Synapse-Specific Trapping of SNARE Machinery Proteins in the Anesthetized Drosophila Brain.

General anesthetics disrupt brain network dynamics through multiple pathways, in part through postsynaptic potentiation of inhibitory ion channels as well as presynaptic inhibition of neuroexocytosis. Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to interact and interfere with core components of the exocytic release machinery to cause impaired neurotransmitter release. Recent studies however suggest that these drugs do not affect all synapse subtypes equally. We investigated the role of the presynaptic release machinery in multiple neurotransmitter systems under isoflurane general anesthesia in the adult female Drosophila brain using live-cell super-resolution microscopy and optogenetic readouts of exocytosis and neural excitability. We activated neurotransmitter-specific mushroom body output neurons and imaged presynaptic function under isoflurane anesthesia. We found that isoflurane impaired synaptic release and presynaptic protein dynamics in excitatory cholinergic synapses. In contrast, isoflurane had little to no effect on inhibitory GABAergic or glutamatergic synapses. These results present a distinct inhibitory mechanism for general anesthesia, whereby neuroexocytosis is selectively impaired at excitatory synapses, while inhibitory synapses remain functional. This suggests a presynaptic inhibitory mechanism that complements the other inhibitory effects of these drugs.

Globus pallidus externus drives increase in network-wide alpha power with propofol-induced loss-of-consciousness in humans.

States of consciousness are likely mediated by multiple parallel yet interacting cortico-subcortical recurrent networks. Although the mesocircuit model has implicated the pallidocortical circuit as one such network, this circuit has not been extensively evaluated to identify network-level electrophysiological changes related to loss of consciousness (LOC). We characterize changes in the mesocircuit in awake versus propofol-induced LOC in humans by directly simultaneously recording from sensorimotor cortices (S1/M1) and globus pallidus interna and externa (GPi/GPe) in 12 patients with Parkinson disease undergoing deep brain stimulator implantation. Propofol-induced LOC is associated with increases in local power up to 20 Hz in GPi, 35 Hz in GPe, and 100 Hz in S1/M1. LOC is likewise marked by increased pallidocortical alpha synchrony across all nodes, with increased alpha/low beta Granger causal (GC) flow from GPe to all other nodes. In contrast, LOC is associated with decreased network-wide beta coupling and beta GC from M1 to the rest of the network. Results implicate an important and possibly central role of GPe in mediating LOC-related increases in alpha power, supporting a significant role of the GPe in modulating cortico-subcortical circuits for consciousness. Simultaneous LOC-related suppression of beta synchrony highlights that distinct oscillatory frequencies act independently, conveying unique network activity.

Neural Ensemble Fragmentation in the Anesthetized Drosophila Brain.

General anesthetics cause a profound loss of behavioral responsiveness in all animals. In mammals, general anesthesia is induced in part by the potentiation of endogenous sleep-promoting circuits, although "deep" anesthesia is understood to be more similar to coma (Brown et al., 2011). Surgically relevant concentrations of anesthetics, such as isoflurane and propofol, have been shown to impair neural connectivity across the mammalian brain (Mashour and Hudetz, 2017; Yang et al., 2021), which presents one explanation why animals become largely unresponsive when exposed to these drugs. It remains unclear whether general anesthetics affect brain dynamics similarly in all animal brains, or whether simpler animals, such as insects, even display levels of neural connectivity that could be disrupted by these drugs. Here, we used whole-brain calcium imaging in behaving female Drosophila flies to investigate whether isoflurane anesthesia induction activates sleep-promoting neurons, and then inquired how all other neurons across the fly brain behave under sustained anesthesia. We were able to track the activity of hundreds of neurons simultaneously during waking and anesthetized states, for spontaneous conditions as well as in response to visual and mechanical stimuli. We compared whole-brain dynamics and connectivity under isoflurane exposure to optogenetically induced sleep. Neurons in the Drosophila brain remain active during general anesthesia as well as induced sleep, although flies become behaviorally inert under both treatments. We identified surprisingly dynamic neural correlation patterns in the waking fly brain, suggesting ensemble-like behavior. These become more fragmented and less diverse under anesthesia but remain wake-like during induced sleep.SIGNIFICANCE STATEMENT When humans are rendered immobile and unresponsive by sleep or general anesthetics, their brains do not shut off - they just change how they operate. We tracked the activity of hundreds of neurons simultaneously in the brains of fruit flies that were anesthetized by isoflurane or genetically put to sleep, to investigate whether these behaviorally inert states shared similar brain dynamics. We uncovered dynamic patterns of neural activity in the waking fly brain, with stimulus-responsive neurons constantly changing through time. Wake-like neural dynamics persisted during induced sleep but became more fragmented under isoflurane anesthesia. This suggests that, like larger brains, the fly brain might also display ensemble-like behavior, which becomes degraded rather than silenced under general anesthesia.

Facilitation of Behavioral and Cortical Emergence from Isoflurane Anesthesia by GABAergic Neurons in Basal Forebrain.

General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep-wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, using in vivo fiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG δ power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.SIGNIFICANCE STATEMENT The basal forebrain (BF) is a key brain region controlling sleep-wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep-wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy for accelerating emergence from general anesthesia.

Mapping general anesthesia states based on electro-encephalogram transition phases.

Cortical electro-encephalography (EEG) served as the clinical reference for monitoring unconsciousness during general anesthesia. The existing EEG-based monitors classified general anesthesia states as underdosed, adequate, or overdosed, lacking predictive power due to the absence of transition phases among these states. In response to this limitation, we undertook an analysis of the EEG signal during isoflurane-induced general anesthesia in mice. Adopting a data-driven approach, we applied signal processing techniques to track θ- and δ-band dynamics, along with iso-electric suppressions. Combining this approach with machine learning, we successfully developed an automated algorithm. The findings of our study revealed that the dampening of the δ-band occurred several minutes before the onset of significant iso-electric suppression episodes. Furthermore, a distinct γ-frequency oscillation was observed, persisting for several minutes during the recovery phase subsequent to isoflurane-induced overdose. As a result of our research, we generated a map summarizing multiple brain states and their transitions, offering a tool for predicting and preventing overdose during general anesthesia. The transition phases identified, along with the developed algorithm, have the potential to be generalized, enabling clinicians to prevent inadequate anesthesia and, consequently, tailor anesthetic regimens to individual patients.

Impact of moderate sedation on electrophysiology lab time for left atrial appendage occlusion using 4D-intracardiac echocardiography.

INTRODUCTION: Left atrial appendage occlusion (LAAO) can be performed using diverse anesthetic approaches ranging from moderate sedation (MS) to general anesthesia (GA), and guided by intracardiac echocardiography (ICE) or transesophageal echocardiography (TEE). Prior studies have demonstrated shorter time in lab for heart rhythm procedures performed under MS. The objective of this study was to compare laboratory times, acute procedural outcomes and complication rates for LAAO procedures performed using MS and 4-dimensional ICE as opposed to GA. METHODS AND RESULTS: This was a retrospective observational cohort study of 135 consecutive patients who were referred for LAAO to be performed with either GA or MS between June 2022 and April 2024. The primary endpoints were total laboratory time, procedure time, nonprocedure time, and fluoroscopy time. The secondary endpoints were stroke, peri-device leak (>5 mm), device-related left atrial thrombus, cardiovascular mortality, and all-cause mortality at 45 days and 6 months postprocedure, where data were available. The mean age of patients in the study was 78.8 ± 7.8 years and 64.4% were male with no difference between GA and MS. In the MS group, 4D-ICE was used for intraprocedural imaging in 95.5% of patients and 2 dimensional-ICE (2D-ICE) was used in 4.5% of patients. In the GA group, intra-procedural imaging was done using TEE in 51.5%, 2D-ICE in 32.4% and 4D-ICE in 16.2% of cases. Total laboratory time was significantly lower in the MS group compared to the GA group (68.3 ± 23.1 vs 117.1 ± 34.3 min; p < 0.001), due to shorter nonprocedure time (15.2 ± 9.1 vs 63.7 ± 22.0 min; p < 0.001), with no significant difference in procedure time and fluoroscopy time. There was no significant difference in complications at 45 days and 6 months postprocedure. CONCLUSION: In this single center study, MS reduced total lab time by reducing nonprocedure time when compared to GA for LAAO, without affecting clinical outcomes.

Impact of the type of anesthesia on adverse events during transcarotid artery revascularization.

OBJECTIVE: The use of local or regional anesthesia (LRA) is encouraged during transcarotid artery revascularization (TCAR) because the procedure is performed through a small incision. LRA permits neurologic evaluation during the procedure and may reduce periprocedural cardiac morbidity compared with general anesthesia (GA). There is limited and conflicting information regarding the preferred anesthesia to use during TCAR. We compared periprocedural clinical and technical complications, and intraprocedural performance metrics of TCAR performed under GA vs LRA. METHODS: Patient, lesion, physician, and procedural information was collected in a worldwide quality assurance program of consecutive TCAR procedures. A composite clinical adverse event rate (death, stroke, transient ischemic attack, myocardial infarction) and a composite technical adverse event rate (aborted procedure, conversion to carotid endarterectomy, bleeding, dissection, cranial-nerve injury, device failure) in the periprocedural period were computed. Four intraprocedural performance measures (flow-reversal time, fluoroscopy time, contrast volume, and skin-to-skin time) were recorded. Deidentified data were analyzed independently at the Center for Vascular Research, University of Maryland. Poisson regressions were used to assess the impact of anesthesia type on adverse event rates. Linear regressions were used to compare performance measures. RESULTS: A total of 27,043 TCARs were performed by 1456 physicians between 2012 and 2021. A majority of patients (83%) received GA, and this proportion increased over time (R2 = 0.74; P < .0001). Some physicians (33.4%) used LRA in some of their procedures; only 2.7% used LRA in all of their procedures. Clinical risk factors were more common in the LRA group (P < .0001) and anatomic risk factors in the GA group (P < .0001); these differences were adjusted for in subsequent analyses. LRA was more likely to be used by vascular surgeons and by physicians with higher prior transfemoral carotid stenting experience (P < .0001). When comparing GA vs LRA, clinical adverse events (1.49%; 95% confidence interval [CI], 1.3-1.8 vs 1.55%; 95% CI, 1.2-2.0; P = .78), technical adverse events (5.6%; 95% CI, 5.2-6.2 vs 5.3%; 95% CI, 4.5-6.3; P = .47), and intraprocedural performance measures did not differ by type of anesthesia. CONCLUSIONS: Almost two-thirds of physicians performed TCAR exclusively under GA, and the overall proportion of procedures performed under GA increased over time. A larger fraction of patients with severe medical risk factors received LRA vs GA, whereas a larger fraction of patients with anatomic risk-factors received GA. Periprocedural clinical and technical adverse events did not differ by type of anesthesia. Intraprocedural performance metrics that drive procedural cost were similar between groups; potential differences in procedural cost driven by anesthetic choice require further study.

Association of anesthetic modality and other variables on 1-year functional patency of cephalic-based arteriovenous fistulae.

OBJECTIVE: Some studies suggest that regional anesthesia provides better patency for arteriovenous fistula (AVF) for hemodialysis access as compared to local and general anesthesia. This study evaluates the impact of anesthetic modality on long term fistula function at 12 months. METHODS: A retrospective review of patients undergoing cephalic vein-based hemodialysis access in consecutive cases between 2014 and 2019 was conducted from five safety net hospitals. The primary endpoint was functional patency at 12 months. Subset analysis individually evaluated cephalic-based lower forearm and wrist vs upper arm AVFs. Bivariate and multivariate logistic regression models evaluated the relationship between anesthetic modality and fistula function at 12 months. RESULTS: There were 818 cephalic-based fistulas created during the study period. The overall 12-month functional patency rate was 78.7%, including an 81.3% patency for upper arm AVF and 73.3% for wrist AVF (P = .009). There was no statistically significant difference among patients with functional and nonfunctional AVFs at 12 months with respect to anesthetic modality when comparing regional, local, and general anesthesia (P = .343). Multivariate regression analysis identified that history of AVF/arteriovenous graft (odds ratio [OR], 0.24; P = .007), receiving intraoperative systemic anticoagulation (OR, 2.49; P < .001), and vein diameter (OR, 1.85; P = .039) as independently associated with AVF functional patency at 12 months. CONCLUSIONS: There was no association between anesthetic modality and functional patency of cephalic-based AVFs at 12 months. Further studies are needed to better define which patients may benefit from regional anesthesia.

Outcomes of patients undergoing edge-to-edge mitral valve repair with the Edwards PASCAL transcatheter valve repair system under conscious sedation.

BACKGROUND: The development of the PASCAL transcatheter valve repair system for treating mitral regurgitation (MR) greatly extends therapeutic options. AIMS: To assess the safety, efficacy, and time efficiency of the PASCAL system in transcatheter edge-to-edge repair (TEER) under conscious sedation (CS). METHODS: This is a retrospective, two-center, German registry study consisting of 211 patients who underwent TEER using the PASCAL system under CS. The endpoints were to assess (1) technical, device, and procedural success as per Mitral Valve Academic Research Consortium (MVARC), (2) conversion rate to general anesthesia (GA), (3) hospital length of stay (LoS), (4) New York Heart Association (NYHA) class, and (5) MR compared to baseline at 30-day. RESULTS: A total of 211 patients with a mean age of 78.4 ± 8.9 years, with 51.4% being female and 86.7% belonging to NYHA functional class III/IV and EuroSCORE II 6.3 ± 4.9%, were enrolled. Procedural success attained was 96.9%, and six patients (2.8%) required conversion from CS to GA. At 30 days follow-up, a significant improvement in MR was found in 96 patients (54.2%) patients with 0/1 grade MR and 45 patients (29.5%) were in NYHA functional class III + IV. Moreover, TEER under CS has a short hospital LoS (6.71 ± 5.29 days) and intensive care unit LoS (1.34 ± 3.49 days) with a 2.8% mortality rate. CONCLUSIONS: Performing TEER with the PASCAL system under CS resulted in appreciable (96.9%) procedural success with low mortality and is a safe and promising alternative to GA with positive clinical outcomes.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

BACKGROUND: The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. METHODS: The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. RESULTS: The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. CONCLUSIONS: This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis.

BACKGROUND: Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery. METHODS: A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed. RESULTS: Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort. CONCLUSIONS: In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

Epidural versus general anesthesia for laparo-endoscopic single-site cholecystectomy: a randomized controlled trial.

INTRODUCTION: This study compares outcomes after LESS cholecystectomy utilizing epidural versus general anesthesia. METHODS: Patients undergoing LESS Cholecystectomy were randomized into receiving epidural or general anesthesia by protocol. Patients used a Visual Analog Scale to rate pain from 0 (no pain) to 10 (severe pain). Data presented as median (mean ± standard deviation). RESULTS: 75 patients underwent LESS cholecystectomy with general anesthesia [32 patients (22% men) after five patients withdrew consent] or epidural anesthesia [23 patients (22% men) after 15 patients withdrew consent]. Respectively, they were of age 38 years (41 ± 15.1) and 47 years (48 ± 13.9), BMI 29 (28 ± 4.9) kg/m2 and 28 (28 ± 3.8) kg/m2, and ASA 2 (2 ± 0.5) and 2 (2 ± 0.3) (p > 0.05 for all). LOS for patients receiving general vs. epidural anesthesia was 72 min (122 ± 104.4) vs. 95 min (113 ± 77.5) (p = 0.25). On POD 0, patients receiving general anesthesia rated pain as 4 (4 ± 2.9) vs. 0 (1 ± 2.2) for epidural anesthesia (p = 0.02). On POD 1, they rated pain as 6 (5 ± 2.3) vs. 6 (6 ± 2.9) (p = 0.68). On POD 6, patients rated pain as 3 (3 ± 2.7) vs. 4 (3 ± 2.2) (p = 1.00). For patient satisfaction with incisional scars for those receiving general vs. epidural anesthesia, patients rated their scars to be 10 (8 ± 3.6) vs. 10 (9 ± 1.2) (p = 0.21). Total costs for the hospital using general vs. epidural anesthesia were found $6,909 (7,167 ± 2,083.8) vs. $6,225 (5,848 ± 1530.1) (p = 0.014), respectively. Patients self-assessed satisfaction on a scale of 1 (worst) to 5 (best) as a 5 (5 ± 0). CONCLUSIONS: Patients undergoing LESS cholecystectomy with general vs. epidural anesthesia had similar demographics, LOS, and pain scores. Patients that received epidural anesthesia reported less pain and incurred less cost. Utilization of epidural anesthesia in lieu of general anesthesia for LESS cholecystectomy is safe, reduces pain, and offers potential cost savings.

A randomized controlled trial of propofol-remifentanil total intravenous anesthesia and sevoflurane-fentanyl anesthesia on early postoperative fatigue in patients undergoing laparoscopic colorectal surgery.

PURPOSE: Even after uncomplicated surgery, postoperative fatigue prevalence has been reported to be 30-80% for various surgeries. We evaluated postoperative fatigue according to anesthetic technique in patients who underwent colorectal surgery. METHODS: One hundred thirty patients who underwent colorectal surgery were randomly assigned to either propofol-remifentanil total intravenous anesthesia (propofol-remifentanil group, n = 65) or sevoflurane-fentanyl anesthesia (sevoflurane-fentanyl group, n = 65). The primary outcome was the prevalence of postoperative fatigue, as defined by the Chalder Fatigue Questionnaire (total score ≥ 16), at 24 h postoperatively. Secondary outcomes were early postoperative complications during hospitalization and laboratory examination. RESULTS: The final analyses included 127 patients. The prevalence of postoperative fatigue on the 1st postoperative day was lower in the propofol-remifentanil group than the sevoflurane-fentanyl group: 56.3% (36/64) in the propofol-remifentanil group and 73.0% (46/63) in the sevoflurane-fentanyl group (relative risk [RR] = 0.77, 95% confidence interval [CI] 0.59-1.00; P = 0.048). However, there was no difference between the two groups in postoperative fatigue at postoperative day 3. Other postoperative outcomes including the severity of pain and the incidence of nausea/vomiting were not different between the two groups, but postoperative atelectasis on chest X-ray was higher in the sevoflurane-fentanyl group (2/64 [3.1%] vs. 9/63 [14.3%], P = 0.025). C-reactive protein change from preoperative to postoperative day 1 and 5 was significantly lower in the propofol-remifentanil group (P = 0.044). CONCLUSION: Propofol-remifentanil total intravenous anesthesia was associated with reduced postoperative fatigue at the 1st postoperative day compared with sevoflurane-fentanyl anesthesia. Clinical trial The Korean Clinical Research Registry (study identifier: KCT0006917, principal investigator's name: MiHye Park, date of registration: January 12, 2022).

Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

Characteristics and outcomes for general anesthesia in Denmark.

BACKGROUND: General anesthesia is common, but concerns regarding post-operative complications and mortality remain. No study has described the Danish patient population undergoing general anesthesia on a national level. The aim of this study was to describe the characteristics and outcomes of patients undergoing general anesthesia in Denmark. METHODS: This study was a registry-based observational cohort study of adult patients (≥18 years) undergoing general anesthesia in Denmark during 2020 and 2021. Data from nationwide registries covering patient characteristics, anesthesia and procedure information, and patient outcomes were combined. Descriptive statistics were used to present findings, both overall and in subgroups based on the American Society of Anesthesiologists (ASA) classification. RESULTS: We identified 453,133 cases of general anesthesia in 328,951 unique patients. The median age was 57 years (quartiles: 41, 71), and 242,679 (54%) were females. Data on ASA classification were missing for less than 1% of the population, and ASA II was the most prevalent ASA classification (49%). Among cases of general anesthesia, 0.1% experienced a stroke, 0.2% had in-hospital cardiac arrest, and 3.9% had a stay in the intensive care unit within 30 days. Mortality at 30 days and 1 year were 1.8% and 6.3%, respectively, increasing with a higher ASA classification. CONCLUSION: This study offers the first comprehensive overview of adult patients undergoing general anesthesia in Denmark. Post-anesthesia complications were few and increased with ASA classification.

Fluid distribution during surgery in the flat recumbent, Trendelenburg, and the reverse Trendelenburg body positions.

BACKGROUND: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position. METHODS: Retrospective data on hemodilution and urine output obtained during and after infusion of 1-2 L of Ringer's solution over 30-60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis. RESULTS: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia-induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space". CONCLUSIONS: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body.

Effect of dexmedetomidine on postoperative high-sensitivity cardiac troponin T in patients undergoing video-assisted thoracoscopic surgery: a prospective, randomised controlled trial.

BACKGROUND: One-lung ventilation and intrathoracic operations during thoracoscopic surgery often result in intraoperative hypoxaemia and haemodynamic fluctuations, resulting in perioperative myocardial injury. Dexmedetomidine, an alpha-2 (α-2) agonist, has demonstrated myocardial protection. We hypothesize that the routine intravenous administration of dexmedetomidine could reduce the extent of myocardial injury during video-assisted thoracoscopic surgery (VATS). METHODS: The study included patients aged ≥ 45 years, classified as American Society of Anesthesiologists physical status I-III, who underwent general anesthesia for video-assisted thoracoscopic surgery. The patients were randomly assigned to either the intervention group, receiving general anesthesia with dexmedetomidine, or the control group, receiving general anesthesia without dexmedetomidine. Patients in the intervention group received a loading dose of dexmedetomidine (0.5 µg·kg-1) before anesthesia induction, followed by a continuous infusion (0.5 µg·kg-1·h-1) until the completion of the surgery. Placebos (saline) were administered for the control group to match the treatment. The primary outcome assessed was the high-sensitivity cardiac troponin T on postoperative day 1. Additionally, the incidence of myocardial injury after noncardiac surgery (MINS) was noted. RESULTS: A total of 110 participants completed this study. The median [interquartile range (IQR)] concentration of hs-cTnT on postoperative day 1 was lower in the intervention group compared with the control group (7 [6-9] vs. 8 [7-11] pg·ml-1; difference in medians,1 pg·ml-1; 95% confidence interval [CI], 0 to 2; P = 0.005). Similarly, on postoperative day 3, the median [IQR] concentration of hs-cTnT in the intervention group was also lower than that in the control group (6 [5-7] vs. 7 [6-9]; difference in medians,1 pg·ml-1; 95%CI, 0 to 2; P = 0.011). Although the incidence of MINS was not statistically significant (the intervention group vs. the control group, 3.8% vs. 9.1%, P = 0.465), there was a decreasing trend in the incidence of MINS in the intervention group. CONCLUSION: The administration of perioperative dexmedetomidine in patients ≥ 45 years undergoing video-assisted thoracoscopic surgery could lower the release of postoperative hs-cTnT without reducing incidence of myocardial injury. TRIAL REGISTRATION: chictr.org.cn (ChiCTR2200063193); prospectively registered 1 September 2022.

Safety of propofol-assisted deep extubation in the dental treatment of children-a retrospective, observational study.

PURPOSE: Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed. MATERIALS AND METHODS: Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator. RESULTS: The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001). CONCLUSIONS: Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.

Exploring thirst incidence and risk factors in patients undergoing general anesthesia after extubation based on ERAS principles: a cross sectional study.

BACKGROUND: This study aims to comprehend the levels of dry mouth and thirst in patients after general anesthesia, and to identify the factors influencing them. METHODS: The study included all patients transferred to the Post Anesthesia Care Unit (PACU) at the Second Affiliated Hospital of Dalian Medical University between August 2021 and November 2021 after undergoing general anesthesia. A thirst numeric rating scale was utilized to conduct surveys, enabling the assessment of thirst incidence and intensity. Statistical analysis was performed to explore patient thirst levels and the associated factors. RESULTS: The study revealed a thirst incidence rate of 50.8%. Among the thirst intensity ratings, 71.4% of patients experienced mild thirst, 23.0% reported moderate thirst, and 5.6% expressed severe thirst. Single-factor statistical analysis of potential risk factors among the enrolled cases indicated that gender, history of coronary heart disease, surgical duration, intraoperative fluid volume, intraoperative blood loss, intraoperative urine output, and different surgical departments were linked to post-anesthetic thirst in patients undergoing general anesthesia. Multifactorial Logistic regression analysis highlighted age, gender, history of coronary heart disease, fasting duration, and intraoperative fluid volume as independent risk factors for post-anesthetic thirst in patients undergoing general anesthesia. Moreover, age, gender, history of coronary heart disease, and intraoperative fluid volume were also identified as risk factors for varying degrees of thirst. CONCLUSION: The incidence and intensity of post-anesthetic thirst after general anesthesia are relatively high. Their occurrence is closely associated with age, gender, history of coronary heart disease, fasting duration, and intraoperative fluid volume.

The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial.

BACKGROUND: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. METHODS: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19-60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. RESULTS: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18-0.20) mg/kg in the male group and 0.29 (0.29-0.30) mg/kg in the female group. CONCLUSIONS: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. TRIAL REGISTRATION: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).