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PubMed2000

Inhibition of glucose transport and direct interactions with type 1 facilitative glucose transporter (GLUT-1) by etomidate, ketamine, and propofol: a comparison with barbiturates.

Ketamine, etomidate, propofol, and pentobarbital were compared for effects on and interactions with the type 1 facilitative glucose transporter (GLUT-1). Fluxes of radiolabeled hexoses were used to determine the effects of anesthetics on GLUT-1 function. Hypotonic hemolysis of human erythrocytes was used to assess perturbations of membrane integrity. Quenching of intrinsic protein fluorescence was used to assess the direct interactions of anesthetics with purified GLUT-1. Pentobarbital, ketamine, etomidate, and propofol inhibited glucose transport in murine fibroblasts with IC(50) values of 0.8, 1. 6, 0.1, and 0.4 mM, respectively. Pentobarbital, ketamine, etomidate, and propofol also inhibited sugar transport in human erythrocytes. The IC(50) values for pentobarbital and ketamine exhibited substrate dependence for equilibrium exchange but not unidirectional effluxes. This was not observed for etomidate. Propofol did not inhibit equilibrium exchange but did inhibit unidirectional efflux with little substrate dependence. Pentobarbital protected against hemolysis, whereas etomidate and ketamine promoted hemolysis of erythrocytes. Propofol had no effect on membrane integrity. Pentobarbital, ketamine, and etomidate all interacted directly with GLUT-1, with apparent K(d) values of 2.2, 0.8, and 0.5 mM, respectively. Like barbiturates, ketamine, etomidate, and propofol inhibited GLUT-1 at concentrations near to those used pharmacologically. Inhibition of GLUT-1 by these intravenous general anesthetics was complex, exhibiting differential kinetic effects on equilibrium exchange versus unidirectional fluxes and contrasting substrate dependencies. Like barbiturates, ketamine and etomidate bound to GLUT-1 with affinities that paralleled inhibition of glucose transport. As a class, intravenous general anesthetics, in contrast to inhalation anesthetics, inhibit GLUT-1-mediated glucose transport.

3T3 Cells↗

PubMed1997

Etomidate inhibits [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells.

We have examined the effects of the intravenous anaesthetic induction agent etomidate on K+ and carbachol evoked [3H]noradrenaline ([3H]NA) release and the associated increase in [Ca2+]i in SH-SY5Y human neuroblastoma cells in a attempt to study potential anaesthetic target site(s). Preincubation with etomidate produced a dose-dependent inhibition of both K+ and carbachol evoked [3H]NA release with estimated IC50 values of 88 and 69 microM, respectively. Only K+ stimulated increase in [Ca2+]i was inhibited by etomidate preincubation with an IC50 of 146 microM. Acute addition of etomidate after K+ challenge also inhibited the increase in [Ca2+]i with an IC50 of 99 microM. In addition etomidate displaced the binding of [3H]PN200-110 to L-type voltage sensitive Ca2+ channels with a Ki of 48 microM. As K+ but not carbachol evoked [3H]NA release is extracellular Ca2+ dependent and was inhibited by etomidate these data coupled with the PN200-110 displacement studies suggest that etomidate may interact with L-type voltage sensitive Ca2+ channels. The inhibition of carbachol evoked release without affecting the associated increase in [Ca2+]i suggests that etomidate may exert additional effects at either the muscarinic receptor or the secretory machinery in these cells.

Calcium↗

PubMed2005

Comparision of etomidate and propofol for fibreoptic intubation as part of an airway management algorithm:a prospective, randomizes, double-blind study.

BACKGROUND AND OBJECTIVE: In our algorithm for management of the anticipated difficult airway the induction agent (etomidate) is administered after the tip of the fibreoptic is placed in the trachea but before the tube is advanced over it. In a previous investigation we demonstrated the safety of this method. Due to its popularity as an induction agent, some would like to replace etomidate with propofol. However, because rapid recovery of spontaneous breathing is crucial with this technique, substitution might not be advisable. We compared the speed of recovery of spontaneous breathing after fibreoptic intubation between etomidate and propofol. METHODS: In this prospective, randomized, double-blind study we used either 0.2 mg kg[-1] etomidate or 2 mg kg[-1] propofol for induction. Our technique of nasotracheal fibreoptic intubation consists of using fentanyl, cocaine instillation into the lower nasal canals, cricothyroid injection of lidocaine, performing bronchoscopy, administration of etomidate and advancing the tube after loss of consciousness. We measured time to loss of consciousness, time to recovery of spontaneous breathing, lowest bi-spectral index value and time to lowest value. RESULTS: Time to loss of consciousness did not differ. The time to recovery of spontaneous breathing differed significantly: the median time (interquartile range [range]) for etomidate was 81 s (62--102 [0--166]), and for propofol 146 s (95--260 [65--315]); P=0.001. The lowest bi-spectral index values were not different. The time of the lowest bi-spectral index values differed significantly: for etomidate 58 s (51--68 [38--100]), and for propofol 90 s (52--125 [38--172]); P=0.015. CONCLUSION: For nasotracheal fibreoptic intubation, where the tube is advanced after induction of anaesthesia, we still recommend etomidate because spontaneous breathing recovers faster than with propofol.

Adolescent↗

PubMed2002

Etomidate for procedural sedation in emergency medicine.

STUDY OBJECTIVE: We describe and analyze the effectiveness and safety of etomidate for procedural sedation and evaluate the patient's perspective on effectiveness, side effects, and satisfaction. METHODS: We conducted an observational retrospective study of all patients who received etomidate for procedural sedation over 2 years in 3 affiliated suburban emergency departments of a large group-model health maintenance organization. Data were abstracted from the ED records. Additionally, a patient questionnaire was prospectively administered by telephone. RESULTS: Etomidate was used for sedation in 134 patients between 6 and 93 years of age during 150 procedures. The mean cumulative dose was 0.20 mg/kg. Adjunctive medication was used in 36 (23%) procedures. Moderate sedation with verbal arousability was induced in 48 (32%) patients, and deep sedation with verbal unresponsiveness was induced in 102 (68%) patients. Full recovery to the preprocedural level of alertness was achieved within 30 minutes in 142 (95%) of procedures. Mean changes in systolic blood pressure, pulse rate, and oxygen saturation were clinically insignificant. There were 7 (4.7%; 95% confidence interval [CI] 1.9% to 9.4%) adverse events, including 5 (3.3%; 95% CI 1.1% to 7.6%) cases of oxygen desaturation below 94% in older patients (>55 years of age) who received slightly higher mean doses of etomidate (0.23 mg/kg). Four of these patients received brief assisted bag-valve-mask ventilation and recovered uneventfully; none required endotracheal intubation. The questionnaire was completed by 120 (90%) of 134 patients and involved 136 procedures. During 127 (93%) of these, etomidate was believed to be extremely effective in causing sleep, and for 127 (93%) it induced complete procedural amnesia. Only 5 (4%) patients experienced nausea or vomiting. Regarding willingness to receive etomidate for their next procedure, the patients' responses were favorable: extremely, 95%; moderately, 2%; slightly, 3%; and not at all, 1%. CONCLUSION: Etomidate is a useful agent for carefully conducted procedural sedation because it provides effective, brief, deep sedation with little hemodynamic compromise. Its safety may be jeopardized by the occurrence of respiratory depression in older patients receiving higher doses. Patients report a high degree of satisfaction with etomidate.

Adolescent↗

PubMed2002

Etomidate and midazolam for reduction of anterior shoulder dislocation: a randomized, controlled trial.

STUDY OBJECTIVE: We determine whether patients with acute, anterior shoulder dislocation undergoing emergency department procedural sedation and analgesia (PSA) with intravenous etomidate would experience a reduced time of impaired consciousness when compared with a group of patients receiving intravenous midazolam. METHODS: This study was a prospective, double-blinded, randomized, institutional review board-approved trial of ED patients with anterior shoulder dislocation. Patients were randomized to receive intravenous boluses of etomidate (0.1 mg/kg) or midazolam (0.033 mg/kg) during PSA. The primary outcome for comparison was PSA duration. RESULTS: Forty-six patients with anterior shoulder dislocation were enrolled: 22 in the etomidate group and 24 in the midazolam group. Three patients sustained reduction without physician or sedative intervention. Two patients were excluded from protocol because of unavailable study drug or fracture dislocation. The median lowest modified postanesthetic recovery score observed during PSA was 5 (95% confidence interval [CI] 4 to 7) in the etomidate group and 6 (95% CI 6 to 7) in the midazolam group. The median time of PSA for patients receiving etomidate was 10 minutes (95% CI 8 to 15) compared with 23 minutes (95% CI 16 to 30) for patients receiving midazolam, with a difference between the group medians of 13 minutes (95% CI 5 to 22). Reduction success was achieved in 37 (90%) of 41 patients: 2 did not experience reduction with etomidate and 2 did not experience reduction with midazolam. There were 15 PSA complications reported. CONCLUSION: Etomidate provides effective PSA for reduction of ED patients with anterior shoulder dislocation. When compared with midazolam, etomidate use confers a significantly shorter period of PSA.

Adult↗

PubMed2003

Bispectral index changes following etomidate induction of general anaesthesia and orotracheal intubation.

BACKGROUND: Etomidate-associated hypnosis has only been studied using standard clinical criteria and raw EEG variables. We conducted a BIS-based investigation of etomidate induction of general anaesthesia. METHODS: Thirty hydroxyzine-premedicated ASA I patients were randomly allocated to receive etomidate 0.2, 0.3, or 0.4 mg kg(-1) intravenously over 30 s. The BIS was continuously recorded. A tourniquet was placed on a lower limb to record purposeful movements and myoclonia. Tracheal intubation was facilitated using rocuronium 0.6 mg kg(-1) when the BIS value was 50. The times to disappearance of the eyelash reflex, to a decrease in the BIS to 50, and to tracheal intubation were compared. The BIS values 30 s following tracheal intubation, and mean arterial pressure (MAP) and heart rate (HR) at all time points were also recorded. RESULTS: The BIS value decreased to 50 for tracheal intubation with no purposeful movement in all but one patient in the 0.2 mg kg(-1) group. There was no difference between the etomidate groups (0.2, 0.3, and 0.4 mg kg(-1)) in regards to time to loss of the eyelash reflex (103 (67), 65 (34), 116 (86) s, P=0.2), or to a decrease in BIS to 50 (135 (81), 82 (36), 150 (84) s, P=0.1). Also, the BIS value 30 s after intubation (41 (10), 37 (4), 37 (4), P=0.4), and plasma etomidate concentrations (161 [29-998], 308 [111-730], 310 [90-869] ng ml(-1), P=0.2) did not differ between groups. The time to loss of the eyelash reflex was 12-140 s shorter than the time to a decrease in BIS to 50 in three patients in each group who received etomidate 0.2 and 0.4 mg kg(-1), and in four patients who received 0.3 mg kg(-1). No awareness was recorded. MAP and HR increases following tracheal intubation were comparable between groups. CONCLUSIONS: Etomidate induction doses do not predict the time for BIS to decrease to 50 as this variable varies markedly following three etomidate dose regimen.

Adult↗

PubMed1998

Etomidate adversely alters determinants of left ventricular afterload in dogs with dilated cardiomyopathy.

UNLABELLED: We tested the hypothesis that etomidate produces similar alterations in left ventricular (LV) afterload in dogs with normal LV function or dilated cardiomyopathy. Dogs were instrumented for LV and aortic pressures, and aortic blood flow. LV afterload was measured with aortic input impedance and quantified with a three-element Windkessel model. In one group of experiments, dogs (n = 6) were paced at 240 bpm for 18 +/- 2 days (mean +/- SEM). Hemodynamic data were recorded in sinus rhythm in the conscious state and during etomidate anesthesia (5, 10, and 20 mg x kg(-1) x h(-1)). Identical experiments were conducted in a separate group of chronically instrumented dogs not subjected to LV pacing (n = 6). No changes in heart rate and arterial and LV pressures were observed during etomidate anesthesia in cardiomyopathic dogs. There were decreases in arterial and LV systolic pressure during the administration of 20 mg x kg(-1) x h(-1) etomidate to dogs with normal LV function. Etomidate significantly (P < 0.05) increased total arterial resistance (R; 3220 +/- 290 dynes x s x cm(-5) during control to 6110 +/- 790 dynes x s x cm(-5) during 10 mg x kg(-1) x h(-1)) and characteristic aortic impedance (Zc; 141 +/- 22 dynes x s x cm(-5) during control to 161 +/- 23 dynes x s x cm(-5) during 20 mg x kg(-1) x h(-1)) and decreased total arterial compliance (C; 0.70 +/- 0.15 mL/mm Hg during control to 0.45 +/- 0.07 mL/mm Hg during 10 mg x kg(-1) x h(-1)) in cardiomyopathic but not healthy dogs. Etomidate markedly reduced mean aortic blood flow (2.26 +/- 0.17 L/min during control to 1.39 +/- 0.20 L/min during 10 mg x kg(-1) x h(-1)) and increased the time constant of LV relaxation (54 +/- 3 ms during control to 74 +/- 9 ms during 20 mg x kg(-1) x h(-1)) in dogs with LV failure. Arterial pressure is maintained during etomidate anesthesia in the presence of LV dysfunction as a result of increases in R and Zc and decreases in C. These deleterious increases in LV afterload further compromise LV systolic and diastolic performance in dogs with dilated cardiomyopathy. IMPLICATIONS: The results of this investigation indicate arterial pressure is maintained during etomidate anesthesia as a consequence of increases in left ventricular (LV) afterload that further diminish LV systolic and diastolic performance in the presence of impaired LV function.

Anesthetics, Intravenous↗

PubMed2000

The effects of etomidate on the contractility of failing and nonfailing human heart muscle.

UNLABELLED: We measured the effects of etomidate on contractility of human cardiac muscle. Muscles were obtained from the left ventricle and right atrium of 12 patients undergoing cardiac transplantation, and from the right atrium of 12 patients undergoing coronary artery bypass surgery. Muscles were studied at 37 degrees C and 1.0 Hz. Variables of isometric contraction were recorded before and after etomidate (0.04-80 microM) or its solvent, propylene glycol. The ability of beta-adrenergic stimulation to cause an inotropic effect after etomidate was also assessed. Etomidate caused a dose-dependent decrease in developed tension, which was statistically significant only at concentrations exceeding clinical doses (> or =20 microM; P < 0. 05). Decreases in maximum rates of contraction and relaxation paralleled changes in developed tension. beta-Adrenergic stimulation reversed the etomidate-induced decreases in developed tension and rates of contraction and relaxation to baseline (P > 0.05 compared with baseline). Thus, in human myocardium, etomidate exerts a dose-dependent negative inotropic effect, which is reversible with beta-adrenergic stimulation. Concentrations required to produce these negative inotropic effects are, however, in excess of those reached during clinical use. Therefore, etomidate-induced negative inotropy is unlikely to be a problem clinically, even in patients with cardiac dysfunction. IMPLICATIONS: Etomidate produced a similar dose-dependent negative inotropic effect in both failing and nonfailing human myocardium. This effect was present only at concentrations exceeding those attained clinically and was reversible with beta-adrenergic stimulation.

Adolescent↗

PubMed1987

Endocrinological changes following etomidate, midazolam, or methohexital for minor surgery.

Etomidate is known to inhibit adrenocorticosteroid synthesis. The extent and duration of the effects of etomidate (63 +/- 6.4 mg) on spontaneous and stimulated corticosteroid levels, as well as on plasma concentrations of ACTH, beta-endorphin, and catecholamines were examined and compared to those following administration of the new benzodiazepine, midazolam, or of methohexital. Twenty-nine healthy, young, male orthopedic patients were randomized into three groups receiving either etomidate/fentanyl (n = 12), midazolam/fentanyl (n = 8), or methohexital/fentanyl (n = 9). Etomidate caused cortisol levels to decrease from 12.5 +/- 1.2 micrograms/dl preoperatively to 5.9 +/- 0.8 micrograms/dl after operation (P less than 0.001), compared to an increase from 12.0 +/- 1.9 micrograms/dl to 18.5 +/- 2.9 micrograms/dl in the group receiving methohexital. At 6 and 20 h postoperatively, all cortisol levels were normal. The cortisol decrease from 12.5 +/- 1.7 to 7.6 +/- 1.5 caused by midazolam was similar to that following etomidate, but the response to exogenous ACTH was significantly impaired in patients receiving etomidate as compared to those receiving midazolam. ACTH and beta-endorphin levels increased in patients receiving etomidate, presumably as a result of the interruption of negative feedback due to cortisol synthesis inhibition. Midazolam on the other hand prevented the increase of ACTH and beta-endorphin levels. Etomidate completely suppressed spontaneous aldosterone levels (from 33 +/- 6.7 to 7 +/- 2.1 pg/ml), as well as the response to stimulation with exogenous ACTH without affecting serum electrolytes. Etomidate had no influence on plasma catecholamines, but midazolam attenuated the stress-related epinephrine increase.

Adrenocorticotropic Hormone↗

PubMed2004

Etomidate alters calcium mobilization induced by angiotensin II in rat aortic smooth muscle cells.

Etomidate is widely used for induction of anesthesia in the hemodynamically compromised patient, because of its moderate direct effect on arterial vasomotoricity and cardiac function, but its effect on blood pressure regulatory systems is not known. We studied the effect of etomidate (10(-8) to 10(-4) mol.L) on Ca++ mobilization elicited by angiotensin II (Ang II) in cultured aortic smooth muscle cells (VSMC) from 6-week-old Wistar Kyoto rats. Intracellular Ca++ (Cai++) variation was assessed in Fura 2-loaded VSMC, using fluorescent imaging microscopy. Ang II (10(-6) mol.L(-1))-induced transient Cai++ mobilization from internal stores was assessed in the absence of external Ca++. Ca++ influx was assessed upon reintroduction of external Ca++ (10(-3) mol.L(-1)). Etomidate moderately decreased both the amplitude (etomidate 10(-4) mol.L(-1): 68% of control value, P < 0.001) and the slope of Cai++ increase (56% of control, P < 0.001) from internal stores induced by Ang II. PD2 values (PD2 = -log(EC50)) for amplitude and slope were 6.4 +/- 0.7 and 6.0 +/- 0.3, respectively. Ang II-elicited Ca++ influx was also significantly decreased (45% of control, P < 0.001; PD2 = 5.5 +/- 0.3). Etomidate alters the Ca++ mobilization elicited by Ang II in rat aortic VSMC, suggesting that the vascular response to Ang II may be altered during etomidate anesthesia. However, this effect was observed at high concentration of etomidate, and may be limited when low doses of etomidate are used.

Angiotensin II↗

PubMed2001

Adrenocortical dysfunction following etomidate induction in emergency department patients.

OBJECTIVE: To assess adrenocortical function following intravenous etomidate use in emergency department (ED) patients requiring intubation. METHODS: This was a prospective, randomized, controlled trial of consecutive patients presenting to the ED requiring intubation. Patients were randomized to receive a single bolus induction dose of either 0.05-0.1 mg/kg midazolam (control group) or 0.3 mg/kg etomidate (etomidate group) during a standardized rapid-sequence intubation (RSI) with succinylcholine. The primary outcome variable was adrenocortical function at 4, 12, and 24 hours post-induction as assessed by measured serum cortisol response to exogenous cosyntropin (cosyntropin stimulation test, CST). Fisher's exact test was used to compare CST results between groups. RESULTS: Thirty-one patients were enrolled: 8 control, 10 etomidate, and 13 excluded from analysis for either incomplete data or steroid use during the study period. The 4-hour CST results were significantly different between study groups, with a normal response in 100% of control patients vs 30% of etomidate patients (p = 0.004). The 12- and 24-hour CSTs did not differ significantly between groups: normal CST in 100% of control patients at 12 and 24 hours vs 100% and 90% among etomidate patients at 12 and 24 hours, respectively (p = 1.0 at 12 and 24 hours). Measured cortisol levels of patients with abnormal CSTs remained within normal laboratory reference ranges. CONCLUSION: Use of etomidate in ED patients requiring RSI results in adrenocortical dysfunction. However, cortisol levels remain within normal laboratory levels during this period of dysfunction. Adrenocortical dysfunction appears to resolve within 12 hours of a single bolus dose of 0.3 mg/kg etomidate.

Adrenal Cortex↗

PubMed2001

Etomidate for pediatric sedation prior to fracture reduction.

OBJECTIVE: While etomidate is reported as a procedural sedative in adults, its use in children has not been extensively reported. The authors describe their experience with etomidate for procedural sedation in children with extremity fractures and major joint dislocations. METHODS: This was a retrospective descriptive chart review. The setting was a university-based emergency department (ED) that follows national guidelines for procedural sedation. Subjects were children less than 18 years old who received etomidate prior to fracture reduction or major joint dislocations. Standardized data were abstracted from the medical records, including patient demographics, diagnosis, weight, types and doses of sedative and analgesic agents used, number of boluses of etomidate, attempts at reduction, complications encountered, vitals signs before, during, and after the reduction, disposition, and the time from procedure to discharge. Descriptive statistics calculated included means and proportions with 95% confidence intervals. RESULTS: Fifty-three children received etomidate for fracture reduction. Their mean age was 9.7; 41.5% were females. Indications for reduction included forearm fractures (38), ankle fractures (12), upper arm fractures (2), and hip dislocations (1). In most cases (83%) reduction was successful after one attempt only. The mean initial and total doses of etomidate were 0.20 mg/kg (range, 0.1 to 0.4) and 0.24 mg/kg (range, 0.13 to 0.52), respectively. Thirteen patients required a second bolus of etomidate or midazolam. Thirty-four patients (64%) were discharged from the ED after a mean observation of 94 minutes (range, 35 to 255). There were no major adverse events (95% CI = 0% to 5.7%). One patient reported nausea and one required a fluid bolus for hypotension. One patient receiving multiple sedatives and opioid analgesics was admitted for observation due to prolonged sedation. No patient required assisted ventilation or intubation. CONCLUSIONS: These results suggest that etomidate is a safe and effective agent for procedural sedation in children requiring fracture and major joint reductions.

Child↗

PubMed2006

The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate.

INTRODUCTION: Etomidate blocks adrenocortical synthesis when it is administered intravenously as a continuous infusion or a single bolus. The influence of etomidate administration on the incidence of relative adrenal insufficiency in patients with septic shock has not been formally investigated. The objective of this study was to determine the incidence of relative adrenal insufficiency in patients with septic shock after etomidate administration compared with patients with septic shock who did not receive etomidate. METHODS: In this retrospective study, 152 adults with septic shock who had a consyntropin stimulation test between March 2002 and August 2003 in a tertiary medical center were included. Relative adrenal insufficiency was defined as a rise in serum cortisol <or= 9 microg/dl after the administration of 250 microg of consyntropin. Patients were divided into those who did and those who did not receive etomidate before the stimulation test. The proportion of patients with relative adrenal insufficiency in these two groups was compared using Fischer's exact test. A P of value < 0.05 was considered statistically significant. RESULTS: The mean age of the patients was 64 years, 59% of patients were male, 97% of patients were white and their hospital mortality rate was 57%. Thirty-eight patients (25%) received etomidate before the cosyntropin stimulation test, and the median (interquartile range) time interval between the administration of the drug and the test was 7 (4-10) hours. The incidence of relative adrenal insufficiency was 76% in the patients who received etomidate compared with 51% in the patients who did not (P = 0.0077). CONCLUSION: The incidence of relative adrenal insufficiency in patients with septic shock is increased when the stimulation test is performed after the administration of etomidate.

Adrenal Insufficiency↗

PubMed2007

Etomidate use for Cushing's syndrome caused by an ectopic adrenocorticotropic hormone-producing tumor.

OBJECTIVE: To report the preparation and use of etomidate in a patient with Cushing's syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-producing tumor. CASE SUMMARY: A 73-year-old man with a 5 year history of prostate cancer was admitted for symptoms consistent with Cushing's syndrome. He was started on oral metyrapone for elevated serum cortisol, ACTH, and 24 hour urinary unbound cortisol levels. Shortly after starting metyrapone, he was transferred to the medical intensive care unit for new-onset atrial fibrillation, neutropenic fever, and respiratory failure. A nasogastric tube could not be inserted to administer metyrapone. Intravenous etomidate 4 mg/h (0.06 mg/kg/h) was initiated to decrease cortisol production and provide sedation for mechanical ventilation. Despite supportive treatment, the patient died from multiple organ dysfunction. DISCUSSION: For patients exhibiting signs and symptoms of Cushing's syndrome who have no enteral access, administering etomidate intravenously may be a viable alternative treatment route. Although several articles report the use of etomidate to control cortisol overproduction, the intravenous preparation and stability are discussed only vaguely. In our patient, etomidate was infused via a 30 mL syringe, 2 mg/mL undiluted through a central venous catheter; syringe use was limited to 24 hours. Etomidate should be infused only with continuous monitoring of hemodynamics and periodic assessment of adrenal function. CONCLUSIONS: When oral or enteral medications cannot be administered and sedation is required in critically ill patients, etomidate is an appropriate intravenous agent for hypercortisolemia. There were no obvious problems with stability when undiluted etomidate 2 mg/mL was infused through a dedicated central venous catheter lumen.

ACTH Syndrome, Ectopic↗

PubMed2006

Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog.

General anesthetics, including etomidate, act by binding to and enhancing the function of GABA type A receptors (GABA(A)Rs), which mediate inhibitory neurotransmission in the brain. Here, we used a radiolabeled, photoreactive etomidate analog ([(3)H]azietomidate), which retains anesthetic potency in vivo and enhances GABA(A)R function in vitro, to identify directly, for the first time, amino acids that contribute to a GABA(A)R anesthetic binding site. For GABA(A)Rs purified by affinity chromatography from detergent extracts of bovine cortex, [(3)H]azietomidate photoincorporation was increased by GABA and inhibited by etomidate in a concentration-dependent manner (IC(50) = 30 microm). Protein microsequencing of fragments isolated from proteolytic digests established photolabeling of two residues: one within the alphaM1 transmembrane helix at alpha1Met-236 (and/or the homologous methionines in alpha2,3,5), not previously implicated in etomidate function, and one within the betaM3 transmembrane helix at beta3Met-286 (and/or the homologous methionines in beta1,2), an etomidate sensitivity determinant. The pharmacological specificity of labeling indicates that these methionines contribute to a single binding pocket for etomidate located in the transmembrane domain at the interface between beta and alpha subunits, in what is predicted by structural models based on homology with the nicotinic acetylcholine receptor to be a water-filled pocket approximately 50 A below the GABA binding site. The localization of the etomidate binding site to an intersubunit, not an intrasubunit, binding pocket is a novel conclusion that suggests more generally that the localization of drug binding sites to subunit interfaces may be a feature not only for GABA and benzodiazepines but also for etomidate and other intravenous and volatile anesthetics.

Animals↗

PubMed2006

Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate.

A fundamental objective of anesthesia research is to identify the receptors and brain regions that mediate the various behavioral components of the anesthetic state, including amnesia, immobility, and unconsciousness. Using complementary in vivo and in vitro approaches, we found that GABAA receptors that contain the alpha5 subunit (alpha5GABAARs) play a critical role in amnesia caused by the prototypic intravenous anesthetic etomidate. Whole-cell recordings from hippocampal pyramidal neurons showed that etomidate markedly increased a tonic inhibitory conductance generated by alpha5GABAARs, whereas synaptic transmission was only slightly enhanced. Long-term potentiation (LTP) of field EPSPs recorded in CA1 stratum radiatum was reduced by etomidate in wild-type (WT) but not alpha5 null mutant (alpha5-/-) mice. In addition, etomidate impaired memory performance of WT but not alpha5-/- mice for spatial and nonspatial hippocampal-dependent learning tasks. The brain concentration of etomidate associated with memory impairment in vivo was comparable with that which increased the tonic inhibitory conductance and blocked LTP in vitro. The alpha5-/- mice did not exhibit a generalized resistance to etomidate, in that the sedative-hypnotic effects measured with the rotarod, loss of righting reflex, and spontaneous motor activity were similar in WT and alpha5-/- mice. Deletion of the alpha5 subunit of the GABAARs reduced the amnestic but not the sedative-hypnotic properties of etomidate. Thus, the amnestic and sedative-hypnotic properties of etomidate can be dissociated on the basis of GABAAR subtype pharmacology.

Action Potentials↗

PubMed1990

Duration of etomidate-induced adrenocortical suppression during surgery in dogs.

Plasma cortisol concentrations were compared in canine surgical patients given etomidate (2 mg/kg of body weight, IV) or thiopental sodium (12 mg/kg, IV) for anesthetic induction. Blood samples to determine plasma concentrations of etomidate were obtained at 0, 5, 10, 15, and 30 minutes and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after induction. Adrenocortical function was evaluated before surgery by use of adrenocorticotropic hormone stimulation tests. Dogs in both induction groups had high plasma cortisol concentrations after induction. Dogs given thiopental had a significant increase (P less than 0.05) in plasma cortisol concentration from baseline at 2, 3, 4, 5, 6, 8, and 12 hours after induction. Dogs given etomidate had a significant increase (P less than 0.05) in plasma cortisol concentration from baseline at 5, 6, and 8 hours after induction. A comparison of plasma cortisol concentrations determined at 2, 3, 4, 5, and 6 hours after induction with thiopental or etomidate revealed a higher (P less than 0.05) concentration in dogs given thiopental. The disposition of etomidate was best described by a 2-compartment model, with a redistribution half-life of 0.12 +/- 0.04 minute and a terminal half-life of 1.70 +/- 0.27 minute. Plasma cortisol concentrations did not correlate with plasma etomidate concentrations. We conclude that, compared with thiopental, a single bolus injection of etomidate reduces the adrenocortical response to anesthesia and surgery from 2 to 6 hours after induction. Because cortisol concentrations were significantly higher than baseline, and because cardiopulmonary function is maintained after a single bolus injection of etomidate, it can be considered a safe induction agent in dogs.

Adrenal Cortex↗

PubMed1985

Malignant hyperthermia: is etomidate safe?

The safety of etomidate for induction of anesthesia in malignant hyperthermia-susceptible (MHS) pigs was evaluated in a two-phase experiment. Two litters of Purebred Poland China pigs, one MHS (n = 4) and the other malignant hyperthermia-resistant (MHR) (n = 4) were used. Phase I compared MHS vs MHR animals in terms of cardiovascular, metabolic, and skeletal muscle rigidity responses to etomidate and fentanyl anesthesia and to a subsequent malignant hyperthermia (MH) challenge with halothane-succinylcholine. When three of the four criteria for the diagnosis of MH occurred (rigidity, tachycardia, or increases in temperature or end-tidal CO2) in an animal, phase I was terminated. In phase II, only the MHS animals were used and experimental procedures were as in phase I except thiopental replaced etomidate. In phase I, evidence was inadequate to support the diagnosis of MH based upon responses of MHS pigs to the infusion of etomidate even though the infusion of etomidate in MHS pigs was associated with statistically significant increases in body temperature and plasma lactate levels above those observed in MHR pigs. Heart rate and bicarbonate levels were lower in MHS than in MHR pigs during etomidate infusion. With discontinuation of etomidate and a subsequent challenge with halothane-succinylcholine, all four pigs developed the MH syndrome within 15-30 min. Thiopental replacement of etomidate in the phase II experiment resulted in a twofold greater time (45-75 min) for halothane-succinylcholine to trigger MH in the susceptible pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

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