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PubMed1984

Adrenocortical suppression by a single induction dose of etomidate.

In a prospective controlled trial we studied the effect of a single induction dose of etomidate or thiopentone on the adrenocortical function in 29 patients undergoing elective surgery. During anesthesia and in the recovery period serum cortisol rose significantly in the thiopentone group only. In contrast, after induction with etomidate serum cortisol decreased and remained below the starting values throughout the study period (5 h). The differences between the two groups were significant at 120, 150, 180, 210, and 240 min after induction (p less than 0.05). Moreover, plasma ACTH increased significantly more after etomidate than after thiopentone (p less than 0.02) indicating relative unresponsiveness of the adrenal cortex to stimulation by endogenous ACTH. We conclude that a single i.v. bolus of etomidate (0.26 mg/kg) leads to significant adrenal insufficiency in patients without preexisting endocrine abnormalities.

Adolescent↗
PubMed1986

Missing effect of etomidate on testosterone secretion in man.

We studied the effect of low dosage (0.26 mg/kg as a single induction dose) and high dosage (30 mg/h for long term sedation) etomidate on serum testosterone and serum luteinizing hormone (LH) concentrations in males. During high dose etomidate we found inhibition of both 11 beta-hydroxylase and cholesterol-side-chain cleavage enzyme with unresponsiveness of progesterone, 17 alpha OH-progesterone and 11-deoxycortisol to stimulation with ACTH. However, neither high dosage nor low dosage etomidate had any influence on serum testosterone or LH concentrations. We conclude that, in contrast to other substituted imidazole derivatives, etomidate does not interfere with testicular testosterone synthesis. It therefore may be possible to find clinically useful imidazole derivatives with endocrine actions confined to either the adrenals or the testes.

17-alpha-Hydroxyprogesterone↗
PubMed1978

Further experience with etomidate.

We report our further anaesthetic experience with Etomidate in 100 patients. The cardiovascular and respiratory systems were not significantly affected but intraocular pressure was reduced. The occurrence of pain during injection of Etomidate was unaffected by analgesic premedication but was reduced by using a solution buffered to a higher pH and by choosing a big vein for injection. The myoclonic movements often seen with Etomidate anaesthesia were transient and have so far not created any major problem; they were reduced by a slower speed of injection but unaffected by diazepam premedication or pretreatment with low dose of a non-depolarizing muscle relaxant (pancuronium). Etomidate is a satisfactory alternative to thiopentone in situations where depression of the cardiovascular and respiratory systems are undersirable or where barbiturates are otherwise contraindicated and is a usefull addition to the induction agents in our anaesthetic practice.

Adolescent↗
PubMed1977

Effect of etomidate on intra-ocular pressure.

Etomidate, a new short-acting non-barbiturate hypnotic, was administered to 40 patients between the ages of 12 years and 65 years. Intra-ocular pressure was measured before and after etomidate injection using a Schiotz tonometer. A significant reduction of intra-ocular pressure was found to follow etomidate injection in spite of the often associated myoclonic movements. The mechanism of reduction of intra-ocular pressure has not been determined in this study. It is suggested that etomidate will be a useful intravenous induction agent where elevation of intra-ocular pressure is undesirable.

Adolescent↗
PubMed1977

Clinical trial of etomidate. Preliminary observations on a new non-barbiturate induction agent.

This is a preliminary report of our clinical experience with etomidate, a new intravenous non-barbiturate anaesthetic agent. Thirty-two patients undergoing minor surgical procedures were anaesthetized, induction being with etomidate 0.3 mg/kg body weight. Induction was fast and smooth. Twenty-eight per cent of the patients complained of pain at site of injection but the pain disappeared on flushing with water for injection. Following etomidate injection, 37.5 per cent of patients developed myoclonic movements which were usually mild and self-limiting. We were impressed by the relative stability of the cardiovascular and respiratory systems. Etomidate looks promising and further work is in progress on other aspects of this drug.

Anesthesia, Intravenous↗
PubMed1998

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs.

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.

Anesthetics↗
PubMed2003

Propofol - not thiopental or etomidate - with remifentanil provides adequate intubating conditions in the absence of neuromuscular blockade.

PURPOSE: Administration of remifentanil followed by propofol provides adequate conditions for tracheal intubation without muscle relaxants. Other hypnotic drugs have not been thoroughly investigated in this regard. Intubating conditions with remifentanil followed by propofol, thiopentone or etomidate are compared in this study. METHODS: In a randomized, double-blind study 45 healthy males were assigned to one of three groups (n = 15). After iv atropine, remifentanil 3 microg x kg(-1) were injected over 90 sec followed by propofol 2 mg x kg(-1) (Group I), thiopentone 6 mg x kg(-1) (Group II) or etomidate 0.3 mg x kg(-1) (Group III). Ninety seconds after the administration of the hypnotic agent, laryngoscopy and intubation were attempted. Intubating conditions were assessed as excellent, good or poor on the basis of ease of ventilation, jaw relaxation, position of the vocal cords, and patient response to intubation and slow inflation of the endotracheal tube cuff. RESULTS: One patient in Group I, three patients in Group II and five patients in Group III could not be intubated on the first attempt. Clinically acceptable intubating conditions were observed in 93.3%, 66.7%, 40.0% of patients in Groups I, II and III, respectively. Overall conditions at intubation were significantly (P < 0.05) better, and the frequency of excellent conditions was significantly (P < 0.05) higher in the propofol group compared with the thiopentone and etomidate groups. No patient was treated for hypotension or bradycardia. CONCLUSION: Propofol 2 mg x kg(-1) was superior to thiopentone 6 mg x kg(-1) and etomidate 0.3 mg x kg(-1) for tracheal intubation when combined with remifentanil 3 microg x kg(-1) and no muscle relaxant.

Adolescent↗
PubMed2006

Profound effects of the general anesthetic etomidate on oxidative phosphorylation without effects on their yield.

We investigated the effects of the general anesthetic Etomidate on oxidative phosphorylation in isolated rat liver mitochondria. The study of each electron transfer site shows that there is an inhibition: mainly at complex I but also, to a lesser extent, at complex III. Moreover, with succinate as substrate, the increase in non-phosphorylating respiration is accompanied by a decrease in DeltaPsi. However, this effect is not due to classical uncoupling of oxidative phosphorylation, since ADP addition at high Etomidate concentrations restores the transmembrane difference of electrical potential. Also, in the same range of Etomidate concentration, the ATP/O ratio is not significantly affected. In conclusion, the main effect of Etomidate is to decrease the oxidative phosphorylation rate without changing yield. The H(+) leak which appears under non-phosphorylating conditions becomes negligible in physiological conditions.

Adenosine Diphosphate↗
PubMed2000

Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus.

The goal of this study was to determine whether etomidate has protective effect against kainic acid (KA)-induced neurotoxicity. Administration of etomidate (20 mg/kg i.p.) was performed in sequence, first being just 1 h after KA (10 mg/kg i.p.) injection, then three times at 1-h intervals. Neuronal damages in hippocampus were evaluated by using the acid fuchsin stain to detect cell death and the heat shock protein-70 (HSP-70) induction as an index of cell injury at 24 h after the administration of KA. HSP-70 induction and acid fuchsin positive neurons were increased in CA1 and CA3 regions of hippocampus after KA injection but significantly decreased by etomidate-injection. These results suggest that the etomidate hold potential effect on the protection of neurons against KA-induced neurotoxicity.

Animals↗
PubMed1998

Distinct structural requirements for the direct and indirect actions of the anaesthetic etomidate at GABA(A) receptors.

1. The intravenous anaesthetic etomidate augments GABA-gated chloride currents (indirect action) and, at higher concentrations, evokes chloride currents in the absence of GABA (direct action). 2. In order to identify amino acid residues essential for these actions, site directed mutagenesis was performed on the beta3 subunit. 3. Mutation of an asparagine to a serine residue at position 290 dramatically reduced both etomidate-induced chloride currents and its ability to enhance [3H]flunitrazepam binding in HEK293 cells expressing alpha1beta3gamma2 recombinant GABA(A) receptors. 4. In contrast, the indirect effect of etomidate was retained, though its potency was reduced. 5. These findings indicate that there are distinct requirements for these dual actions of etomidate at GABA(A) receptors.

Anesthetics, Intravenous↗
PubMed1990

[Comparison of the pharmacokinetics of etomidate in children and in adults].

Etomidate pharmacokinetics were compared in 12 children (P group) (age 7 to 13 years, weight 22 to 48 kg) and in 4 adult women (A group) (age 28 to 52 years, weight 46 to 72 kg), A.S.A. 1, undergoing minor non abdominal surgery. They were unpremedicated and anaesthetized with alfentanil 100 micrograms.kg-1, and isoflurane 2 vol % in N2O/O2 (1/1). Etomidate was administered as a bolus: 0.3 mg.kg-1 in adults and 0.4 mg.kg-1 in children. Venous plasma samples were frozen until further etomidate assay with a HPLC technique. In all patients but two children, data were fitted to a three rather than a two compartment model. Differences between groups (mean +/- SD values) included Vdc (P: 0.66 +/- 0.31 l.kg-1; A: 0.27 +/- 0.15 l.kg-1; p less than 0.01), t1/2 pi (P: 5.4 +/- 2.9 min; A: 2.7 +/- 5.7 min; p less than 0.05) and plasma clearance (P: 17.2 +/- 4.6 ml.kg-1.min-1; A: 10.9 +/- 3.3 ml.kg-1.min-1; p less than 0.05). No statistical difference was found between A and P groups for the following parameters: t1/2 alpha (37.1 +/- 12.0 min vs 26.8 + 15.1 min), t1/2 beta (260 +/- 99 min vs 175 +/- 99 min), Vdss (2.5 +/- 1.11.kg-1 vs 2.8 +/- 1.61.kg-1), Vd beta (4.1 +/- 2.41.kg-1 vs 4.0 +/- 2.21.kg-1), and MRT (228 +/- 80 min vs 172 +/- 101 min). No age-related difference was found inside P group with regard to pharmacokinetic parameters. In conclusion, a 30% higher etomidate bolus dosage is required in children than in adults to achieve similar plasma concentrations, due to a higher volume of the initial compartment. In comparison to adults the higher clearance suggests higher maintenance dose requirements in children.

Adult↗
PubMed1991

[Pharmacokinetics of continuous infusion of etomidate in cirrhotic patients].

The pharmacokinetics of etomidate were studied in 9 control subjects (with normal liver function) and in 5 patients with cirrhosis scheduled for gastro-intestinal surgery. Anaesthetic induction included an initial bolus of etomidate 0.3 mg.kg-1, together with fentanyl 2 micrograms.kg-1, and pancuronium 60 micrograms.kg-1. An etomidate infusion was then started according to one of two following schemes: a (0.03 mg.kg-1.min-1 for 10 min, and then 0.01 mg.kg-1.min-1), or B (0.1 mg.kg-1.min-1 for 10 min, followed by 0.02 mg.kg-1.min-1 for a further 110 min, and 0.01 mg.kg-1.min-1 thereafter). Plasma concentrations of etomidate were determined at regular intervals throughout anaesthesia, and up to four hours afterwards, using inverse phase high pressure liquid chromatography. The infusion was given for 273 +/- 87 min in controls, and for 259 +/- 56 min in the cirrhotic group. Scheme A, only used in 3 controls and 1 cirrhotic in a preliminary study, resulted in very low plasma concentrations: 0.2 to 0.4 micrograms.ml-1. Those measured during the apparent plateau phase (steady state) of infusion protocol B were close to predicted values (0.5 to 0.6 micrograms.ml-1) in controls, whereas higher concentrations (approximately 1.5 micrograms.ml-1) were reached in cirrhotic patients. For all the patients the time interval to spontaneous recovery was 41 +/- 27 min; plasma levels were then 0.199 +/- 0.092 micrograms.ml-1. There were significant alterations in pharmacokinetic parameters in the cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Histamine release after injection of benzodiazepines and of etomidate. A problem associated with the solvent propylene glycol.

Many drugs, especially when given in rapid sequence can cause histamine release. Ten healthy volunteers were premedicated with diazepam 10 mg.70 kg-1 i.v. and lormetazepam 1 mg.70 kg-1 i.v., respectively, 30 min prior to etomidate 0.15 mg.kg-1 i.v. in a single-blind, crossover study. The benzodiazepine lormetazepam and the hypnotic etomidate caused distinct increases in histamine plasma levels in two subjects. Maximal histamine levels after lormetazepam were 2.05 and 2.7 ng.ml-1, and after etomidate 1.85 and 3.2 ng.ml-1, respectively. Both drugs are solved in propylene glycol, a solvent that conveys very high osmolality (lormetazepam 6,750 mosm.kg-1, etomidate 4,900 mosm.kg-1). Clinical symptoms, like tachycardia, hypotension or allergic reactions, associated with similar histamine levels were not seen in either case. This limited histamine release appears to be caused by osmotic damage of tissue and blood cells.

Adult↗
PubMed1998

Induction of anesthesia by titration of eltanolone compared with thiopental and etomidate for coronary artery bypass grafting.

STUDY OBJECTIVE: To evaluate whether induction of anesthesia with eltanolone in coronary artery bypass graft (CABG) patients is associated with greater hemodynamic stability than either thiopental sodium or etomidate. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 75 ASA physical status III and IV patients scheduled for elective CABG over 18 years of age, with left ventricular ejection fraction over 30%. INTERVENTIONS: The participants were prospectively randomized into three groups, each group consisting of 25 patients. Anesthesia was induced by titration of either eltanolone, thiopental sodium, or etomidate. The end point was "loss of verbal contact." MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were recorded in the awake state, 2 minutes after induction, after administration of fentanyl 0.01 mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia, cardiac index (CI) decreased from 2.6 +/- 0.5 to 2.2 +/- 0.5 Lxmin-1xm-2 in the eltanolone group and remained at this value throughout the study period in contrast to the control groups. After fentanyl was given, mean arterial pressure was significantly lower in the case of eltanolone (69 +/- 15 mmHg) compared with thiopental (81 +/- 19 mmHg) and etomidate (84 +/- 18 mmHg). Mean arterial pressure remained significantly lower at the points of measurement after intubation. Two minutes after intubation, CI was likewise significantly lower in the eltanolone group (2.2 +/- 0.4 Lxmin-1xm-2) compared with the thiopental group (2.7 +/- 0.7 Lxmin-1xm-2). CONCLUSIONS: Eltanolone produces more hemodynamic depression compared with etomidate and thiopental when administered in combination with fentanyl 10 micrograms/kg.

Aged↗
PubMed2001

Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro.

BACKGROUND: Intravenous anaesthetics and sedatives can influence polymorphonuclear cell (PMN) functions. Some of the drugs for sedation and anaesthesia have been alternatively dissolved in lipid solutions containing medium (MCT) and/or long chain (LCT) triglycerides. The in vitro effects of two different diazepam (benzyl-alcohol, LCT/MCT), etomidate (propylene-glycol, LCT/MCT), and propofol (LCT, LCT/MCT) preparations on respiratory burst (RB) and phagocytosis of human PMNs were studied. METHODS: Diazepam (2, 20 microg ml(-1)), etomidate (0.5, 5 microg ml(-1)), and propofol (6, 60 microg ml(-1)) were investigated in clinical and 10-fold concentrations with flow cytometric assays. The RB was measured with the fluorescent dye rhodamine after induction with Escherichia coli or formyl-methionyl-leucylphenylalanine (FMLP) following priming with tumour necrosis factor alpha (TNF-alpha). Phagocytosis of PMNs was carried out in whole blood after incubation with fluorescein-labelled E. coli. RESULTS: LCT-propofol at 60 microg ml(-1) reduced the percentage of PMNs with RB activity after induction with E. coli (52.8+/-20.4) and TNF-alpha/FMLP (10.8+/-5.1)) as well as the percentage of phagocytosing PMNs (48.9+/-19.5) in contrast to LCT/MCT-propofol, which augmented all parameters (85.4+/-10.1, 50.3+/-12.7, 66.5+/-12.5). Also the higher concentrations of LCT/MCT-diluted etomidate and diazepam increased the percentage of RB positive PMNs compared to the alternative compositions. The percentage of phagocytosing PMNs was less reduced with 20 microg ml(-1) LCT/MCT-diazepam (85.2+/-6.9) than with the same concentration of benzyl-alcohol diluted diazepam (68.8+/-12.2) compared to the control. CONCLUSION: The in vitro effects of diazepam, etomidate, and propofol are dependent on the solvent applied. The tested LCT/MCT preparations reduce the inhibitory effects on the bacterial killing capacity of PMNs found after incubation with propyleneglycol, benzyl-alcohol, or LCT preparations, respectively.

Anesthetics, Intravenous↗
PubMed1996

The role of ascorbic acid and xylitol in etomidate-induced adrenocortical suppression in humans.

Etomidate-induced suppression of cortisol biosynthesis is a result of a blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazol radical of etomidate. Since the generation of steroids requires reductive and energy rich equivalents, the present study examined whether supplementation with ascorbic acid or xylitol, a major source of NADPH, could attenuate adrenal suppression by etomidate in human subjects by promoting the turnover rate of 11-beta-hydroxylase. During continuous etomidate/alfentanil anaesthesia for pelviscopic surgery 30 female patients received either Ringer's lactate, xylitol (0.25 g kg-1 h-1) or ascorbic acid (0.5 g h-1) intravenously (i.v.). The plasma concentrations of cortisol, aldosterone and dehydroepiandrosterone (DHEA) were recorded for 5 h after end of surgery and a stimulation with synthetic ACTH was performed. The results showed no evidence of a clinically relevant attenuating effect of ascorbic acid or xylitol on etomidate-induced adrenocortical suppression. However, the observed suppression of cortisol levels was not enough to allow an attenuating affect to be measured.

Adolescent↗
PubMed2001

The influence of fentanyl vs. s-ketamine on intubating conditions during induction of anaesthesia with etomidate and rocuronium.

BACKGROUND AND OBJECTIVE: In the present study, we investigated the combination of etomidate and s-ketamine with regard to its suitability for modified rapid-sequence induction using rocuronium for muscle relaxation. METHODS: In a prospective, randomized and double-blinded study, 90 patients were assigned to one of three groups for induction of anaesthesia in combination with etomidate (0.3 mg kg-1) and muscle relaxation with rocuronium (0.6 mg kg-1). The groups were as follows: (a) control, i.e. placebo; (b) fentanyl, fentanyl (1.5 microg kg-1); (c) ketamine, s-ketamine (0.5 mg kg-1). Tracheal-intubating conditions after 1 min were classified as excellent, good or poor. During the induction of anaesthesia, arterial pressure and heart rate were measured every 60 s. RESULTS: Intubating conditions were best using etomidate and s-ketamine (23 excellent, 7 good, 0 poor) compared with the control (8, 16, 6 respectively) and fentanyl groups (7, 21, 2 respectively) (P < 0.01). While heart rate and arterial pressure remained stable in the control and fentanyl groups during induction, both significantly increased in the ketamine group (P < 0.01). CONCLUSIONS: The combination of etomidate and s-ketamine for anaesthesia induction produces mostly excellent intubating conditions after 60 s using only 0.6 mg kg-1 of rocuronium. This combination of drugs may be a useful alternative, if succinylcholine needs to be avoided, for modified rapid-sequence induction.

Adult↗
PubMed1999

The effect of etomidate on sensory transmission in the dorsal column pathway in the urethane-anaesthetized rat.

The effect of Etomidate, a general anaesthetic, on sensory afferent transmission was measured in the dorsal column pathway in urethane-anaesthetized rats. Extracellular recordings were made of peripherally evoked responses by single cells in the cuneate nucleus, ventroposterolateral nucleus of the thalamus and laminae IV-VI of the primary somatosensory cortex. Cortical mass responses were also recorded. In further experiments, cortical mass responses were evoked antidromically by stimulation in the pyramidal tract. The effect of incremental administration of Etomidate on evoked responses was recorded. These results are compared with the previously reported effects of urethane, a 'conventional' anaesthetic. Etomidate did not alter cuneate or ventroposterolateral thalamic cell responses but it caused a dose-dependent reduction in cortical cell responsiveness. It failed to alter antidromically evoked cortical mass responses. Etomidate differs from the majority of anaesthetics, which act in the thalamus, and appears to cause perturbation at the cortical level.

Anesthesia↗