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PubMed1998

The effect of etomidate induction on plasma cortisol levels in children undergoing cardiac surgery.

OBJECTIVE: To investigate the effect of a single induction dose of etomidate on plasma cortisol and adrenocorticotrophic hormone (ACTH) levels in pediatric patients with congenital heart disease. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Thirty children undergoing cardiopulmonary bypass. INTERVENTIONS: Patients were randomly allocated into two groups to receive etomidate, 0.3 mg/kg, and fentanyl, 1 microg/kg, or ketamine, 1 mg/kg, and fentanyl, 1 microg/kg intravenously, for anesthesia induction. Anesthesia was maintained with 50% nitrous oxide and 0.5% isoflurane in oxygen. Plasma cortisol and ACTH levels were measured on five occasions: preoperatively, after induction of anesthesia, after cross-clamping, at the end of surgery, and 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Plasma cortisol levels of the etomidate group decreased with anesthesia induction and remained significantly low during cardiopulmonary bypass, at the end of operation, and 24 hours postoperatively. Plasma cortisol levels of the etomidate group after the anesthesia induction, during cardiopulmonary bypass, and at the end of the operation were significantly lower than the ketamine group. CONCLUSION: These results show that etomidate is a suitable agent for suppressing the increase in cortisol levels associated with the stress response caused by cardiopulmonary bypass in children with congenital heart defects, and can be used safely.

Adrenocorticotropic Hormone↗
PubMed2006

Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels.

To locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABAA receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia.

Allosteric Regulation↗
PubMed1999

Relationship between etomidate plasma concentration and EEG effect in the rat.

PURPOSE: The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. METHODS: Etomidate was infused (50 mg/kg/h) in chronically instrumented rats (n=6) until isoelectric periods of 5 s or longer were observed in the electroencephalogram (EEG). The EEG was continuously recorded during the experiment and frequent arterial blood samples were taken for determination of etomidate plasma concentrations. The changes observed in the raw EEG signal were quantified using aperiodic analysis in the 2.5-7.5 Hz frequency band. The return of the righting reflex was used as another parameter of anesthesia. RESULTS: A mean dose of 8.58+/-0.41 mg/kg needed to be infused to reach the end point of 5 s isoelectric EEG. The plasma concentration time profiles were most adequately fitted using a three-exponential model. Systemic clearance, volume of distribution at steady-state and elimination half-life averaged 93+/-6 ml/min/kg, 4.03+/-0.24 l/kg and 59.4+/-10.7 min respectively. The EEG effect-plasma concentration relationship was biphasic exhibiting profound hysteresis. Semi-parametric minimization of this hysteresis revealed an equilibration half-life of 2.65+/-0.15 min, and the biphasic effect-concentration relationship was characterized nonparametrically by descriptors. The effect-site concentration at the return of the righting reflex was 0.44+/-0.03 microg/ml. CONCLUSIONS: The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5-7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.

Anesthetics, Intravenous↗
PubMed2001

Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgery.

BACKGROUND: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. METHODS: Platelet function was determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20 microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. RESULTS: In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200 microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%, respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. CONCLUSIONS: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders.

Aged↗
PubMed2003

Pretreatment with sufentanil reduces myoclonus after etomidate.

BACKGROUND: Myoclonic movements are a common problem during the induction of general anesthesia with etomidate. We investigated the influence of pretreatment with the opioid sufentanil on the incidence of etomidate-induced myoclonus. METHODS: Forty female patients (ASA physical status I-III) were randomly assigned to receive double-blinded either 0.3 micro g kg-1 of sufentanil or placebo 150 s before the induction of sleep with 0.3 mg kg-1 of etomidate. The patients were observed for any myoclonic movement. Grade of dizziness, breathing frequency, non-invasive blood pressure and heart rate were measured during the study period. RESULTS: None of the 20 patients receiving sufentanil had myoclonic movements after the administration of etomidate, whereas 16 patients in the placebo group (80%) experienced such movements (P<0.01). No cases of apnoea before induction of sleep were seen in the sufentanil group. CONCLUSION: Sufentanil 0.3 micro g kg-1 is an effective and safe drug to reduce myoclonus after etomidate without causing any harmful side-effect.

Adult↗
PubMed1998

Evaluation of intubating conditions with rocuronium and either propofol or etomidate for rapid sequence induction.

We have assessed the effect of two induction agents on tracheal intubating conditions after rocuronium 0.6 mg.kg-1 in unpremedicated patients undergoing simulated rapid sequence induction. Following pre-oxygenation, anaesthesia was induced with propofol up to 2.5 mg.kg-1 (n = 35) or etomidate 0.3 mg.kg-1 (n = 36), and further increments as required. After loss of verbal contact, cricoid pressure was applied and rocuronium was injected. Laryngoscopy was performed at 45 s and intubation attempted at 60 s after rocuronium had been given. Ninety-four per cent of patients in the propofol group had clinically acceptable (good or excellent) intubating conditions compared to only 75% in the etomidate group (p = 0.025). Owing to coughing, one patient in the etomidate group could not be intubated on the first attempt. A greater pressor response also followed intubation after induction with etomidate. We conclude that etomidate and rocuronium alone cannot be recommended for intubation at 60 s under rapid sequence induction conditions.

Adolescent↗
PubMed2003

Etomidate vs. thiopentone in electroconvulsive therapy. An interdisciplinary challenge for anesthesiology and psychiatry.

The choice of anesthetic for electroconvulsive therapy is based on the anesthetic requirements to be met and on the agent's impact on the seizure threshold. Thus, the non-barbiturate anesthesia etomidate revealed properties to enhance the seizure duration. Even though precisely this feature makes etomidate so valuable, little research has been done on the use of etomidate in ECT. The aim of the present study was to compare the barbiturate anesthesia thiopentone with etomidate, with the focus of attention being the quality of seizure. In 13 patients, the paradigm of a single intra-individual crossover anesthesia during maintenance ECT was selected. The excitatory effects and the electroencephalographic changes were described. Furthermore, significant differences in motor seizure duration (26.69 sec +/- 9.7 vs. 35.92 sec +/- 9.2; p < 0.007) and EEG seizure duration (39 sec +/- 14.1 sec vs. 61 sec +/- 22.2 sec; p < 0.0009) were observed. Our results confirm previous findings and reveal that after etomidate the quality of seizure can be improved not only in terms of duration. The growing knowledge of the mode of action of anesthetics/hypnotics from an anesthesiological point of view and the better understanding of subcortical and cortical mechanisms, with particular consideration of the motor seizure threshold, facilitate a differentiated choice of the narcotic and the optimization of short anesthesia in the course of electroconvulsive therapy.

Adult↗
PubMed1996

[Etomidate versus propofol for anesthesia in ambulatory cardioversion].

OBJECTIVE: This study compared the two short-acting intravenous anaesthetic agents, etomidate in lipid emulsion and propofol, for anaesthesia during elective outpatient cardioversion. METHODS: After institutional approval and informed consent, 40 patients (ASA II/III) scheduled for cardioversion were studied. Patients with a left ventricular ejection fraction < 30% were excluded. The anti-arrhythmic medication was not discontinued, and no patient was given pharmacological premedication. Anaesthesia was induced either with etomidate (in lipid emulsion) 0.25 mg/kg or propofol 1.5 mg/kg. Both agents were administered over 30 seconds. Subsequent increments were given until the patients no longer followed verbal commands and the lid reflex was absent. Patients were allowed to breathe 40% oxygen via face mask. Artificial ventilation was performed if a patient became apnoeic for more than 20 seconds. The blood pressure was monitored continuously with the Finapres noninvasive blood pressure monitor, and the heart rate was recorded simultaneously. All data were collected electronically. The duration of anaesthesia was taken as the period from the start of induction until the opening of the eyes on command. For assessment of recovery from anaesthesia, patients were asked to perform a series of psychomotor tests. RESULTS: The two groups were similar in their demographic and haemodynamic baseline data. In both groups, a significant decrease in blood pressure occurred 120 seconds after anaesthesia induction, which was due to the performance of the cardioversion. Five minutes after induction, the blood pressure returned to baseline in the etomidate group, while it remained below baseline in the propofol group. Propofol caused a significant decrease in heart rate. Significantly more patients needed artificial ventilation after propofol administration because of apnoea. Involuntary muscle movements occurred only in patients receiving etomidate. The immediate emergence from anaesthesia was faster after propofol. However, 15 minutes after awakening there was no difference in psychomotor skills between the two groups. No residual psychomotor impairment was evident 60 minutes after anaesthesia in any patient. All patients were discharged four hours after the cardioversion. CONCLUSIONS: Because the recovery characteristics were similar in both groups, the occurrence of side effects may be a major factor when choosing between etomidate and propofol for outpatient cardioversion.

Adult↗
PubMed1997

The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.

The gamma-aminobutyric acid type A (GABAA) receptor is a transmitter-gated ion channel mediating the majority of fast inhibitory synaptic transmission within the brain. The receptor is a pentameric assembly of subunits drawn from multiple classes (alpha1-6, beta1-3, gamma1-3, delta1, and epsilon1). Positive allosteric modulation of GABAA receptor activity by general anesthetics represents one logical mechanism for central nervous system depression. The ability of the intravenous general anesthetic etomidate to modulate and activate GABAA receptors is uniquely dependent upon the beta subunit subtype present within the receptor. Receptors containing beta2- or beta3-, but not beta1 subunits, are highly sensitive to the agent. Here, chimeric beta1/beta2 subunits coexpressed in Xenopus laevis oocytes with human alpha6 and gamma2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate. The mutation of an amino acid (Asn-289) present within the channel domain of the beta3 subunit to Ser (the homologous residue in beta1), strongly suppressed the GABA-modulatory and GABA-mimetic effects of etomidate. The replacement of the beta1 subunit Ser-290 by Asn produced the converse effect. When applied intracellularly to mouse L(tk-) cells stably expressing the alpha6beta3gamma2 subunit combination, etomidate was inert. Hence, the effects of a clinically utilized general anesthetic upon a physiologically relevant target protein are dramatically influenced by a single amino acid. Together with the lack of effect of intracellular etomidate, the data argue against a unitary, lipid-based theory of anesthesia.

Amino Acids↗
PubMedDate not supplied

The use of etomidate for prehospital rapid-sequence intubation.

Prehospital hypoxia and hypotension increase morbidity and mortality in head-injured patients. Etomidate is a sedative agent with increasing use for emergent rapid-sequence intubation (RSI) because of its favorable hemodynamic profile. This prospective, observational study documents the authors' preliminary experience with etomidate as part of an aeromedical RSI protocol. Major trauma victims received etomidate 0.1 to 0.3 mg/kg intravenously (IV) before administration of a neuromuscular-blocking agent. After confirmation of endotracheal tube position, 1 to 2 mg midazolam IV was administered. The main outcome measure was systolic blood pressure (SBP) before and after the RSI procedure and the incidence of hypotension after RSI; individual patient plots of SBP versus time were also included for graphic analysis. An improvement in SBP after RSI with etomidate was observed (123 mm Hg to 136 mm Hg, p = 0.011) with a 9% incidence of hypotension, defined as a decrease in SBP to 90 mm Hg or less. Graphic analysis of individual SBP-time plots reveals hemodynamic stability, especially in patients with lower initial SBP values. These data suggest that the use of etomidate as part of a prehospital RSI protocol is associated with hemodynamic stability and a low incidence of hypotension.

Adolescent↗
PubMed1979

Comparison of etomidate in combination with fentanyl or diazepam, with thiopentone as an induction agent for general anaesthesia.

In 104 premedicated patients undergoing general surgery, anaesthesia was induced either with etomidate 0.3 mg kg-1 preceded by fentanyl 1.25 or 2.5 microgram kg-1 i.v.or diazepam 0.0625 or 0.125 mg kg-1 i.v., or with thiopentone preceded by fentanyl 1.25 microgram kg-1 i.v. Despite the use of fentanyl or diazepam, the frequency of pain on injection in patients receiving etomidate was between 32% and 53%, being rated as severe in 5-20% of patients. No pain was experienced by patients receiving thiopentone. The frequency of involuntary movement was 15-35% with etomidate and 15% with thiopentone. The frequency of both pain and involuntary muscle movements was least when fentanyl 2.5 microgram kg-1 preceded the administration of etomidate. There was no significant relationship between the pain and muscle movement; three of 10 patients given etomidate into a central vein had such movements.

Adult↗
PubMed1992

Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum.

We have measured concentrations of etomidate and thiopentone in maternal plasma, umbilical venous plasma and colostrum after induction of anaesthesia in 40 patients undergoing Caesarean section. Mean plasma etomidate concentration declined rapidly (1242.0 ng ml-1 at 5 min, 434.0 ng ml-1 at 15 min, 64.2 ng ml-1 at 30 min, 7.0 ng ml-1 at 60 min and undetectable 2 h after the injection). Mean plasma concentrations of thiopentone declined more slowly (6.09 micrograms ml-1 at 5 min, 2.64 micrograms ml-1 at 2 h, 1.35 micrograms ml-1 at 4 h, 0.86 microgram ml-1 at 9 h and 0.59 micrograms ml-1 at 12 h). Mean umbilical venous thiopentone concentration was 4.72 micrograms ml-1, whereas the thiopentone concentration in the maternal sample at 5 min was 6.09 micrograms ml-1, giving an umbilical:maternal vein ratio of 1:1.3. Mean umbilical etomidate concentration was 51.7 ng ml-1 and the corresponding maternal vein sample (5 min) was 1242.0 ng ml-1 (P < 0.001), giving an umbilical:maternal vein ratio of 1:24. Mean concentrations of thiopentone in colostrum were 1.98 micrograms ml-1 at 30 min, 0.91 microgram ml-1 at 4 h and 0.59 microgram ml-1 at 9 h, colostrum:plasma ratios at 4 h and 9 h being 0.67 and 0.68, respectively. Mean concentrations of etomidate in colostrum were 79.3 ng ml-1 at 30 min and 16.3 ng ml-1 at 2 h, being undetectable at 4 h. The colostrum:plasma etomidate concentration ratio was 1.2 at 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Etomidate reduces ischemia-induced glutamate release in the hippocampus in rats subjected to incomplete forebrain ischemia.

Etomidate and thiopental reduce ischemic neuronal injury but the mechanism by which they do so is not clear. Ischemia-induced release of the excitatory neurotransmitters glutamate and glycine is thought to play a major role in the pathophysiology of ischemic injury. To determine how etomidate and thiopental modulate excitatory transmitter release, their effect on the release of glycine and glutamate during ischemia was evaluated by microdialysis in the hippocampus and cortex of rats. Three groups of Wistar-Kyoto rats (n = 5/group) were studied. In the etomidate and thiopental groups, electroencephalogram (EEG) burst-suppression was achieved and maintained by a continuous infusion of either etomidate (0.6 mg.kg-1.min-1) or thiopental (3 mg.kg-1.min-1) 40 min prior to ischemia. Halothane anesthetized (1 minimum alveolar anesthetic concentration [MAC]) rats served as controls. Ischemia was induced in all three groups by bilateral carotid artery occlusion with simultaneous hypotension to 35 mm Hg for 10 min. Pericranial temperature was controlled at 38 degrees C. Dialysate was collected before, during, and after ischemia. The levels of glutamate and glycine in the dialysate were measured by high-performance liquid chromatography. Within the hippocampus, both glutamate and glycine levels increased significantly in the thiopental and control groups. By contrast, in the etomidate group, glutamate and glycine levels did not increase during ischemia, and peak levels were significantly less than those in the thiopental group. Peak glutamate levels in the thiopental group were significantly larger than in the control group, whereas the peak glycine levels were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects of etomidate on hormonal responses to surgical stress.

The hormonal responses to surgical stress were examined in 10 patients scheduled for elective gynecologic laparotomy. Anesthesia was induced with either thiopental, 4 mg/kg, or etomidate, 0.35 mg/kg, and maintained with nitrous oxide and enflurane. Plasma cortisol, aldosterone, ACTH, and catecholamines were measured during the 24 h after the induction of anesthesia. The catecholamine responses of the patients whose anesthesia was induced with either drug were similar. The plasma ACTH concentrations for the etomidate group were greater than baseline values and the concentrations in the thiopental group (P less than 0.05) in the fourth and fifth hours. In the patients receiving thiopental, both cortisol and aldosterone concentrations were greater than the baseline value (P less than 0.05) in the second to fourth hours after induction. In the etomidate group, the plasma concentrations of cortisol were less than baseline values (P less than 0.05) in the first and second hours after induction of anesthesia and both cortisol and aldosterone were lower than those in the thiopental group (P less than 0.05) in the half to fourth hours after induction. These results confirm an earlier report of the suppression of cortisol after etomidate administration and, because aldosterone also was suppressed, suggests that etomidate exerts its effect by inhibiting early stages of steroidogenesis in the adrenal cortex.

Adrenocorticotropic Hormone↗
PubMed1987

Etomidate reversibly depresses human neutrophil chemiluminescence.

The effect of etomidate on human neutrophil chemiluminescence was evaluated. The latter is an index of oxygen free-radical generation, which is an important bactericidal mechanism. Five drug concentrations representing the free plasma concentrations ranging from deep anesthesia (0.5 microgram/ml) to the plasma level that may be found approximately 1 h after an etomidate anesthetic (0.0156 microgram/ml) were studied. The importance of the duration of drug incubation was assessed by incubating the neutrophils with the drug concentrations for 10, 20, 30, 40, or 50 min before stimulation. The reversibility of any depression in chemiluminescence was assessed by gently washing the cells twice after incubation and then stimulating them. The two higher etomidate concentrations (0.5 microgram/ml and 0.125 microgram/ml) produced reductions in chemiluminescence of 43% and 35%, respectively (P less than 0.05). The reductions in activity only occurred when the cells had been incubated with etomidate for 50 min and were completely reversed by washing. These results show that clinically relevant concentrations of etomidate will reversibly depress neutrophil chemiluminescence in vitro when the cells are exposed to the drug for more than 50 min.

Dose-Response Relationship, Drug↗
PubMed1996

Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle.

BACKGROUND: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. METHODS: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. RESULTS: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC50s (mean +/- SEM; microM) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. CONCLUSIONS: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol, midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation.

Anesthetics, Intravenous↗
PubMed1998

Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid type A receptors and animals.

BACKGROUND: The intravenous anesthetic etomidate is optically active and exists in two mirror-image enantiomeric forms. However, although the R(+) isomer is used as a clinical anesthetic, quantitative information on the relative potencies of the R(+) and S(-) isomers is lacking. These data could be used to test the relevance of putative molecular targets. METHODS: The anesthetic concentrations for a half-maximal effect (EC50) needed to induce a loss of righting reflex in tadpoles (Rana temporaria) were determined for both etomidate enantiomers. The effects of the isomers on gamma-aminobutyric acid (GABA)-induced currents in stably transfected mouse fibroblast cells was also investigated using the patch-clamp technique. In addition, the effects of the isomers on a lipid chain-melting phase transition were determined. RESULTS: The EC50 concentrations for general anesthesia for the R(+) and S(-) isomers were 3.4 +/- 0.1 microM and 57 +/- 1 microM, with slopes of n = 1.9 +/- 0.1 and n = 2.9 +/- 0.2, respectively. The R(+) isomer was also much more effective than the S(-) isomer at potentiating GABA-induced currents, although the degree of stereoselectivity varied with anesthetic concentration. R(+) etomidate potentiated the GABA-induced currents by increasing the apparent affinity of GABA for its receptor. Both isomers were equally effective at disrupting lipid bilayers. CONCLUSIONS: These data are consistent with the idea that the GABA(A) receptor plays a central role in the actions of etomidate. Etomidate exerts its effects on the receptor by binding directly to a specific site or sites on the protein and allosterically enhancing the apparent affinity of GABA for its receptor.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Inhibitory effects of etomidate and ketamine on endothelium-dependent relaxation in canine pulmonary artery.

BACKGROUND: The authors recently demonstrated that acetylcholine-induced pulmonary vasorelaxation had two primary components, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The goal was to investigate the effects of etomidate and ketamine on the NO- and EDHF-mediated components of pulmonary vasorelaxation in response to acetylcholine, bradykinin, and the calcium ionophore, A23187. METHODS: Canine pulmonary arterial rings with an intact endothelium were suspended in organ chambers for isometric tension recording. The effects of etomidate and ketamine (10(-5) M and 10(-4) M) on vasorelaxation responses to acetylcholine, bradykinin, and A23187 were assessed in phenylephrine-contracted rings. The NO- and EDHF-mediated components of relaxation were assessed using a NO synthase inhibitor (N-nitro-L-arginine methylester [L-NAME]: 10(-4) M) and a Ca2+-activated potassium channel inhibitor (tetrabutylammonium hydrogen sulfate [TBA]: 10(-3) M) in rings pretreated with a cyclooxygenase inhibitor (ibuprofen: 10(-5) M). Intracellular calcium concentration ([Ca2+]i) was measured in cultured bovine pulmonary artery endothelial cells loaded with acetoxylmethyl ester of fura-2. RESULTS: Etomidate and ketamine attenuated pulmonary vasorelaxation in response to acetylcholine and bradykinin, whereas they had no effect on the response to A23187. The relaxant responses to acetylcholine and bradykinin were attenuated by L-NAME or TBA alone and were abolished by combined inhibition in rings pretreated with ibuprofen. Etomidate and ketamine further attenuated both L-NAME-resistant and TBA-resistant relaxation. These anesthetics also inhibited increases in endothelial [Ca2+]i in response to bradykinin, but not A23187. CONCLUSION: These results indicate that etomidate and ketamine attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both NO- and EDHF-mediated components. Moreover, our results suggest that these anesthetics do not directly suppress NO or EDHF activity, but rather inhibit the endothelial [Ca2+]i transient in response to receptor activation.

Acetylcholine↗