Comparison of different weight-based scalars of remimazolam tosylate for anesthesia induction in obese patients: study protocol for a prospective, controlled trial.

BACKGROUND: The physiologic and anthropometric characteristics changes associated with obesity may result in the alternation of pharmacologic management. Remimazolam tosylate is a new type of ultra-short-acting benzodiazepine with stable context-sensitive half-time (CSHT) and no lipid accumulation after long-time infusion. Although remimazolam tosylate has potential advantages for the induction and maintenance of anesthesia in obese patients, the appropriate induction dosing scalars among obese patients are unknown. Therefore, we aim to compare the different weight-based scalars for dosing remimazolam tosylate of anesthesia induction among obese patients. METHODS/DESIGN: The study will be performed as a prospective, single-center, double-blind, controlled clinical trial. The study design is a comparison of remimazolam tosylate requirements based on total body weight (TBW) or lean body weight (LBW) to reach a Modified Observer's Assessment of Alertness and Sedation (MOAA/S) score of 0 among obese subjects (BMI ≥ 35 kg/m2). Another twenty normal-weight subjects (18.5 kg/m2 ≤ BMI < 25 kg/m2) will be enrolled as a control group, whose induction dose is scaled based on TBW. The infusion rate of remimazolam tosylate during induction is 12 mg/kg/h in all groups. DISCUSSION: Results of the present study will provide evidence of dose scalar of remimazolam tosylate to guide the clinical practice of anesthesia induction in obese patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR220005664. Registered on 9 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151150 .

The effect of intraoperative transnasal humidified rapid-insufflation ventilatory exchange on emergence from general anesthesia in patients undergoing microlaryngeal surgery: a randomized controlled trial.

BACKGROUND: Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) has received extensive attention for its utility in tubeless anesthesia. Still, the effects of its carbon dioxide accumulation on emergence from anesthesia have not been reported. This randomized controlled trial aimed at exploring the impact of THRIVE combined with laryngeal mask (LM) on the quality of emergence in patients undergoing microlaryngeal surgery. METHODS: After research ethics board approval, 40 eligible patients receiving elective microlaryngeal vocal cord polypectomy were randomly allocated 1:1 to two groups, THRIVE + LM group: intraoperative apneic oxygenation using THRIVE followed by mechanical ventilation through a laryngeal mask in the post-anesthesia care unit (PACU), or MV + ETT group: mechanically ventilated through an endotracheal tube for both intraoperative and post-anesthesia periods. The primary outcome was duration of PACU stay. Other parameters reflecting quality of emergence and carbon dioxide accumulation were also recorded. RESULTS: Duration of PACU stay (22.4 ± 6.4 vs. 28.9 ± 8.8 min, p = 0.011) was shorter in the THRIVE + LM group. The incidence of cough (2/20, 10% vs. 19/20, 95%, P < 0.001) was significantly lower in the THRIVE + LM group. Peripheral arterial oxygen saturation and mean arterial pressure during intraoperative and PACU stay, Quality of Recovery Item 40 total score at one day after surgery and Voice Handicap Index-10 score at seven days after surgery were of no difference between two groups. CONCLUSIONS: The THRIVE + LM strategy could accelerate emergence from anesthesia and reduce the incidence of cough without compromising oxygenation. However, these benefits did not convert to the QoR-40 and VHI-10 scores improvement. TRIAL REGISTRATION: ChiCTR2000038652.

Risk factors for difficult mask ventilation and difficult intubation among patients undergoing pharyngeal and laryngeal surgery.

Background: The prediction of difficult mask ventilation (DMV) and difficult intubation (DI) are key questions in anesthesia fields. DMV or DI related to pharyngeal and laryngeal diseases are a special kind of difficult airways. However, there is a lack of risk factors for prediction. Methods: This study retrospectively collected data from patients who were admitted to the Eye & ENT Hospital of Fudan University from May 2014 to May 2018 and underwent laryngopharyngeal surgery under general anesthesia. Results: A total of 126 patients were included. Twenty patients suffered from DMV. Preoperative laryngeal obstruction classification (OR = 7.46, 95% CI: 2.56-21.76, P < 0.001) and airway patency after sevoflurane inhalation (OR = 10.96, 95% CI: 2.70-44.43, p = 0.001) were independently associated with DMV. Seventy-six patients could be intubated at the first attempt. Preoperative laryngeal obstruction grade (OR = 0.28, 95% CI: 0.13-0.62, P = 0.002), neoplasm size (OR = 0.43, 95% CI: 0.22-0.82, P = 0.011), and airway patency after sevoflurane inhalation (OR = 0.14, 95% CI: 0.05-0.36, P < 0.001) were independently associated with first-attempt successful intubation. Conclusion: Among patients with pharyngeal and laryngeal diseases, the degree of laryngeal obstruction before the operation and the degree of airway obstruction after inhaling sevoflurane are the risk factors of DMV. The degree of laryngeal obstruction before the operation, airway obstruction after inhaling sevoflurane, and the neoplasm size are the risk factors of DI.

SCAMPP: Scaling Alignment-Based Phylogenetic Placement to Large Trees.

Phylogenetic placement, the problem of placing a "query" sequence into a precomputed phylogenetic "backbone" tree, is useful for constructing large trees, performing taxon identification of newly obtained sequences, and other applications. The most accurate current methods, such as pplacer and EPA-ng, are based on maximum likelihood and require that the query sequence be provided within a multiple sequence alignment that includes the leaf sequences in the backbone tree. This approach enables high accuracy but also makes these likelihood-based methods computationally intensive on large backbone trees, and can even lead to them failing when the backbone trees are very large (e.g., having 50,000 or more leaves). We present SCAMPP (SCaling AlignMent-based Phylogenetic Placement), a technique to extend the scalability of these likelihood-based placement methods to ultra-large backbone trees. We show that pplacer-SCAMPP and EPA-ng-SCAMPP both scale well to ultra-large backbone trees (even up to 200,000 leaves), with accuracy that improves on APPLES and APPLES-2, two recently developed fast phylogenetic placement methods that scale to ultra-large datasets. EPA-ng-SCAMPP and pplacer-SCAMPP are available at https://github.com/chry04/PLUSplacer.

Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice.

Propofol is widely used for the induction and maintenance of anesthesia, which causes a rapid loss of consciousness. However, the mechanisms underlying the hypnosis effect of propofol are still not fully understood. The thalamic reticular nucleus (TRN) is crucial for regulating wakefulness, sleep rhythm generation, and sleep stability, while the role of TRN in the process of propofol-induced anesthesia is still unknown. Here, we investigated the function of the anterior TRN in propofol general anesthesia. Our results demonstrated that the neural activity of anterior TRN is suppressed during propofol anesthesia, whereas it is robustly activated from anesthesia by recording the calcium signals using fiber photometry technology. The results showed that the activation of anterior TRN neurons by chemogenetic and optogenetic methods shortens the emergency time without changing the induction time. Conversely, chemogenetic or optogenetic inhibition of the TRN neurons leads to a delay in the recovery time. Our study showed that anterior TRN is crucial for behavioral arousal without affecting the induction time of propofol anesthesia.

Hippocampus is more vulnerable to neural damages induced by repeated sevoflurane exposure in the second trimester than other brain areas.

During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring's CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure.

Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway.

The commonly used inhalational anesthetic, sevoflurane, can cause toxicity to the central nervous system of the developing fetus. Lin28 has been reported to regulate let-7a, thereby modulating embryo development, neurodegeneration, and even neuron-related tumorigenesis. We demonstrate that pregnant mice receiving sevoflurane treatment during the early stage of pregnancy give birth to fewer offspring presenting a lower birth weight. We have also treated mouse embryonic stem cells (mESCs) with sevoflurane for 6 h and determined that mESCs self-renewal is repressed, and that differentiation is initiated earlier than in controls. We have induced neural differentiation in the treated mESCs and determined that their neurogenesis is weakened. Furthermore, sevoflurane upregulates the level of let-7a, which might repress mESC self-renewal by directly targeting the Lin28 3'-untranslated region. Lin28 overexpression attenuates the influence of sevoflurane or of let-7a on the self-renewal of mESCs and their subsequent neural differentiation. The let-7a inhibitor also abolishes the influence of sevoflurane. Thus, the let-7a-Lin28 pathway is involved in the sevoflurane-induced inhibition of ESC self-renewal and subsequent neurogenesis. Our study demonstrates the molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on the safe and reasonable usage of other inhalational anesthetics.

Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling.

Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95), and FAS ligand (FASL or CD95L) proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM) to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

A time series observation of Chinese children undergoing rigid bronchoscopy for an inhaled foreign body: 3,149 cases in 1991-2010.

BACKGROUND: In China, tracheobronchial foreign body (TFB) aspiration, a major cause of emergency episode and accident death in children, remains a challenge for anesthetic management. Here, we share our experience and discuss the anesthetic consideration and management of patients with TFB aspiration. METHODS: This was a single-institution retrospective study in children with an inhaled foreign body between 1991 and 2010 that focused on the complications following rigid bronchoscopy (RB). Data including the clinical characteristics of patients and TFB, anesthetic method, and postoperative severe complications were analyzed by different periods. RESULTS: During the 20-year study period, the charts of 3149 patients who underwent RB for suspected inhaled TFB were reviewed. There were 2079 male and 1070 female patients (1.94:1). A nut (84%) was the most commonly inhaled object. The study revealed a 9% (n = 284) overall rate of severe postoperative complications related to severe hypoxemia, laryngeal edema, complete laryngospasm, pneumothorax, total segmental atelectasis, and death with incidences of 3.2%, 0.9%, 1.3%, 0.3%, 0.3%, and 0.1%, respectively. The rates of preoperative airway impairment, negative findings of TFB, and adverse postoperative events have been on the rise in the past 5 years. CONCLUSIONS: The survey results confirmed that hypoxemia remains the most common postoperative complication in different periods. Both controlled ventilation and spontaneous ventilation were effective during the RB extraction of the foreign body at our hospital in the modern technique period. An active respiratory symptom was commonly seen in the groups with negative findings.

Efficacy and safety of spontaneous ventilation technique using dexmedetomidine for rigid bronchoscopic airway foreign body removal in children.

BACKGROUND: In children, removal of an airway foreign body is usually performed by rigid bronchoscopy under general anesthesia. Debate continues regarding the respiratory mode (spontaneous or controlled ventilation) and appropriate anesthetic drugs. Dexmedetomidine has several desirable pharmacologic properties and appears to be a useful agent for airway surgeries. OBJECTIVES: This study evaluates the efficacy of spontaneous ventilation (SV) technique using dexmedetomidine for bronchoscopic removal of foreign bodies in children. METHODS: Eighty pediatric patients undergoing rigid bronchoscopy for airway foreign body removal were randomly divided into two groups. In the SV group, dexmedetomidine (4 µg∙kg(-1)) and topical lidocaine (3-5 mg∙kg(-1)) were administered and the patients were breathing spontaneously throughout the procedure. In the manual jet ventilation (MJV) group, anesthesia was induced with fentanyl (2 µg∙kg(-1)), propofol (3-5 mg∙kg(-1)), and succinylcholine (1 mg∙kg(-1)), and MJV was performed. RESULTS: The success rates of foreign body removal, the incidence of body movement and other perioperative adverse events, and hemodynamic changes were similar between the two groups. The SV patients required longer stays in the postanesthesia care unit (P < 0.01) but experienced less coughing (P = 0.029) in the recovery room. CONCLUSION: Dexmedetomidine may provide appropriately deep anesthesia and ideal conditions for rigid bronchoscopic airway foreign body removal without respiratory depression or hemodynamic instability.

Prognostic study of sevoflurane-based general anesthesia on cognitive function in children.

PURPOSE: It is unclear whether volatile general anesthetics have sustained adverse effects on the immature brains of children. We performed a self-controlled study to evaluate the effects of strabismus surgery under sevoflurane-based general anesthesia on the cognitive function of pediatric patients. METHODS: The study included 100 children of ages 4 to 7 years old scheduled to undergo strabismus correction under sevoflurane-based general anesthesia. Cognitive function was tested 1 day before the operation (T1), 1 month after the operation (T2), and 6 months after the operation by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Third Edition) method, which consists of 150 items. The scores at T1 were compared with scores at T2 and T3. RESULTS: Seventy-two children completed the three tests. At T1, they were 66.1 ± 7.7 months old and had a mean body weight of 21.6 ± 4.0 kg. The mean anesthesia time was 67.3 ± 9.8 min. The mean interval between T1 and T2 was 25.4 ± 6.8 days, and that between T1 and T3 was 182.1 ± 27.7 days. No statistically significant decrease in WPPSI scores was observed between T1 and T2, or between T1 and T3. CONCLUSION: These findings from our self-controlled study show that sevoflurane-based general anesthesia does not have significantly adverse effects on the cognitive function of 4- to 7-year-old children at 1 month and 6 months after strabismus surgery. Additional studies with a larger sample size are needed.

Electromyographic monitoring of facial nerve under different levels of neuromuscular blockade during middle ear microsurgery.

BACKGROUND: The evoked electromyography (EMG) is frequently used to identify facial nerve in order to prevent its damage during surgeries. Partial neuromuscular blockade (NMB) has been suggested to favor EMG activity and insure patients' safety. The aim of this study was to determine an adequate level of NMB correspondent to sensible facial nerve identification by evaluating the relationship between facial EMG responses and peripheral NMB levels during the middle ear surgeries. METHODS: Facial nerve evoked EMG and NMB monitoring were performed simultaneously in 40 patients who underwent tympanoplasty. Facial electromyographic responses were recorded by insertion of needle electrodes into the orbicularis oris and orbicularis oculi muscles after electrical stimulation on facial nerve. The NMB was observed objectively with the hypothenar muscle's twitching after electrical stimulation of ulnar nerve, and the intensity of blockade was adjusted at levels of 0, 25%, 50%, 75%, 90%, and 100% respectively with increased intravenous infusion of Rocuronium (muscle relaxant). RESULTS: All of the patients had detectable EMG responses at the levels of NMB or= 75%. A significant linear positive correlation was present between stimulation thresholds and NMB levels while a linear negative correlation was present between EMG amplitudes and NMB levels. CONCLUSIONS: The facial nerve monitoring via facial electromyographic responses can be obtained when an intraoperative partial neuromuscular blockade is induced to provide an adequate immobilization of the patient. The 50% NMB should be considered as the choice of anesthetic management for facial nerve monitoring in otologic microsurgery based on the relationship of correlation.