar did not increase overall gas leakage during positive pressure ventilation with an LMA mask, but it did slightly improve gas exchange and compliance. Overall, our study does not provide strong arguments for using PEEP during ventilation with an LMA mask in elective surgery.

COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.