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.

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.

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.

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.

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.

Anesthesia timing for children undergoing therapeutic cardiac catheterization after upper respiratory infection: a prospective observational study.

BACKGROUND: We aimed to analyze anesthesia timing and perioperative respiratory adverse event (PRAE) risk factors in children undergoing therapeutic cardiac catheterization after upper respiratory tract infection (URI). METHODS: We prospectively included children for elective therapeutic cardiac catheterization. Parents or legal guardians were asked to complete a questionnaire on the child's demographics, tobacco exposure, and URI symptoms. PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) as well as details of anesthesia management were recorded. RESULTS: Of 332 children, 201 had a history of URI in the preceding eight weeks. The occurrence rate of PRAEs in children with URI≤two weeks reached the highest proportion, which was higher than that in children without URI (66.3% vs. 46.6%, P=0.007). The overall incidence of PRAEs in children with URI in 3-8 weeks was significantly lower than that in children with URI in the recent ≤two weeks (49.0% vs. 66.3%, P=0.007), and similar to that in the control group (49.0% vs. 46.6%). Multivariate analysis showed association between PRAEs and type of congenital heart disease (CHD) (P<0.001), anesthesia timing (P=0.007), and age (P=0.021). Delayed schedule (two weeks after URI) minimized the risk of PRAEs to the level comparable to that observed in children without URI (OR, 1.11; 95% CI: 0.64-1.91; P=0.707). CONCLUSIONS: If treatment is not urgent, a pediatric patient at a high risk of PRAEs will be benefit from the postponement of an interventional operation by at least two weeks after URI.

Lung ultrasound evaluation of incremental PEEP recruitment maneuver in children undergoing cardiac surgery.

AIM: To explore the effect of incremental positive end-expiratory pressure recruitment maneuver (iPEEPRM) in children with congenital heart diseases (CHDs) using lung ultrasound. METHODS: Thirty-six children aged 3 months to 5 years scheduled for cardiac surgery participated. iPEEPRM was performed with PEEP stepwise increase (0-5-10-15 cmH2 O) and decrease at the same rate before and after surgery. Atelectatic areas, ultrasound scores, arterial oxygen pressure (PaO2 ), and respiratory system dynamic compliance per kilogram body weight (CDyn/kg) were analyzed before and after iPEEPRM. The primary outcome is the incidence of atelectasis. Secondary outcomes are oxygenation, ventilation, CDyn/kg, and atelectasis area. RESULTS: iPEEPRM was successfully applied in 92% (33/36) children before surgery and 71% (24/34) children after surgery. The incidence of atelectasis was significantly reduced by iPEEPRM from 76% to 15% before surgery and from 92% to 38% after surgery, respectively (P < .001). Before surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 32.5 (0-128.1) mm2 vs 0 (0-0) mm2 and 8 (3-12) vs 2 (0-4). PaO2 and CDyn/kg were significantly increased after iPEEPRM: 243 (129-275) mm Hg vs 278 (207-323) mm Hg and 0.6 (0.4-0.7) mL/cmH2 O/kg vs 0.8 (0.6-1.0) mL/cmH2 O/kg. After surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 45.7 (13.1-115.8) mm2 vs 0 (0-34.7) mm2 , and 9 (6-12) vs 3 (0-5). PaO2 and CDyn/kg were also significantly increased after iPEEPRM. CONCLUSIONS: iPEEPRM effectively reduced atelectasis, improved lung aeration, oxygenation, and CDyn/kg in children undergoing cardiac surgery.

Dilation of the cystic duct confluence in laparoscopic common bile duct exploration and stone extraction in patients with secondary choledocholithiasis.

BACKGROUND: Many options exist for the management of cholelithiasis and secondary choledocholithiasis. Among them, laparoscopic common bile duct exploration (LCBDE) with choledocotomy followed by laparoscopic cholecystectomy has gained popularity. However, efforts should be made to ensure minimally invasive or noninvasive management of the common bile duct (CBD). The purpose of this study was to explore the clinical experience of non-invasive surgical modality, i.e., laparoscopic transcystic dilation of the cystic duct confluence in CBD exploration (LTD-CBDE), including feasibility, safety, adverse events, and incidence. METHODS: In this retrospective analysis, 68 patients were offered the LTD-CBDE technique from December 2015 to April 2018 based on patient's own intention. During the surgery, the cystic duct confluence was dilated with separation forceps and/or a columnar dilation balloon. Subsequently, CBD exploration and stone extraction were performed with a choledochoscope. The entrance of the CBD was covered with a cystic duct stump wall and was subjected to primary closure at the end of surgery. RESULTS: Forty-nine females and 19 males with cholelithiasis and secondary choledocholithiasis were included. The mean age was 53 years old (18 to 72 year). Of these patients, 62 (91.2%) were successfully treated with the LTD-CBDE technique, and bile leakage was observed in 3 patients (4.4%). The mean operation time was 106 min, and the mean hospital stay was 5.9 days. Among the other 6 patients, 3 were converted to open cholecystectomy due to severe fibrosis, unclear anatomical structure at Calot's triangle (n = 2) or Mirizze syndrome (n = 1); LCBDE was performed in 3 patients due to cystic duct atresia (n = 2) and low level of flow from the gallbladder duct into the CBD (n = 1). These patients had a smooth postoperative course. In total, 43/68 of the patients presented no radiological evidence of retained CBD stones at the postoperative follow-up (40 patients treated with LTD-CBDE) 1 year later. CONCLUSIONS: The current work suggests that LTD-CBDE for the management of cholelithiasis and secondary choledocholithiasis is a feasible, safe and effective technique with a low complication rate. LTD-CBDE offers another alternative for surgeons to treat patients in similar scenarios. However, additional randomized, controlled studies are needed to demonstrate its efficacy, safety, and impact on CBD stenosis.

Comparison of Postoperative Analgesic Effects Between Nalbuphine and Fentanyl in Children Undergoing Adenotonsillectomy: A Prospective, Randomized, Double-Blind, Multicenter Study.

Objective: There is no universal agreement on optimal pharmacological regimens for pain management during surgeries. The aim of this study to compare the postoperative analgesic effects of nalbuphine with fentanyl in children undergoing adenotonsillectomy. Design, Setting, Participants: We conducted a prospective, randomized, double-blind, non-inferiority and multicenter trial in 311 patients admitted to four different medical facilities in China from October 2017 to November 2018. Main Outcome Measure: The primary outcome was postoperative pain score. The secondary outcomes were as follows: the numbers of patients who developed moderate or severe pain (FLACC ≥4 points); time to first rescue analgesic top up and the actual number of rescue pain medicine given in pain control in post-anesthesia care unit (PACU), and additional analgesics requirement (received ≥2 rescue analgesics or/and other analgesics except study medications administered in PACU and ward); emergence and extubation time; Waking up time; time of PACU stay, and other side effects (desaturation, nausea/vomiting etc.). Results: A total of 356 children were screened and 322 patients were randomized. The mean age was 5.8 (5.5, 6.1) in the nalbuphine group and 5.6 (5.3, 5.8) in the fentanyl group (p = 0.2132). FLACC score of nalbuphine group was lower than that of fentanyl group upon patients' arrival at PACU (p < 0.05). The time to first required rescue dose of pain drug for nalbuphine group was longer than for the fentanyl group (2.5 vs 1.2 h, p < 0.0001). Only one patient (0.6%) in nalbuphine group presented a slow respiratory rate (RR) at 9/min while 29 patients (18.5%) in fentanyl group developed slow RR ≤10/min in PACU. Meanwhile, SpO2 was lower in the fentanyl group at 10 min after patients' arrival in PACU (p < 0.05). The other profiles observed from these two drug groups were similar. Conclusion: Nalbuphine provided better pain relief with minimal respiration depression than fentanyl in children undergoing Adenotonsillectomy.

Newborn infant parasympathetic evaluation (NIPE) as a predictor of hemodynamic response in children younger than 2 years under general anesthesia: an observational pilot study.

BACKGROUND: It is still unknown whether newborn infant parasympathetic evaluation (NIPE), based on heart rate variability (HRV) as a reflection of parasympathetic nerve tone, can predict the hemodynamic response to a nociception stimulus in children less than 2 years old. METHODS: Fifty-five children undergoing elective surgery were analyzed in this prospective observational study. Noninvasive mean blood pressure (MBP), heart rate (HR) and NIPE values were recorded just before and 1 min after general anesthesia with endotracheal intubation as well as skin incision. The predictive performance of NIPE was evaluated by receiver-operating characteristic (ROC) curve analysis. A significant hemodynamic response was defined by a > 20% increase in HR and/or MBP. RESULTS: Endotracheal intubation and skin incision caused HR increases of 22.2% (95% confidence interval [CI] 17.5-26.9%) and 3.8% (2.1-5.5%), MBP increases of 18.2% (12.0-24.4%) and 10.6% (7.7-13.4%), and conversely, NIPE decreases of 9.9% (5.3-14.4%) and 5.6% (2.1-9.1%), respectively (all P < 0.01 vs. pre-event value). Positive hemodynamic responses were observed in 32 patients (62.7%) during tracheal intubation and 13 patients (23.6%) during skin incision. The area under the ROC curve values for the ability of NIPE to predict positive hemodynamic responses at endotracheal intubation and skin incision were 0.65 (0.50-0.78) and 0.58 (0.44-0.71), respectively. CONCLUSIONS: NIPE reflected nociceptive events as well as anesthestic induction in children less than 2 years undergoing general anaesthetia. Nevertheless, NIPE may not serve as a sensitive and specific predictor to changes in hemodynamics. TRIAL REGISTRATION: This study was registered on May 3, 2018 in the Chinese Clinical Trail Registry; the registration number is ( ChiCTR1800015973 ).

Modified Lung Ultrasound Examinations in Assessment and Monitoring of Positive End-Expiratory Pressure-Induced Lung Reaeration in Young Children With Congenital Heart Disease Under General Anesthesia.

OBJECTIVES: Lung ultrasound can reliably diagnose pulmonary atelectasis. The object of this study is to determine the most efficient region to assess changes in atelectasis in children with congenital heart disease under general anesthesia. DESIGN: Randomized controlled trial. SETTING: Operating room at university-affiliated children's hospital. PATIENTS: Children between 3 months and 3 years old, scheduled for elective congenital heart disease surgery under general anesthesia. INTERVENTIONS: Forty children with congenital heart disease were randomly allocated to either a 5 cm H2O positive end-expiratory pressure group or a standard therapy control group. MEASUREMENTS AND MAIN RESULTS: Preoperative lung ultrasound was performed twice in each patient-after 1 and 15 minutes of mechanical ventilation. Atelectatic areas and B-lines were compared between two examinations. Different ultrasound regions were evaluated using Bland-Altman plots. The occurrence rate of atelectasis was much higher in inferoposterior lung regions (Scans 4-6) than in anterior and lateral regions (Scans 1-3). The median (interquartile range) lung ultrasound scores were lower in the positive end-expiratory pressure group than in the control group after treatment: 8 (3.3-9.8) versus 13 (8.3-17.5; p < 0.001). The atelectatic area was significantly decreased after treatment in the positive end-expiratory pressure group: 128 mm (34.5.5-213.3 mm) versus 49.5 mm (5.3-75.5 mm; p < 0.001). Bland-Altman plots revealed concordance between measurements in Scans 1-6 and those in Scans 4-6. In the posterior axillary line regions, changes in atelectatic area were significantly larger in the positive end-expiratory pressure group than in the control group (p = 0.03, 0.007, and 0.018). CONCLUSIONS: Lung ultrasound in inferoposterior lung regions may be more likely to reflect changes in atelectasis and save examination time; 5 cm H2O positive end-expiratory pressure may be useful in lung reaeration and can reduce, but not eliminate, atelectasis in children with congenital heart disease.

Statistical Analysis Plan for "An international multicenter study of isoelectric electroencephalography events in infants and young children during anesthesia for surgery".

This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background; (b) Definitions of protocol violations; (c) Definitions of objectives and other terms; (d) Variables for analyses; (e) Handling of missing data and study bias; (f) Statistical analysis of the primary and secondary study outcomes; (g) Reporting of study results; and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan.

Population Pharmacokinetic Modeling of Remifentanil in Infants with Unrepaired Tetralogy of Fallot.

BACKGROUND: Although there is literature suggesting that pathophysiologic changes in children with congenital heart disease alter the pharmacokinetics of anesthetics and may result in dosage adjustment, limited information exists regarding the pharmacokinetics of remifentanil in infants with unrepaired tetralogy of Fallot (TOF). The objectives of the current analysis were to characterize the population pharmacokinetics of remifentanil in infants, and to evaluate the effects of TOF on remifentanil's pharmacokinetics. METHODS: Twenty-seven infants (16 with TOF and 11 with normal cardiac anatomy; aged 114-360 days) scheduled to undergo elective surgery under general anesthesia were recruited in the study. All children received remifentanil 1 µg/kg/min intravenously for anesthesia induction and early maintenance [until ~ 20 min before cardiopulmonary bypass (CPB) for patients with TOF]. Serial arterial blood samples were drawn and analyzed. Population pharmacokinetics of remifentanil was characterized using NONMEM software. The estimates were standardized to a 70-kg adult using a per-kilogram model. RESULTS: A two-compartment disposition model adequately described the pharmacokinetics of remifentanil. Besides body weight, the introduction of any other covariates, including TOF status, did not improve the model significantly (P > 0.05). The population parameter estimates for systemic clearance (Cl1) and inter-compartment clearances (Cl2) were 6.03 × (WT/70 kg) and 1.23 × (WT/70 kg) L/min, respectively, and central volume of distribution (V1) and peripheral volumes of distribution (V2) were 19.6 × (WT/70 kg) and 21.7 × (WT/70 kg) L, respectively. CONCLUSIONS: Unrepaired TOF does not change the pharmacokinetics of remifentanil, suggesting a similar dosage for infants with TOF compared to normal cardiac anatomy infants. CLINICAL TRIAL REGISTRATION: The patient enrollment in this study started at 2012, so we do not have clinic trial number, but we still think this is a valuable research and hope it could be considered for publication.

Selection of cuffed endotracheal tube for children with congenital heart disease based on an ultrasound-based linear regression formula.

It remains to be discovered whether a formula predicting the subglottic transverse diameter measured by ultrasound (SGDformula) for the selection of an appropriate endotracheal tube (ETT) for children without congenital heart disease (CHD) is useful for children with CHD. A formula for predicting SGD was established after assessing 60 children ≤ 8 years without CHD and validated on 60 children with CHD. We selected the cuffed ETT size based on the SGD by ultrasound (SGDultra). Subsequently, the fit of the ETT cuff in 60 children with CHD was examined via air-leak test. The maximum allowed difference between the SGDformula and the ETT size that fit was 0.2 mm. The agreement among and accuracy of SGDultra, SGDformula, and the ETT used in children was analyzed. For children without CHD, we adopted a linear formula, given by SGDformula (mm) = 0.4 × age + 5.3. For children with CHD, allometric formula was adopted, given by SGDformula (mm) = 5.4 × age0.18. A stronger agreement exists between SGDultra and ETT size compared to that between SGDformula and ETT size. And the mean bias (SGDformula-ETT size and SGDultra-ETT size) was 0.21 mm (95% confidence interval, - 0.59 to 1.01 mm) and 0.00 mm (- 0.79 to 0.84 mm). For the CHD group, the ultrasound-based method yielded a 78% success rate of ETT size choice, while the formula-based method permitted an appropriate ETT size in only 32% of subjects (P < 0.001). Our analysis showed that measuring the SGDultra was more accurate in predicting the correct OD of the ETT in children with CHD undergoing cardiovascular surgery, based on the correlation and agreement with ETT OD.

Membrane potential synchrony of neurons in anterior cingulate cortex plays a pivotal role in generation of neuropathic pain.

The pathophysiology of neuropathic pain generation has not been fully investigated. Previous studies have primarily focused on changes in the properties of single neurons in the brain after nerve injury; however, little is known concerning the role of neuron-to-neuron connections in neuropathic pain pathogenesis. Synaptic transmission potentiation in anterior cingulate cortex (ACC) has been confirmed to be responsible for the formation of neuropathic pain. Thus, analysis of interneuronal connections in the ACC is an important approach for understanding the mechanism of neuropathic pain since it provides information on the potency of synaptic transmission. Here, we recorded membrane potentials from pairs of ACC neurons in anaesthetised rats and found that cross-correlations between pairs of ACC neurons significantly increased after surgery for chronic constriction injury (CCI). Moreover, CCI surgery could also enhance the power spectrum density of lower and higher-frequency membrane oscillations while having no effect on middle-frequency oscillations. The activation of membrane potential synchrony and power spectrum was reversed by the electrical synapse blocker mefloquine and pain behaviour was simultaneously alleviated. Our results may indicate that activation of membrane potential synchrony contributes to generation of neuropathic pain.

Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway.

Apoptosis has been identified as the primary cause of fetal alcohol spectrum disorder (FASD), and the development of methods to prevent and treat FASD have been based on the mechanisms of alcohol-induced apoptosis. The present study aimed to explore the effects of dopamine on alcohol­induced neuronal apoptosis using whole­mount cultures of rat retinas (postnatal day 7). Retinas were initially incubated with ethanol (100, 200 or 500 mM), and in subsequent analyses retinas were co­incubated with ethanol (200 mM) and dopamine (10 µM). In addition, several antagonists and inhibitors were used, including a D1 dopamine receptor (D1R) antagonist (SCH23390; 10 µM), a D2R antagonist (raclopride; 40 µM), an adenosine A2A receptor (AA2AR) antagonist (SCH58261; 100 nM), an adenylyl cyclase (AC) inhibitor (SQ22536; 100 µM) and a PKA inhibitor (H­89; 1 µM). The results demonstrated that exposure increased neuroapoptosis in the retinal ganglion cell layer (GCL) in a dose­dependent manner. Dopamine treatment significantly attenuated ethanol­induced neuronal apoptosis. D1R, D2R and AA2AR antagonists partially inhibited the protective effects of dopamine against ethanol­induced apoptosis; similar results were observed with AC and PKA inhibitor treatments. In summary, the present study demonstrated that dopamine treatment may be able to attenuate alcohol­induced neuroapoptosis in the developing rat retina by activating D1R, D2R and AA2AR, and by upregulating cyclic AMP/protein kinase A signaling.