RESUMO
Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of the paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of the PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on the PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVTâprefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which is mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.
Assuntos
Astrócitos , Estado de Consciência , Núcleos da Linha Média do Tálamo , Canais de Potássio Corretores do Fluxo de Internalização , Sevoflurano , Animais , Astrócitos/fisiologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Masculino , Camundongos , Sevoflurano/farmacologia , Estado de Consciência/fisiologia , Estado de Consciência/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/citologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Camundongos Endogâmicos C57BL , Anestésicos Inalatórios/farmacologia , Vias Neurais/fisiologia , Vias Neurais/efeitos dos fármacos , Neurônios/fisiologia , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Lobo Frontal/efeitos dos fármacos , Período de Recuperação da AnestesiaRESUMO
Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1ß. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.
Assuntos
Analgésicos Opioides , Hiperalgesia , Animais , Feminino , Masculino , Camundongos , Astrócitos/metabolismo , Gliose , Hiperalgesia/induzido quimicamente , Hiperalgesia/genética , Hiperalgesia/metabolismo , Morfina , Dor , Via de Sinalização WntRESUMO
BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.
Assuntos
Anestésicos Inalatórios , Núcleos da Linha Média do Tálamo , Neurônios , Sevoflurano , Animais , Sevoflurano/farmacologia , Camundongos , Anestésicos Inalatórios/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/fisiologia , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Canais Iônicos , Proteínas de MembranaRESUMO
Anesthesia induction and emergence are critical periods for perioperative safety in the clinic. Traditionally, the emergence from general anesthesia has been recognized as a simple inverse process of induction resulting from the elimination of general anesthetics from the central nervous system. However, accumulated evidence has indicated that anesthesia induction and emergence are not mirror-image processes because of the occurrence of hysteresis/neural inertia in both animals and humans. An increasing number of studies have highlighted the critical role of orexinergic neurons and their involved circuits in the selective regulation of emergence but not the induction of general anesthesia. Moreover, additional brain regions have also been implicated in distinct neural mechanisms for anesthesia induction and emergence, which extends the concept that anesthetic induction and emergence are not antiparallel processes. Here, we reviewed the current literature and summarized the evidence regarding the differential mechanism of neural modulation in anesthesia induction and emergence, which will facilitate the understanding of the underlying neural mechanism for emergence from general anesthesia.
RESUMO
BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.
Assuntos
Anestesia , Anestésicos Gerais , Anestésicos Inalatórios , Isoflurano , Éteres Metílicos , Simportadores , Ratos , Animais , Isoflurano/farmacologia , Sevoflurano/farmacologia , Animais Recém-Nascidos , Bumetanida/farmacologia , Ácido gama-Aminobutírico/farmacologia , Eletroencefalografia , Hipnóticos e Sedativos , Anestésicos Inalatórios/farmacologiaRESUMO
BACKGROUND: Marital status is a potentially essential factor for cognitive impairment. Relevant research examining the potential pathways through which the marital status of spouseless older people is associated with cognitive impairment needs to be more adequate. Therefore, this study aims to investigate the serial mediating effects of various forms of social support and depression between marital status and cognitive impairment in older Chinese people. METHODS: This study involved a secondary analysis of data from the 2014-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with a total of 2,647 Chinese older adults and 53.6% being males. Mediation analysis using the SPSS process macro was conducted. RESULTS: The results indicated that marital status was significantly predictive of cognitive impairment among older people, and those with a spouse exhibited higher cognitive functioning. Informal social support and depression were found to play partial mediating roles in the association between marital status and cognitive impairment. The findings also revealed that marital status was unrelated to formal social support, and no association between formal social support and cognitive impairment was found. CONCLUSIONS: The study findings highlight the need for social service providers to design programs for promoting connections associated with informal support to reduce their risk of depression and cognitive impairment and for policymakers to develop effective formal social support systems for older people without spouses. This study indicated that older people could regain the benefits of marriage to lower the risk of depression and improve their mental health.
Assuntos
Disfunção Cognitiva , Depressão , Estado Civil , Apoio Social , Humanos , Masculino , Feminino , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Depressão/psicologia , Depressão/epidemiologia , Depressão/etnologia , China/epidemiologia , Estudos Longitudinais , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
A randomized controlled trial was conducted to examine the effects of bright light therapy on agitation in older adults with dementia in Macao. This study involved 31 participants: 10 in the outdoor light treatment group, 11 in the indoor light-box treatment group, and 10 in the control group. Significant reductions in agitation were observed in the two treatment groups over four weeks compared to the control group. However, no statistical difference in cognitive function between experimental and control groups was found. This study supports the use of bright light therapy to reduce agitation in older people with dementia.
RESUMO
BACKGROUND: The dentate gyrus (DG) has been implicated in the pathophysiology of depression. Many studies have revealed the cellular types, neural circuits, and morphological changes of the DG involved in the development of depression. However, the molecular regulating its intrinsic activity in depression is unknown. METHODS: Utilizing the mode of depression induced by lipopolysaccharide (LPS), we investigate the involvement of the sodium leak channel (NALCN) in inflammation-induced depressive-like behaviors of male mice. The expression of NALCN was detected by immunohistochemistry and real-time polymerase chain reaction. DG microinjection of the adeno-associated virus or lentivirus was carried out using a stereotaxic instrument and followed by behavioral tests. Neuronal excitability and NALCN conductance were recorded by whole-cell patch-clamp techniques. RESULTS: The expression and function of NALCN were reduced in both the dorsal and ventral DG in LPS-treated mice; whereas, only knocking down NALCN in the ventral pole produced depressive-like behaviors and this effect of NALCN was specific to ventral glutamatergic neurons. The excitability of ventral glutamatergic neurons was impaired by both the knockdown of NALCN and/or the treatment of LPS. Then, the overexpression of NALCN in the ventral glutamatergic neurons decreased the susceptibility of mice to inflammation-induced depression, and the intracranial injection of substance P (non-selective NALCN activator) into the ventral DG rapidly ameliorated inflammation-induced depression-like behaviors in an NALCN-dependent manner. CONCLUSIONS: NALCN, which drives the neuronal activity of the ventral DG glutamatergic neurons, uniquely regulates depressive-like behaviors and susceptibility to depression. Therefore, the NALCN of glutamatergic neurons in the ventral DG may present a molecular target for rapid antidepressant drugs.
Assuntos
Giro Denteado , Depressão , Canais Iônicos , Lipopolissacarídeos , Animais , Masculino , Camundongos , Giro Denteado/metabolismo , Giro Denteado/patologia , Depressão/genética , Depressão/metabolismo , Ácido Glutâmico/metabolismo , Inflamação/complicações , Canais Iônicos/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Sódio/metabolismoRESUMO
Elevated excitability of glutamatergic neurons in the lateral parabrachial nucleus (PBL) is associated with the pathogenesis of inflammatory pain, but the underlying molecular mechanisms are not fully understood. Sodium leak channel (NALCN) is widely expressed in the central nervous system and regulates neuronal excitability. In this study, chemogenetic manipulation was used to explore the association between the activity of PBL glutamatergic neurons and pain thresholds. Complete Freund's adjuvant (CFA) was used to construct an inflammatory pain model in mice. Pain behaviour was tested using von Frey filaments and Hargreaves tests. Local field potential (LFP) was used to record the activity of PBL glutamatergic neurons. Gene knockdown techniques were used to investigate the role of NALCN in inflammatory pain. We further explored the downstream projections of PBL using cis-trans-synaptic tracer virus. The results showed that chemogenetic inhibition of PBL glutamatergic neurons increased pain thresholds in mice, whereas chemogenetic activation produced the opposite results. CFA plantar modelling increased the number of C-Fos protein and NALCN expression in PBL glutamatergic neurons. Knockdown of NALCN in PBL glutamatergic neurons alleviated CFA-induced pain. CFA injection induced C-Fos protein expression in central nucleus amygdala (CeA) neurons, which was suppressed by NALCN knockdown in PBL glutamatergic neurons. Therefore, elevated expression of NALCN in PBL glutamatergic neurons contributes to the development of inflammatory pain via PBL-CeA projections.
Assuntos
Núcleos Parabraquiais , Camundongos , Animais , Núcleos Parabraquiais/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Canais de Sódio/metabolismo , Dor/metabolismo , Neurônios/metabolismo , Sódio/metabolismoRESUMO
BACKGROUND: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl- co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development. METHODS: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg-1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift. RESULTS: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1ß) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1ß mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1ß or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation. CONCLUSIONS: Sustained elevation of IL-1ß in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.
Assuntos
Disfunção Cognitiva , Simportadores , Animais , Disfunção Cognitiva/induzido quimicamente , Hipocampo/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Ratos , Simportadores/genética , Simportadores/metabolismo , Ácido gama-Aminobutírico/metabolismo , Cotransportadores de K e Cl-RESUMO
BACKGROUND: Isoflurane can induce anterograde amnesia. Hippocampal ripples are high-frequency oscillatory events occurring in the local field potentials of cornu ammonis 1 involved in memory processes. The authors hypothesized that isoflurane suppresses hippocampal ripples at a subanesthetic concentration by modulating the excitability of cornu ammonis 1 neurons. METHODS: The potencies of isoflurane for memory impairment and anesthesia were measured in mice. Hippocampal ripples were measured by placing recording electrodes in the cornu ammonis 1. Effects of isoflurane on the excitability of hippocampal pyramidal neurons and interneurons were measured. A simulation model of ripples based on the firing frequency of hippocampal cornu ammonis 1 neurons was used to validate the effects of isoflurane on neuronal excitability in vitro and on ripples in vivo. RESULTS: Isoflurane at 0.5%, which did not induce loss of righting reflex, impaired hippocampus-dependent fear memory by 97.4 ± 3.1% (mean ± SD; n = 14; P < 0.001). Isoflurane at 0.5% reduced ripple amplitude (38 ± 13 vs. 42 ± 13 µV; n = 9; P = 0.003), rate (462 ± 66 vs. 538 ± 81 spikes/min; n = 9; P = 0.002) and duration (36 ± 5 vs. 48 ± 9 ms; n = 9; P < 0.001) and increased the interarrival time (78 ± 7 vs. 69 ± 6 ms; n = 9; P < 0.001) and frequency (148.2 ± 3.9 vs. 145.0 ± 2.9 Hz; n = 9; P = 0.001). Isoflurane at the same concentration depressed action potential frequency in fast-spiking interneurons while slightly enhancing action potential frequency in cornu ammonis 1 pyramidal neurons. The simulated effects of isoflurane on hippocampal ripples were comparable to recordings in vivo. CONCLUSIONS: The authors' results suggest that a subanesthetic concentration of isoflurane can suppress hippocampal ripples by differentially modulating the excitability of pyramidal neurons and interneurons, which may contribute to its amnestic action.
Assuntos
Anestésicos Inalatórios/farmacologia , Hipocampo/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Isoflurano/farmacologia , Células Piramidais/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos AnimaisRESUMO
BACKGROUND Atelectasis occurs in patients of all ages during various surgeries. Previous studies have mainly focused on perioperative atelectasis in infants. However, research on the incidence of atelectasis among elderly patients, particularly those undergoing laparoscopic surgeries, is limited. Therefore, this prospective study aimed to investigate the effect of lung recruitment maneuvers (LRMs) on the reduction of atelectasis determined by lung ultrasound in patients more than 60 years old undergoing laparoscopic surgery for colorectal carcinoma. MATERIAL AND METHODS In this evaluator-blinded clinical study, 42 patients more than 60 years old diagnosed with colorectal carcinoma were randomly grouped either into a lung recruitment maneuver (RM) group or control (C) group. All patients were scheduled for laparoscopic surgery under general anesthesia using the lung-protective ventilation strategy. Lung ultrasonography was carried out at 3 predetermined time intervals. Patients in the RM group received ultrasound-guided recruitment maneuvers once atelectasis was discovered by lung ultrasound. Scores of lung ultrasound were used for assessing the severity of lung atelectasis. RESULTS At the end of the operation, the occurrence of atelectasis was 100% in the RM group and 95% in the C group. After RMs, the frequency of atelectasis in the RM group and C group was 50% and 95%, respectively (P<0.01). Postoperative pulmonary complications were not different between the 2 groups. CONCLUSIONS At a single center, patients more than 60 years old undergoing laparoscopic surgery for colorectal carcinoma had a prevalence of lung atelectasis of 100% and although LRMs significantly reduced the incidence of pulmonary atelectasis, they did not improve postoperative pulmonary complications.
Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Atelectasia Pulmonar/prevenção & controle , Respiração Artificial/métodos , Ultrassonografia/métodos , Idoso , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Atelectasia Pulmonar/epidemiologiaRESUMO
BACKGROUND: Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. METHODS: Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean - SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. RESULTS: The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. CONCLUSIONS: Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. TRIAL REGISTRATION: www.chictr.org.cn . identifier: ChiCTR1800014327 .
Assuntos
Abdome/cirurgia , Anestésicos Inalatórios/farmacologia , Metaboloma , Sevoflurano/farmacologia , Anestesia Geral , Ácido Cítrico/sangue , Feminino , Glucose/análise , Ácido Glutâmico/metabolismo , Glutamina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Pirrolidonocarboxílico/sangue , Selenocisteína/sangue , Esfingosina/análogos & derivados , Esfingosina/sangue , Sacarose/sangueRESUMO
OBJECTIVE: To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats. METHODS: On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65). RESULTS: In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( P=0.048). CONCLUSION: The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.
Assuntos
Anestésicos Inalatórios , Transtorno do Deficit de Atenção com Hiperatividade , Anestésicos Inalatórios/toxicidade , Animais , Animais Recém-Nascidos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , SevofluranoRESUMO
INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.
Assuntos
Músculos Abdominais , Metanálise como Assunto , Bloqueio Nervoso , Dor Pós-Operatória , Revisões Sistemáticas como Assunto , Ultrassonografia de Intervenção , Humanos , Bloqueio Nervoso/métodos , Músculos Abdominais/inervação , Músculos Abdominais/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória/prevenção & controle , Abdome/cirurgia , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: The flipped classroom teaching model is widely used in medical education and is indicated to be better than traditional lecture approaches in many medical specialties. Emerging studies have evaluated the effects of the flipped classroom teaching model on anaesthesiology residents. This protocol aims to perform a systematic review and meta-analysis to determine whether the flipped classroom teaching model is superior to traditional teaching methods for anaesthesiology residents. METHODS AND ANALYSIS: Seven databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, Wanfang Data and the VIP database, will be systematically searched from their inception to 1 June 2024. Randomised controlled trials that compared the effects of flipped classrooms versus traditional teaching methods in anaesthesiology residents will be included. The primary outcome will be the theoretical knowledge score. The secondary outcomes will include skill scores and the proportion of anaesthesiology residents who preferred the flipped classroom model. RevMan V.5.4 software will be used to perform the statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will assess the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not applicable to this protocol. The results of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024497935.
Assuntos
Anestesiologia , Internato e Residência , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Humanos , Anestesiologia/educação , Internato e Residência/métodos , Projetos de Pesquisa , Competência Clínica , Aprendizagem Baseada em Problemas/métodosRESUMO
INTRODUCTION: Ultrasound-guided quadratus lumborum blocks are commonly used for postoperative analgesia during caesarean section. Ultrasound-guided quadratus lumborum blocks can be performed through four approaches, including lateral, posterior, anterior, and intramuscular quadratus lumborum blocks. This systematic review and meta-analysis aims to determine the optimal approach to ultrasound-guided quadratus lumborum blocks for postoperative analgesia in elective caesarean section. METHODS AND ANALYSIS: The PubMed, EMBASE, Cochrane Library and Web of Science databases will be systematically searched from their inception to 30 July 2024. Randomised controlled trials that compared the analgesic effects of different ultrasound-guided quadratus lumborum block approaches in elective caesarean section will be included. Only publications in English will be eligible for inclusion. The total postoperative analgesic consumption over 24 hours will be the primary outcome. The time to first analgesic request, postoperative pain scores at rest and during movement, and incidence of adverse effects will be secondary outcomes. RevMan V.5.4 will be used for the statistical analysis. Network meta-analysis will be used for indirect comparisons between different approaches across studies. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of evidence for each outcome. ETHICS AND DISSEMINATION: Ethical approval was not required. The results of this study will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42024503694.
Assuntos
Músculos Abdominais , Cesárea , Metanálise como Assunto , Bloqueio Nervoso , Dor Pós-Operatória , Revisões Sistemáticas como Assunto , Ultrassonografia de Intervenção , Humanos , Dor Pós-Operatória/prevenção & controle , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Feminino , Gravidez , Músculos Abdominais/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Eletivos , Projetos de PesquisaRESUMO
INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly performed for postoperative analgesia in elective cesarean section. Ropivacaine is the most commonly used local anesthetic for TAP blocks. Currently, the concentration of ropivacaine for TAP blocks is various, and increasing number of randomized controlled trials (RCTs) have compared the effects of different concentration of ropivacaine for TAP blocks in cesarean section. This protocol of a systematic review and meta-analysis aims to identify the optimal concentration of ropivacaine for TAP blocks in elective cesarean section. METHODS AND ANALYSIS: Databases including PubMed, Web of science, the Cochrane library, and EMBASE will be searched from their inception to May 1, 2024. RCTs that investigated the analgesia of different concentrations of ropivacaine for TAP blocks in elective cesarean section will be identified. The analgesia duration will be the primary outcome. Secondary outcomes will include the analgesics consumption over postoperative 24 hours, postoperative pain scores at rest and movement, and the incidence of adverse effects. RevMan 5.4 software will used for statistical analysis. The evidence quality of synthesized results will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval is not applicable. The results of this study will be published on completion. TRIAL REGISTRATION: PROSPERO registration number: CRD42024496907.
Assuntos
Músculos Abdominais , Anestésicos Locais , Cesárea , Metanálise como Assunto , Bloqueio Nervoso , Dor Pós-Operatória , Ropivacaina , Revisões Sistemáticas como Assunto , Ropivacaina/administração & dosagem , Humanos , Cesárea/métodos , Bloqueio Nervoso/métodos , Músculos Abdominais/inervação , Músculos Abdominais/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Feminino , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Procedimentos Cirúrgicos Eletivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Ultrasound-guided quadratus lumborum block and erector spinae plane block are widely used for postoperative analgesia in adult patients undergoing abdominal surgeries. This protocol aims to compare the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries. METHODS AND ANALYSIS: Four databases, including PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), will be searched. Randomised controlled trials that compared the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in adult patients will be identified. The primary outcomes are time to the first analgesic request and postoperative analgesic consumption over 24 hours. Secondary outcomes will include postoperative pain scores and the incidence of side effects. RevMan V.5.3 software will be used for data processing and statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will be used to assess the evidence quality of outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Results of this present study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023445802.