Background: The emergence of etomidate-containing e-cigarettes represents a significant and rapidly evolving public health challenge, marking a transition of this clinical anesthetic into illegal use of an anesthetic agent. Originally utilized as a short-acting intravenous anesthetic for intubation induction, etomidate's high lipophilicity allows it to be easily aerosolized for inhalation via vaping devices. Misuse is primarily driven by its rapid-onset effects, including relaxation, dissociation, and transient euphoria, as well as a pervasive "illusion of safety" among users who perceive hospital-grade medications as less harmful than traditional illegal drugs.Method: A PubMed search was conducted to identify literature on etomidate vaping and e-cigarette use published between 2024 and May 2026. The retrieved publications were critically reviewed and evaluated across four core scientific dimensions: geographic distribution, clinical manifestations, publication types, and analytical detection methods.Results: The clinical implications of repeated exposure are severe, notably involving the suppression of 11-β hydroxylase, which leads to clinical hyperaldosteronism (hypertension and hypokalemia), virilization but apparent biochemical hypoadrenalism, and electrolyte imbalances. While analytical advances like Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and novel zirconium-based extraction materials have improved detection capabilities in biological samples and e-liquids, the discreet nature of vaping continues to lower barriers to misuse.Conclusions: Addressing this trend necessitates urgent regulatory intervention, expanded toxicological screening, and targeted education to dismantle misconceptions regarding the safety of etomidate inhalation.

Endogenous Cushing syndrome is a metabolic syndrome that results from the excessive production of cortisol from the adrenal gland. Hypercortisolism can result in serious complications, such as hypertension, myocardial ischemia, glucose intolerance, immunosuppression, and electrolyte disturbances. The mainstay of treatment is surgical resection for resectable tumors, along with pharmacological therapy in selected cases, because severe hypercortisolism often requires prompt medical stabilization before definitive surgical management can be safely performed. We report a 34-year-old male patient who presented with generalized weakness, peripheral numbness, and palpitations and was found to have severe hypokalemia, metabolic alkalosis, and high levels of cortisol. Diagnostic laboratory tests showed adrenocorticotropic hormone (ACTH)-independent Cushing syndrome, which was confirmed with magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging. Etomidate was used to control hypercortisolism preoperatively as a bridge to definitive surgical resection of right adrenal adenocarcinoma after failure of a course of mitotane therapy. Sub-anesthetic doses of etomidate dramatically lowered cortisol levels, reduced the need for potassium replacement, and controlled blood pressure with fewer side effects.

Background Post-intubation hypotension (PIH) is a common and clinically significant complication of emergency airway management in critically ill patients and is associated with adverse short-term outcomes. Objective The objective of this study was to determine the incidence, clinical outcomes, and factors associated with post-intubation hypotension among critically ill adults undergoing emergency endotracheal intubation. Methodology This retrospective observational study was conducted at Mayo Hospital, Lahore, Pakistan. Medical records of 234 adult patients who underwent emergency endotracheal intubation between March 2023 to March 2026 were reviewed. PIH was defined as systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or a ≥20% reduction in systolic blood pressure from the pre-intubation baseline within 30 minutes after successful intubation. Multivariable logistic regression was performed to identify factors independently associated with PIH. Results PIH occurred in 68 of 234 patients (29.1%). Patients with PIH were significantly older and had higher Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) score, and Shock Index values than those without PIH. On multivariable analysis, increasing age (adjusted OR (AOR) 1.03, 95% CI 1.01-1.06; p = 0.011), chronic kidney disease (AOR 2.08, 95% CI 1.01-4.29; p = 0.047), sepsis (AOR 2.64, 95% CI 1.38-5.05; p = 0.003), higher APACHE II score (AOR 1.11, 95% CI 1.04-1.18; p = 0.001), elevated Shock Index (AOR 3.42, 95% CI 1.74-6.74; p < 0.001), ketamine use compared with etomidate (AOR 1.89, 95% CI 1.01-3.53; p = 0.045), and difficult airway (AOR 2.27, 95% CI 1.07-4.83; p = 0.033) were independently associated with PIH. PIH was also associated with higher vasopressor requirement, longer mechanical ventilation and ICU and hospital stays, increased AKI, and higher ICU and in-hospital mortality. Conclusion PIH occurred in nearly one-third of critically ill adults undergoing emergency endotracheal intubation and was associated with worse short-term clinical outcomes. Older age, sepsis, chronic kidney disease, higher APACHE II score, elevated Shock Index, ketamine use, and difficult airway were independently associated with PIH. These findings support early recognition of patients at increased risk and warrant prospective multicentre studies to determine whether standardized peri-intubation strategies can reduce PIH and improve outcomes.

Neuronal hyperexcitability often results from impaired inhibition; however, the upstream regulators of GABAergic gene programs remain unclear. We identified a role for terfa, the zebrafish ortholog of human TERF2, in maintaining inhibitory tone and network stability. Homozygous terfa mutant larvae exhibit microcephaly, behavioral hyperactivity, and abnormal neuronal calcium dynamics, indicating a hyperexcitable state. Transcriptomic and RT-qPCR analyses showed coordinated downregulation of multiple GABAA receptor subunit genes, accompanied by reduced gad1b reporter activity in the optic tectum. Pharmacological enhancement of inhibition with etomidate or valproic acid alleviated seizure-like behaviors and normalized calcium activity, supporting impaired inhibition as a major contributor to neuronal hyperexcitability. Integrative ATAC-seq and RNA-seq analyses suggested altered chromatin accessibility near GABAA loci that were enriched in FOX family motifs. Mechanistically, Terfa physically associates with Foxj3 and attenuates Foxj3-dependent repression of GABAA promoters. These findings define a Terfa-Foxj3-GABAA regulatory axis that links telomere-associated factors to inhibitory control and neuronal excitability in a vertebrate model.

General anesthetics such as propofol and etomidate exert their clinical effects primarily through positive allosteric modulation of γ-aminobutyric acid type A receptors (GABAAR). Despite decades of research, the quantitative structure-activity relationships governing anesthetic binding remain incompletely characterized at the atomic level. Here, we employ rigorous alchemical free energy perturbation (FEP) calculations using a CHARMm GPU-accelerated protocol to compute relative binding free energies for a series of 13 propofol analogs at the wild-type GABAAR, as well as for the stereoisomeric pair of etomidate (R-etomidate vs S-etomidate). For propofol analogs at the wild-type receptor, computed relative binding free energies (ΔΔG) correlate with experimentally measured GABA EC 50 potentiation values, with propofol (2,6-diisopropylphenol) and disec-butylphenol predicted as the most potent analogs, consistent with experimental data (Pearson r = 0.85, 95% CI 0.50-0.96, p = 0.001; mean of three independent runs). For etomidate, FEP calculations correctly predict that R-etomidate binds approximately 1.8 kcal/mol more favorably than S-etomidate, corresponding to a ∼10-fold difference in potency consistent with the known stereoselective pharmacology of this agent. These results demonstrate that alchemical FEP calculations, implemented through a standardized computational protocol, can quantitatively rank-order anesthetic binding affinities and discriminate stereoisomeric preferences at Cys-loop receptor binding sites, providing a framework for rational design of next-generation anesthetic agents that is more quantitatively robust than simple molecular docking methodologies.

The aim of the present study was to evaluate the effects of etomidate on tear secretion and tear oxidative stress parameters, including total oxidant status (TOS), total antioxidant capacity (TAC), and Oxidative Stress Index (OSI), in domestic male cats. Thirty client-owned male domestic shorthair cats were enrolled in a prospective controlled clinical study and allocated to either an intervention group receiving etomidate (2 mg/kg intravenously) or a control group that did not receive any anesthetic or sedative drugs. Tear secretion and oxidative stress parameters were assessed at baseline (T0) and at 5 (T1), 10 (T2), and 15 (T3) minutes following etomidate administration in the intervention group and at corresponding observation time points in the control group using the Schirmer tear test. Tear production was significantly reduced in the etomidate-treated group at all postadministration time points compared to baseline (p < 0.001), with a clear time-dependent decrease observed during the first 15 min after administration. In contrast, no significant changes in tear secretion were detected in the control group. Tear oxidative stress analysis revealed a significant increase in TOS and OSI at T2 and T3 compared to baseline (p < 0.001), accompanied by a significant reduction in TAC at the same time points. No significant alterations in oxidative stress markers were observed in control cats. These findings demonstrate that etomidate has a marked suppressive effect on tear secretion and induces oxidative stress in tear fluid shortly after administration. Reduced tear production combined with increased oxidative stress may compromise tear film stability and ocular surface integrity, increasing the risk of dry eye-related complications. Accordingly, the use of etomidate should be carefully considered in patients with preexisting ocular disease, and appropriate ocular protection should be implemented during anesthesia, particularly in cases requiring prolonged immobilization.

The adrenocortical-specific PET tracer [11C]metomidate (11C-MTO) shows high diagnostic accuracy in adrenocortical carcinoma (ACC), but complex radiochemistry and short half-life limit clinical implementation. The novel tracer para-chloro-2-[18F]fluoroethyletomidate (18F-CETO) may enable broader use. In this bicentric study, 20 ACC patients underwent PET/CT with 18F-CETO and [18F]fluoro-2-deoxy-D-glucose (18F-FDG), with 235 lesions identified. 18F-CETO detected more lesions than 18F-FDG at initial staging in 5/13 patients, whereas fewer lesions were detected at re-staging in 5/7 patients (P = 0.002). A further 70 patients with 18F-CETO or 11C-MTO-PET/CT and an anatomical imaging reference were used to explore the utility of adrenocortical imaging. Three adrenocortical imaging phenotypes were defined: homogeneous-high (n = 71), homogeneous-low (n = 11), and heterogeneous (n = 8), which showed differences in overall survival in exploratory analyses. Tumors were characterized by RNA sequencing and immunohistochemistry showing correlation between tracer-uptake to CYP11B1 expression and adrenocortical differentiation. These findings suggest a potential role for 18F-CETO in ACC phenotyping and initial staging.

This report describes a rare instance of an adrenocorticotropic hormone (ACTH)-secreting metastatic hepatic neuroendocrine tumour (MHNET) exhibiting as an ectopic Cushing's syndrome. A 41-year-old woman with a history of supraglottic neuroendocrine tumour presented with rapid weight gain, severe hypokalemia, and hypercortisolism. Pituitary imaging was unremarkable. However, the DOTATATE PET/CT showed a large liver lesion. Initiating etomidate infusion caused a rapid drop in cortisol, leading to severe vasoplegic and septic shock, which delayed the surgery. The patient required intensive care stabilization pre-operatively and treatment with osilodrostat, which was then followed by surgical management: left lateral hepatectomy and gastric wedge resection. ACTH levels markedly decreased postoperatively, reflecting successful management. This emphasizes that careful medical management and multidisciplinary collaboration are essential in treating severe, potentially life-threatening ectopic hypercortisolism.

Electroconvulsive therapy (ECT) remains one of the most effective treatments in psychiatry, but cognitive side effects still pose a clinical concern. Delayed postictal reorientation is linked to worse cognitive outcomes, adversely affecting patient-perceived treatment tolerability and acceptability, while also increasing post-ECT and post-anesthesia care demands. Despite its clear clinical and operational relevance, comparative evidence on anesthetic effects remains scarce. This study therefore investigates the impact of different anesthetic agents (S-ketamine, propofol, etomidate, thiopental, and the combination of S-ketamine and propofol) on reorientation time following ECT. Retrospective data from 5148 ECT sessions were analyzed using a linear mixed-effects model controlling for age, sex, diagnosis, stimulation dose, electrode placement, seizure quality, ECT session number, need for restimulation, ECT duration, and postictal agitation. Compared with S-ketamine, propofol reduced reorientation time by 6.2 min, and the combination of S-ketamine and propofol reduced reorientation time by 1.5 min. Neither thiopental nor etomidate differed significantly from S-ketamine. The differences may be attributed to the distinct pharmacodynamic profiles of the anesthetic agents. The findings demonstrate that anesthetic choice is a significant and independent determinant of reorientation time following ECT, with propofol and the combination of S-ketamine and propofol associated with markedly faster cognitive recovery compared to S-ketamine.