Effect of Mechanical Ventilation Mode Type on Postoperative Pulmonary Complications After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: It is unknown whether there is a difference in pulmonary outcome in different intraoperative ventilation modes for cardiac surgery with cardiopulmonary bypass (CPB). The aim of this trial was to determine whether patients undergoing cardiac surgery with CPB could benefit from intraoperative optimal ventilation mode. DESIGN: This was a single-center, prospective, randomized controlled trial. SETTING: The study was conducted at a single-center tertiary-care hospital. PARTICIPANTS: A total of 1,364 adults undergoing cardiac surgery with CPB participated in this trial. INTERVENTIONS: Patients were assigned randomly (1:1:1) to receive 1 of 3 ventilation modes: volume-controlled ventilation (VCV), pressure-controlled ventilation (PCV), and pressure-controlled ventilation-volume guaranteed (PCV-VG). All arms of the study received the lung-protective ventilation strategy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications (PPCs) within the first 7 postoperative days. Pulmonary complications occurred in 168 of 455 patients (36.9%) in the PCV-VG group, 171 (37.6%) in the PCV group, and 182 (40.1%) in the VCV group, respectively. There was no statistical difference in the risk of overall pulmonary complications among groups (p = 0.585). There were no significant differences in the severity grade of PPCs within 7 days, postoperative ventilation duration, intensive care unit stay, postoperative hospital stay, or 30-day postoperative mortality. CONCLUSIONS: Among patients scheduled for cardiac surgery with CPB, intraoperative ventilation mode type did not affect the risk of postoperative pulmonary complications.

The effect of driving pressure-guided versus conventional mechanical ventilation strategy on pulmonary complications following on-pump cardiac surgery: A randomized clinical trial.

STUDY OBJECTIVE: Postoperative pulmonary complications occur frequently and are associated with worse postoperative outcomes in cardiac surgical patients. The advantage of driving pressure-guided ventilation strategy in decreasing pulmonary complications remains to be definitively established. We aimed to investigate the effect of intraoperative driving pressure-guided ventilation strategy compared with conventional lung-protective ventilation on pulmonary complications following on-pump cardiac surgery. DESIGN: Prospective, two-arm, randomized controlled trial. SETTING: The West China university hospital in Sichuan, China. PATIENTS: Adult patients who were scheduled for elective on-pump cardiac surgery were enrolled in the study. INTERVENTIONS: Patients undergoing on-pump cardiac surgery were randomized to receive driving pressure-guided ventilation strategy based on positive end-expiratory pressure (PEEP) titration or conventional lung-protective ventilation strategy with fixed 5 cmH2O of PEEP. MEASUREMENTS: The primary outcome of pulmonary complications (including acute respiratory distress syndrome, atelectasis, pneumonia, pleural effusion, and pneumothorax) within the first 7 postoperative days were prospectively identified. Secondary outcomes included pulmonary complication severity, ICU length of stay, and in-hospital and 30-day mortality. MAIN RESULTS: Between August 2020 and July 2021, we enrolled 694 eligible patients who were included in the final analysis. Postoperative pulmonary complications occurred in 140 (40.3%) patients in the driving pressure group and 142 (40.9%) in the conventional group (relative risk, 0.99; 95% confidence interval, 0.82-1.18; P = 0.877). Intention-to-treat analysis showed no significant difference between study groups regarding the incidence of primary outcome. The driving pressure group had less atelectasis than the conventional group (11.5% vs 17.0%; relative risk, 0.68; 95% confidence interval, 0.47-0.98; P = 0.039). Secondary outcomes did not differ between groups. CONCLUSION: Among patients who underwent on-pump cardiac surgery, the use of driving pressure-guided ventilation strategy did not reduce the risk of postoperative pulmonary complications when compared with conventional lung-protective ventilation strategy.

Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 µM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 µM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 µM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 µM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 µM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.