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PubMed1993

A comparison of propofol and etomidate for cardioversion.

Bolus doses of propofol in patients for cardioversion often produce hypotension and apnea. Etomidate provides cardiovascular stability in these patients, but myoclonus may interfere with electrocardiographic interpretation. This study was designed to demonstrate whether propofol, when given as a low-dose infusion, can attain etomidate's hemodynamic stability without its attendant side effects. Forty consenting patients were randomly assigned to receive either propofol infusion (50 mg/min) for induction of anesthesia followed by a maintenance infusion (100 micrograms.kg-1.min-1) or etomidate (8 mg/min and 20 micrograms.kg-1.min-1). Calculation of loading infusion rates for propofol and etomidate resulted in averages of 0.64 mg.kg-1.min-1 (range, 0.39-1.04) and 0.09 mg.kg-1.min-1 (range, 0.05-0.14), respectively. Induction times (2.2 min) and the times from terminating drug administration to awake states (4.5 min) were similar for each group. Etomidate produced myoclonus in 45% of the patients; otherwise side effects were minimal, with no significant differences between groups. The means of systolic blood pressures in the etomidate group rose a maximum of 15.3 +/- 7.9% (95% confidence), while a modest decrease of 7.2 +/- 7.3% occurred with propofol. Administration of propofol by infusion for cardioversion retains all its beneficial qualities while attenuating its hypotensive effects, making it a suitable choice for these patients with cardiac arrhythmias.

Adult↗
PubMed2003

The effects of propofol and etomidate on airway contractility in chronically hypoxic rats.

UNLABELLED: We investigated the effect of two IV anesthetics, propofol and etomidate, on airway responsiveness in a rat model of chronic hypoxia (CH) in comparison with normoxic rats. CH rats were obtained using a hypobaric chamber (14 days at a barometric pressure of 380 mm Hg). The ability of both anesthetics to relax and prevent agonist-induced contraction was assessed in isolated tracheal rings precontracted with the muscarinic agonist carbachol (CCh) and the depolarizing agent KCl. Cumulative concentrations of both compounds relaxed tracheal rings precontracted with CCh or KCl with a similar amplitude in CH and normoxic rats. In tracheal rings precontracted with CCh, the negative logarithm of anesthetics that reduced the maximal contraction by 30%, i.e., -log half-maximal inhibitory concentration, for propofol and etomidate were 4.10 +/- 0.09 and 4.12 +/- 0.15 in normoxic rats and 4.20 +/- 0.22 and 3.61 +/- 0.19 in CH rats, respectively. At a fixed concentration, propofol (3 x 10(-4) M) or etomidate (10(-4) M) also inhibited CH tracheal rings contraction in response to cumulative concentrations of CCh and KCl. However, in contrast with the equivalent relaxant effect of both anesthetics, etomidate was two-fold less effective than propofol for inhibiting the subsequent contraction to CCh and KCl. These results indicate that propofol and etomidate retain their relaxant properties in CH rat airways by acting on the pharmaco- and electromechanical coupling. IMPLICATIONS: Anesthesia may cause airway constriction or bronchospasm in patients with normal or pathological airways. This study investigated the ability of propofol and etomidate to both reverse precontraction and inhibit contraction of tracheal rings isolated from chronically hypoxic rats.

Algorithms↗
PubMed2005

R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta3 subunit.

A photoactivable diazirine derivative of etomidate, azietomidate, shares many actions of etomidate, including a capacity to abolish the righting reflexes in tadpoles and enhance gamma-aminobutyric acid (GABA)-induced currents. Azietomidate's usefulness in studies of mechanisms of anesthesia depends on the assumption that it shares a site of action with etomidate. Mice bearing an N265M beta3 subunit point mutation in GABA(A) receptors have a markedly decreased sensitivity to loss of righting reflexes induced by etomidate over a range of doses. Accordingly, in the present study we measured the time to recovery of righting reflexes of wild type and mutant mice as a function of dose given as an IV bolus. Analysis of the data for azietomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 10.0 +/- 0.9 min and 3.0 +/- 1.6 min for wild type and mutant mice, respectively (mean +/- sd). A similar analysis for etomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 12.0 +/- 1.3 min and 4.0 +/- 0.7 min for wild type and mutant mice respectively. Thus, at this dose a single mutation, N265M on the beta3 subunit of the GABA(A) receptor, approximately halved the time to recovery of righting reflexes for both etomidate and azietomidate (by 7.6 +/- 1.5 min and 7.2 +/- 1.8 min, respectively), emphasizing the contribution of this residue as a determinant of a behavioral response of azietomidate in mice.

Anesthetics, Intravenous↗
PubMed2005

Magnesium sulfate pretreatment reduces myoclonus after etomidate.

Myoclonic movements and pain on injection are common problems during induction of anesthesia with etomidate. We investigated the influence of pretreatment with magnesium and two doses of ketamine on the incidence of etomidate-induced myoclonus and pain. A prospective double-blind study was performed on 100 ASA physical status I-III patients who were randomized into 4 groups according to the pretreatment drug: ketamine 0.2 mg/kg, ketamine 0.5 mg/kg, magnesium sulfate (Mg) 2.48 mmol, or normal saline. Ninety seconds after the pretreatment, anesthesia was induced with etomidate 0.2 mg/kg. Vecuronium 0.1 mg/kg was used as the muscle relaxant. An anesthesiologist, blinded to group allocation, recorded the myoclonic movements, pain, and sedation on a scale between 0-3. Nineteen of the 25 patients receiving Mg (76%) did not have myoclonic movements after the administration of etomidate, whereas 18 patients (72%) in the ketamine 0.5 mg/kg, 16 patients (64%) in the ketamine 0.2 mg/kg, and 18 patients (72%) in the control group experienced myoclonic movements (P < 0.05). We conclude that Mg 2.48 mmol administered 90 s before the induction of anesthesia with etomidate is effective in reducing the severity of etomidate-induced myoclonic muscle movements and that ketamine does not reduce the incidence of myoclonic movements.

Adult↗
PubMed2006

Etomidate depresses lumbar dorsal horn neuronal responses to noxious thermal stimulation in rats.

Etomidate is a widely used IV anesthetic, but little is known about its analgesic properties, in particular, its effects on spinal cord neuronal responses to noxious stimuli. We hypothesized that etomidate would depress lumbar neuronal responses to noxious heat. Rats (n = 15) were anesthetized with isoflurane (1.2%) and laminectomy was performed to record single unit activity. Lumbar neuronal responses to noxious thermal (52 degrees C, 12 s) stimulation of the hindpaw were recorded before and every 2 min (up to 13 min postinjection) after administration of etomidate. The responses at peak effect of etomidate (as a percentage of the control response) were 63% +/- 16%, 63% +/- 16%, 38% +/- 25%, 36% +/- 30%, and 41% +/- 26% for the 0.125, 0.25, 0.5, 1 and 2 mg/kg doses, respectively. The responses quickly recovered, usually by the 10-min period postinjection. Similar responses were obtained in decerebrate, isoflurane-free rats administered etomidate and in isoflurane-anesthetized rats administered propofol. These data demonstrate that etomidate depresses spinal cord neuronal responses to noxious stimulation and is a possible mechanism by which this drug might produce analgesia.

Action Potentials↗
PubMed1985

Effect of etomidate on cortisol biosynthesis: site of action after induction of anaesthesia.

To determine the site of inhibition of etomidate on cortisol biosynthesis, plasma cortisol, aldosterone, 17 alpha-hydroxyprogesterone, 11-deoxycortisol and ACTH levels were measured in healthy women before and after the administration of a single dose of either 0.20 mg kg-1 etomidate (mean value, n = 10) or 3.15 mg kg-1 thiopental (n = 9) for induction of anaesthesia in a randomized trial. Etomidate produced a smaller increase in plasma cortisol and had a later onset of action than thiopental. Plasma ACTH levels, however, rose higher in the etomidate-induced patients to reach peak levels 6 h after drug administration. In the same group, plasma aldosterone remained below the control levels but still within the normal range, whereas it rose about 2-fold in the thiopental group. Plasma levels of 17 alpha-hydroxyprogesterone and 11 beta-deoxycortisol were hardly modified after thiopental but increased significantly and remained high for 6 h after etomidate injection. This marked rise in precursors together with a blunted and delayed cortisol response to high ACTH levels, and slightly lowered plasma aldosterone concentration indicates a blockage of 11 beta-hydroxylation in adrenal cortisol synthesis after induction of anaesthesia with etomidate.

17-alpha-Hydroxyprogesterone↗
PubMed1976

A comparative study of etomidate and methohexital as induction agents for analgesic anesthesia.

Two hundred current surgical procedures were done in adult patients using neuroleptanalgesia with either methohexital (1 mg/kg) or etomidate induction (0.3 mg/kg) in half of the cases. The cardiovascular function was less altered with etomidate (less occurrence of tachycardia, blood pressure drops or systolo-diastolic pinching). The etomidate dosage chosen more often gave an immediate satisfactory sleep. However, with methohexital induction, less signs of awakening were observed during the surgical procedure. The frequent postoperative somnolence also points, although indirectly, to a longer residual effect of the barbiturate. Both drugs sometimes gave erythema. The injection of etomidate was more frequently painful in the arm. On the other hand, hiccups occurred with methohexital induction only. Etomidate induced myoclonia in one-third of the cases premedicated with diazepam and after preliminary injection of a minimal amount of fentanyl. Without these precautions, myoclonia can occur in two-thirds of the patients. However, these myoclonia are bothersome and of prolonged duration in rare instances and would be of real annoyance only when this drug would be used alone for surgical procedures of short duration where perfect patient immobility is required. We therefore conclude and confirm that etomidate is a good induction agent for neuroleptanalgesia anesthesia procedures.

Anesthesia↗
PubMedDate not supplied

[Adverse effects reported after inductive doses of the intravenous anesthetics, thiopentone, etomidate and propofol].

It was confirmed that even 10 minutes long general anesthesia necessary for surgery can cause postoperative morbidity. This fact is of the utmost importance for the choice of anesthetics, especially when the operation is to take place in out-patient conditions. The aim of this study was to compare clinical efficacy, tolerability and adverse effects of thiopental, etomidate and propofol. The study comprised 165 out-patients scheduled for legal abortion under general intravenous anaesthesia. Patients were randomly divided into three groups. In patients from the first group (n = 53) anesthesia was induced with thiopental 5 mg/kg, in the second group (n = 54) with etomidate 0.3 mg/kg, and in the third group (n = 58) with propofol 2.5 mg/kg. Blood pressure, heart rate and adverse effects were monitored during anesthesia and operation and immediately thereafter. The best quality of anesthesia and the best working conditions of gynaecologist were after the use propofol, then after thiopental, followed by etomidate. Frequency of adverse effects was significantly greater after anesthesia with etomidate (26.06%), when compared to propofol (9.69%) and thiopental (9.09%). Immediately after induction to anesthesia, adverse effects were found after the use of thiopental, etomidate and propofol in 7.5%, 9.07% and 5.1% of patients, respectively. During anaesthesia, adverse effects were registered in 5.6%, 37.03% and 5.1% of patients in thiopental, etomidate and propofol group, respectively. In the same three groups, frequency of adverse effects in the immediate post-anesthetic recovery period was 15.09%, 62.09% and 17.06%, respectively. It could be concluded that in this study, out of the three anesthetics investigated, propofol had the greatest clinical efficacy and tolerability and the lowest incidence of adverse effects.

Abortion, Induced↗
PubMed1976

[Study of a new anesthetic agent: Etomidate (R 26490). Unusual electroencephalic aspects].

Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentany1. In protocol no 1, the mean consumption was for 1,85 mg/kg/h, in protocol no2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system.

Adolescent↗
PubMed1977

[Study of a new anesthetic agent: etomidate (R 26490). Electroencephalographic aspects].

Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentanyl. In protocol no. 1, the mean consumption was for 1,85 mg/kg/h, in protocol no. 2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system.

Adolescent↗
PubMed1991

Total intravenous anaesthesia with propofol or etomidate.

In combination with fentanyl, propofol was compared with etomidate for total intravenous anaesthesia in 21 women (ASA Grades I-II) admitted for elective hysterectomy. They received either propofol (bolus 1.5 mg kg-1, infusion 9 mg kg-1 h-1 for 10 min thereafter 6 mg kg-1 h-1) or etomidate (bolus 0.10 mg kg-1, infusion 3 mg kg-1 h-1 reduced to 0.6 mg kg-1 h-1). Fentanyl 10 micrograms kg-1 was given for induction followed by an infusion of 30 micrograms kg-1 h-1 for 10 min reduced to 6 micrograms kg-1 h-1 for the first hour and successively reduced over time. Induction was smooth and maintenance easy to manage in both groups. There was no difference in time from end of infusion until extubation, but the time until the patients could report their date of birth was significantly shorter in the propofol group. Nausea and vomiting were more pronounced in the etomidate group, and mental side-effects were only seen after etomidate. After 3 months, more patients in the etomidate group complained of reduced power of concentration. We conclude that total intravenous anaesthesia with either propofol or etomidate is equally easy to manage, but in the recovery situation propofol was advantageous in time and quality.

Adult↗
PubMed1991

The cardiopulmonary and metabolic effects of hypoxia during acute adrenocortical suppression by etomidate in the dog.

Cortisol is secreted as part of the stress response and has been shown to be potentially beneficial to protect against acute stress. Etomidate specifically suppresses endogenous cortisol production. The author studied cardiopulmonary and metabolic effects of hypoxia in dogs during acute adrenocortical suppression by etomidate. Six chronically tracheotomized dogs were induced with either etomidate or thiamylal. Spontaneous ventilation with constant enflurane concentration was maintained. Two hours after induction of anesthesia, isocarbic hypoxia was induced for 20 minutes. Cardiopulmonary and metabolic variables were recorded at specific intervals. The exact sequence was repeated after 1 hour. Cortisol was measured before, during the experiment, and 24 hours later. The experimental protocol was repeated 6 weeks later on the same dog using the other induction agent (thiamylal group versus etomidate group). Two-factor analysis of variance with contrasts tests was used for statistical analysis. The thiamylal group had a significant decrease in minute ventilation, respiratory rate, partial pressure of oxygen in arterial blood, with increases in partial pressure of carbon dioxide in arterial blood, heart rate and cortisol as compared to the etomidate group. Cardiopulmonary and metabolic responses to hypoxia were comparable in both groups. Therefore, acute suppression of cortisol secretion by etomidate did not adversely alter the responses to hypoxia under enflurane anesthesia in dogs.

Adrenal Cortex↗
PubMedDate not supplied

The effect of etomidate on rabbit liver microsomal drug metabolism in vitro.

Etomidate, an imidazole-containing anesthetic agent, is shown to be a reversible inhibitor of rabbit liver microsomal enzymes in vitro. Inhibition of aniline hydroxylation by etomidate follows competitive kinetics, while inhibition of microsomal N-demethylase and O-demethylase activities is of the mixed type. The concentrations of etomidate required to cause 50% inhibition of these enzyme activities are in the 7-10 microM range. NADPH-cytochrome c reductase is not inhibited by concentrations of etomidate below 100 microM. Spectrophotometric studies show that the addition of etomidate to liver microsomes results in a type II binding spectrum. We suggest that etomidate binds with high affinity to cytochrome(s) P-450, resulting in the inhibition of liver drug metabolism.

Animals↗
PubMed1989

Comparison of sedative infusions during regional anesthesia--methohexital, etomidate, and midazolam.

Using a randomized, double-blind study design, the intra- and postoperative sedative effects of three intravenous central nervous system depressants were compared in 64 patients during regional anesthesia. After establishing regional anesthesia, methohexital 59 +/- 29 mg IV, etomidate 12.6 +/- 8 mg IV, or midazolam 3.7 +/- 1.5 mg IV (mean dose +/- SD) were infused in a titrated fashion over 5-15 minutes to achieve similar end points of sedation. This level of sedation was then maintained with a variable-rate infusion of either methohexital 180 +/- 65 mg/hr, etomidate 32 +/- 12 mg/hr, or midazolam 7.5 +/- 4 mg/hr (mean dose +/- SD) To maintain a stable level of sedation, changes in the maintenance infusion rate were required more frequently with methohexital (4.6 +/- 3 times) than with etomidate (2.6 +/- 2 times) or midazolam (2.7 +/- 3 times). Decreases in oxygen saturation below 95% were more frequent with midazolam than with methohexital and etomidate, while recall of intraoperative events was less frequent after midazolam. Observer evaluations found less sedation in the methohexital and etomidate groups than in the midazolam group during the early postoperative period. However, the patients' evaluation of residual sedative effects (e.g., postoperative sedation visual analogue scores) and discharge times from the recovery room were similar in all three groups. Nevertheless, patients given midazolam had significantly greater impairment of performance on the digit-symbol substitution test in the early postoperative period than did patients given either methohexital or etomidate.

Adult↗
PubMed1985

The effect of anaesthetic induction with etomidate on the endocrine response to surgical trauma.

In order to investigate the effects of anaesthetic induction with a single bolus dose of etomidate on the endocrine response to a standard surgical stress, five patients were randomly allocated to receive etomidate and five to receive thiopentone as an induction agent prior to elective inguinal hernia repair. The group receiving etomidate showed a significant suppression in the circulating level of cortisol at 90 and 120 min post-induction (P less than 0.001) and an elevation in their plasma adrenocorticotrophic hormone at 240 and 360 min post-induction (P less than 0.001). The effect of a bolus dose of etomidate upon circulating cortisol levels was transient and no cardiovascular instability was noted during the study. The etomidate group also showed suppression of their circulating testosterone levels at 90 min post-induction (P less than 0.001), suggesting that etomidate inhibits steroidogenesis at a site other than 11 beta-hydroxylase.

Adrenocorticotropic Hormone↗
PubMed1988

[Relation of the inhibition of cortisol synthesis in vivo to plasma etomidate concentrations].

Young, healthy male patients undergoing body surface surgery under fentanyl-nitrous oxide-oxygen anesthesia were given an etomidate bolus for induction (0.3 mg/kg body weight) followed by a continuous infusion (0.36 mg.kg-1.h-1). The total etomidate dose was 63 +/- 6.4 mg (mean +/- standard error). Basal cortisol levels as well as the adrenocortical response to exogenous synthetic ACTH1-24 (0.25 mg i.m.) were determined preoperatively, at the end of anesthesia, and 6 and 20 h postoperatively. The reduction of the response to ACTH stimulation measured postoperatively as compared to preoperatively was calculated as percentage of the preoperative response. Plasma concentrations of etomidate were measured at the same sample times by gas chromatography. At the end of anesthesia the plasma level was 570 +/- 131 nM (mean +/- standard error). It decreased to 99 +/- 23 nM 6 h later and to 43 +/- 3 nM 20 h postoperatively. The plasma concentrations were plotted against the inhibition data. We found a sigmoid relationship between the relative inhibition and the log of the etomidate concentrations. We determined an EC50 for inhibition of 110 nM that agrees well with published data. We also found that the cortisol response was not completely suppressed at the concentrations measured here. This supports the results of a previous study in which we found that patients undergoing cardiovascular surgery still exhibited intra- and postoperative cortisol increases although they had been given large doses of etomidate. We conclude that the suppression of corticosteroid synthesis caused by etomidate is concentration-dependent. The suppression is negligible at concentrations lower than 40 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[Hormones of the pituitary-adrenal cortex system in patients under long-term sedation with etomidate and fentanyl].

The influence of a long-term sedation with etomidate and fentanyl on the hormones of the pituitary gland and the adrenal cortex now five mechanically ventilated patients were studied. There is evidence that etomidate might diminish the plasma cortisol level in a dose dependent relationship. The urinary excretion of 17-OH-corticosteroids was found to stay within the normal range, whereas the corresponding excretion of the unbound cortisol stayed subnormal. In general no cortisol response was seen in connection with raised ACTH-plasma-levels. Surgical trauma and changes of dressing induced stress reactions with an exceeding rise in plasma cortisol levels. The plasma levels of prolactin showed a marked increase after the administration of fentanyl even in the presence of a high etomidate plasma level. 17-alpha-OH-progesterone and progesterone were found diminished at etomidate plasma levels greater than 1.0 micrograms/ml. In the "therapeutic range" there is found no linear dependency on the plasma etomidate level. From our preliminary results we cannot draw any conclusions about the mechanism how etomidate might inhibit cortisol synthesis and its influence on the metabolic rate, the hormonal feedback mechanisms and the cardiovascular system.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Plasma levels of alfentanil and etomidate in patients and their relation to compressed power spectral analysis of the EEG.

In 22 patients alfentanil-etomidate anesthesia was used for orthopedic procedures using for the induction period 300 micrograms/kg of the hypnotic and 100 micrograms/kg of the opioid. Maintenance of anesthesia consisted of 20 micrograms/kg of alfentanil given every 15 min and 20 micrograms/kg/min of etomidate given over an infusion. The patients were intubated and mechanically ventilated with pure oxygen. In order to access the state of vigilance with respect to etomidate and alfentanil plasma levels, EEG power spectra were computed from electrical cortical activity of the occipital region (P3-O1); respectively venous blood samples were assayed by means of gas chromatography for alfentanil and etomidate plasma concentration. In the EEG power spectrum, anesthesia replaced the high dominant alpha-peaks of the control-awake period by a disharmonious pattern over the whole frequency range (0.5-16.0 Hz). At the end of anesthesia vigilance recording indicated a correlation with plasma etomidate level. Once concentration had dropped below 100 ng/ml power spectra were characterized by a stable harmonious peak in the alpha-range (8.0-10.0 Hz). Plasma levels above 100 ng/ml induced a fluctuating pattern with peaks in the theta to delta band (0.5-8.0 Hz); the latter was characterized by drowsiness and a reduced respiratory drive. Opioid plasma levels above 100 ng/ml with etomidate levels below 80 ng/ml did not influence to the same extent. EEG power spectra seem to be a useful tool in pinpointing to a reduced state of vigilance. Such a state when present with opioid ingestion is often accompanied by respiratory depression.

Adult↗