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.

Etomidate alleviates ovarian ischemia-reperfusion injury in rats.

BACKGROUND: This study investigates the protective effects of etomidate against oxidative damage in an experimental model of ovarian ischemia-reperfusion injury. METHODS: A total of 24 female rats were randomized into three groups. Group 1 served as the control. Group 2 underwent an ovarian torsion/detorsion procedure. Group 3 underwent similar procedures as Group 2; additionally, 4 mg/kg of etomidate was administered intraperitoneally 30 minutes before ovarian detorsion. Blood samples were analyzed for lipid peroxidation, pro-inflammatory cytokine levels, and antioxidant enzyme activity RESULTS: Biochemical analysis of blood samples revealed reductions in pro-inflammatory cytokines, including interleukin-1 Beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), in Group 3 compared to Group 2 (p=0.005, p=0.016, and p<0.001, respectively). Additionally, a decrease in malondialdehyde (MDA) levels was observed in Group 3 compared to Group 2 (p<0.001). In contrast, activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased in Group 3 compared to Group 2 (p=0.031 and p=0.001, respectively). Furthermore, Group 3 demonstrated notable reductions in histopathological scores for follicular degeneration, vascular occlusion, bleeding, and inflammation compared to Group 2 (p<0.001, p<0.001, p<0.001, and p=0.001, respectively). CONCLUSION: Etomidate alleviates ischemia-reperfusion injury in a rat ovarian torsion-detorsion model by improving both histopathological and biochemical outcomes.

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.

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.

Effects of dexmedetomidine combined with etomidate on postoperative cognitive function in older patients undergoing total intravenous anaesthesia: a randomized, double-blind, controlled trial.

BACKGROUND: Etomidate has been advocated for anesthesia in older and critically ill patients because of its hemodynamic stability. Clinical studies have shown that dexmedetomidine has neuroprotective and anti-inflammatory properties and improves postoperative cognitive dysfunction in older patients. The present study was to evaluate the effects of the combination of etomidate and dexmedetomidine with different anaesthesia time on postoperative cognitive function in older patients. METHODS: A total of 132 older patients undergoing ureteroscopic holmium laser lithotripsy were randomly divided into EN group and ED group equally. Patients whose surgery time was less than or equal to 1 h in each group were allocated to short-time surgery group (EN1 group and ED1 group), and whose surgery time was more than 1h were allocated to long-term surgery group (EN2 group and ED2 group). The primary outcome was the score of the Mini-Mental State Examination. The secondary outcomes were State-Trait Anxiety Inventory scores, Riker sedation agitation scores, Zung Self-Rating Depression Scale scores, the memory span for Arabic numerals, the plasma concentrations of S-100 calcium-binding protein B and neuron specific enolase, the time to spontaneous respiration, recovery, and extubation. RESULTS: The MMSE scores at t2-3 were higher in ED1 and ED2 groups than in EN1 and EN2 groups (p<0.05). Compared with ED1 and ED2 groups, the ZSDS scores, the S-AI scores and the T-AI scores at t1-2 were higher in EN1 and EN2 groups (p<0.05), respectively. The recalled Arabic numbers at t1-3 were higher in ED2 group than in EN2 group (p<0.05). The plasma concentration of S-100ß at t1-2 in EN1 group and t1-3 in EN2 group were higher than that in ED1 and ED2 groups (p<0.05), respectively. Compared with ED1 and ED2 groups, the plasma concentrations of NSE were higher at t1-3 in EN1 group and t1-4 in EN2 group (p<0.05), respectively. CONCLUSION: The administration of dexmedetomidine could improve postoperative cognitive dysfunction, emergence agitation, depression and anxiety, attenuate the plasma concentrations of S-100ß and NSE in older patients undergoing total intravenous anaesthesia with etomidate. TRIAL REGISTRATION: Registration number: ChiCTR1800015421, Date: 29/03/2018.

The Effect of Propofol on Peri-Induction Hemodynamics and Resuscitation in Operative Penetrating Trauma.

BACKGROUND: Hemorrhaging trauma patients may be disproportionately affected by choice of induction agent during rapid sequence intubation (RSI). Etomidate, ketamine, and propofol are safe in the trauma population-at-large but have not been assessed in patients with ongoing hemorrhage. We hypothesize that in hemorrhaging patients with penetrating injury, propofol deleteriously affects peri-induction hypotension compared to etomidate and ketamine. METHODS: Retrospective cohort study. Primary outcome was the effect of induction agent on peri-induction systolic blood pressure. Secondary outcomes were the incidence of peri-induction vasopressor use and quantity of peri-induction blood transfusion requirements. Linear multivariate regression modeling assessed the effect of induction agent on the variables of interest. RESULTS: 169 patients were included, 146 received propofol and 23 received etomidate or ketamine. Univariate analysis revealed no difference in peri-induction systolic blood pressure (P = .53), peri-induction vasopressor administration (P = .62), or transfusion requirements within the first hour after induction (PRBC P = .24, FFP P = .19, PLT P = .29). Choice of RSI agent did not independently predict peri-induction systolic blood pressure or blood product administration. Rather, only presenting shock index independently predicted peri-induction hypotension. CONCLUSIONS: This is the first study to directly assess the peri-induction effects of anesthetic induction agent choice in penetrating trauma patients undergoing emergent hemorrhage control surgery. Propofol does not appear to worsen peri-induction hypotension regardless of dose. Patient physiology is most predictive of peri-induction hypotension.

Remimazolam vs Etomidate: Haemodynamic Effects in Hypertensive Elderly Patients Undergoing Non-Cardiac Surgery.

Background: Remimazolam tosilate (RT) is a novel ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with several advantages including rapid induction and recovery, stable haemodynamics, and mild respiratory inhibition. However, studies have not been conducted to explore the haemodynamic effects of RT in elderly hypertensive subjects undergoing non-cardiac surgery. Therefore, we sought to compare the effects of anaesthesia induction using different doses of RT and etomidate on the haemodynamics of this group of patients. Methods: Patients were recruited into this single-center, prospective, randomized, double-blind trial from October 2022 to June 2023. A total of 150 hypertensive elderly undergoing non-cardiac surgery were randomly assigned into 0.2 mg/kg RT group (Group RL), 0.3 mg/kg RT group (Group RH) and 0.3 mg/kg etomidate group (Group E). The primary outcome of the study was haemodynamic changes (mean arterial pressure fluctuation value -∆MAP and heart rate fluctuation value -∆HR) observed during anaesthesia induction. Secondary outcomes included incidence of adverse cardiovascular events and adverse drug reactions (injection pain and myoclonus), cumulative doses of vasoactive drugs and vital signs at different time points. Results: Patients in Group E and Group RL had significantly lower haemodynamic fluctuations (∆MAP), lower incidence of hypotension and cumulative dose of ephedrine than subjects in Group RH. Patients in groups RL and RH had significantly lower incidence of injection pain and myoclonus compared with patients in group E. The results showed no statistically significant differences in ∆HR, hypertension, bradycardia, tachycardia, and time to loss of eye-opening reflex and start of intubation, and vital signs at different time points among the three groups. Conclusion: Use of low-dose RT (0.2 mg/kg) for induction of non-cardiac surgical anaesthesia in elderly hypertensive patients is more effective in maintaining haemodynamic stability and has fewer adverse effects compared with etomidate.

[Postoperative Delirium in Patients on Cardiopulmonary Bypass for Cardiovascular Surgeries: Incidence and Influencing Factors].

Objective: To investigate the incidence and influencing factors of postoperative delirium (POD) and subsyndromal delirium (SSD) in patients connected to cardiopulmonary bypass during cardiovascular surgeries. Methods: We collected the general data and the data for the perioperative hematological, physiological, and biochemical indicators and the surgical and therapeutic conditions of patients connected to cardiopulmonary bypass during the course of cardiovascular surgeries conducted at a tertiary-care hospital in Hubei province between May 2022 and September 2022. The outcome indicators, including the incidence of POD and SSD, were assessed with the Nursing Delirium Screening Scale (Nu-DESC). Multinomial logistic regression was performed to analyze the influencing factors of patients with different statuses of POD and SSD. Results: Among the 202 patients, the incidence of SSD, SSD progressing to POD, and no POD or SSD (ND) progressing to POD were 13.4%, 6.4%, and 34.2%, respectively. Regression analysis showed that, with ND patients as the controls, the influencing factors for SSD were preoperative blood glucose (odds ratio [ OR]=0.38, 95% confidence interval [ CI]: 0.19-0.76), intraoperative platelet transfusion ( OR=0.37, 95% CI: 0.15-0.92), intraoperative etomidate ( OR=0.93, 95% CI: 0.87-0.98), and postoperative total bilirubin level ( OR=1.04, 95% CI: 1.01-1.07). For the progression of SSD to POD, the influencing factors were age ( OR=1.09, 95% CI: 1.01-1.17), ASA classification of IV and above ( OR=10.72, 95% CI: 1.85-62.08), intraoperative dexmedetomidine ( OR=1.01, 95% CI: 1.003-1.02), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). For the progression of ND to POD, the influencing factors were age ( OR=1.06, 95% CI: 1.02-1.10), middle or high school education ( OR=0.35, 95% CI: 0.15-0.83), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). Conclusion: Age, education, ASA classification, preoperative blood glucose, intraoperative platelet transfusion, intraoperative etomidate, intraoperative dexmedetomidine, postoperative total bilirubin, and the duration of mechanical ventilation are influencing factors for different statuses of POD and SSD among patients connected to cardiopulmonary bypass when they are undergoing cardiovascular surgeries. The influencing factors vary across groups of patients with different statuses of POD and SSD. Therefore, we should accurately assess the risk factors of patients with different statuses of POD and SSD and carry out corresponding interventions, thereby preventing or reducing the occurrence of POD and SSD, and ultimately promoting enhanced recovery after surgery.

Substituted Cysteine Modification and Protection with n-Alkyl-MTS Reagents Quantifies Steric Changes Induced by a Mutation in Anesthetic Binding Sites on GABA Type A Receptors.

Multiple approaches, including cryogenic electron microscopy (cryo-EM), indicate that the anesthetics etomidate and propofol modulate α1ß2/3γ2 GABAA receptors by binding in overlapping transmembrane inter-subunit sites near ßM286 and αL232 sidechains. High-precision approaches in functional receptors are needed for comparisons with cryo-EM. We previously used substituted cysteine modification and protection (SCAMP) with n-alkyl-methanethiosulfonate (MTS) reagents and electrophysiology in α1ß3M286Cγ2L receptors to estimate the distance from etomidate to ß3M286 with precision near 1.3 Å. Here, we address three more aims using this approach: (i) SCAMP with etomidate was tested in α1L232Cß3γ2L receptors; (ii) studies in α1L232Wß3M286Cγ2L receptors assessed whether α1L232W displaces etomidate relative to ß3M286C; and (iii) results with propofol were compared with those with etomidate. Voltage-clamp electrophysiology in Xenopus oocytes was used to assess persistent functional changes after exposing cysteine-substituted receptors to methyl-MTS through n-decyl-MTS. Overlap of modified cysteine sidechains with bound anesthetic was inferred when anesthetic co-application with alkyl-MTS reagent blocked the development of persistent effects. In α1L232Cß3γ2L receptors, only pentyl-MTS and hexyl-MTS induced persistent effects that were unaltered by etomidate co-application, precluding a direct estimate of intermolecular distance. In α1L232Wß3M286Cγ2L receptors, sidechain overlap with bound etomidate was inferred for modifications with ethyl-MTS through n-pentyl-MTS, with unambiguous cut-on and cut-off. Comparison with results in α1ß3M286Cγ2L reveals that α1L232W, which increases maximal sidechain length by 2.1 Å, displaces etomidate closer to ß3M286C by about 1.3 Å. Propofol results largely mirrored those with etomidate. These findings indicate that both etomidate and propofol bind within 1 Å of α1L232, consistent with cryo-EM structures. SIGNIFICANCE STATEMENT: We combined electrophysiology, cysteine substitutions, and n-alkyl-methanethiosulfonate modifiers in functional GABAA receptors to enable precise estimates of the distance between ß3M286C sidechains and anesthetics (etomidate and propofol) bound in transmembrane ß+/α- inter-subunit pockets. Comparing results in α1ß3M286Cγ2L and α1L232Wß3M286Cγ2L receptors reveals that α1L232W mutations displace both anesthetics toward ß3M286C, indicating that these anesthetics bind within 1 Å of the α1L232 sidechain in functional receptors, consistent with cryogenic electron microscopy structures derived under nonphysiologic conditions.

Sedation with a 1:1 mixture of etomidate and propofol for gastroscopy in hypertensive elderly patients.

We hypothesized that the combined use of etomidate and propofol for endoscopic sedation in elderly hypertensive patients could reduce adverse reactions while providing ideal sedation. To validate our hypothesis, we conducted a prospective, randomized, controlled, double-blinded study. A total of 360 elderly hypertensive patients scheduled for gastroscopy at our hospital were enrolled in the study, of whom 328 completed the trial. The patients were randomly assigned to one of three groups: the propofol group (group P), the etomidate group (group E), or the propofol-etomidate combination group (mixed at a ratio of 1:1, group PE). We collected and analyzed the cardiopulmonary effects and side effects in each group. Regardless of the sedation drug used, the systolic blood pressure, mean blood pressure, and heart rate of involved patients were significantly affected. Oxygen desaturation and injection pain were more common in group P compared to groups E (33.6% vs. 14.8%, 31.8% vs. 2.7%, both P < 0.01) and group PE (33.6% vs. 13.6%, 31.8% vs. 6.4%, both P < 0.01). The incidence of myoclonus in the PE group was lower than that in the E group (10.9% vs. 61.2%, P < 0.01). Our results indeed demonstrated that the combined use of etomidate and propofol appeared to maintain cardiopulmonary stability with minimal side effects in older hypertensive patients scheduled for gastroscopy, which further implied that this sedation strategy could be a safe and pain-free option for managing patients undergoing gastroscopy, particularly those at a higher risk of adverse cardiovascular events.

Influences of Etomidate Combined with Propofol on Cognitive Function, Inflammation and Immunity in Patients Undergoing Gastric Cancer Surgery.

This study examined how etomidate combined with propofol affected cognitive function, inflammation, and immunity in patients undergoing gastric cancer surgery. 182 gastric cancer patients treated in our hospital were enrolled and randomly divided into two groups, namely group A (anesthetized using etomidate) and group B (anesthetized using etomidate combined with propofol). Then the cognitive function, inflammation and immunity indicators were determined in the two groups. Compared with group A, group B exhibited shorter operation duration and hospital stay and smaller bleeding volume (p<0.01). At 3 d after the operation, group B had a higher Ramsay score, but a lower visual analogue scale (VAS) score than group A (p<0.05). Moreover, the mini-mental state examination (MMSE) score was lower in group A than that in group B (p<0.01). At the end of the operation, the heart rate (HR), mean arterial pressure (MAP) and saturation of pulse oxygen (SpO2) were decreased to a great extent in both groups compared with those before anesthesia (p<0.05). Compared with those before anesthesia, the levels of immunoglobulin (Ig)M, IgG and IgA were lower in group A at the end of the operation and 1 and 3 d after the operation (p<0.05), but they were substantially higher in group B than those in group A (p<0.05). At the end of the operation and 1 and 3 d after the operation, the levels of the T-cell subset indicators decreases in group A were greater than those in group B (p<0.05). Etomidate combined with propofol has few influences on the immune and cognitive functions of gastric cancer patients and can effectively lower the expression levels of inflammatory factors in these patients.

Structural interplay of anesthetics and paralytics on muscle nicotinic receptors.

General anesthetics and neuromuscular blockers are used together during surgery to stabilize patients in an unconscious state. Anesthetics act mainly by potentiating inhibitory ion channels and inhibiting excitatory ion channels, with the net effect of dampening nervous system excitability. Neuromuscular blockers act by antagonizing nicotinic acetylcholine receptors at the motor endplate; these excitatory ligand-gated ion channels are also inhibited by general anesthetics. The mechanisms by which anesthetics and neuromuscular blockers inhibit nicotinic receptors are poorly understood but underlie safe and effective surgeries. Here we took a direct structural approach to define how a commonly used anesthetic and two neuromuscular blockers act on a muscle-type nicotinic receptor. We discover that the intravenous anesthetic etomidate binds at an intrasubunit site in the transmembrane domain and stabilizes a non-conducting, desensitized-like state of the channel. The depolarizing neuromuscular blocker succinylcholine also stabilizes a desensitized channel but does so through binding to the classical neurotransmitter site. Rocuronium binds in this same neurotransmitter site but locks the receptor in a resting, non-conducting state. Together, this study reveals a structural mechanism for how general anesthetics work on excitatory nicotinic receptors and further rationalizes clinical observations in how general anesthetics and neuromuscular blockers interact.

Effects of total intravenous anesthesia with etomidate and propofol on postoperative cognitive dysfunction.

Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00?2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00?2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100?, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100?, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100?, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia.

The effects of etomidate on expression of high mobility group box 1 via the nuclear factor kappa B pathway in rat model of sepsis.

Etomidate is an anesthetic agent used in hemodynamically unstable patients, but its use has been controversial in septic patients. The response of high-mobility group box 1 (HMGB1), a late-phase lethal cytokine in sepsis, to etomidate has not been reported. This study investigated the effects of etomidate on the expression and release of HMGB1 and the underlying mechanism using a cecal ligation and puncture (CLP) model. Thirty-six male Sprague-Dawley rats were divided into sham, CLP, and Etomi groups. Sepsis was induced in the CLP and Etomi groups, and intravenous etomidate (4 mg/kg) was infused for 40 min immediately after operation in the Etomi group. Serum creatinine, alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and HMGB1 levels were measured 6 and 24 hours after surgery. Activation of nuclear factor (NF)-ĸB and HMGB1 mRNA expression in the liver, lung, kidney, and ileum tissues were measured, and immunohistochemical staining of HMGB1 was implemented. Increases of the TNF-α level 6 h after CLP and ALT and IL-6 levels 24 h after CLP were significantly inhibited by etomidate treatment. Etomidate treatment also significantly attenuated the increase in serum HMGB1 level at 6 and 24 h after CLP and suppressed the NF-ĸB and HMGB1 mRNA in multiple organs 24 h after CLP. Immunohistochemical staining also revealed that etomidate treatment inhibited HMGB1 expression. Etomidate inhibited the systemic release of HMGB1 and its expression in various organs. The mechanism may be associated with the inhibitory effects of etomidate on pro-inflammatory cytokine release and NF-ĸB activity.

Propofol decreased the etomidate-induced myoclonus in adult patients: a meta-analysis and systematic review.

OBJECTIVE: Myoclonus is one of the main complications of etomidate anesthesia, which would develop into serious consequences during surgery. The present analysis was performed to evaluate systematically the effect of propofol on preventing etomidate-induced myoclonus in adult patients. MATERIALS AND METHODS: Systematic electronic literature search was performed in the databases PubMed, Cochrane Library, OVID, Wanfang and China National Knowledge Infrastructure (CNKI) from inception to May 20, 2021, without any language restrictions. All randomized controlled trials evaluating the efficacy of propofol on preventing etomidate-induced myoclonus were enrolled. The primary outcome included the incidence and degree of etomidate-induced myoclonus. RESULTS: 1,420 patients (with 602 received etomidate anesthesia and 818 received propofol plus etomidate anesthesia) from 13 studies were eventually included. Whatever the intravenous propofol dose for anesthesia induction 0.8-2 mg/kg (RR:4.04, 95% CI [2.42,6.74] p<0.0001, I2=56.5%), or the dose of propofol for anesthesia induction 0.5-0.8 mg/kg (RR:3.26, 95% CI [2.03,5.22] p<0.0001, I2=0%), or the dose of propofol for anesthesia induction 0.25-0.5mg/kg (RR:1.68, 95% CI [1.1,2.56] p=0.0160, I2=0%), combination of propofol and etomidate could significantly decrease the occurrence of etomidate-related myoclonus (RR=2.99, 95% CI [2.40, 3.71] p<0.0001, I2=43.4%), compared with etomidate alone. In addition, propofol plus etomidate attenuated the incidence of mild (RR:3.40, 95% CI [1.7,6.82] p=0.0010, I2=54.3%), moderate (RR:5.4, 95% CI [3.01, 9.67] p<0.0001, I2=12.6%), severe (RR:4.15, 95% CI [2.11, 8.13] p<0.0001, I2=0%) of etomidate-induced myoclonus without adverse effects except for the increased incidence of pain on injection (RR:0.47, 95% CI [0.26, 0.83] p=0.0100, I2=41.5%) compared with etomidate alone. CONCLUSIONS: The meta-analysis currently generates the evidence of combination of propofol with the dosage of 0.25-2 mg/kg and etomidate can alleviate the occurrence and severity of etomidate-induced myoclonus, with decreased incidence of postoperative nausea and vomiting (PONV) and comparative side effects of hemodynamic and respiratory depression of patients in comparison with etomidate alone.

Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial.

Background: Remimazolam tosilate (RT) is a new ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with the characteristics of rapid onset and offset, minimal cardiorespiratory depression. Currently, few studies have compared the effect of RT and etomidate on hemodynamics during anesthesia induction. Here, we aimed to compare the hemodynamic effects of different doses of RT and etomidate for anesthesia induction in patients undergoing cardiac surgeries. Methods: Patients were recruited from January to September 2022 in this single-center, prospective, randomized, double-blind trial. A total of 117 patients undergoing selective valve replacement surgery were randomly divided into low-dose RT (0.2 mg/kg) group (group LR), high-dose RT (0.3 mg/kg) group (group HR), or etomidate (1.5 mg/kg) group (group E), respectively. The primary outcome was hemodynamic fluctuations (mean arterial pressure fluctuation value [∆MAP]; heart rate fluctuation value [∆HR]) during anesthesia induction. Secondary outcomes included the incidence of adverse drug reactions (injection pain and myoclonus) and adverse cardiovascular events, vital signs at different time points and the cumulative doses of vasoactive drugs. Results: The hemodynamic fluctuations (∆MAP) in group LR and group E were significantly lower than that in group HR. In addition, the incidence of hypotension and the cumulative norepinephrine doses in group E and group LR were also significantly lower than that in group HR. Furthermore, the incidence of injection pain and myoclonus in group LR and group HR were less frequently recorded compared with group E. There were no significant differences in terms of ∆HR, tachycardia, hypertension, severe bradycardia, vital signs at different time points, lactic acid and blood glucose between both groups. Conclusion: Compared with etomidate, low-dose RT (0.2mg/kg) can not only provide stable hemodynamic parameters but also cause fewer adverse reactions when used for anesthesia induction in patients with cardiac disease.

Etomidate versus propofol for sedation in gastrointestinal endoscopy: A systematic review and meta-analysis of outcomes.

BACKGROUND: Propofol is increasingly being used for sedation in gastrointestinal endoscopy; however, owing to its side effects, an alternative drug is needed. We aimed to compare the safety, satisfaction, and efficacy outcomes of etomidate versus propofol in patients undergoing gastrointestinal endoscopy, including advanced endoscopic procedures. METHODS: We systematically searched Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL (via EBSCO), China National Knowledge Infrastructure, and Web of Science (1946-April 2020) databases for randomized controlled trials of gastrointestinal endoscopy (upper gastrointestinal endoscopy, colonoscopy, and advanced endoscopy) using etomidate or propofol as sedatives. We pooled odds ratios (ORs) for the safety profile and patient and anesthesiologist satisfaction using mixed-effects conditional logistic models and standardized mean differences for efficiency outcomes using random-effects models. RESULTS: Twenty-four studies involving 3875 patients were included. Compared with propofol, etomidate resulted in significantly reduced apnea (OR: 0.22; 95% confidence interval [CI]: 0.13-0.37; P < .001), hypoxemia (OR: 0.43; 95% CI: 0.35-0.54; P < .001), hypotension (OR: 0.20; 95% CI: 0.11-0.36; P < .001), and bradycardia (OR: 0.52; 95% CI: 0.30-0.91; P = .02) but led to increased myoclonus (OR: 8.54; 95% CI: 5.20-14.01; P < .001) and lowered anesthesiologist satisfaction (OR: 0.60; 95% CI: 0.39-0.91; P = .02). CONCLUSION: Etomidate may be a good alternative to propofol for gastrointestinal endoscopy, especially advanced endoscopy. Etomidate appears to be safe as an inducer for hemodynamically unstable patients or older adult patients undergoing gastrointestinal endoscopy.

Safety and efficacy of etomidate in combination with oxycodone in painless gastroscopic procedures in the elderly: A prospective randomized controlled trial study.

OBJECTIVE: Etomidate is often combined in rapid succession during induction of anesthesia. However, the effect of pretreatment with oxycodone on recovery of cognitive function and adverse effects has rarely been studied. We conducted a prospective randomized controlled trial to compare etomidate alone with etomidate combined with oxycodone in elderly patients undergoing painless gastroscopy. METHODS: Hundred elderly patients undergoing painless gastroscopy were divided into a control and an observation group, with 50 cases in each group. The age, gender, height, weight, body mass index and American Society of Anesthesiologists physical status (I/II) of patients in both groups were recorded. The recovery of cognitive function was compared in both groups using the Neurobehavioral Cognitive Status Examination. Adverse events, including somatic motor reactions, hypotension, bradycardia, myocardial tremor, nausea and vomiting, and injection pain, were also recorded in both groups. Moreover, heart rate, peripheral capillary oxygen saturation, systolic blood pressure, and diastolic blood pressure were evaluated in the 2 groups at different time points. RESULTS: A total of 100 patients were enrolled in this study. The demographic characteristics in the 2 groups were not significantly different (P > .05). Regarding the recovery of cognitive functions, more subjects in the observation group passed the memory, arithmetic and orientation test than in the control group (P < .05). Fewer adverse events such as dynamic body reactions, cardiac tremor, nausea and vomiting, and injection pain occurred in the observation group than in the control group (P < .05). During anesthesia and after awakening, the results of peripheral capillary oxygen saturation, systolic blood pressure and diastolic blood pressure were better in the observation group than in the control group (P < .05). CONCLUSION: Etomidate in combination with oxycodone for painless gastroscopic operation in the elderly is a safe and effective anesthetic strategy.