Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine Among Critically Ill Patients.

RATIONALE: Uncertainty remains regarding the risks associated with single dose use of etomidate. OBJECTIVES: To assess use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. METHODS: We assessed patients who received invasive mechanical ventilation (IMV), admitted to an ICU in the Premier Healthcare Database, 2008-2021. The exposure was receipt of etomidate on the day of IMV initiation and the main outcome was hospital mortality. Using multivariable regression we compared patients who received IMV within the first two days of hospitalization who received etomidate with propensity-score matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. MEASUREMENTS AND MAIN RESULTS: Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first two days of hospitalization, we established 22,273 matched pairs given either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs 18.7%; absolute risk difference: 2.8%, 95% CI 2.1%, 3.6%; adjusted odds ratio: 1.28, 95% CI 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days following etomidate use. CONCLUSIONS: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality compared with ketamine. This finding is independent of subsequent treatment with corticosteroids.

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.

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.

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 ).

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.

The need to monitor emerging issues in etomidate usage: the misuse or abuse potential.

Since 2011, the misuse or abuse of etomidate has gradually increased when propofol was designated a controlled drug under the Narcotics Control Act in Korea. Accordingly, the Ministry of Food and Drug Safety announced that etomidate would be under the 'Regulation on the designation of drugs that may cause concerns of misuse or abuse' rule in June 2020, which is less stringent than the Narcotics Control Act. Therefore, this review investigates potential misuse or abuse cases of etomidate to consider strengthening its management. A literature search was conducted to compare etomidate with other sedatives in their efficacy and side effects, as well as identify the adverse health outcomes, abuse cases, and analytical methods of etomidate. Etomidate has an equal or higher sedative efficacy and lower risk of adverse cardiopulmonary events than propofol. However, major adverse effects of etomidate include adrenocortical suppression and unproven associated deaths, as well as myoclonus requiring pre-treatment. Although the issue of abuse and misuse of etomidate is emerging in recent years, there are few academic reports on these issues and analytical methods in the forensic field. In order to effectively manage the misuse or abuse of etomidate, it is necessary to continuously monitor related cases with great interest and to be more intensively studied on its abuse potential.

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.

Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

Etomidate Depresses Spontaneous Complex Spikes Activity of Cerebellar Purkinje Cells via Cannabinoid 1 Receptor in vivo in Mice.

INTRODUCTION: Complex spikes (CSs) activity of cerebellar Purkinje cells plays critical roles in motor coordination and motor learning by transferring information to cerebellar cortex, which is an accessible and useful model for neurophysiological investigation. Etomidate is an ultrashort-acting nonbarbiturate intravenous anesthetic, which inhibits the spontaneous activity of cerebellar Purkinje cells through activation of GABAA and glycine receptors in vivo in mice. However, the effect of etomidate on the spontaneous CSs activity of cerebellar Purkinje cells in living mouse is not clear. METHODS: We here investigated the effects of etomidate on spontaneous CSs activity of cerebellar Purkinje cell in urethane-anesthetized mice by electrophysiology recording technique and pharmacological methods. RESULTS: Our results showed that cerebellar surface perfusion of etomidate significantly depressed the activity of spontaneous CSs, which exhibited decreases in the number of spikelets and the area under curve (AUC) of the CSs. The etomidate-produced inhibition of CSs activity was persisted in the presence of GABAA and glycine receptors antagonists. However, application of cannabinoid 1 (CB1) receptor antagonist, AM-251, completely blocked the etomidate-induced inhibition of CSs. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease of CSs. Moreover, in the presence of a specific protein kinase A (PKA) inhibitor, KT5720, etomidate failed to produce decreases in the spikelets number and the AUC of the spontaneous CSs. CONCLUSION: These results indicate that cerebellar surface application of etomidate facilitates CB1 receptor activity resulting in a depression of spontaneous CSs activity of Purkinje cells via PKA signaling pathway in mouse cerebellar cortex. Our present results suggest that the etomidate administration may impair the function of cerebellar cortical neuronal circuitry by inhibition of the climbing fiber - Purkinje cells synaptic transmission through activation of CB1 receptors in vivo in mice.

Effect of vitamin C on adrenal suppression following etomidate for rapid sequence induction in trauma patients: a randomized clinical trial.

BACKGROUND: Etomidate is an imidazole derivative that is widely used in the emergency department for Rapid Sequence Intubation (RSI). Although it has a safe hemodynamic profile, there are some concerns about its suppressant effects on the adreno-cortical axis. Vitamin C, as an antioxidant, can play a protective role in this issue. METHOD: In a controlled clinical trial, we studied adult traumatic patients who needed RSI with etomidate. In one group underwent RSI with etomidate and cortisol levels were measured three hours later. In the other group, we administered one gram of vitamin C before etomidate administration, and the cortisol level was measured three hours later. RESULTS: Fifty-one patients have been studied. The serum cortisol level was significantly lower after RSI with etomidate in both groups. In the Vitamin C group, there was a significantly higher cortisol level after RSI in comparison to the control group. CONCLUSION: Etomidate can suppress the cortisol level in trauma patients who undergo RSI. Vitamin C can reduce this suppressant effect of etomidate. TRIAL REGISTRATION: IRCT registration number: IRCT20090923002496N11, URL of trial registry record: https://en.irct.ir/trial/34586 , Date of trial registration: 19/04/2019. Full date of the first registration: 30/05/2019.

The effect-site concentration of remifentanil blunting endotracheal intubation responses during anesthesia induction with etomidate: a dose-finding study.

BACKGROUND: Remifentanil can inhibit the hemodynamic responses caused by endotracheal intubation, but the effect-site concentration of it required to control intubation responses when combined with etomidate has not been demonstrated. The purpose of this study was to determine the effect-site concentration of remifentanil blunting tracheal intubation responses in 50% and 95% of patients (EC50 and EC95) during etomidate anesthesia. METHODS: American Society of Anesthesiologists physical status (ASA) I-II elective surgical patients receiving target-controlled infusion (TCI) of remifentanil, followed by etomidate and rocuronium for anesthesia were enrolled. The Belive Drive A2 monitor was used to calculate the MGRSSI (Maygreen Sedative state index) of hypnotic effect and the MGRNOX (Maygreen Nociception index) of nociception. The MGRSSI and the MGRNOX value were generated every 1 s. Mean arterial pressure (MAP) and heart rate (HR) were measured every minute, noninvasively. Using the modified Dixon's up-and-down method, the concentration of remifentanil was determined based on the intubation response of the previous patient. The cardiovascular response during endotracheal intubation was defined as positive when MAP or HR is 20% higher than the pre-intubation value. A probit analysis was used for calculating EC50, EC95 and 95% confidence interval (CI). RESULTS: The EC50 and EC95 of remifentanil blunting tracheal intubation responses were found to be 7.731 ng/ml (95%CI: 7.212-8.278 ng/ml) and 8.701 ng/ml (95%CI: 8.199-11.834 ng/ml). There were statistically significant increases in HR, MGRSSI and MGRNOX value to tracheal intubation in the positive responses group compared to the negative group. The most common adverse event was postoperative nausea and vomiting, which occurred in 3 patients. CONCLUSION: Remifentanil effect-site concentration of 7.731 ng/ml is effective in blunting sympathetic responses to tracheal intubation in 50% of patients when combined with etomidate anesthesia. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry ( www.chictr.org.cn , registration number: ChiCTR2100054565, date of registration: 20/12/2021).

The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial.

BACKGROUND: The use of induction agents for rapid sequence intubation (RSI) has been associated with hypotension in critically ill patients. Choice of induction agent may be important and the most commonly used agents are etomidate and ketamine. OBJECTIVE: This study aimed to compare the effects of a single dose of ketamine vs. etomidate for RSI on maximum Sequential Organ Failure Assessment (SOFA) score and incidence of hypotension. METHODS: This single-center, randomized, parallel-group trial compared the use of ketamine and etomidate for RSI in critically ill adult patients in the emergency department. The study was performed under Exception from Informed Consent. The primary outcome was the maximum SOFA score within 3 days of hospitalization. RESULTS: A total of 143 patients were enrolled in the trial, 70 in the ketamine group and 73 in the etomidate group. Maximum median SOFA score for the ketamine group was 6.5 (interquartile range [IQR] 5-9) vs. 7 (IQR 5-9) for etomidate with no significant difference (-0.2; 95% CI -1.4 to 1.1; p = 0.79). The incidence of post-intubation hypotension was 28% in the ketamine group vs. 26% in the etomidate group (difference 2%; 95% CI -13% to 17%). There were no significant differences in intensive care unit outcomes. Thirty-day mortality rate for the ketamine group was 11% (8 deaths) and for the etomidate group was 21% (15 deaths), which was not statistically different. CONCLUSIONS: There were no significant differences in maximum SOFA score or post-intubation hypotension between critically ill adults receiving ketamine vs. etomidate for RSI.

Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea.

BACKGROUND: Ketamine and etomidate are commonly used as sedatives in rapid sequence intubation (RSI). However, there is no consensus on which agent should be favored when treating patients with trauma. This study aimed to compare the effects of ketamine and etomidate on first-pass success and outcomes of patients with trauma after RSI-facilitated emergency intubation. METHODS: We retrospectively reviewed 944 patients who underwent endotracheal intubation in a trauma bay at a Korean level 1 trauma center between January 2019 and December 2021. Outcomes were compared between the ketamine and etomidate groups after propensity score matching to balance the overall distribution between the two groups. RESULTS: In total, 620 patients were included in the analysis, of which 118 (19.9%) were administered ketamine and the remaining 502 (80.1%) were treated with etomidate. Patients in the ketamine group showed a significantly faster initial heart rate (105.0 ± 25.7 vs. 97.7 ± 23.6, p = 0.003), were more hypotensive (114.2 ± 32.8 mmHg vs. 139.3 ± 34.4 mmHg, p < 0.001), and had higher Glasgow Coma Scale (9.1 ± 4.0 vs. 8.2 ± 4.0, p = 0.031) and Injury Severity Score (32.5 ± 16.3 vs. 27.0 ± 13.3, p < 0.001) than those in the etomidate group. There were no significant differences in the first-pass success rate (90.7% vs. 90.1%, p > 0.999), final mortality (16.1% vs. 20.6, p = 0.348), length of stay in the intensive care unit (days) (8 [4, 15] (Interquartile range)), vs. 10 [4, 21], p = 0.998), ventilator days (4 [2, 10] vs. 5 [2, 13], p = 0.735), and hospital stay (days) (24.5 [10.25, 38.5] vs. 22 [8, 40], p = 0.322) in the 1:3 propensity score matching analysis. CONCLUSION: In this retrospective study of trauma resuscitation, those receiving intubation with ketamine had greater hemodynamic instability than those receiving etomidate. However, there was no significant difference in clinical outcomes between patients sedated with ketamine and those treated with etomidate.

Etomidate versus propofol for electroconvulsive therapy: An intraindividual comparative study during the COVID-19 pandemic.

OBJECTIVES: The Coronavirus disease 2019 (COVID-19) pandemic markedly influenced mental health care practices, notably regarding electroconvulsive therapy (ECT). This was due to the redistribution of anesthetic agents used during ECT such as propofol, for intensive care units. Because in our center propofol was switched to etomidate to avoid ECT activity discontinuation, we undertook this study in order to compare Propofol and Etomidate regarding electroencephalographic seizure duration and stimulus intensity. METHODS: We performed a retrospective and comparative study, each patient being its own control. We included patients with at least two courses of ECT on propofol and two others with etomidate over the period from September 2019 to April 2021, regardless of the psychiatric diagnosis. Our data collection process notably targeted stimulus intensity, seizure duration recorded using electroencephalography, and medication used for anesthetic induction. RESULTS: Overall, we included 18 patients with a male: female ratio of 1:2.6 and a mean (and standard deviation) age of 62.7±13.4 years. We found that the mean intensity of stimulation was significantly lower with etomidate when compared to propofol (425.3±250.0 vs. 658.9±280.2 mC, P=0.001). The mean duration of electroencephalographic seizure was significantly higher with etomidate in comparison to propofol (53.5±16.6 vs. 35.0±12.2seconds, P<0.001). CONCLUSION: By using each patient as its own control, our study found that etomidate, while compared to propofol, was related to a lower level of stimulatory intensity and a longer electroencephalographic seizure duration.

UPLC-MS/MS Method for Detection of Etomidate and Its Metabolite Etomidate Acid Quantity in Blood.

OBJECTIVES: To establish a method for the simultaneous quantitative analysis of etomidate and its metabolite etomidate acid in blood, and to discuss its application value in actual cases. METHODS: Acetonitrile precipitate protein method was used, and C18 column was selected. Gradient elution was performed with acetonitrile and 5 mmol/L ammonium acetate within 6 min. Electrospray ionization source in positive ion mode was used. The internal standard etomidate acid-d5 was obtained by etomidate-d5 alkaline hydrolysis reaction. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for quantitative analysis. The methodological verification was conducted. RESULTS: Etomidate and etomidate acid in blood showed good linear relationship in the quantitative linear range (r>0.999), with the lower limit of quantification was 2.5 ng/mL and 7.5 ng/mL, respectively. The accuracy, precision, recovery rate, and matrix effect of the method met the professional verification standards. The practical application results showed that etomidate and etomidate acid could be detected in the blood of the abusers, and their mass concentrations ranged from 17.24 to 379.93 ng/mL. CONCLUSIONS: The method established in this study can simultaneously quantify etomidate and etomidate acid in blood, which is simple and convenient to operate with accuracy. It can meet the detection needs of actual cases and provide technical support for law enforcement to crack down on etomidate abuse.

Effect of etomidate and propofol on airway mechanics during induction - A prospective randomized trial.

Background and Aims: Intravenous induction agents like propofol and etomidate change the airway mechanics and thus influence mask ventilation. These changes have an impact on the administration of muscle relaxant in a difficult mask ventilation scenario. The difference in dynamics of airway after administration of two different intravenous agents has been assessed in this study. Material and Methods: After formal registry in clinical trials, patients undergoing general anesthesia were recruited and randomized into group P and E. Patients were induced with either of the intravenous agents, and mask ventilation was performed with a ventilator. After 60 s, rocuronium was administered and ventilation continued. Measurements of tidal volume, peak airway pressure, and compliance were taken from the anesthesia ventilator at different time points - induction, relaxant, and intubation. Results: There was no statistically significant difference between the two groups with respect to demographics, airway parameters, and airway mechanics, as measured by tidal volume, peak airway pressure, and lung compliance. There was an improvement in the tidal volume and compliance following induction with propofol, with a P value of 0.007 and 0.032, respectively, obtained in within-group comparison. Conclusion: Propofol and etomidate were comparable in airway mechanics, but compliance and tidal volumes improved with propofol, which facilitated face mask ventilation.

Ketamine is not associated with more post-intubation hypotension than etomidate in patients undergoing endotracheal intubation.

INTRODUCTION: Emergency department (ED) patients undergoing emergent tracheal intubation often have multiple physiologic derangements putting them at risk for post-intubation hypotension. Prior work has shown that post-intubation hypotension is independently associated with increased morbidity and mortality. The choice of induction agent may be associated with post-intubation hypotension. Etomidate and ketamine are two of the most commonly used agents in the ED, however, there is controversy regarding whether either agent is superior in the setting of hemodynamic instability. The goal of this study is to determine whether there is a difference in the rate of post-intubation hypotension who received either ketamine or etomidate for induction. Additionally, we provide a subgroup analysis of patients at pre-existing risk of cardiovascular collapse (identified by pre-intubation shock index (SI) > 0.9) to determine if differences in rates of post-intubation hypotension exist as a function of sedative choice administered during tracheal intubation in these high-risk patients. We hypothesize that there is no difference in the incidence of post-intubation hypotension in patients who receive ketamine versus etomidate. METHODS: A retrospective cohort study was conducted on a database of 469 patients having undergone emergent intubation with either etomidate or ketamine induction at a large academic health system. Patients were identified by automatic query of the electronic health records from 1/1/2016-6/30/2019. Exclusion criteria were patients <18-years-old, tracheal intubation performed outside of the ED, incomplete peri-intubation vital signs, or cardiac arrest prior to intubation. Patients at high risk for hemodynamic collapse in the post-intubation period were identified by a pre-intubation SI > 0.9. The primary outcome was the incidence of post-intubation hypotension (systolic blood pressure < 90 mmHg or mean arterial pressure < 65 mmHg). Secondary outcomes included post-intubation vasopressor use and mortality. These analyses were performed on the full cohort and an exploratory analysis in patients with SI > 0.9. We also report adjusted odds ratios (aOR) from a multivariable logistic regression model of the entire cohort controlling for plausible confounding variables to determine independent factors associated with post-intubation hypotension. RESULTS: A total of 358 patients were included (etomidate: 272; ketamine: 86). The mean pre-intubation SI was higher in the group that received ketamine than etomidate, (0.97 vs. 0.83, difference: -0.14 (95%, CI -0.2 to -0.1). The incidence of post-intubation hypotension was greater in the ketamine group prior to SI stratification (difference: -10%, 95% CI -20.9% to -0.1%). Emergency physicians were more likely to use ketamine in patients with SI > 0.9. In our multivariate logistic regression analysis, choice of induction agent was not associated with post-intubation hypotension (aOR 1.45, 95% CI 0.79 to 2.65). We found that pre-intubation shock index was the strongest predictor of post-intubation hypotension. CONCLUSION: In our cohort of patients undergoing emergent tracheal intubation, ketamine was used more often for patients with an elevated shock index. We did not identify an association between the incidence of post-intubation hypotension and induction agent between ketamine and etomidate. Patients with an elevated shock index were at higher risk of cardiovascular collapse regardless of the choice of ketamine or etomidate.

The influence of anaesthetic choice on seizure duration of electroconvulsive therapy; etomidate versus methohexital.

BACKGROUND: Many of the anaesthetic drugs used for electroconvulsive therapy have anticonvulsant properties and may influence efficacy of electroconvulsive therapy. With this study we aim to provide more information on the effect of etomidate and methohexital on seizure duration. We explore the relationship between induction drug, motor and electroencephalography seizure duration. Moreover, we study the relationship of seizure duration and number of therapies. METHODS: In this retrospective study we collected data from patient records from 2005 until 2016. Inclusion criteria were the use of etomidate and/or methohexital and documentation of dosage, electroconvulsive therapy dosage and seizure duration. Exclusion criteria were missing data on either induction drug, dosage or seizure duration. RESULTS: Thirty seven patients were analysed. The mean age was 52 years and seventy six percent were female. Most patients were suffering from affective disorders (81%). Motor and electroencephalography seizure duration were analysed in 679 and 551 electroconvulsive therapies, respectively. Compared to methohexital, motor and electroencephalography seizures under etomidate were 7 and 13 s longer, respectively. Furthermore, there was a negative association between seizure duration and number of treatment and a negative association between seizure duration and electroconvulsive therapy dosage. CONCLUSIONS: This study demonstrates significant longer motor and electroencephalography seizure duration using etomidate compared to methohexital. Etomidate might therefore increase the effectiveness of electroconvulsive therapy. Moreover, we observed a negative association between seizure duration, number of treatment and electroconvulsive therapy dosage. With this study we contribute to the available literature comparing methohexital and etomidate as induction agents for electroconvulsive therapy.

Determination of the median effective dose of sufentanil for inhibiting the laryngeal mask insertion response in geriatric patients: a prospective, double-blinded, dose-response trial.

BACKGROUND: Laryngeal mask airway(LMA) have been widely used in clinical practice. Irritation to the patient during the insertion of a laryngeal mask can cause hemodynamic fluctuations, which is particularly unsafe for geriatric patients. We used probit regression analysis to determine the median effective dose of sufentanil to inhibit the response to LMA insertion in geriatric patients. METHODS: A total of 90 patients were selected for the study using the following inclusion criteria: age ≥ 65 years old, ASA grade I-III, and scheduled to undergo intravenous general anesthesia with LMA insertion. Each patient received a dose of sufentanil for anesthesia induction in one of six levels: 0.05, 0.1, 0.15, 0.2, 0.25, or 0.3 µg kg-1. LMA insertion was scored with a 3-point, 6-category scale, with scores ≥ 16 indicating effective LMA insertion, and < 16 indicating ineffective LMA insertion. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded 1 min before induction (T1), 1 min after induction (T2), 1 min after LMA insertion (T3), and 5 min after LMA insertion (T4) in each group. In addition, the plasma norepinephrine (NE) levels and adverse reactions were measured at T2 and T3 in each dosage group. RESULTS: Probit regression analysis showed that the ED50 of sufentanil inhibiting the response to LMA insertion in geriatric patients was 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1), and the ED95 was 0.31 µg kg-1 (95% CI: 0.27-0.38 µg kg-1), and the probit(p) = -2.34 + 12.90 × ln(Dose)([Formula: see text] = 0.725, p = 0.948). Among all the patients, the number of effective LMA insertions was 57 (group A), and the number of ineffective LMA insertions was 33 (group B). The MAP, HR, and NE in group B were significantly higher than in group A at T3. CONCLUSIONS: Sufentanil can effectively inhibit the patient's response to LMA insertion, with stable hemodynamics and small stress response. The ED50 and ED95 were 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1) and 0.31 µg kg-1(95% CI: 0.27-0.38 µg kg-1), respectively. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100051827 ) on October 6, 2021.

Effects of adding low-dose ketamine to etomidate on serum cortisol levels in critically ill cardiac patients: a randomized clinical trial.

BACKGROUND: Etomidate was associated with an inhibition of adrenal steroid synthesis. This study aimed to evaluate the effects of adding low-dose ketamine to etomidate to minimize the decrease in serum cortisol level in critically ill cardiac patients. METHODS: Sixty adult cardiac patients, ≥ 18 years, who underwent upper endoscopy and Colonoscopy to manage acute anemia in the cardiac intensive care units were enrolled. Patients were randomly divided into two groups: (group (E): n = 30) received etomidate 0.2 mg/kg IV followed by etomidate 0.05 mg/kg IV, and (group (KE): n = 30) received ketamine 0.5 mg/kg IV, then etomidate 0.1 mg/kg IV, followed by etomidate 0.05 mg/kg IV. The primary outcome was Serum cortisol level at 6 h after the procedure. RESULTS: The mean postoperative cortisol level was significantly lower in group E (295.60 ± 49.218 nmol/L) versus group KE (461.00 ± 67.946 nmol/L), with 95% CI = 351.94 to 404.66; p = 0.000. In addition, the estimated serum cortisol reduction level was also significant between groups; In group E, the estimated cortisol level decreased nearly 53% from 632.40 ± 35.066 nmol/L to 295.60 ± 49.218 nmol/L 6 hours postoperative. While in group KE, the estimated cortisol level decreased only 27% from 639.13 ± 43.035 nmol/L to 461.00 ± 67.946 nmol/L. CONCLUSIONS: Single-dose ketamine (0.5 mg/kg) was helpful to decrease the total dose of etomidate and hence decreased the percentage of serum cortisol level in such critically ill patients with preservation of patient satisfaction. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov ( NCT04857450 ; principal investigator: Mostafa Mohammed Elsaid Elhamamsy; registration date: 23/04/ 2021).