Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway.

Children repeatedly exposed to anaesthesia have a high risk of cognitive impairment, but the mechanism of its regulation in this context is unknown. The objective of this study was to investigate the possible toxic mechanism of sevoflurane through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway. The hippocampal neuronal HT22 cell line was used in this study. The intervention group was treated with the WNK1 inhibitor WNK-463, CaN inhibitor FK506 and Drp-1 inhibitor Mdivi-1 respectively in the medium for 30 min before sevoflurane anaesthesia. The sevofluane group and all intervention group treated with 4.1% sevoflurane for 6 h. Compared with the control group, sevoflurane treatment decreased cell viability and increased cellular apoptosis. Our study found that WNK-463, FK506 and Mdivi-1 can all alleviate the sevoflurane-induced reduction in cell viability, decrease the cell apoptosis. In addition, WNK-463 pretreatment could inhibit the increase of WNK1 kinase and NKCC1 protein concentration caused by sevoflurane. Further, sevoflurane anaesthesia causes intracellular calcium overload, increases the expression of CaN and induces the dephosphorylation of Drp-1 protein at ser637, while CaN inhibitor FK506 pretreatment could reduce the dephosphorylation of Drp-1. Therefore, the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway plays an important role in sevoflurane-related neurotoxicity. Reducing intracellular calcium influx may be one of the important mechanism to ameliorate sevoflurane toxicity.

Postoperative analgesia for pediatric craniotomy patients: a randomized controlled trial.

BACKGROUND: Pain is often observed in pediatric patients after craniotomy procedures, which could lead to some serious postoperative complications. However, the optimal formula for postoperative analgesia for pediatric neurosurgery has not been well established. This study aimed to explore the optimal options and formulas for postoperative analgesia in pediatric neurosurgery. METHODS: Three hundred and twenty patients aged 1 to 12-years old who underwent craniotomy were randomly assigned to receive 4 different regimens of patient-controlled analgesia. The formulas used were as follows: Control group included normal saline 100 ml, with a background infusion of 2 ml/h, bolus 0.5 ml; Fentanyl group was used with a background infusion of 0.1-0.2 µg/k·h, bolus 0.1-0.2 µg/kg; Morphine group was used with a background infusion of 10-20 µg/kg·h, bolus 10-20 µg/kg; while Tramadol group was used with a background infusion of 100-400 µg/kg·h, bolus 100-200 µg/kg. Postoperative pain scores and analgesia-related complication were recorded respectively. Comparative analysis was performed between the four groups. RESULTS: In comparison of all groups with each other, lower pain scores were shown at 1 h and 8 h after surgery in Morphine group versus Tramadol, Fentanyl and Control groups (P < 0.05). Both Tramadol and Fentanyl groups showed lower pain scores in comparison to Control group (P < 0.05). Nausea and vomiting were observed more in Tramadol group in comparison to all other groups during the 48 h of PCIA usage after operation (P = 0.020). Much more rescue medicines including ibuprofen and morphine were used in Control group (CI = 0.000-0.019). Changes in consciousness and respiratory depression were not observed in study groups. Moderate-to-severe pain was observed in a total of 56 (17.5%) of the study population. Multiple regression analysis for identifying risk factors for moderate-to-severe pain revealed that, younger children (OR = 1.161, 1.027-1.312, P = 0.017), occipital craniotomy (OR = 0.374, 0.155-0.905, P = 0.029), and morphine treatment (OR = 0.077, 0.021-0.281, P < 0.001) are the relevant factors. CONCLUSIONS: Compared with other analgesic projects, PCIA or NCIA analgesia with morphine appears to be the safest and most effective postoperative analgesia program for pediatric patients who underwent neurosurgical operations. TRIAL REGISTRATION: Chinese Clinical Trial Registry. No: ChiCTR-IOC-15007676. Prospective registration. http://www.chictr.org.cn/index.aspx .

Transcutaneous electrical acupuncture stimulation (TEAS) for gastrointestinal dysfunction in adults undergoing abdominal surgery: study protocol for a prospective randomized controlled trial.

BACKGROUND: Postoperative gastrointestinal (GI) dysfunction (PGD) is a common problem after abdominal surgery. PGD can increase the length of hospital stay and may lead to serious complications. Acupuncture and moxibustion are alternative therapies for PGD that have been used in some settings. However, the effect of preventive application of acupuncture or transcutaneous electrical acupuncture stimulation (TEAS) is still uncertain. The purpose of this study is to investigate the efficacy of the continuous application of TEAS on GI function recovery in adults undergoing abdominal surgery. At the same time, we will try to confirm the mechanism of TEAS through the brain-gut axis. METHODS/DESIGN: This study is a prospective, single-center, two-arm, randomized controlled trial that will be performed in a general hospital. In total, 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e. gastric or colorectal procedure) and randomized into two treatment groups. The experimental group will receive TEAS stimulation at L14 and PC6, ST36 and ST37. The sham group will receive pseudo-TEAS at sham acupoints. The primary outcome will be the time to the first bowel motion by auscultation. The recovery time of flatus, defecation, the changes in perioperative brain-intestinal peptides, postoperative pain, perioperative complications, and hospitalization duration will be the secondary outcomes. DISCUSSION: The results of this study will demonstrate that continuous preventive application of TEAS can improve the GI function recovery in patients undergoing abdominal surgery and that this effect may act through brain-gut peptides. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023263 . Registered on 11 May 2019.

Effects of intraoperative individualized PEEP on postoperative atelectasis in obese patients: study protocol for a prospective randomized controlled trial.

BACKGROUND: Obese patients undergoing general anesthesia and mechanical ventilation during laparoscopic abdominal surgery commonly have a higher incidence of postoperative pulmonary complications (PPCs), due to factors such as decreasing oxygen reserve, declining functional residual capacity, and reducing lung compliance. Pulmonary atelectasis caused by pneumoperitoneum and mechanical ventilation is further aggravated in obese patients. Recent studies demonstrated that individualized positive end-expiratory pressure (iPEEP) was one of effective lung-protective ventilation strategies. However, there is still no exact method to determine the best iPEEP, especially for obese patients. Here, we will use the best static lung compliance (Cstat) method to determine iPEEP, compared with regular PEEP, by observing the atelectasis area measured by electrical impedance tomography (EIT), and try to prove a better iPEEP setting method for obese patients. METHODS: This study is a single-center, two-arm, prospective, randomized control trial. A total number of 80 obese patients with body mass index ≥ 32.5 kg/m2 scheduled for laparoscopic gastric volume reduction and at medium to high risk for PPCs will be enrolled. They will be randomly assigned to control group (PEEP5 group) and iPEEP group. A PEEP of 5 cmH2O will be used in PEEP5 group, whereas an individualized PEEP value determined by a Cstat-directed PEEP titration procedure will be applied in the iPEEP group. Standard lung-protective ventilation methods such as low tidal volumes (7 ml/kg, predicted body weight, PBW), a fraction of inspired oxygen ≥ 0.5, and recruitment maneuvers (RM) will be applied during and after operation in both groups. Primary endpoints will be postoperative atelectasis measured by chest electrical impedance tomography (EIT) and intraoperative oxygen index. Secondary endpoints will be serum IL-6, TNF-α, procalcitonin (PCT) kinetics during and after surgery, incidence of PPCs, organ dysfunction, length of in-hospital stay, and hospital expense. DISCUSSION: Although there are several studies about the effect of iPEEP titration on perioperative PPCs in obese patients recently, the iPEEP setting method they used was complex and was not always feasible in routine clinical practice. This trial will assess a possible simple method to determine individualized optimal PEEP in obese patients and try to demonstrate that individualized PEEP with lung-protective ventilation methods is necessary for obese patients undergoing general surgery. The results of this trial will support anesthesiologist a feasible Cstat-directed PEEP titration method during anesthesia for obese patients in attempt to prevent PPCs. TRIAL REGISTRATION: www.chictr.org.cn ChiCTR1900026466. Registered on 11 October 2019.