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.

Preemptive analgesic effectiveness of single dose intravenous ibuprofen in infants undergoing cleft palate repair: a randomized controlled trial.

BACKGROUND: Correction surgery for cleft palate is recommended between 9 and 18 months of age. Patients suffer from acute pain after palatoplasty. Clinicians are hesitant to use opioids for analgesia concerning the potential high risk of respiratory adverse events. Intravenous ibuprofen perhaps be a suitable adjuvant to pain relief. We try to assess whether preoperative administration of intravenous ibuprofen can decrease opioid requirements following cleft palate repair in infants. METHODS: This single center prospective randomized clinical trial was performed from February to April 2021 at Department of Anesthesiology in Shanghai Children's Medical Center. Forty patients ASA I-II, aged 9-24 months with isolated cleft palate and undergoing palatoplasty were randomized in a 1:1 ratio to receive either a single dose of 10 mg/kg ibuprofen intravenously or normal saline at induction. Children and infants postoperative pain scale (CHIPPS) was used for pain assessment. Those patients CHIPPS pain score equal or higher than 4 received analgesic rescue with titrating intravenous fentanyl 0.5 µg/kg and repeated in 10 min if required. The primary outcome was the amount of postoperative fentanyl used for rescue analgesia in postanesthesia care unit (PACU). RESULTS: Patients (n = 20 in each group) in IV-Ibuprofen group required less postoperative fentanyl than those in placebo group (p<0.001). There was no significant difference between two groups in first rescue analgesia time (p = 0.079) and surgical blood loss (p = 0.194). No incidence of obvious adverse events had been found within the first 24 h after surgery in both groups. CONCLUSIONS: Preemptive intravenous administration ibuprofen 10 mg/kg at induction had a significant opioid sparing effect in early postoperative period without obvious adverse effects in infants undergoing palatoplasty. TRIAL REGISTRATION: CHICTR, CTR2100043718, 27/02/2021 http://www.chictr.org.cn/showproj.aspx?proj=122187.

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.

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.

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.

The prediction probabilities for emergence from sevoflurane anesthesia in children: A comparison of the perfusion index and the bispectral index.

BACKGROUND: Predicting recovery of consciousness is one of the most essential functions of anesthesia depth monitors in anesthesia practice. Perfusion index and bispectral index are 2 indicators of the anesthesia depth monitoring with different working principles. The progression of the anesthesia emergence stages reflected by those monitors has not been well understood, especially in pediatric patients. The goals of this study were to compare the prediction probabilities of perfusion index and bispectral index in predicting awakening and in differentiating the different levels of arousal during emergence after sevoflurane anesthesia in children undergoing open inguinal hernia repairs. METHODS: Forty-five patients, aged 1 to 5 years, ASA Status I or II and scheduled for elective open inguinal hernia repairs under general anesthesia were enrolled. The perfusion index and bispectral index were monitored simultaneously during anesthesia recovery. The University of Michigan Sedation Scale was applied to evaluate the clinical arousal levels during emergence. The prediction probability was used to assess the performance of perfusion index and bispectral index in predicting awakening and distinguishing different levels of arousal corresponding to the University of Michigan Sedation Scale during recovery. RESULTS: The prediction probability of perfusion index (PkPI-Awakening  = .81, 95% CI 0.73-0.89) in differentiating full consciousness from unconsciousness during recovery was comparable to that of bispectral index (PkBIS- Awakening  = .86, 95% CI 0.79-0.92) (P = .47). The prediction probability for perfusion index (PkPI-UMSS  = .61, 95% CI 0.55-0.73) and bispectral index (PkBIS-UMSS  = .64, 95% CI 0.53-0.69) had similar performance in distinguishing different University of Michigan Sedation Scale levels. CONCLUSION: Both the perfusion index and bispectral index performed comparably well in predicting awakening and different arousal levels when emerging from sevoflurane anesthesia in children.

A developmental switch in the excitability and function of the starburst network in the mammalian retina.

Dual patch-clamp recording and Ca2+ uncaging revealed Ca2+-dependent corelease of ACh and GABA from, and the presence of reciprocal nicotinic and GABAergic synapses between, starburst cells in the perinatal rabbit retina. With maturation, the nicotinic synapses between starburst cells dramatically diminished, whereas the GABAergic synapses remained and changed from excitatory to inhibitory, indicating a coordinated conversion of the starburst network excitability from an early hyperexcitatory to a mature nonepileptic state. We show that this transition allows the starburst cells to use their neurotransmitters for two completely different functions. During early development, the starburst network mediates recurrent excitation and spontaneous retinal waves, which are important for visual system development. After vision begins, starburst cells release GABA in a prolonged and Ca2+-dependent manner and inhibit each other laterally via direct GABAergic synapses, which may be important for visual integration, such as the detection of motion direction.