How to trace etomidate in illegal E-cigarettes from authentic human hair: identification, quantification and multiple-factor analysis.

PURPOSE: The abusive consumption of illegal E-cigarettes containing etomidate (ET) can have a significant impact on public mental and physical well-being. The purpose of this study is to establish a rapid quantitative method using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) for the targeted screening of etomidate (ET) and its metabolite etomidate acid (ETA) in hair samples. METHODS: A 1 mL methanol solution containing the internal standard ET-d5 at a concentration of 50 pg/mg was added to 20 mg of hair and milled below 4 °C. After centrifugation, 5 µL of the supernatant was injected into a UHPLC-MS/MS system. RESULTS: The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 1 pg/mg and 10 pg/mg, respectively, for ET, and 10 pg/mg and 25 pg/mg, respectively, for ETA. Calibration curves for all analytes showed good linearity (r > 0.997), indicating a reliable method. Accuracies were between 92.12% and 110.72%. Intra-day and inter-day precision for all analytes at all concentration levels were below 10.13%. Analyte recoveries ranged from 86.90% to 101.43%, with a matrix effect ranging from -18.55% to -14.93%. CONCLUSIONS: The validated method was successfully used to analyze 105 hair samples from suspected ET users. Of these, 50 tested positive for ET and 43 tested positive for ETA above the LOQ. This demonstrates the effectiveness of the developed UHPLC-MS/MS method in detecting ET and ETA in hair samples, which could be instrumental in addressing the issue of illegal E-cigarette abuse and its impact on public health.

Effects of different doses of alfentanil on cardiovascular response to rapid sequence intubation in elderly patients: a parallel-controlled randomized trial.

BACKGROUND: Rapid sequence intubation (RSI) have been shown to be effective in preventing reflux aspiration in patients with a full stomach during anaesthesia induction and endotracheal intubation. However, there is currently no standardized operation protocol or anaesthesia induction drug standard for RSI. Furthermore, there is a lack of evidence regarding the use of RSI in patients older than 65. In this study, we aimed to investigate the cardiovascular effects of different doses of alfentanil combined with propofol and etomidate during RSI in elderly patients aged 65-80 years. METHODS: A total of 96 patients aged 65-80 years who underwent general anaesthesia with tracheal intubation were selected for this study. The patients were randomly assigned to one of four groups using a random number table. Group A patients received an induction dose of 10 µg/kg alfentanil, group B patients received 15 µg/kg alfentanil, group C patients received 20 µg/kg alfentanil, and group D patients received 25 µg/kg alfentanil. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and ejection fraction (EF) were measured at three time points: 5 min before anaesthesia induction (T0), 1 min after endotracheal intubation (T1), and 5 min after endotracheal intubation (T2). Concurrently, 4 ml of arterial blood was collected from patients at three time points, and the concentrations of norepinephrine (NE) and cortisol (Cor) in plasma were detected. Occurrences of hypertension, hypotension, bradycardia and tachycardia during anesthesia induction to 5 min after tracheal intubation were noted. RESULTS: Compared with T0, the HR, MAP, NE and Cor concentrations in group A and group B were increased at the T1 and T2 time points, CI and EF values were decreased (P < 0.05). HR and MAP in groups C and D were increased at the T1 time point, while they were decreased at the T2 time point in group D (P < 0.05). The changes in CI and EF values, concentrations of NE and Cor, were not significant at T1 and T2 time points in group C (P > 0.05). Additionally, they were not significant in group D at the T1 time point (P > 0.05), but decreased at the T2 time point (P < 0.05). Compared with group A, the HR, MAP, NE and Cor concentrations in groups C and D were decreased at T1 and T2 time points (P < 0.05). The CI and EF values of groups C and D were increased at T1 time point but decreased at T2 time point in group D (P < 0.05). The incidence of hypertension and tachycardia in group A was significantly higher than that in group C and group D (P < 0.05), and the incidence of hypotension and bradycardia in group D was significantly higher than that in group A and group B (P < 0.05). CONCLUSION: Alfentanil 20 µg/kg for RSI in elderly patients, can effectively inhibit the violent cardiovascular reaction caused by intubation, and avoid the inhibition of cardiovascular system caused by large dose, hemodynamics more stable. TRIAL REGISTRATION: ChiCTR2200062034 ( www.chictr.org.cn ).

Case report: Side effects of etomidate in propylene glycol in five Göttingen Minipigs.

Etomidate, an agonist of the GABA A receptors, is available for clinical use either in combination with 35% propylene glycol or in a lipid emulsion. Its recognized ability to minimally impact the cardiovascular system made etomidate a suitable option for cardiac-compromised patients. Myoclonus and pain at the injection site are recognized side effects of etomidate in propylene glycol, affecting both human and veterinary species. There is no information available concerning potential side effect in minipigs. In the present case series, we report the side effects related to the use of etomidate in 35% propylene glycol in five Ellegaard Göttingen Minipigs that underwent general anesthesia for cardiac magnetic resonance imaging days or weeks after experimentally induced myocardial infarction. Following intravenous injection of etomidate, laryngeal edema and hyperemia were observed in one case. In another case, tachycardia, apnea, and decreased oxygen saturation, accompanied by laryngeal edema and hyperemia, were observed, which resolved spontaneously in a few minutes. In the arterial or venous samples collected shortly after the induction of general anesthesia, hemolysis was macroscopically visible and subsequently confirmed with a hematological exam in all five cases, as well as hemoglobinuria. Necropsies carried out immediately after euthanasia confirmed macroscopic laryngeal edema, marked diffuse lung alveolar and interstitial edema and hyperemia at histology in one animal, and marked acute lung congestion in another animal. These side effects were not observed when etomidate in a lipid emulsion was injected into another 24 animals. The role played by the different formulations (propylene glycol versus lipidic formulation) has not yet been fully elucidated. Based on our observations, we recommend caution in using the formulation of etomidate in 35% propylene glycol in Göttingen Minipigs.

Postintubation hypotension following rapid sequence intubation with full- vs reduced-dose induction agent.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Rapid sequence intubation (RSI) is a common emergency department (ED) procedure with an associated complication of postintubation hypotension (PIH). It has not been clearly established whether the selection and dose of induction agent affect risk of PIH. The objective of this study was to determine the incidence of PIH in patients receiving full-dose compared to reduced-dose induction agent for RSI in the ED. METHODS: This was a health system-wide, retrospective cohort study comparing incidence of PIH based on the induction medication and dose given for RSI in the ED. Patients were included if they underwent RSI from July 1, 2018, through December 31, 2020, were 18 years of age or older, and received etomidate or ketamine. A reduced dose was defined as a ketamine dose of 1.25 mg/kg or less and an etomidate dose of 0.2 mg/kg or less. RESULTS: A total of 909 patients were included in the final analysis, with most receiving etomidate (n = 764; 84%) and a smaller number receiving ketamine (n = 145; 16%). Patients who received ketamine had a higher mean pre-intubation shock index (full dose, 1.08; reduced dose, 1.04) than those who received etomidate (full dose, 0.89; reduced dose, 0.92) (P ≤ 0.001). Reduced doses of induction agent were observed for 107 patients receiving etomidate (14.0%) and 60 patients receiving ketamine (41.4%). Patients who received full-dose ketamine for induction had the highest rate of PIH (n = 31; 36.5%), and the difference was statistically significant compared to patients receiving reduced-dose ketamine (16.7%; P = 0.021) and full-dose etomidate (22.8%; P = 0.010). CONCLUSION: We observed that full-dose ketamine was associated with the highest rate of PIH; however, this group had the poorest baseline hemodynamics, confounding interpretation. Our results do not support broad use of a reduced-dose induction agent.

Dexamethasone alleviates etomidate-induced myoclonus by reversing the inhibition of excitatory amino acid transporters.

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial.

Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3µg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.

Rapid and sensitive detection of etomidate based on functionalized copper nanoclusters fluorescent probe.

Etomidate as a non-barbiturate sedative, has central inhibitory effect and addiction and has been listed as a controlled drug in some countries due to the abusing trend nowadays. Therefore, rapid and sensitive detection of etomidate is of great significance. In this work, a novel fluorescent sensing probe (CuNCs@MIPs) based on copper nanoclusters (CuNCs) and molecular imprinted polymers (MIPs) has been firstly reported. CuNCs was environment-friendly synthesized using poly(vinylpyrrolidone) as a template and ascorbic acid as a reducing agent. After functionalized with molecular imprinting technique, the CuNCs@MIPs probe has special binding cavities on surface to target etomidate, causing the fluorescence intensity rapidly decrease, which confirmed it has excellent sensitivity, selectivity and stability. Under optimal conditions, the fluorescent sensing probe presented high precision linear relationship for etomidate in range of 10-500 ng/ml with detection limit of 10 ng/ml, and the whole detection process was completed within 10 min. This sensing method has also been applied to real samples detection, still demonstrated excellent feasibility in electronic cigarette liquids and urine. More importantly, compared with previous methods, this fluorescent sensing method has advantages such as rapid, simple and easy to operate. Collectively, the proposed CuNCs@MIPs sensing probe has good fluorescence characteristics and simple synthesis strategy, showed a great potential in etomidate detection and application.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

Etomidate-induced hypokalemia in electronic cigarette users: two case reports and literature review.

Hypokalemia is a common clinical condition that can lead to muscle weakness, difficulty breathing, malignant arrhythmias, and even death. This report describes two cases of severe hypokalemia resulting from the use of electronic cigarettes containing etomidate, both accompanied by varying degrees of adrenal hyperplasia. In both cases, the patients were admitted to the hospital with lower limb weakness and difficulty walking. Relevant examinations revealed low blood potassium, low cortisol, high adrenocorticotropic hormone, low renin, and low aldosterone levels in the patients, with Case 2 also having significant hypertension. In both cases, adrenal CT scans showed thickening of the adrenal glands. After the delivery of potassium supplementation in both cases, blood potassium levels gradually returned to normal and muscle strength gradually improved. The case reports are followed by a review of the literature on etomidate and its related mechanisms of action with discussion of its association with hypokalemia.

Efficacy and Safety of Remimazolam Versus Etomidate for Induction of General Anesthesia: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are "randomized controlled trials," "etomidate," and "remimazolam." The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. TRIAL REGISTRATION: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55948.

Optimizing sedation in gastroscopy: a study on the etomidate/propofol mixture ratio.

Objective: Propofol and etomidate are the most commonly used sedative agents in procedural sedation, each with its own advantages and disadvantages. However, there remains considerable controversy regarding the optimal ratio for the mixture of these two drugs, warranting further investigation. Therefore, this study aims to investigate the optimal ratio for combining propofol and etomidate during gastroscopy. Methods: This study is a prospective, double-blinded, randomized controlled clinical trial. One hundred and sixty-two patients from July 2019 to December 2022 were evenly classified into three groups using a random number table as follows: (1) P group (propofol); (2) EP1 group (5 mL etomidate +10 mL propofol); (3) EP2 group (10 mL etomidate +10 mL), 54 patients per group. The medications, including a pre-sedation dose of 50 µg/kg dezocine followed by sedatives, ceasing when the patient's eyelash reflex vanished, indicating adequate sedation. Mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) measurements taken before anesthesia (T1), immediately after the administration of sedatives (T2), immediately gastroscopic insertion (T3) and immediately recovery (T4) were determined. Additional, perioperative related outcomes and adverse events were also recorded. Results: The EP2 group exhibited a higher MAP at T2 compared to the P and EP1 groups (p < 0.05). Calculated decreases in MAP revealed values of 19.1, 18.8, and 13.8% for the P, EP1, and EP2 groups at T2, respectively. Adverse events: Group EP2 exhibited a significantly lower hypotension incidence (11.1%) compared to the Propofol group (50%) and EP1 (31.5%). Concerning injection pain, Group EP2 also showing a significant decrease in comparison to P and EP1 groups (p < 0.05). Conclusion: The use of a mixture of 10 mL etomidate and 10 mL propofol (at a 1:1 ratio) combined with dezocine for painless gastroscopy demonstrates hemodynamic stability, a low incidence of adverse reactions. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=39874.

HIF1A overexpression caused by etomidate activates PGK1-induced oxidative stress in postoperative cognitive dysfunction.

Etomidate (ETO), a hypnotic agent used for anesthesia induction, has been shown to induce long-lasting cognitive deficits. In the present study, we investigated whether ETO could activate the HIF1A/PGK1 pathway to antagonize oxidative damage in mice with postoperative cognitive dysfunction (POCD). A mouse model of ETO-mediated POCD was established, and pathological changes, apoptosis, and inflammatory factors in mouse hippocampal tissues were analyzed by HE staining, TUNEL assay, and ELISA. ETO was revealed to cause cognitive dysfunction in mice. Integrated database mining was conducted to screen out transcription factors that are both related to ETO and POCD. Hypoxia-inducible factor 1-alpha (HIF1A) was overexpressed in mice with POCD, and downregulation of HIF1A alleviated cognitive dysfunction in mice. HIF1A downregulation inhibited the transcription of phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 abated the alleviating effects of HIF1A knockdown on oxidative stress in mice with POCD. In addition, HIF1A activation of PGK1 induced oxidative stress and apoptosis in HT-22 cells while inhibiting cell viability. Taken together, we demonstrated that HIF1A activation of PGK1 induced oxidative stress in ETO-mediated POCD.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Long-term use of etomidate disrupts the intestinal homeostasis and nervous system in mice.

Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1 mg/kg and 3 mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO. The levels of 5-hydroxytryptamine in the brain, serum, and colon decreased by 37%, 51%, and 42% respectively, while the levels of γ-aminobutyric acid reduced by 38%, 52%, and 41% respectively. H&E staining revealed that ETO reduced goblet cells in the colon and damaged the intestinal barrier. The expression of tight junction-related genes Claudin4 and ZO-1 was downregulated. The intestinal flora changed, the abundance of Akkermansia and Lactobacillus decreased by 33% and 14%, respectively, while Klebsiella increased by 18%. TUNEL results showed that high-dose ETO increased apoptotic cells in the brain. The expression of Claudin1 in the brain was downregulated. Untargeted metabolomics analysis of the colon and brain indicated that ETO caused abnormalities in glycerophospholipid metabolism. Abnormal lipid metabolism might lead to the production or accumulation of lipotoxic metabolites, causing central nervous system diseases. ETO induced changes in the intestinal flora and metabolism, further affecting the central nervous system through the gut-brain axis. The study unveiled the detrimental effects on the brain and gastrointestinal system resulting from long-term intake of ETO, which holds significant implications for comprehending the adverse impact of ETO abuse on human health.

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice.

Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.

Etomidate inhibits tumor growth of glioblastoma by regulating M1 macrophage polarization.

Glioblastoma (GBM) is a common primary central nervous system tumor. Although the multimodal integrated treatment for GBM has made great progress in recent years, the overall survival time of GBM is still short. Thus, novel treatments for GBM are worth further investigation and exploration. This study aimed to investigate the effects of etomidate on GBM tumor growth and the underlying mechanism. A xenograft tumor model was established and treated with etomidate to assess tumor growth. Immunohistochemistry (IHC) assay evaluated the positive rate of Ki67 cells in tumor tissues. Cell counting kit (CCK)-8 and EdU assays accessed the cell viability and proliferation. Immunofluorescence (IF) staining detected the distribution of macrophage markers in tumor tissues. The percentages of M1- and M2-like macrophages in tumor-associated macrophages (TAMs) and co-culture system (macrophages and GBM cells) were detected using flow cytometry. Macrophage polarization-related genes were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Etomidate treatment inhibited the tumor growth, and increased the CD86+ cells but decreased the CD206+ cells in TAMs. The gene expression of M1 markers was increased in TAMs of etomidate-treated mice, whereas that of M2 markers was decreased. Moreover, etomidate treatment increased the number of CD86+ M1-like macrophages co-cultured with tumor cells but decreased that of CD206+ M2-like macrophages, with the upregulation of M1 markers and downregulation of M2 markers. Etomidate inhibited GBM tumor growth by promoting M1 macrophage polarization, suggesting a new insight into the clinical treatment of GBM.