Postoperative cognitive dysfunction (POCD) in the elderly is a serious clinical concern. Although microglial phagocytosis is known to depend on mitochondrial metabolism, and its dysregulation can lead to abnormal synaptic pruning and neuronal injury, the molecular link between these processes in POCD pathogenesis requires further elucidation. In this study, we established a POCD animal model of aged mice using isoflurane exposure and partial hepatectomy to investigate how anesthesia and surgery impacted synaptic plasticity via microglial phagocytosis. Our findings demonstrated that anesthesia and surgery significantly reduced hippocampal peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) expression, leading to impaired mitochondrial energy metabolism, abnormal microglial phagocytosis and excessive synaptic pruning, which was associated with synaptic deficits and cognitive dysfunction. Importantly, the treatment with the PGC-1α activator ZLN005 or AAV-mediated overexpression of PGC-1α not only successfully restored PGC-1α level in the hippocampus of aged mice, but also effectively ameliorated mitochondrial dysfunction, reversed abnormal microglia-mediated synaptic pruning, restored synaptic plasticity, and improved POCD. Our findings identify microglial PGC-1α as a critical mediator in the pathogenesis of POCD, linking mitochondrial energy metabolism with microglia-mediated synaptic pruning, and highlight the potential of microglial PGC-1α as a promising therapeutic target for prevention and treatment of POCD.

Neonatal brain injury, including hypoxic–ischemic encephalopathy, preterm brain injury, and neonatal infectious brain injury, remains a major cause of death and long-term neurodevelopmental disability worldwide. The immature brain is highly dependent on oxidative metabolism yet particularly vulnerable to energy failure and oxidative stress, placing mitochondria at the core of injury cascades. By integrating disturbances in energy production, redox balance, calcium homeostasis, and cell death signaling, mitochondrial dysfunction is increasingly recognized as a unifying driver of diverse neonatal brain injury phenotypes. This narrative review synthesizes current knowledge on the main clinical forms of neonatal brain injury and their developmental context, alongside an overview of mitochondrial physiology in neural cells, including the regulation of bioenergetics, reactive oxygen species, calcium signaling, mitochondrial dynamics, and inter‑organelle communication. It critically examines how mitochondrial dysfunction contributes to injury across hypoxic–ischemic, preterm, and infectious or inflammatory insults, emphasizing links between impaired oxidative phosphorylation, excessive oxidative and nitrosative stress, calcium overload with pathological opening of the mitochondrial permeability transition pore, activation of apoptosis and regulated necrosis, disrupted mitochondrial fusion–fission balance and biogenesis, and defective mitophagy and mitochondrial quality control. These mitochondrial disturbances precipitate acute neuronal and oligodendroglial injury and hinder the long-term maturation and connectivity of neural circuits. Finally, we review emerging mitochondria‑targeted neuroprotective strategies, focusing on approaches that enhance mitochondrial biogenesis, reduce mitochondrial oxidative stress, and target mitochondrial dynamics to restore mitochondrial homeostasis and improve cellular resilience in the immature brain. By linking specific patterns of mitochondrial dysfunction to distinct forms and stages of neonatal brain injury, this review provides a mechanistic framework for identifying high‑risk infants, refining pathophysiological understanding, and guiding the rational development of mitochondria‑targeted interventions aimed at improving neurological outcomes in vulnerable newborns.

Perioperative neurocognitive disorders (PND) are prevalent neurological complications that may delay postoperative recovery in elderly patients, but effective preventive and therapeutic targets remain lacking. Protein S-palmitoylation is essential for normal neuronal function and synaptic plasticity, but its detailed role in PND development remains largely undefined. Here, we established a PND model in aged mice using partial hepatectomy under isoflurane anesthesia. We found that anesthesia and surgery markedly reduced S-palmitoylation of synaptosome-associated protein 25 (SNAP25) at four conserved cysteine residues (Cys85/Cys88/Cys90/Cys92) in the hippocampal neurons. Depalmitoylation impaired SNAP25 localization to the mitochondrial outer membrane and reduced its stability, causing defective mitophagy in hippocampal neurons. Mechanistically, palmitoyltransferase 17 (ZDHHC17) was identified as a major palmitoyl acyltransferase responsible for SNAP25 palmitoylation, and hippocampal ZDHHC17 expression was downregulated after anesthesia and surgery. ZDHHC17 interacted physically with SNAP25 and mediated the palmitoylation of SNAP25. Neuron-specific overexpression of ZDHHC17 restored SNAP25 palmitoylation, mitochondrial membrane localization and protein stability, and promoted neuronal mitophagy, ultimately improving hippocampal synaptic plasticity and cognitive function. Consistently, SNAP25 overexpression enhanced mitophagy and ameliorated cognitive impairments, whereas pharmacological inhibition of mitophagy with Mdivi-1 attenuated these neuroprotective effects. Collectively, our findings uncover a novel ZDHHC17-SNAP25 palmitoylation axis that can preserve hippocampal mitophagy and synaptic integrity, offering a promising therapeutic target for PND prevention and treatment.

In the perioperative setting, the administration of intravenous lidocaine is widespread. This study investigates the effects of varying frequencies of intravenous lidocaine on cognitive function in mice of differing ages. Young adult and aged mice received systemic lidocaine either once or three times. Our findings indicated that repeated exposure to systemic lidocaine in aged mice resulted in cognitive impairment, accompanied by neuronal apoptosis and synaptic loss in the hippocampus. Additionally, repeated lidocaine exposure activated microglia and neurotoxic A1 astrocytes in aged mice. Notably, the adverse effects were significantly diminished when aged mice were treated with dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor. Furthermore, depleting microglia with PLX5622 effectively prevented the activation of A1 astrocytes and synaptic loss following lidocaine exposure. This study provides evidence linking age and exposure frequency to cognitive impairment due to systemic lidocaine administration, correlating with the activation of microglia and neurotoxic A1 astrocytes.

BACKGROUND:Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation; however, it frequently leads to cardiovascular adverse events and respiratory depression. Propofol target-controlled infusion (TCI) can provide safe sedation but may require higher dosages of propofol. On the contrary, etomidate offers hemodynamic stability. AIM:To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy. METHODS:A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups: P, 0.1EP, and 0.15EP. Patients in the P group received propofol TCI only, with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL. Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection, respectively, followed by propofol TCI. RESULTS:Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups (P group: 78 mmHg, 0.1EP group: 82 mmHg, 0.15EP group: 88 mmHg; P < 0.05). Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups (P group: 260.6 mg, 0.1EP group: 228.1 mg, 0.15EP group: 201.2 mg; P < 0.05). The induction time was longer in the P group than in the other groups (P group: 1.9 ± 0.7 minutes, 0.1EP group: 1.2 ± 0.4 minutes, 0.15EP group: 1.1 ± 0.3 minutes; P < 0.01). The recovery time was shorter in the 0.15EP group than in the other groups (P group: 4.8 ± 2.1 minutes, 0.1EP group: 4.5 ± 1.6 minutes, 0.15EP group: 3.9 ± 1.4 minutes; P < 0.01). The incidence of hypotension (P group: 36.4%, 0.1EP group: 29.1%, 0.15EP group: 11.8%; P < 0.01) and injection pain was lower in the 0.15EP group than in the other groups (P < 0.05). Furthermore, the incidence of respiratory depression was lower in the 0.15EP group than in the P group (P < 0.05). Additionally, the satisfaction of the patient, endoscopist, and anesthesiologist was higher in the 0.15EP group than in the other groups (P < 0.05). CONCLUSION:Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption, which is followed by fewer cardiovascular adverse events and respiratory depression, along with higher patient, endoscopist, and anesthesiologist satisfaction.

Lidocaine is widely used for perioperative pain management, but repeated exposure may cause neurotoxicity, including neurological deficits. This study investigates mechanisms underlying cognitive decline induced by repeated lidocaine exposure. Eighteen-month-old mice received repeated clinically relevant lidocaine infusions over 3 days. Cognitive function was assessed by Morris water maze, Y-maze and open field tests. Hippocampal pathology was examined via TEM, Nissl staining, immunofluorescence for astrocyte polarisation and Aβ deposition, and western blot for tau, BDNF, TrkB, mTOR and autophagy proteins. The TrkB agonist 7,8-DHF was used to modulate BDNF/TrkB/mTOR signalling. Repeated lidocaine exposure impaired cognition and induced Alzheimer's-like hippocampal pathology, as evidenced by increased accumulation of Aβ and tau toxic proteins, along with neuronal death. It reduced BDNF expression, inhibited TrkB phosphorylation, and activated mTOR signalling, leading to autophagy inhibition and pathological protein accumulation. Lidocaine shifted astrocytes towards the neurotoxic A1 phenotype, decreasing neuroprotective A2 astrocytes and BDNF synthesis. TrkB agonist treatment restored signalling, enhanced autophagy and improved cognitive deficits and pathology. Repeated lidocaine exposure promotes A1 astrocyte increase and A2 decrease, inhibiting autophagy via the BDNF/TrkB/mTOR pathway, resulting in toxic protein deposition and Alzheimer's-like cognitive impairment.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality and neurological disabilities in children. Recent evidence indicates that gut microbiota significantly contributes to the development of inflammation and cognitive impairments following brain injury. However, the mechanisms by which gut microbiota influence inflammation and cognitive function in the neonates after HIBD are not well understood. This study established a neonatal rat model of HIBD by the classic Rice-Vannucci technique to investigate gut dysbiosis following hypoxic-ischemic (HI) insult and to elucidate the causal relationship between gut dysbiosis and cognitive impairments. Our results demonstrated that HI insult resulted in significant gut microbial dysbiosis, characterized by an expansion of Enterobacteriaceae. This dysbiosis was associated with intestinal barrier damage, lipopolysaccharides (LPS) leakage, and systemic inflammation. Conversely, administration of aminoguanidine (AG) to inhibit Enterobacteriaceae overgrowth restored intestinal barrier integrity and reduced systemic inflammation. Importantly, AG treatment effectively suppressed microglial activation, neuronal damage, and cognitive impairments in the neonatal rats subjected to HI insult. Additionally, RNA sequencing analysis revealed that differentially expressed genes in both colonic and hippocampal tissues were primarily associated with inflammation and neuronal apoptosis after HI insult. Further mechanistic exploration revealed that AG treatment mitigated intestinal LPS leakage, thereby reducing the activation of the TLR4/MyD88/NF-κB signaling pathway and production of the downstream inflammatory cytokines in both the colon and hippocampus. Notably, fecal microbiota transplantation (FMT) from the HIBD rats to the antibiotic cocktail-treated recipient rats resulted in microglial activation, neuronal damage, and cognitive impairments in the recipients. However, these adverse effects were effectively mitigated in the recipient rats that received FMT from the AG-treated donors, as well as in those undergoing hippocampal TLR4 knockdown. In conclusion, our findings indicate that LPS derived from gut Enterobacteriaceae overgrowth plays a critical role in the TLR4-mediated inflammatory signaling, providing a novel microbiota-based therapeutic approach for cognitive impairments following neonatal HIBD.

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist extensively used for sedation in clinical anesthesia, has recently attracted significant attention for its neuroprotective properties. These effects are mediated through multiple mechanisms, including anti-inflammatory and antioxidative stress responses, inhibition of apoptosis and autophagy, preservation of mitochondrial function, and maintenance of blood-brain barrier integrity. Brain injury, encompassing neonatal hypoxic-ischemic encephalopathy, ischemic stroke, traumatic brain injury, and other related cerebral pathologies, remains a leading cause of global neurological disability. Despite advances in critical care, effective interventions to prevent secondary neuronal damage and long-term neurological dysfunction remain limited. The neuroprotective actions of DEX suggest its potential as a therapeutic candidate for mitigating neurological deficits following brain injury. This review synthesizes preclinical and clinical evidence on DEX across various forms of brain injury, spanning molecular mechanisms, animal models, and clinical applications, thereby providing a foundation for exploring its therapeutic strategies in neurocritical care.

Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.

Chen, Andi PhDa; Chen, Xiaohui MD, PhDa; Huang, Shishi MMb; Zheng, Xiaochun MD, PhDa,c Author Information

Following hypoxic-ischemic brain damage (HIBD), there is a decline in cognitive function; however, there are no effective treatment strategies for this condition in neonates. This study aimed to evaluate the role of the cluster of differentiation 200 (CD200)/CD200R1 axis in cognitive function following HIBD using an established model of HIBD in postnatal day 7 rats. Western blotting analysis was conducted to evaluate the protein expression levels of CD200, CD200R1, proteins associated with the PI3K/Akt-NF-κB pathway, and inflammatory factors such as TNF-α, IL-1β, and IL-6 in the hippocampus. Additionally, double-immunofluorescence labeling was utilized to evaluate M1 microglial polarization and neurogenesis in the hippocampus. To assess the learning and memory function of the experimental rats, the Morris water maze (MWM) test was conducted. HIBDleads to a decrease in the expression of CD200 and CD200R1 proteins in the neonatal rat hippocampus, while simultaneously increasing the expression of TNF-α, IL-6, and IL-1β proteins, ultimately resulting in cognitive impairment. The administration of CD200Fc, a fusion protein of CD200, was found to enhance the expression of p-PI3K and p-Akt, but reduce the expression of p-NF-κB. Additionally, CD200Fc inhibited M1 polarization of microglia, reduced neuroinflammation, improved hippocampal neurogenesis, and mitigated cognitive impairment caused by HIBD in neonatal rats. In contrast, blocking the interaction between CD200 and CD200R1 with the anti-CD200R1 antibody (CD200R1 Ab) exerted the opposite effect. Furthermore, the PI3K specific activator, 740Y-P, significantly increased the expression of p-PI3K and p-Akt, but reduced p-NF-κB expression. It also inhibited M1 polarization of microglia, reduced neuroinflammation, and improved hippocampal neurogenesis and cognitive function in neonatal rats with HIBD. Our findings illustrate that activation of the CD200/CD200R1 axis inhibits the NF-κB-mediated M1 polarization of microglia to improve HIBD-induced cognitive impairment and hippocampal neurogenesis disorder via the PI3K/Akt signaling pathway.

Background: Hypotension often occurs following the induction of general anesthesia in elderly patients undergoing surgery and can lead to severe complications. This study assessed the effect of carotid corrected flow time (FTc) combined with perioperative fluid therapy on preventing hypotension after general anesthesia induction in elderly patients. Materials and methods: The prospective cohort study was divided into two parts. The first part (Part I) consisted of 112 elderly patients. Carotid FTc was measured using Color Doppler Ultrasound 5 min before anesthesia induction. Hypotension was defined as a decrease of greater than 30% in systolic blood pressure (SBP) or a decrease of greater than 20% in mean arterial pressure (MAP) from baseline, or an absolute SBP below 90 mmHg and MAP below 60 mmHg within 3 min after induction of general anesthesia. The predictive value of carotid FTc was determined using receiver operating characteristic (ROC) curve. The second part (Part II) consisted of 65 elderly patients. Based on the results in Part I, elderly patients with carotid FTc below the optimal cut-off value received perioperative fluid therapy at a volume of 8 ml/kg of balanced crystalloids (lactated Ringer's solution) in 30 min before induction. The effect of carotid FTc combined with perioperative fluid therapy was assessed by comparing observed incidence of hypotension after induction. Results: The area under the ROC for carotid FTc to predict hypotension after induction was 0.876 [95% confidence interval (CI) 0.800-0.952, P<0.001]. The optimal cut-off value was 334.95 ms (sensitivity of 87.20%; specificity of 82.20%). The logistic regression analysis revealed that carotid FTc is an independent predictor for post-induction hypotension in elderly patients. The incidence of post-induction hypotension was significantly lower (P<0.001) in patients with carotid FTc less than 334.95 ms who received perioperative fluid therapy (35.71%) compared to those who did not (92.31%). Conclusions: Carotid FTc combined with the perioperative fluid therapy could significantly reduce the incidence of hypotension after the induction of general anesthesia in elderly patients.

AIMS:Dexmedetomidine (DEX) has been reported to alleviate hypoxic-ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF/TrkB/CREB signaling pathway in neonatal rats with HIBD. METHODS:HIBD was induced in postnatal day 7 rats using the Rice-Vannucci method, and DEX (25 μg/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF/TrkB/CREB pathway was regulated by administering the TrkB receptor antagonist ANA-12 through intraperitoneal injection or by delivering adeno-associated virus (AAV)-shRNA-BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability. RESULTS:The levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA-sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF/TrkB/CREB pathway using either ANA-12 or AAV-shRNA-BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement. CONCLUSIONS:DEX promoted neurogenesis in the hippocampus by activating the BDNF/TrkB/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.

Hypoxic-ischemic brain damage (HIBD) can result in significant global rates of neonatal death or permanent neurological disability. N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism, and m6A dysregulation is implicated in various neurological diseases. However, the biological roles and clinical significance of m6A in HIBD remain unclear. We currently evaluated the effect of HIBD on cerebral m6A methylation in RNAs in neonatal rats. The m6A dot blot assay showed a global augmentation in RNA m6A methylation post-HI. Herein, we also report on demethylase FTO, which is markedly downregulated in the hippocampus and is the main factor involved with aberrant m6A modification following HI. By conducting a comprehensive analysis of RNA-seq data and m6A microarray results, we found that transcripts with m6A modifications were more highly expressed overall than transcripts without m6A modifications. The overexpression of FTO resulted in the promotion of Akt/mTOR pathway hyperactivation, while simultaneously inhibiting autophagic function. This is carried out by the demethylation activity of FTO, which selectively demethylates transcripts of phosphatase and tensin homolog (PTEN), thus promoting its degradation and reduced protein expression after HI. Moreover, the synaptic and neurocognitive disorders induced by HI were effectively reversed through the overexpression of FTO in the hippocampus. Cumulatively, these findings demonstrate the functional importance of FTO-dependent hippocampal m6A methylome in cognitive function and provides novel mechanistic insights into the therapeutic potentials of FTO in neonatal HIBD.

Background Postoperative cognitive dysfunction (POCD) is a neurological complication occurring after anesthesia and surgery. Neuroinflammation plays a critical role in the pathogenesis of POCD, and the activation of the cluster of differentiation 200 (CD200)/CD200R1 axis improves neurological recovery in various neurological disorders by modulating inflammation. The aim of this study was to investigate the impact and underlying mechanism of CD200/CD200R1 axis on POCD in aged mice.Methods The model of POCD was established in aged mice. To assess the learning and memory abilities of model mice, the Morris water maze test was implemented. CD200Fc (CD200 fusion protein), CD200R1 Ab (anti-CD200R1 antibody), and 740Y-P (a specific PI3K activator) were used to evaluate the effects of the CD200/CD200R1/PI3K/Akt/NF-kappa B signaling pathway on hippocampal microglial polarization, neuroinflammation, synaptic activity, and cognition in mice.Results It was observed that anesthesia/surgery induced cognitive decline in aged mice, increased the levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-1 beta and decreased the levels of postsynaptic density protein 95 (PSD-95), synaptophysin (SYN) in the hippocampus. Moreover, CD200Fc and 740Y-P attenuated neuroinflammation and synaptic deficits and reversed cognitive impairment via the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor-kappa B (NF-kappa B) signaling pathway, whereas CD200R1 Ab administration exerted the opposite effects. Our results further show that the CD200/CD200R1 axis modulates M1/M2 polarization in hippocampal microglia via the PI3K/Akt/NF-kappa B signaling pathway.Conclusions Our findings indicate that the activation of the CD200/CD200R1 axis reduces neuroinflammation, synaptic deficits, and cognitive impairment in the hippocampus of aged mice by regulating microglial M1/M2 polarization via the PI3K/Akt/NF-kappa B signaling pathway.

Abstract Background Propofol has been widely used in painless gastrointestinal endoscopy; however, it frequently leads to cardiovascular adverse events and respiratory depression. Propofol target-controlled infusion (TCI) can provide safe sedation but may require higher dosages of propofol. On the contrary, etomidate offers hemodynamic stability. This study aimed to investigate the efficacy and safety of propofol TCI combined with etomidate in painless gastrointestinal endoscopy. Methods A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups: P, 0.1EP, and 0.15EP. Patients in the P group received propofol TCI only, with an initial effect-site concentration of the propofol TCI system of 3.0 µg/mL. Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection, respectively, followed by propofol TCI. Results Patients in the 0.15EP group had higher mean blood pressure (MBP) after induction than the other groups (P < 0.05). Propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups (P < 0.05). The induction time was longer in the P group than in the other groups (P < 0.01). The recovery time was shorter in the 0.15EP group than in the other groups (P < 0.01). The incidence of hypotension and injection pain was lower in the 0.15EP group than in the other groups (P < 0.05). Furthermore, the incidence of respiratory depression was lower in the 0.15EP group than in the P group (P < 0.05). Additionally, the satisfaction of the patient, endoscopist, and anesthesiologist was higher in the 0.15EP group than in the other groups (P < 0.05). Conclusions Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption, which is followed by fewer cardiovascular adverse events and respiratory depression, along with higher patient, endoscopist, and anesthesiologist satisfaction. Thus, this anesthesia strategy is suitable for painless gastrointestinal endoscopy.