Effects of intraoperative PEEP on postoperative pulmonary complications in high-risk patients undergoing laparoscopic abdominal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

Effects of intraoperative PEEP on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer: study protocol for a randomized controlled trial.

BACKGROUND: There are increasing studies showing that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery; however, the appropriate positive end-expiratory pressure (PEEP) has not yet defined. Adopting a suitable PEEP may prevent postoperative pulmonary complications. Robot-assisted laparoscopic surgery is the newest and most minimally invasive treatment for bladder cancer or prostate cancer. It is also necessary to consider the effects of Trendelenburg position with pneumoperitoneum on airway pressure and pulmonary function. The role of PEEP during the intraoperative period in preventing postoperative pulmonary complications for robot-assisted laparoscopic surgery is not clearly defined. METHODS/DESIGN: A total of 208 patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer will be enrolled and then randomly assigned to a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive an inspired oxygen fraction of 0.50 and a tidal volume of 8 mL/kg ideal body weight. Standard perioperative fluid management standardization and analgesic treatments will be applied in both groups. The primary endpoint is postoperative pulmonary complications within 7 days after surgery. Secondary endpoints are the modified clinical pulmonary infection score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, and 30-day mortality. DISCUSSION: This trial aimed to assess the effects of low tidal volumes combined with intraoperative PEEP ventilation strategy on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer. TRIAL REGISTRATION: ID: ChiCTR1800019867 . Registered on December 2, 2018.

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling.

It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.