An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Effect of Ciprofol on Left Ventricular Myocardial Strain and Myocardial Work in Children Undergoing Cardiac Surgery: A Single-center Double-blind Randomized Noninferiority Study.

OBJECTIVE: The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking echocardiography in children undergoing surgical repair of atrial septal or ventricular septal defects. DESIGN: A single-center double-blind randomized noninferiority study was conducted. SETTING: The research occurred at a tertiary care center affiliated with Shanghai Jiao Tong University, China. PARTICIPANTS: One hundred and twelve children aged 1 month to 16 years undergoing atrial septal or ventricular septal defect surgery with cardiopulmonary bypass were included. INTERVENTIONS: One hundred and twelve children were allocated randomly to receive ciprofol (n = 67) or propofol (n = 45) in a 1.5:1 ratio. Ciprofol or propofol were intravenously infused at loading doses of 0.4 mg/kg or 2.0 mg/kg, respectively, over 30 seconds, depending on the physical condition of each patient. When the bispectral index was maintained between 45 and 55 after induction, transthoracic echocardiography, including apical two-chamber, three-chamber, and four-chamber views, were collected bedside. MEASUREMENTS AND MAIN RESULTS: Of the 112 patients enrolled, 104 completed the study. Global longitudinal strain in the ciprofol and propofol groups after anesthesia was -17.3% (95% confidence interval [CI] -18.0% to -16.6%) and -17.8% (95% CI -18.7 to -17.0%) in the full analysis set and -17.5% (95% CI -18.2% to -16.9%) and -17.8% (95% CI -18.7% to -17.0%) in the per-protocol set, respectively. The noninferiority margin was set at 2% and confirmed with a lower limit of two-sided 95% CI for the intergroup difference of 1.58% in the full analysis set and 1.34% in the per-protocol set. There were no significant differences between the groups in left ventricular systolic and diastolic function and myocardial work indices. Postoperative vasoactive-inotropic score, NT-proBNP, duration of mechanical ventilation, and the length of stay in the cardiac intensive care unit and hospital were also comparable between the two groups (all p > 0.05). CONCLUSIONS: Ciprofol did not show different effects on myocardial function and postoperative outcomes from propofol. Further, on the sensitive cardiac systole marker global longitudinal strain, ciprofol demonstrated noninferiority to propofol. Ciprofol might be an alternative solution for cardiac anesthesia in children with congestive heart disease with mild lesion.

Pediatric anesthesia in China.

In China, healthcare has lagged relative to its economic boom during the past 40 years. While the top tier hospitals offer pediatric perioperative care like high-income countries, lower-tier hospitals deliver lesser services of variable quality and safety related to equipment, supplies, clinician education, and availability. The national residency training program and the pediatric anesthesia fellowship program was established in 2013 and 2018 respectively. Increasing clinician workload from patient demand and a lack of consistency in quality and capability between rural and urban areas remain challenging.

Machine learning prediction model of major adverse outcomes after pediatric congenital heart surgery: a retrospective cohort study.

BACKGROUND: Major adverse postoperative outcomes (APOs) can greatly affect mortality, hospital stay, care management and planning, and quality of life. This study aimed to evaluate the performance of five machine learning (ML) algorithms for predicting four major APOs after pediatric congenital heart surgery and their clinically meaningful model interpretations. METHODS: Between August 2014 and December 2021, 23 000 consecutive pediatric patients receiving congenital heart surgery were enrolled. Based on the split date of 1 January 2019, the authors selected 13 927 participants for the training cohort, and 9073 participants for the testing cohort. Four predefined major APOs including low cardiac output syndrome (LCOS), pneumonia, renal failure, and deep venous thrombosis (DVT) were investigated. Thirty-nine clinical and laboratory features were inputted in five ML models: light gradient boosting machine (LightGBM), logistic regression (LR), support vector machine, random forest, and CatBoost. The performance and interpretations of ML models were evaluated using the area under the receiver operating characteristic curve (AUC) and Shapley Additive Explanations (SHAP). RESULTS: In the training cohort, CatBoost algorithms outperformed others with the mean AUCs of 0.908 for LCOS and 0.957 for renal failure, while LightGBM and LR achieved the best mean AUCs of 0.886 for pneumonia and 0.942 for DVT, respectively. In the testing cohort, the best-performing ML model for each major APOs with the following mean AUCs: LCOS (LightGBM), 0.893 (95% CI: 0.884-0.895); pneumonia (LR), 0.929 (95% CI: 0.926-0.931); renal failure (LightGBM), 0.963 (95% CI: 0.947-0.979), and DVT (LightGBM), 0.970 (95% CI: 0.953-0.982). The performance of ML models using only clinical variables was slightly lower than those using combined data, with the mean AUCs of 0.873 for LCOS, 0.894 for pneumonia, 0.953 for renal failure, and 0.933 for DVT. The SHAP showed that mechanical ventilation time was the most important contributor of four major APOs. CONCLUSIONS: In pediatric congenital heart surgery, the established ML model can accurately predict the risk of four major APOs, providing reliable interpretations for high-risk contributor identification and informed clinical decisions-making.

Development and external validation of a novel model for predicting new clinically important atrial fibrillation after thoracoscopic anatomical lung cancer surgery: a multicenter retrospective cohort study.

BACKGROUND: New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. METHODS: This retrospective study included 14 074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. RESULTS: Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705-0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0-100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. CONCLUSIONS: This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

A novel nomogram for predicting the decision to delayed extubation after thoracoscopic lung cancer surgery.

OBJECTIVE: Delayed extubation was commonly associated with increased adverse outcomes. This study aimed to explore the incidence and predictors and to construct a nomogram for delayed extubation after thoracoscopic lung cancer surgery. METHODS: We reviewed medical records of 8716 consecutive patients undergoing this surgical treatment from January 2016 to December 2017. Using potential predictors to develop a nomogram and using a bootstrap-resampling approach to conduct internal validation. For external validation, we additionally pooled 3676 consecutive patients who underwent this procedure between January 2018 and June 2018. Extubation performed outside the operating room was defined as delayed extubation. RESULTS: The rate of delayed extubation was 1.60%. Multivariate analysis identified age, BMI, FEV1/FVC, lymph nodes calcification, thoracic paravertebral blockade (TPVB) usage, intraoperative transfusion, operative time and operation later than 6 p.m. as independent predictors for delayed extubation. Using these eight candidates to develop a nomogram, with a concordance statistic (C-statistic) value of 0.798 and good calibration. After internal validation, similarly good calibration and discrimination (C-statistic, 0.789; 95%CI, 0.748 to 0.830) were observed. The decision curve analysis (DCA) indicated the positive net benefit with the threshold risk range of 0 to 30%. Goodness-of-fit test and discrimination in the external validation were 0.113 and 0.785, respectively. CONCLUSION: The proposed nomogram can reliably identify patients at high risk for the decision to delayed extubation after thoracoscopic lung cancer surgery. Optimizing four modifiable factors including BMI, FEV1/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.Key Messages:This study identified eight independent predictors for delayed extubation, among which lymph node calcification and anaesthesia type were not commonly reported.Using these eight candidates to develop a nomogram, we could reliably identify high-risk patients for the decision to delayed extubation.Optimizing four modifiable factors, including BMI, FEV1/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.

Progesterone alleviates esketamine-induced hypomyelination via PI3K/Akt signaling pathway in the developing rat brain.

The neurodevelopmental toxicity of anesthetics has been confirmed repeatedly, and esketamine is now widely used in pediatric surgeries. Oligodendrocyte precursor cells (OPCs) evolved into mature oligodendrocytes (OLs) and formed myeline sheath during the early brain development. In this study, we investigated whether esketamine exposure interrupted development of OPCs and induced hypomyelination in rats. Further we explored the roles of PI3K/Akt phosphorylation in OPCs development and myelination. Sprague Dawley rats with different ages (postnatal day (P) 1, 3, 7 and 12) were exposed to 40mg/kg esketamine. Progesterone treatment was given (16 mg/kg per day for 3 days) 24 h after esketamine exposure via the intraperitoneal route. Corpus callosum tissues were collected at P8 or P14 for western blot and immunofluorescence analyses. Esketamine exposure at P7 and P12 significantly reduced myelin basic protein (MBP) expression and CC1+ OLs number in corpus callosum. Esketamine exposure at P7 not only aggravated the mature OLs apoptosis, also decreased the OPCs proliferation and differentiation, which was related with dephosphorylation of PI3K/Akt. Progesterone was able to promote OPCs differentiation and ameliorate esketamine-induced hypomyelination by enhancing PI3K/Akt phosphorylation. Stage-dependent abnormality of OPCs/OLs after esketamine leads to the esketamine-induced hypomyelination. Esketamine interrupted OPCs evolution via PI3K/Akt signaling pathway, which can be ameliorated by progesterone.

Current Anesthesia Practices of Pediatric Cardiac Surgeries in Tertiary Maternity and Children's Hospitals in China: A National Survey.

OBJECTIVES: To describe the current development of Chinese pediatric cardiac anesthesia practices. DESIGN: Descriptive research study. SETTING: This study used electronic questionnaires. The authors searched the official website of the National Health Commission of the People's Republic of China for tertiary maternity and children's hospitals across the country. PARTICIPANTS: Tertiary maternity and children's hospitals. INTERVENTIONS: All representatives of the invited hospitals were asked to report the official statistics of their hospitals whenever possible. MEASUREMENTS AND MAIN RESULTS: The survey questions were related to the geographic distribution and caseloads of pediatric cardiac surgical resources, technical capacities, anesthetic regimens, monitoring practices, and qualification requirements of anesthesiologists. A total of 130 hospitals were confirmed, using the registration information of the National Health Commission of the People's Republic of China, and 108 hospitals agreed to participate in this study. All enrolled hospitals completed the questionnaires, of which 52 could perform cardiac surgeries and were located in provinces, autonomous regions, and municipalities across the country, except for the Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Tibet Autonomous Region. The authors found that most hospitals' caseload of pediatric cardiac surgeries was relatively small (<500 cases per year). Hospitals capable of performing high-risk pediatric cardiac surgeries are mainly located in Eastern China. Most hospitals prefer total intravenous anesthesia in cardiac surgeries, and commonly used anesthetics include propofol, sufentanil, rocuronium, and cisatracurium. Except for the basic intraoperative monitoring items (including electrocardiography, invasive blood pressure, central venous pressure, pulse oxygen saturation, intake-output volume, and body temperature), bispectral index and near-infrared spectroscopy are relatively commonly used in some hospitals. Postoperative analgesia for children undergoing cardiac surgeries was provided in 38 hospitals, and an intravenous analgesia pump was the most widely used analgesia measure. In addition, the most frequently mentioned qualification requirements for pediatric cardiac anesthesiologists in these hospitals specializing in cardiac surgeries were a further study in domestic hospitals specializing in cardiac surgeries and the professional titles of the attending doctors. CONCLUSIONS: Pediatric cardiac medical resources are mainly concentrated in Eastern China, and most hospitals capable of performing high-risk cardiac surgeries are located in the eastern part of the country. The authors found that pediatric cardiac anesthesia practices varied widely among the hospitals, and the main problem with pediatric cardiac anesthesia in China is that there is no systemic fellowship training curriculum at present; therefore, there is an urgent need to develop a fellowship training curriculum to further improve the quality of Chinese pediatric cardiac anesthesia.

Continuous Relationship of Operative Duration with Risk of Adverse Perioperative Outcomes and Early Discharge Undergoing Thoracoscopic Lung Cancer Surgery.

Background: For thoracoscopic lung cancer surgery, the continuous relationship and the trigger point of operative duration with a risk of adverse perioperative outcomes (APOs) and early discharge remain unknown. Methods: This study enrolled 12,392 patients who underwent this surgical treatment. Five groups were stratified by operative duration: <60 min, 60−120 min, 120−180 min, 180−240 min, and ≥240 min. APOs included intraoperative hypoxemia, delayed extubation, postoperative pulmonary complications (PPCs), prolonged air leakage (PAL), postoperative atrial fibrillation (POAF), and transfusion. A restricted cubic spline (RCS) plot was used to characterize the continuous relationship of operative duration with the risk of APOs and early discharge. Results: The risks of the aforementioned APOs increased with each additional hour after the first hour. A J-shaped association with APOs was observed, with a higher risk in those with prolonged operative duration compared with those with shorter values. However, the probability of early discharge decreased from 0.465 to 0.350, 0.217, and 0.227 for each additional hour of operative duration compared with counterparts (<60 min), showing an inverse J-shaped association. The 90 min procedure appears to be a tipping point for a sharp increase in APOs and a significant reduction in early discharge. Conclusions: Our findings have important and meaningful implications for risk predictions and clinical interventions, and early rehabilitation, for APOs.

Do COVID-19 pandemic-related behavior changes affect perioperative respiratory adverse events in children undergoing cardiac interventional catheterization?

BACKGROUND: The novel coronavirus disease (COVID-19) suddenly broke out in China in December 2019. Pandemic-related behavioral changes can cause perioperative respiratory adverse events in children with congenital heart disease (CHD). Here, we compared the incidence of perioperative respiratory adverse events (PRAEs) in CHD children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during the COVID-19 pandemic. METHODS: This prospective observational single-center study was based at a tertiary care center in Shanghai, China. A total of 359 children with CHD with and without recent URI were included between January 2019 and March 2021. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing elective cardiac catheterization was compared before and during the COVID-19 pandemic. A logistic regression model was fitted to identify the potential risk factors associated with PRAEs. RESULTS: Of the 564 children enrolled, 359 completed the study and were finally analyzed. The incidence of URIs decreased substantially during the COVID-19 pandemic (14% vs. 41%, P < 0.001). Meanwhile, the overall PRAEs also significantly declined regardless of whether the child had a recent URI (22.3% vs. 42.3%, P = 0.001 for non-URI and 29.2% vs. 58.7%, P = 0.012 for URI, respectively). Post-operative agitation in children without URI occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P = 0.001). Behaviors before the COVID-19 pandemic (odds ratio = 2.84, 95% confidence interval [CI] 1.76-4.58) and recent URI (odds ratio = 1.79, 95% CI 1.09-2.92) were associated with PRAEs. CONCLUSIONS: COVID-19 pandemic-related behavioral changes were associated with a reduction in PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.

A novel nomogram for predicting respiratory adverse events during transport after interventional cardiac catheterization in children.

Objective: The rate and predictors of respiratory adverse events (RAEs) during transport discharged from operating room after interventional cardiac catheterization in children remain unclear. This study aimed to investigate the incidence and predictors, and to construct a nomogram for predicting RAEs during transport in this pediatric surgical treatment. Methods: This prospective cohort study enrolled 290 consecutive pediatric patients who underwent ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) between February 2019 and December 2020. Independent predictors were used to develop a nomogram, and a bootstrap resampling approach was used to conduct internal validation. Composite RAEs were defined as the occurrence of at least 1 complication regarding laryngospasm, bronchospasm, apnea, severe cough, airway secretions, airway obstruction, and oxygen desaturation. Results: The rate of RAEs during transport was 23.1% (67 out of 290). Multivariate analysis identified age (vs. ≤3 years, adjusted odds ratio (aOR) = 0.507, 95% confidence interval (CI), 0.268-0.958, P = 0.036), preoperative upper respiratory tract infections (URI, aOR = 2.335, 95% CI, 1.223-4.460, P = 0.01), type of surgery (vs. VSD, for ASD, aOR = 2.856, 95% CI, 1.272-6.411, P = 0.011; for PDA, aOR = 5.518, 95% CI, 2.425-12.553, P < 0.001), morphine equivalent (vs. ≤0.153 mg/kg, aOR = 2.904, 95% CI, 1.371-6.150, P = 0.005), atropine usage (aOR = 0.463, 95% CI, 0.244-0.879, P = 0.019), and RAEs during extubation to transport (aOR = 5.004, 95% CI, 2.633-9.511, P < 0.001) as independent predictors of RAEs during transport. These six candidate predictors were used to develop a nomogram, which showed a C-statistic value of 0.809 and good calibration (P = 0.844). Internal validation revealed similarly good discrimination (C-statistic, 0.782; 95% CI, 0.726-0.837) and calibration. Decision curve analysis (DCA) also demonstrated the clinical usefulness of the nomogram. Conclusion: The high rate of RAEs during transport reminds us of the need for more medical care and attention. The proposed nomogram can reliably identify pediatric patients at high risk of RAEs during transport and guide clinicians to make proper transport plans. Our findings have important and meaningful implications for RAEs risk prediction, clinical intervention and healthcare quality control.

Albumin alleviated esketamine-induced neuronal apoptosis of rat retina through downregulation of Zn2+-dependent matrix metalloproteinase 9 during the early development.

AIMS: Esketamine upregulates Zn2+-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn2+-dependent MMP9. METHODS: We investigate the role of Zn2+ in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used. RESULTS: We demonstrated that esketamine exposure increased Zn2+ in the retinal GCL during the early development. Zn2+-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation. CONCLUSION: Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn2+ accumulation in GCL and downregulating Zn2+-dependent MMP9.

Quality improvement and patient safety in China, present and future.

With continued political support and increased health financing, China has achieved great progress in medical and health quality during the two decades. The strategy to improve health in China is built on reliable cross-sectoral information and data sharing along with quality improvement science and safety analytics balancing equitability, accessibility, quality outcomes, and safety in healthcare for everyone. As part of the healthcare system, pediatric anesthesiology has made great efforts to align with the China healthcare strategy to achieve quality outcomes, accessibility, and patient safety, but it still faces many problems such as unbalanced regional development, lack of awareness and relevant knowledge, and increased workload due to insufficient number of anesthesiologists. To address these problems, the Chinese Society of Anesthesiology and Chinese Society for Pediatric Anesthesiology supported by the Chinese hospital associations are strengthening interregional cooperation and international collaboration. In our experience, quality improvement can be successfully implemented at major centers through collaboration with experienced international institutions. In turn, the major centers educate and collaborate with the district hospitals to empower local improvements in safety and quality. Since the science in QI and patient safety is relatively new to anesthesiology in China, such collaborations must be greatly scaled up to reach the large geography and patient population in China. While the future is promising, there is still a long way to go.

Obesity Does Not Increase Perioperative Outcomes in Older Patients Undergoing Thoracoscopic Anatomic Lung Cancer Surgery.

Objectives: To investigate the relationship between obesity status and perioperative outcomes in elderly patients undergoing thoracoscopic anatomic lung cancer surgery. Methods: From January 2016 to December 2018, we performed a monocentric retrospective cohort study among 4164 consecutive patients aged 65 years or older who underwent thoracoscopic anatomic lung cancer surgery at Shanghai Chest Hospital. Two groups were stratified by body mass index (BMI): nonobese (BMI<28kg/m2) and obese status (BMI≥28kg/m2). Using a 1:1 propensity score matching (PSM) analysis to compare perioperative outcomes between two groups. Results: 4035 older patients were eventually enrolled, with a mean age of 69.8 years (range: 65-87), and 305 patients were eligible for obese status, with a mean BMI of 29.8 ± 1.7kg/m2. Compared with nonobese patients, obese patients were more likely to have higher rates of intraoperative hypoxemia (1.2% vs 3.9%, P=0.001) and new-onset arrhythmia (2.3% vs 4.3%, P=0.034). The difference in intraoperative transfusion and conversion rates and postoperative outcomes regarding pulmonary complications, new-onset arrhythmia, transfusion, length of hospital stay, 30-day readmission and hospitalization costs between two groups were not significant (P>0.05). After a 1:1 PSM analysis, the difference in both intraoperative and postoperative complications among two groups were not significant (P>0.05). In subgroup analysis, patients with BMI≥30kg/m2 had a similar incidence of perioperative complications compared to patients with BMI between 28 and 30 kg/m2 (P>0.05). Conclusions: Our research data support evidence for "obesity paradox" and also contribute the growing body of evidence that obesity in older patients should not exclude candidates for thoracoscopic anatomic lung cancer surgery.

ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

WHAT IS KNOWN AND OBJECTIVE: Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ). METHODS: After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient. RESULTS AND DISCUSSION: The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001). WHAT IS NEW AND CONCLUSION: In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.

The effects of paravertebral blockade usage on pulmonary complications, atrial fibrillation and length of hospital stay following thoracoscopic lung cancer surgery.

STUDY OBJECTIVE: Although combined thoracic paravertebral blockade (TPVB)-general anesthesia (GA) could improve pain control compared to GA alone after thoracoscopic lung cancer surgery, it has not been established whether this improvement in pain control could reduce associated adverse outcomes. Thus, this study aimed to explore the association between TPVB usage and adverse outcomes after thoracoscopic lung cancer surgery. DESIGN: Retrospective cohort study from a prospective database. SETTING: A high-volume thoracic center in China. PATIENTS: 13966 consecutive patients who received thoracoscopic lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital were enrolled. MEASUREMENTS: With a 1:1 propensity score matching (PSM) analysis, adverse outcomes between GA alone and GA-TPVB were investigated. Multivariate and multiple linear regression analysis were used to identify factors and calculate odds radio (OR) for adverse outcomes. RESULTS: The rate of TPVB usage was 14.8% (2070 out of 13,966). TPVB combined with GA was associated with lower rates of postoperative pulmonary complications (PPCs) (30.4% vs 33.5%, P = 0.005) and postoperative atrial fibrillation (POAF) (2.1% vs 2.9%, P = 0.041), and shorter length of hospital stay (LOS) (Median [IQR]; 5[4-5] vs 5[4-6]) days, P < 0.001) compared to GA alone. After a 1:1 PSM analysis, we investigated adverse outcomes in 2640 (1320 pairs) patients with or without TPVB usage, and this association remained existed, namely, the rates of PPCs (29.8% vs 34.2%, P = 0.014) and POAF (2.2% vs 3.6%, P = 0.028) were lower and LOS was shorter (5[4-5] vs 5[4-6] days, P < 0.001) in the GA-TPVB group. In multivariate analysis, the combination of GA plus TPVB was independent predictor for PPCs (OR = 0.879, 95%CI, 0.793-0.974, P = 0.014) and POAF (OR = 0.714, 95%CI, 0.516-0.988, P = 0.042), respectively. However, in multiple linear analysis, lower rates of PPCs and POAF associated with TPVB usage, rather than TPVB usage, were responsible for the reduced LOS. CONCLUSIONS: The usage of TPVB may be a feasible and adjustable approach to reduce the rates of PPCs and POAF and associated LOS in thoracoscopic lung cancer surgery.

Effects of advance exposure to an animated surgery-related picture book on preoperative anxiety and anesthesia induction in preschool children: a randomized controlled trial.

BACKGROUND: Our aim was to investigate whether early surgical preparation by reading an animated picture book about procedure-related events could reduce the preoperative anxiety in preschoolers. METHODS: 131 patients, aged 3-6 years and underwent elective minor surgery were randomized either to a control or a picture book group. Both groups received general information about surgery and anesthesia in pre-anesthesia clinic. Patients in study group also received a surgery-depicting picture book for them to read at home a week earlier before surgery. Child anxiety was evaluated with the modified Yale Preoperative Anxiety Scale Short Form in six observing time points before anesthesia induction, and the compliance of anesthesia induction was assessed with the Induction Compliance Checklist (ICC). RESULTS: There were significantly lower anxiety scores in picture book group than in control group at the time of ready for intravenous cannulation in operating room [51.9 (23.6) vs. 67.2 (22.0); mean difference 15.3; 95% confidence interval (CI) 6.4-24.1; P = 0.001] and at the time of pre-anesthesia visit [27.8 (7.6) vs. 33.2 (13.6); mean difference 5.3; 95%CI 0.93-9.8; P = 0.018]. No significant differences of anxiety levels were found between two groups at other observed time points: in the anesthesia outpatient clinic, in the holding area, at separation from parent to operating room (OR), and on entrance to OR (P = 0.584, 0.335, 0.228, 0.137, respectively). The percentage of children with poor induction compliance (i.e., ICC ≥ 6) was higher in control group compared with that in picture book group [38% vs.21%; odds ratio(95%CI): 0.78(0.61-0.99); P = 0.041]. CONCLUSIONS: Home-reading an animated picture book to get familiar with the perioperative events earlier prior to surgery could effectively reduce the preoperative anxiety level and increase the compliance during the induction of anesthesia in preschool children. TRIAL REGISTRATION: ChiCTR2000033583, 06/06/2020 www.chictr.org.cn .

Age-Related Changes in Cerebral Hemodynamics in Children Undergoing Congenital Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: To explore age-related cerebral hemodynamic characteristics before and after pediatric cardiac surgery. DESIGN: Prospective observational study. SETTING: Single-center study based at a tertiary care center in Shanghai, China. PATIENTS: Fifty-three children with congenital heart disease (CHD) aged zero-to-six years undergoing cardiac surgery with cardiopulmonary bypass were enrolled, and 44 children finally were analyzed. INTERVENTION: Cerebral hemodynamics were measured by transcranial color-coded duplex sonography in the right temporal window before and after surgery. The resistance index (RI), pulsatility index (PI), and cerebral blood flow velocity (CBFV), including time average maximum flow velocity (Vtamax), mean blood flow velocity (Vmean), and the peak systolic flow velocity (Vpeak), of the right middle cerebral artery (MCA) and regional cerebral oxygen saturation (rScO2) of the right frontal lobe were measured and analyzed. Heart rate and mean arterial pressure were also recorded during ultrasound. MEASUREMENTS AND MAIN RESULTS: RI and PI decreased exponentially with age before and after cardiac surgery. While PI remained unchanged after cardiac surgery, RI was significantly reduced. Furthermore, RI reduction after cardiac surgery was more significant in children >18 months compared to those ≤18 months. CBFV of the right MCA also showed exponential increase with age, but rScO2 linearly increased. Cardiac surgery significantly changed the cerebral hemodynamics, but it did not affect rScO2 in children regardless of age. CONCLUSIONS: Age-related cerebral hemodynamic changes exist in children with CHD. Cardiopulmonary bypass surgery led to greater cerebrovascular dilation in children aged ≤18 months than those >18 months.

Yohimbine Directly Induces Cardiotoxicity on Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Yohimbine is a highly selective and potent α2-adrenoceptor antagonist, which is usually treated as an adjunction for impotence, as well for weight loss and natural bodybuilding aids. However, it was recently reported that Yohimbine causes myocardial injury and controversial results were reported in the setting of cardiac diseases. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to explore electrophysiologic characterization after exposure to Yohimbine. HiPSC-CMs were differentiated by employment of inhibitory Wnt compounds. For analysis of electrophysiological properties, conventional whole-cell patch-clamp recording was used. Specifically, spontaneous action potentials, pacemaker currents (If), sodium (Na+) channel (INa), and calcium (Ca++) channel currents (ICa) were assessed in hiPSC-CMs after exposure to Yohimbine. HiPSC-CMs expressed sarcomeric-α-actinin and MLC2V proteins, as well as exhibited ventricular-like spontaneous action potential waveform. Yohimbine inhibited frequency of hiPSC-CMs spontaneous action potentials and significantly prolonged action potential duration in a dose-dependent manner. In addition, rest potential, threshold potential, amplitude, and maximal diastolic potential were decreased, whereas APD50/APD90 was prolonged. Yohimbine inhibited the amplitude of INa in low doses (IC50 = 14.2 µM, n = 5) and inhibited ICa in high doses (IC50 = 139.7 µM, n = 5). Whereas Yohimbine did not affect the activation curves, treatment resulted in left shifts in inactivation curves of both Na+ and Ca++ channels. Here, we show that Yohimbine induces direct cardiotoxic effects on spontaneous action potentials of INa and ICa in hiPSC-CMs. Importantly, these effects were not mediated by α2-adrenoceptor signaling. Our results strongly suggest that Yohimbine directly and negatively affects electrophysiological properties of human cardiomyocytes. These findings are highly relevant for potential application of Yohimbine in patients with atrioventricular conduction disorder.

Predictive value of EEG-derived pain threshold index for acute postoperative pain in children.

Background: Electroencephalogram (EEG)-derived pain threshold index (PTI) has been developed as a novel pain recognition indicator and has been proved to be useful in the prediction of acute postoperative pain in adults. Evidence of its usability in children is limited. The aim of this study was to investigate the prediction value of this novel pain indicator PTI for acute postoperative pain in children. Methods: A total of 80 patients undergoing laparoscopic surgery under general anesthesia were enrolled. Blood pressure, heart rate (HR), surgical pleth index (SPI), PTI, and EEG-derived sedative index-wavelet index (WLI) data were recorded at the end of the surgery. The postoperative pain scores Face, Legs, Activity, Cry, Consolability (FLACC) were obtained in the emergence room 5 min after the children wake up. Receiver-operating characteristic curve was performed to analyze the predictive value of PTI, SPI, HR, and mean arterial pressure (MAP). The consistency between SPI and PTI was also evaluated. Results: Results showed that the areas under curves (95%CI) of PTI and SPI were 0.796 (95% CI: 0.694-0.895) and 0.753 (95% CI: 0.632-0.874), respectively, with the best cut-off value of 58 and 45 to discriminate between mild and moderate to severe pain. Conclusion: This study suggested that PTI obtained at the end of the surgery could predict acute postoperative pain in children with an acceptable accuracy. It will help with early recognition and treatment of postoperative pain, thus reducing the pain in children. In addition, PTI had a good consistency with SPI in predicting acute postoperative pain in children.