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.

Comparison of postoperative analgesia and side effects in pediatric laparoscopic surgery with morphine and nalbuphine.

There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine's analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p < 0.001), PONV (2.4% vs. 18.1%, p = 0.002), and pruritus (0% vs. 16.9%, p < 0.001) than morphine. Additionally, nalbuphine showed a shorter laryngeal mask airway removal time (13.9 [12.7, 15.1]) compared with morphine (17.0 [15.1, 18.9], p = 0.011). Nalbuphine provides equipotent analgesia with significantly lower incidences of respiratory depression, PONV, and pruritus compared with morphine in pediatric laparoscopic surgery.

Development and validation of a predictive model for low cardiac output syndrome after surgical repair of tetralogy of Fallot.

Background: Low cardiac output syndrome (LCOS) remains a serious postoperative complication for children with tetralogy of Fallot (TOF), which often leads to increased morbidity and mortality. Early identification of LCOS and timely management are critical for better outcomes. This study aimed to develop a prediction model incorporating pre- and intraoperative characteristics for LCOS within 24 hours after surgical repair of TOF in children. Methods: The training dataset consisted of patients with TOF who underwent surgical repair in 2021, while the validation dataset consisted of patients in 2022. The univariable and multivariable logistic regression analyses were performed to recognize the risk factors of postoperative LCOS and a predictive model was established based on multivariable logistic regression analysis in the training dataset. Model predictive power was assessed using the area under the receiver operating characteristic curve (AUC). The calibration of the nomogram was evaluated and the Hosmer-Lemeshow test was used to assess the good fit. Decision curve analysis (DCA) was used to estimate the net benefits of the prediction model at different threshold probabilities. Results: In the multivariable logistic analysis, peripheral oxygen saturation, mean blood pressure, and central venous pressure were independent risk factors for postoperative LCOS. The AUC of the predictive model for postoperative LCOS was 0.84 (95% CI: 0.77-0.91) and 0.80 (95% CI: 0.70-0.90) in the training and validation datasets, respectively. The calibration curve for the probability of LCOS showed good agreement between the prediction by nomogram and actual observation both in the training and validation datasets. The Hosmer-Lemeshow test yielded nonsignificant statistics both in the training and validation datasets (P=0.69 and 0.54, respectively), indicating a good fit. The DCA revealed that more net benefits would be obtained by using the nomogram to predict LCOS than that achieved in either the treat-all-patient scheme or the treat-none scheme both in the training and validation datasets. Conclusions: This study is the first to incorporate pre- and intraoperative characteristics to develop a predictive model for LCOS after surgical repair of TOF in children. This model showed good discrimination, good fit and clinical benefits.

Efficacy and safety comparison of esketamine-propofol with nalbuphine-propofol for upper gastrointestinal endoscopy in children: a multi-center randomized controlled trial.

Background and Aims: Anesthetics such as propofol, esketamine and nalbuphine are used during the upper gastrointestinal endoscopy to achieve and maintain the desired sedation level. The aim of the study was to evaluate the effectiveness and safety of propofol-nalbuphine and propofol-esketamine in children. Methods: A multi-centered study was performed at three tertiary class-A hospitals. Children between 3 and 12 years old undergoing diagnostic painless upper gastrointestinal endoscopy were included and randomly divided into esketamine or nalbuphine group to estimate the primary outcome of successful endoscope insertion. The patients were given esketamine 0.5 mg/kg and propofol 2 mg/kg intravenously in esketamine group, with nalbuphine 0.2 mg/kg and propofol 2 mg/kg in the nalbuphine group. The primary outcome was success rate for the first attempt of endoscope insertion in each group. Secondary outcomes included the safety of both anesthesia regimens and gastroenterologist's satisfaction. We used the Face, Leg, Activity, Cry and Consolability (FLACC) scale to evaluate the level of pain before and during the procedure and the Pediatric Anesthesia Emergence Delirium (PAED) scale to assess the level of agitation and delirium after awakening from anesthesia. Results: Among 246 patients, 200 were randomly included in the final intention-to-treat analysis, with 100 patients in each group. The success rate for the first attempt of endoscope insertion in the esketamine group was higher than the nalbuphine group (97% vs. 66%; P < 0.01). The heart rate and mean arterial pressure after intraoperative administration in the esketamine group were higher than those in the nalbuphine group, while the delirium incidence during awakening was higher in esketamine group (all P < 0.05). Conclusion: The success rate for the first attempt of endoscope insertion of children undergoing upper gastrointestinal endoscopy in the esketamine group was higher than the nalbuphine group, propofol-related hemodynamic changes were reduced accordingly, while the incidence of esketamine-related adverse effects could be high. Clinical Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000040500.

Sub-Anesthesia Dose of S-Ketamine Reduces Postoperative Pain and Anxiety in Patients Receiving Breast and Thyroid Surgery: A Randomized, Controlled Trial.

BACKGROUND: Postoperative pain and anxiety affect patients' recovery and increase the family burden. S-ketamine presents analgesic effects and anti-depressive effects in clinics. The effect of a sub-anesthesia dose of S-ketamine on postoperative pain and anxiety remains to be clarified. OBJECTIVES: This study aimed to evaluate the analgesic and anxiolytic effects of a sub-anesthesia dose of S-ketamine on postoperative pain and anxiety and explored the risk factors for postoperative pain in patients receiving breast or thyroid surgery under general anesthesia. STUDY DESIGN: A randomized, double-blind, controlled trial. SETTING: A university hospital. METHODS: One hundred twenty patients receiving breast or thyroid surgery, stratified by surgery type, were randomized to S-ketamine and control groups in a 1:1 ratio. S-ketamine (0.3 mg/kg) or an equal volume of normal saline was administrated after anesthesia induction. Visual analog scale (VAS) of pain and self-rating anxiety scale (SAS) were tested before surgery and on postoperative day 1, 2, and 3. VAS and SAS score between the 2 groups were compared, and the risk factors for postoperative moderate to severe pain were explored with logistic regression analysis. RESULTS: Intraoperative S-ketamine decreased VAS and SAS scores on postoperative day 1, 2, and 3 (P < 0.05, 2-way ANOVA for repeated measurements followed by Bonferroni post-analysis). Subgroup analysis showed S-ketamine decreased VAS and SAS scores both in breast surgery and thyroid surgery patients on postoperative day 1, 2, and 3. Logistic regression identified S-ketamine and regular exercise are protective factors, and anxiety before surgery is a risk factor for postoperative moderate to severe pain (P < 0.05). LIMITATIONS: The anxiety score in our study is not so high, which may under-evaluate the anxiolytic effect of S-ketamine. However, S-ketamine decreased the SAS scores postoperatively in our study. CONCLUSIONS: Intraoperative sub-anesthesia dose of S-ketamine reduces postoperative pain and anxiety intensity. Anxiety before surgery is a risk factor, and S-ketamine and regular exercise are protective factors for postoperative pain. The study was registered at www.chictr.org.cn with the number: ChiCTR2200060928.

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.

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.

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.

Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study.

BACKGROUND: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. METHODS: Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. RESULTS: Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95% CI, 2.57 to 7.4; P < 0.001), endotracheal tube use (odds ratio, 1.78; 95% CI, 1.16 to 2.73; P = 0.008), and propofol bolus for airway placement after sevoflurane induction (odds ratio, 2.92; 95% CI, 1.78 to 4.8; P < 0.001), and less likely with use of muscle relaxant for intubation (odds ratio, 0.67; 95% CI, 0.46 to 0.99; P = 0.046]. Expired sevoflurane was higher in patients with isoelectric events during preincision (mean difference, 0.2%; 95% CI, 0.1 to 0.4; P = 0.005) and surgical maintenance (mean difference, 0.2%; 95% CI, 0.1 to 0.3; P = 0.002). Isoelectric events were associated with moderate (8 of 12, 67%) and severe hypotension (11 of 18, 61%) during preincision (odds ratio, 4.6; 95% CI, 1.30 to 16.1; P = 0.018) (odds ratio, 3.54; 95% CI, 1.27 to 9.9; P = 0.015) and surgical maintenance (odds ratio, 3.64; 95% CI, 1.71 to 7.8; P = 0.001) (odds ratio, 7.1; 95% CI, 1.78 to 28.1; P = 0.005), and lower Pediatric Quality of Life scores at baseline in patients 0 to 12 months (median of differences, -3.5; 95% CI, -6.2 to -0.7; P = 0.008) and 25 to 36 months (median of differences, -6.3; 95% CI, -10.4 to -2.1; P = 0.003) and 30-day follow-up in 0 to 12 months (median of differences, -2.8; 95% CI, -4.9 to 0; P = 0.036). Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs. propofol). CONCLUSIONS: Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.

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.

Obstructive Jaundice does not Change the Population Pharmacokinetics of Etomidate in Patients who Underwent Bile Duct Surgery.

BACKGROUND: Etomidate is commonly used in the induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during Endoscopic Retrograde Cholangiopancreatography (ERCP) results in more stable hemodynamics compared to propofol. The aim of the present study is to investigate whether obstructive jaundice affects the pharmacokinetics of etomidate in patients who underwent bile duct surgery. METHODS: A total of 18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after the bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A nonlinear mixed-effects population modeling approach was used to characterize etomidate pharmacokinetics. The covariates of age, gender, height, weight, Body Surface area (BSA), Body Mass Index (BMI), Lean Body Mass (LBM), Total Bilirubin (TBL), Alanine Aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), creatinine (CR), and blood urea nitrogen (BUN) were tested for significant effects on parameters using a multiple forward selection approach. Covariate effects were judged based on changes in the Objective Function Value (OFV). RESULTS: A three-compartment disposition model adequately described the pharmacokinetics of etomidate. The model was further improved when height was a covariate of total clearance [Cl1=1.30+0.0232(HT-162), ΔOFV=-7.33; P<0.01)]. The introduction of any other covariates, including bilirubin and total bile acids, did not improve the model significantly (P>0.01). For the height of 162cm, the final pharmacokinetic parameter values were as follows: V1=1.42 (95% CI, 1.01-1.83, L), V2=5.52 (95% CI, 4.07-6.97, L), V3=63.9 (95% CI, 41.95-85.85, L),Cl1= 1.30 (95% CI, 1.19-1.41, L/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min), and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively. CONCLUSION: A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate did not change by the presence of obstructive jaundice.

Dexmedetomidine Alleviates Microglia-Induced Spinal Inflammation and Hyperalgesia in Neonatal Rats by Systemic Lipopolysaccharide Exposure.

Noxious stimulus and painful experience in early life can induce cognitive deficits and abnormal pain sensitivity. As a major component of the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS) injection mimics clinical symptoms of bacterial infections. Spinal microglial activation and the production of pro-inflammatory cytokines have been implicated in the pathogenesis of LPS-induced hyperalgesia in neonatal rats. Dexmedetomidine (DEX) possesses potent anti-neuroinflammatory and neuroprotective properties through the inhibition of microglial activation and microglial polarization toward pro-inflammatory (M1) phenotype and has been widely used in pediatric clinical practice. However, little is known about the effects of DEX on LPS-induced spinal inflammation and hyperalgesia in neonates. Here, we investigated whether systemic LPS exposure has persistent effects on spinal inflammation and hyperalgesia in neonatal rats and explored the protective role of DEX in adverse effects caused by LPS injection. Systemic LPS injections induced acute mechanical hyperalgesia, increased levels of pro-inflammatory cytokines in serum, and short-term increased expressions of pro-inflammatory cytokines and M1 microglial markers in the spinal cord of neonatal rats. Pretreatment with DEX significantly decreased inflammation and alleviated mechanical hyperalgesia induced by LPS. The inhibition of M1 microglial polarization and microglial pro-inflammatory cytokines expression in the spinal cord may implicate its neuroprotective effect, which highlights a new therapeutic target in the treatment of infection-induced hyperalgesia in neonates and preterm infants.

Exercise Reduces Morphine-Induced Hyperalgesia and Antinociceptive Tolerance.

Chronic morphine intake for treating various pain is frequently concomitant with morphine-induced hyperalgesia and tolerance. The mechanisms can be explained by the activation of p38-MAPK proteins in microglia in the spinal cord horn. Exercise has been shown to prevent the development of microglia overactivation. Thus, we designed to test whether exercise prevents the morphine-induced hyperalgesia and tolerance as well as suppression of p38 phosphorylation. A p38 inhibitor SB203580, exercise, and exercise preconditioning were used for treating morphine-induced hyperalgesia and tolerance development in the present study. The behavior tests for hyperalgesia and tolerance were performed in male Wistar rats before and after morphine administration. Western blotting and immunostaining for examining phosphorylated-p38 expression were performed after the behavior tests. Our results showed that SB203580 and exercise, but not exercise preconditioning, prevented the occurrence of morphine-induced hyperalgesia and tolerance. Meanwhile, exercise decreased morphine-induced phosphorylated-p38 overexpression. In summary, exercise prevented the development of morphine-induced hyperalgesia and tolerance. The mechanism may be related to inhibition of p38 phosphorylation.

Paediatric preoperative sedation practices in tertiary maternity and children's hospitals in China: a questionnaire survey.

BACKGROUND: Preoperative anxiety is a common problem in the paediatric population, and several studies have reported that it is related to adverse events such as emergence delirium and postoperative psychological and behavioural changes. In recent years, increasing attention has been paid to paediatric preoperative anxiety in China. A variety of strategies, including sedatives, parental presence, and audio-visual interventions, have been used to relieve paediatric preoperative anxiety, but there is no well-recognised procedure for paediatric preoperative sedation. Therefore, this study aimed to investigate current paediatric preoperative sedation practices in tertiary children's hospitals in China. METHODS: All tertiary maternity and children's hospitals registered with the National Health Commission of the People's Republic of China were invited to participate in an electronic survey, which included information on the preoperative sedation caseload, sites where preoperative sedation was performed, preoperative sedation methods used in different age groups, choice of sedatives, contraindications for premedication, staff structure for sedative administration and monitoring, and patient-monitoring practices. RESULTS: All 81 hospitals participating in our study completed the survey, and 38 hospitals (46.9 %) provided their preoperative sedation protocols. Twenty-four hospitals performed fewer than 5,000 preoperative sedation cases annually, and 9 hospitals performed more than 10,000 cases annually. Preoperative sedation was performed in preoperative preparation areas, preoperative holding areas, and operation rooms in 47.4 %, 26.3 %, and 13.2 % of hospitals, respectively. Sedatives were the most used interventions for paediatric preoperative sedation in all age groups, and the most widely used sedatives were propofol (intravenous) and dexmedetomidine (intranasal). The most common contraindications were American Society of Anesthesiologists class ≥ 3, emergency operation, and airway infection within 2 weeks. Sedatives were administered mainly by anaesthesiologists (63.2 %), and children were monitored mainly by anaesthesiologists (44.7 %) and nurses (39.5 %) after administration. Pulse oximetry was the most widely used monitoring device. CONCLUSIONS: Fewer than half of the tertiary maternity and children's hospitals in China provide paediatric preoperative sedation service, and the service practices vary widely. Further improvements are required to ensure the quality of paediatric preoperative sedation services and establish standard operating procedures.

Comparison of the ED50 propofol requirements during the insertion of laryngeal mask airway Ambu AuraFlex with Ambu AuraOnce in children undergoing strabismus surgery.

WHAT IS KNOWN AND OBJECTIVE: Optimal airway management is crucial in strabismus surgery due to the inaccessibility of the airway throughout the procedure. Laryngeal mask airway offers advantages over tracheal intubation in ophthalmic surgery as it does not increase the intraocular pressure. The purpose of this study was to determine the median effective dose of propofol required, when combined with 0.2 µg/kg of sufentanil, for smooth insertion of Ambu AuraFlex in the first attempt in children undergoing strabismus surgery, and to compare it with that for Ambu AuraOnce. METHODS: Forty-three paediatric patients undergoing strabismus surgery under general anaesthesia were recruited. For induction, the initial dosage of propofol was 2 mg/kg in the AuraOnce group or 3 mg/kg in the AuraFlex group. In accordance with Dixon's up-and-down method, the dose of propofol for consecutive patients in each group was adjusted in increments or decrements of 0.25 mg/kg based on the previous patient's "three-point, six-category scale" response to the first attempt of insertion of the randomized device. Insertion of the device was attempted when the bispectral index was ≤60 for 5 s after propofol administration without the use of neuromuscular blocking agents. RESULTS AND DISCUSSION: The median effective dose (95% confidence interval) of propofol was significantly lower in the Ambu AuraOnce group than in the Ambu AuraFlex group (1.92 [1.50-2.32] mg/kg vs. 2.98 [2.49-3.94] mg/kg; p = 0.002). The incidence of dislodgement of the device was significantly higher with the use of the Ambu AuraOnce than with the use of AuraFlex (p = 0.023), whereas insignificant differences were observed between the two groups in the incidence of other perioperative adverse events. WHAT IS NEW AND CONCLUSION: Ambu AuraFlex requires a significantly higher dose of propofol for insertion and provides more effective and stable airway management in strabismus surgery than AuraOnce.

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

Integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis during postnatal rat retinal development.

PURPOSE: Remodeling of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) plays a pivotal role for microglia in developing retina. We tested whether integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis in the developing rat retina. METHODS: We performed immunofluorescence assays to investigate the role of integrin receptors expressed in the microglia in ketamine-induced neuronal apoptosis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protein and mRNA levels of cytokines (TNF-α, IL-1ß) and/or chemokines (CCL2, CXCL6, CXCL10, and CXCL12). Experiments were performed using whole-mount retinas dissected from P7 Sprague-Dawley rats. RESULTS: Integrin receptors expressed in microglia were upregulated in ketamine-induced neuronal apoptosis in the early developing rat retina. Downregulating integrin receptors with RGD peptide ameliorated ketamine-induced microgliosis through: 1) ameliorating the change in microglia morphology from immature ramified microglia to an amoeboid state; 2) decreasing the number of microglia and intensity of activated microglia in the retinal ganglion cell layer (GCL); and 3) decreasing cytokine (TNF-α and IL-1ß) and chemokine (CCL2, CXCL10) levels in the retinal tissue. Inhibition of activated microglia with minocycline or the blockade of cytokines (TNF-α and IL-1ß) with a receptor antagonist (RA) attenuated neuronal apoptosis after exposure to ketamine. CONCLUSIONS: The upregulation of integrin ß1 receptors in the microglia acts as a signaling molecule, triggering microgliosis to aggravate ketamine-induced neuronal apoptosis via the release of TNF-α and IL-1ß in the early developing rat retina.

Effectiveness of postural lung recruitment on postoperative atelectasis assessed by lung ultrasound in children undergoing lateral thoracotomy cardiac surgery with cardiopulmonary bypass.

OBJECTIVES: To assess the effects of postural lung recruitment maneuvers on the postoperative atelectasis assessed by lung ultrasound (LUS) compared with supine position recruitment maneuvers in children undergoing right lateral thoracotomy cardiac surgery with cardiopulmonary bypass. METHODS: In this randomized and controlled trial, 84 patients aged 3 years or younger, scheduled for right lateral thoracotomy cardiac surgery with cardiopulmonary bypass (CPB) were randomly allocated to postural lung recruitment group or control group. The first LUS exam was performed immediately upon completion of the cardiac surgery (T1), and a repeat ultrasound exam started 1 min after lung recruitment maneuvers (T2). The primary outcome was the incidence of significant atelectasis at T2. RESULTS: The incidence of significant atelectasis at T2 in the postural lung recruitment maneuver group was lower compared with that in the control group (30.2% vs. 58.1%; odds ratio: 0.31; 95% confidence interval: 0.13-0.76; p = .009). The LUS scores for consolidations and B-lines of the left lung were higher than those of the right lung in both groups at T1. More significant reduction of the left LUS scores and sizes of atelectatic areas were found in the postural lung recruitment group than those in the control group. CONCLUSIONS: Postoperative postural recruitment maneuver was more effective to improve reaeration of lung than supine position recruitment maneuver in children undergoing right lateral thoracotomy cardiac surgery with CPB.

Effect of recorded maternal voice on emergence agitation in children undergoing bilateral ophthalmic surgery: A randomised controlled trial.

AIM: This study was designed to investigate whether the playing-back of the recorded maternal voice through the headphones to children undergoing bilateral ophthalmic surgery has clinical effects on the incidence of emergence agitation, and the anaesthesia recovery course. METHODS: In this prospective, blinded and randomised study, 127 children, aged 2-8 years and undergoing bilateral ophthalmic surgery were randomly allocated to one of the two groups: group T (treatment group, listening to recorded mother's voice via headphones) or group C (control group, wearing headphones without auditory stimuli). The primary outcome was the incidence of emergence agitation, and the secondary outcomes were the awakening time, and the post-anaesthesia care unit (PACU) stay time. RESULTS: Children in the group of listening recorded mother's voice exhibited significantly low incidence of emergence agitation compared with those in the control group (32.8 vs. 55.6%; odds ratio (95% confidence interval): 0.39(0.19-0.80); P = 0.010). The awakening time was shorter in group T as compared to that in group C (22.9 (10.4) vs. 27.3 (13.7); P = 0.048). As results, the group T had significantly less PACU stay time with early discharge than the group C did (29.7 (12.1) vs. 34.8 (14.1); P = 0.031). CONCLUSIONS: Recorded mother's voice is an efficient method to reduce emergence agitation in children undergoing bilateral ophthalmic surgery with sevoflurane anaesthesia. Also, patients woke faster and PACU stay time was shorter in the mother's voice group as compared with the control group.