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PubMed1986

Increased sensitivity to etomidate in the elderly: initial distribution versus altered brain response.

To determine the effect of aging on the pharmacokinetics and pharmacodynamics of etomidate, we administered etomidate (5 to 10 mg/min) by intravenous infusion to 21 healthy surgical patients, age 22 to 82 yr. Etomidate produced progressive slowing of the EEG to an easily recognized pattern (stage 3) that determined the dosage endpoint. Subsequent power-spectrum analysis of the EEG gave the median frequency. Median frequency values and simultaneous measurements of blood etomidate concentration were incorporated into a sigmoid Emax pharmacodynamic model that permitted an estimate of IC50, the blood etomidate concentration which produced a 50% reduction in the median frequency. The dose of etomidate required to reach the uniform EEG endpoint decreased significantly with increasing age (r2 = .68) as did the dose needed to produce maximal median frequency depression (r2 = .69). None of the parameters of the pharmacodynamic effect model, including IC50, correlated with age, suggesting that increased brain sensitivity in the elderly does not cause the age-related change in dose requirement. The initial distribution volume for etomidate decreased significantly with increasing age (r = .56), implying that a higher initial blood concentration in the elderly following any given dose of etomidate is part of the cause of the lower dose requirement in the elderly patient. A contracted initial distribution volume in the elderly may result from well described physiologic changes of age. Etomidate clearance also decreased with age. Age-dependent changes in etomidate pharmacokinetics rather than altered brain responsiveness may be the basis for the decreased etomidate dose requirement in the elderly.

Adult↗
PubMed1998

Etomidate does not alter recovery after anoxia of evoked population spikes recorded from the CA1 region of rat hippocampal slices.

BACKGROUND: Etomidate is an anesthetic agent that reduces the cerebral metabolic rate and causes minimal cardiovascular depression. Its ability to improve recovery after anoxia or ischemia is equivocal. An in vitro neuronal preparation was used to examine the action of etomidate on electrophysiologic and biochemical parameters during and after anoxia. METHODS: The Schaffer collateral pathway was stimulated, and a postsynaptic evoked population spike was recorded from the CA1 pyramidal cell layer of rat hippocampal slices. Etomidate or propylene glycol, its solvent, was present 15 min before, during, and 10 min after anoxia. Adenosine triphosphate, sodium, and potassium concentrations were measured at the end of anoxia in tissue treated with etomidate, propylene glycol, or with no added drugs. RESULTS: Etomidate did not alter recovery after 6 min of anoxia. The population spikes from untreated slices recovered to 32% of their preanoxic amplitude, and slices treated with 0.5, 3, and 30 microg/ml etomidate recovered to 24%, 35%, and 13%, respectively. Slices treated with propylene glycol, equivalent to that in 3 and 30 microg/ml etomidate, recovered to 46% and 12%, respectively, and this was not significantly different from untreated slices. Etomidate did not attenuate the decrease in adenosine triphosphate concentrations during anoxia. The increase in sodium and the decrease in potassium during anoxia were significantly attenuated by 30 but not by 3 microg/ml etomidate. CONCLUSIONS: A range of etomidate concentrations did not significantly alter recovery of the evoked population spike after anoxia in rat hippocampal slices. A high concentration of etomidate did attenuate the increase in sodium and the decrease in potassium during anoxia.

Adenosine Triphosphate↗
PubMed2007

Determination of the EC50 amnesic concentration of etomidate and its diffusion profile in brain tissue: implications for in vitro studies.

BACKGROUND: Etomidate is a widely used general anesthetic that has become a useful tool to investigate mechanisms of anesthetic action in vivo and in brain slices. However, the free aqueous concentration of etomidate that corresponds to amnesia in vivo and the diffusion profile of etomidate in brain slices are not known. METHODS: The authors assessed the effect of intraperitoneally injected etomidate on contextual fear conditioning in mice. Etomidate concentrations in brain tissue were obtained by high-performance liquid chromatography. Uptake studies in 400-microm-thick brain slices were used to calculate the diffusion and partition coefficients of etomidate. A diffusion model was used to calculate the expected concentration profile within a brain slice as a function of time and depth. The predicted rate of drug equilibration was compared with the onset of electrophysiologic effects on inhibitory circuit function in recordings from hippocampal brain slices. RESULTS: Etomidate impaired contextual fear conditioning with an ED50 dose of 11.0+/-0.1 mg after intraperitoneal injection, which corresponded to an EC50 brain concentration of 208+/-9 ng/g. The brain:artificial cerebrospinal fluid partition coefficient was 3.35, yielding an EC50,amnesia aqueous concentration of 0.25 microm. The diffusion coefficient was approximately 0.2x10 cm/s. The development of etomidate action in hippocampal brain slices was compatible with the concentration profile predicted by this diffusion coefficient. CONCLUSIONS: The free aqueous concentration of etomidate corresponding to amnesia, as defined by impaired contextual fear conditioning in mice, is 0.25 microM. Diffusion of etomidate into brain slices requires approximately an hour to reach 80% equilibration at a typical recording depth of 100 microm. This information will be useful in designing and interpreting in vitro studies using etomidate.

Amnesia↗
PubMed2004

Etomidate versus pentobarbital for sedation of children for head and neck CT imaging.

OBJECTIVES: We compare etomidate to pentobarbital for sedation of children for head and neck computed tomography imaging. METHODS: We performed a prospective, randomized, double-blinded trial of patients aged 6 months to 6 years enrolled from the emergency department or radiology department at a large urban children's hospital. The primary outcome measure was sedation success rate. RESULTS: A total of 61 patients were enrolled in the study (27 etomidate group, 34 pentobarbital group) at 2 different dosing regimens for etomidate. The final analysis group included 17 etomidate patients and 33 pentobarbital patients. The success rate for the etomidate group was 57% at total doses of up to 0.3 mg/kg (n = 7) and 76% at total doses of up to 0.4 mg/kg (n = 17), in contrast to a success rate of 97% for pentobarbital at a total dose of up to 5 mg/kg (n = 33). The success rate for pentobarbital was significantly greater than the final etomidate group (P = 0.04; difference in proportions 20.5%, 95% CI 1.9% to 44.4%). Patients receiving etomidate had significantly shorter induction times (P = 0.02; difference of means 2.1 minutes, 95% CI 0.35 to 3.86), sedation times (P < 0.001; difference of means 31.3 minutes, 95% CI 24.0 to 38.5), and total examination times (P < 0.001; difference of means 53.1 minutes, 95% CI 40.8 to 65.3). Significantly more parents in the etomidate group perceived their child to be back to baseline by discharge from the hospital (P < 0.001; difference of proportions 60.7, 95% CI 29.1 to 92.4) and expressed fewer concerns about their child's behavior after discharge (P = 0.024; difference of proportions 28.6, 95% CI 6.5 to 50.7). CONCLUSIONS: At the dosing used in this study, pentobarbital is superior to etomidate when comparing success rates for sedation. However, among the successful sedations, the duration of sedation was shorter in the etomidate group than in the pentobarbital group. Pentobarbital is associated with more frequent side effects and parental concerns compared to etomidate.

Child↗
PubMed2005

The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats.

We evaluated the effect of N(G)-nitro-L-arginine-methyl-ester (l-NAME, a nitric oxide synthase [NOS] inhibitor) and L-arginine (nitric oxide substrate) on cerebral mitochondrial dysfunction (hereafter referred to as "injury") after temporary middle cerebral artery occlusion (MCAo) during halothane or etomidate anesthesia in spontaneously hypertensive rats. Sixty minutes before MCAo, rats were randomized to 1 of 5 regimens (n = 8 per group): h/control, 1.2 minimum alveolar anesthetic concentration of halothane; h/L-NAME, 1.2 minimum alveolar anesthetic concentration of halothane and L-NAME (30 mg/kg); etomidate, an electroencephalographic (EEG) burst suppression dose of etomidate; e/L-NAME, an EEG burst suppression dose of etomidate and L-NAME (30 mg/kg); or e/L-NAME/arg, an EEG burst suppression dose of etomidate, L-NAME (30 mg/kg), and L-arginine (bolus of 300 mg/kg with an infusion at 35 mg x kg(-1) x min(-1)). After 180 min of MCAo and 120 min of reperfusion, volume of injury was determined using 2,3,5-triphenytetrazolium stain. Injury volume (mm(3), mean +/- sd) was larger in the etomidate group (153 +/- 17) than the halothane anesthetized h/control group (93 +/- 16) (P < 0.05) but did not differ between the e/L-NAME (162 +/- 17) and h/L-NAME groups (155 +/- 26). Injury volume in the e/L-NAME/arg group (88 +/- 15) was not different from the h/control group (93 +/- 16) and was less than that in either the etomidate or the e/L-NAME groups (P < 0.05). The data reproduce our previous observation that, relative to a halothane-anesthetized control state, etomidate has an adverse effect on ischemic injury in the setting of temporary focal cerebral ischemia. Prior inhibition of NOS with L-NAME resulted in no difference in the volume of injury between groups receiving etomidate or halothane (162 +/- 17 versus 155 +/- 26). Administration of a large dose of L-arginine prevented the adverse effect of etomidate. The data were obtained after only 2 h of reperfusion and therefore cannot be construed as representative of final neurologic outcome. They nonetheless suggest that etomidate produces an adverse effect on mitochondrial function early in the course of focal cerebral ischemia, in part, by inhibition of NOS.

Animals↗
PubMed1995

Limited protective effects of etomidate during brainstem ischemia in dogs.

To evaluate etomidate as a neuroprotective agent in the brain stem, 33 dogs were divided into seven groups and were exposed to isolated, reversible brainstem ischemia in the presence or absence of etomidate using a newly developed canine model of brainstem ischemia. Brainstem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured during ischemia and for 5 hours after reperfusion. This model provides a potential physiological environment in which to test the efficacy of putative brainstem ischemic protective strategies. During ischemia, BAEP were abolished in all animals. Without etomidate 10 minutes of ischemia was of short enough duration to allow complete recovery of BAEP. Ischemia of 20 or 30 minutes' duration resulted in minimal recovery. The dose of etomidate administered did not suppress BAEP or brainstem cardiovascular response to ischemia. In animals receiving etomidate and rendered ischemic for 20 minutes, a significant but only temporary recovery in BAEP was seen. Etomidate failed to have a significant effect in animals rendered ischemic for 30 minutes. The minimal effect of etomidate on the current measures of brainstem function is in contrast to etomidate's known suppressive effect on cortical electroencephalogram and predicts that etomidate does little to alter brainstem metabolism. Etomidate's failure to provide for permanent recovery of BAEP suggests that the drug does not give sufficient protection from ischemia to the brainstem neurons in the auditory pathway. If these auditory neurons reflect brainstem function as a whole, etomidate may not be the protective agent of choice during temporary arterial occlusion of posterior circulation.

Animals↗
PubMed1991

A comparison of etomidate and thiopental anesthesia for cardioversion.

Sixteen ASA class II or III male patients (aged, 52 to 66 years) undergoing elective cardioversion were randomly assigned to receive either thiopental or etomidate according to an observer-blinded, parallel study design. The appropriate drug was administered in 2-mL aliquots every 15 seconds until the patient no longer responded to verbal commands, at which time cardioversion was attempted. The total dose for induction was 0.22 +/- 0.2 mg/kg and 3.2 +/- 0.4 mg/kg for etomidate and thiopental, respectively. The cardiorespiratory data after induction were evaluated for maximal percent change from baseline. The baseline heart rate was 106 +/- 6 beats/min and 98 +/- 8 beats/min for the etomidate and thiopental groups, respectively (mean +/- SEM). The heart rate decreased 5% after induction with etomidate and increased 7% with thiopental (P less than 0.05). The baseline mean arterial pressure (MAP) was 96 +/- 3 mm Hg and 105 +/- 11 mm Hg for the etomidate and thiopental groups, respectively (mean +/- SEM). The MAP decreased 4% with etomidate and 3% with thiopental. Respiratory rate was significantly increased by 22% after etomidate compared with a 22% decrease in respiratory rate with thiopental (P less than 0.05). Seven of eight patients in the thiopental group required only one countershock, whereas four of eight patients in the etomidate group required only one shock. One patient in each group could not be successfully cardioverted. Recovery time and clinical side effects were similar between groups except for mild myoclonus in the etomidate group. Titration to effect of either etomidate or thiopental provided satisfactory anesthesia for elective cardioversion in hemodynamically stable patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

The in vitro and in vivo enantioselectivity of etomidate implicates the GABAA receptor in general anaesthesia.

General anaesthetics exhibiting enantioselectivity afford valuable tools to assess the fundamental mechanisms underlying anaesthesia. Here, we characterised the actions of the R-(+)- and S-(-)-enantiomers of etomidate. In mice and tadpoles, R-(+)-etomidate was more potent (approximately 10-fold) than S-(-)-etomidate in producing loss of the righting reflex. In electrophysiological and radioligand binding assays, the enantiomers of etomidate positively regulated GABAA receptor function at anaesthetic concentrations and with an enantioselectivity paralleling their in vivo activity. GABA-evoked currents mediated by human recombinant GABAA receptors were potentiated by either R-(+)- or S-(-)-etomidate in a manner dependent upon receptor subunit composition. A direct, GABA-mimetic, effect was similarly subunit dependent. Modulation of GABA receptor activity was selective; R-(+)-etomidate inhibited nicotinic acetylcholine, or 5-hydroxytryptamine3 receptor subtypes only at supra-clinical concentrations and ionotropic glutamate receptor isoforms were essentially unaffected. Acting upon reticulothalamic neurones in rat brain slices, R-(+)-etomidate prolonged the duration of miniature IPSCs and modestly enhanced their peak amplitude. S-(-)-etomidate exerted qualitatively similar, but weaker, actions. In a model of locomotor activity, fictive swimming in Xenopus laevis tadpoles, R-(+)- but not S-(-)-etomidate exerted a depressant influence via enhancement of GABAergic neurotransmission. Collectively, these observations strongly implicate the GABAA receptor as a molecular target relevant to the anaesthetic action of etomidate.

Anesthetics, Intravenous↗
PubMed1997

Subunit-dependent interaction of the general anaesthetic etomidate with the gamma-aminobutyric acid type A receptor.

1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. It is concluded that the subtype of beta-subunit influences the potency with which etomidate potentiates GABA-evoked currents and that the beta isoform is a crucial determinant of the GABA-mimetic activity of this compound. The nature of the alpha-subunit also impacts upon the maximal potentiation and activation that the compound may elicit. Such pronounced influences may aid the identification of the site that recognises etomidate. More generally, these results provide a clear example of structural specificity in anaesthetic action.

Anesthetics, Intravenous↗
PubMed1999

[L-nitroargininemethylester (L-NAME), a nitric oxide synthase inhibitor, increases the anesthetic potency of etomidate].

OBJECTIVE: Comparable to other intravenous anaesthetics, etomidate is thought to mediate its anaesthetic effect through an action on gamma-amino-butyric-acid (GABA) receptors. Recently, there is evidence that general anaesthetics act on second messenger systems such as the nitric oxide (NO) metabolism too. This study was designed to evaluate the effects of the NO-synthase inhibitor nitro-L-arginine methyl ester (L-NAME) on the anaesthetic potency of the intravenous anaesthetic etomidate. METHODS: With approval of the local animal care committee, the effect of L-NAME on the anaesthetic potency of etomidate was studied in Xenopus laevis tadpoles. The animals were exposed to different concentrations of the anaesthetic etomidate or a combination of etomidate and 1 mM L-NAME for 120 min. Anaesthesia was defined as loss of righting reflex for more than 5 s. A concentration-response curve was fitted to the data according to the method of Waud for quantal biological data and half maximal effects (EC50) and slopes of the curves were calculated. RESULTS: In both groups, the fraction of anaesthetised animals increased with increasing etomidate concentrations. The calculated values were EC50 4.5 +/- 0.2 microM in the etomidate group with a slope of 2.6 +/- 0.3 (mean +/- SE). The etomidate plus L-NAME group exhibited a significantly different EC50 of 3.0 +/- 0.2 microM with a slope of 2.3 +/- 0.3. CONCLUSION: The NO-metabolism has been suggested to be involved in the anaesthetic action of volatile as well as intravenous anaesthetics. The reduction in EC50 of etomidate in presence of L-NAME is comparable to that observed for thiopental or halothane, and thus may indicate an additional mechanism of action of etomidate.

Anesthesia, Intravenous↗
PubMedDate not supplied

Etomidate as a sole agent for endotracheal intubation in the prehospital air medical setting.

INTRODUCTION: Etomidate is an anesthetic agent with rapid onset, short duration of action, a generally stable hemodynamic profile, and cerebroprotective effects. It is used in the hospital setting to facilitate emergency endotracheal intubation. This helicopter EMS used etomidate as an intubating agent without paralytics for 2 years. METHODS: Intubations performed by the helicopter crew using etomidate alone were reviewed. Intubation was classified as successful or unsuccessful. Successful intubations requiring three or more attempts or repeated doses of etomidate were interpreted as difficult. RESULTS: Fifty patients received etomidate to facilitate orotracheal intubation. Etomidate was the sole agent in 44 of these cases. Mean age was 31 years (range 4-79); 35 patients (80%) were men. Most patients (79%) were victims of blunt trauma. The mean dose of etomidate was 0.5 mg/kg (range 0.3-1.1). Hemodynamic parameters remained stable. Intubation was successful in 39 patients (89%). Intubation was difficult in seven patients (16%) and unsuccessful in five (11%). Masseter muscle spasm was noted in three of the five patients for whom intubation was unsuccessful. Other complications included emesis in eight patients and seizure-like activity in one patient. CONCLUSION: Etomidate can be used to facilitate emergency endotracheal intubation in the prehospital air medical setting, with a success rate of 89%. At the doses used in the study, hemodynamic parameters remained stable, but intubation was difficult or unsuccessful in 27% of patients. Masseter muscle spasm, which may represent orofacial myoclonus or inadequate relaxation, is common in patients who cannot be intubated with etomidate. Etomidate is recommended as a sole agent for facilitating intubation only when rapid sequence intubation with paralysis is contraindicated or otherwise undesirable.

Adolescent↗
PubMed1984

Etomidate inhibits adrenocortical function in surgical patients.

Postoperative adrenocortical function was compared in 23 out-patients receiving either thiopental, 4 mg/kg, for induction and a thiopental infusion, 0.26 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance of anesthesia (control); etomidate, 0.4 mg/kg, for induction followed by an etomidate infusion, 0.02 mg . kg-1 . min-1, and nitrous oxide 70% for maintenance (etomidate I); or etomidate, 0.4 mg/kg, for induction and a thiopental infusion, 0.22 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance (etomidate II). The norepinephrine response to anesthesia and surgery did not differ significantly between the three groups. The postoperative cortisol response to ACTH stimulation was normal in the control group (maximum rise in plasma cortisol was 20.1 +/- 2.9 micrograms/dl [mean +/- SEM] ), however, it was decreased in all patients receiving etomidate, whether by a short infusion (mean change in plasma cortisol was -3.8 +/- 1.9 micrograms/dl) or as a single induction dose (mean change in plasma cortisol was -4.0 +/- 2.0 micrograms/dl). Similarly, the postoperative aldosterone levels in the control group increased normally in response to ACTH (+ 10.2 +/- 3.0 ng/dl) but decreased in both the etomidate I and etomidate II groups (-3.0 +/- 0.7 ng/dl and -3.3 +/- 1.0 ng/dl, respectively). Because ACTH was administered exogenously, etomidate-induced suppression of adrenocortical response appeared to be a direct effect on the adrenal gland, which was present at a time when the serum etomidate levels were in the subhypnotic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of etomidate on the cardiac papillary muscle of normal hamsters and those with cardiomyopathy.

BACKGROUND: Etomidate has been shown to induce no significant inotropic effect on normal myocardium, but its effects on diseased myocardium remain unknown. METHODS: The effects of etomidate (1 and 5 micrograms/ml) on the intrinsic contractility of left ventricular papillary muscle from normal hamsters and those with cardiomyopathy (strain BIO 82.62, 6 months old) were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca++ 2.5 mM, stimulation frequency 3/min). RESULTS: The contractility of papillary muscles from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in maximum shortening velocity (-25%, P < .001), isometric active force (-45%, P < .01), peak power output (-57%, P < .01), and sarcoplasmic reticulum function (P < .01). Etomidate did not induce a significant inotropic effect, as shown by the absence of changes in maximum shortening velocity and active isometric force, except at 5 micrograms/ml in cardiomyopathic hamsters (+8 +/- 10%, P < .05). The effects of etomidate on these inotropic parameters were not different in normal and cardiomyopathic hamsters. Etomidate impaired contraction-relaxation coupling under low load in both groups, suggesting that etomidate decreased sarcoplasmic function. This impairment was less (P < .02) pronounced in cardiomyopathic muscles. The effects of etomidate on contraction-relaxation coupling under heavy load were not different between groups. In both groups, etomidate had no effect on the peak power output and the curvature of the total force-velocity curve, suggesting that it did not modify the muscle myothermal economy. CONCLUSIONS: Etomidate had only a slight effect on the intrinsic mechanical properties of hamster cardiac papillary muscles, and these effects did not depend on the pathophysiologic state of the myocardium. These results may be clinically useful as, unlike etomidate, most anesthetics depress myocardial contractility.

Animals↗
PubMed1999

Reducing myoclonus after etomidate.

BACKGROUND: The authors hypothesized that myoclonus after etomidate is dose-related, could be suppressed when small doses of etomidate were administered before induction, and is unassociated with seizure-like activity on electroencephalogram (EEG). METHODS: Three studies were performed. In the first study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100, 0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for subjects in the first two studies. In a third study, 60 patients were randomly allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075 mg/kg before 0.300 mg/kg was given. RESULTS: In Study 1, myoclonus was not observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after 0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after 0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05). EEG changes, other than delta waves, were not seen during myoclonic epochs. In Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or 0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). CONCLUSIONS: Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.

Adult↗
PubMed1993

Effects of etomidate and hypothermia on cerebral metabolism and blood flow in a canine model of hypoperfusion.

Etomidate is a nonbarbiturate hypnotic agent which, like the barbiturates, decreases the cerebral metabolic rate of oxygen consumption (CMRO2) 35-50%. The present studies assessed whether etomidate decreased CMRO2 through temperature-dependent mechanisms and whether the combination of etomidate and moderate hypothermia (28 degrees C) decreased CMRO2 more than hypothermia alone. Nineteen anesthetized dogs were treated with saline, etomidate (burst-suppressive doses), etomidate with hypothermia, or hypothermia alone. Etomidate did not affect (p > 0.05) the mean arterial pressure (MAP, mm Hg) but modestly lowered the heart rate [HR; 124 +/- 6 to 105 +/- 14, (mean +/- SEM); p < 0.05] whereas hypothermia (without or with etomidate) lowered (p < 0.05) both MAP (141 +/- 4 to 116 +/- 5 and 135 +/- 6 to 81 +/- 7) and HR (135 +/- 14 to 84 +/- 3 and 135 +/- 10 to 69 +/- 5, respectively). Etomidate administration did not result in a change (p > 0.05) in the esophageal, brain parenchymal, or subdural temperature. CMRO2 (ml/100 g/min) decreased (p < 0.05) during etomidate administration (3.2 +/- 0.4 to 1.7 +/- 0.2) and hypothermia (3.5 +/- 0.2 to 1.1 +/- 0.2), but the addition of etomidate to hypothermia did not further reduce CMRO2 in the animals (3.1 +/- 0.5 to 1.3 +/- 0.2) despite decreasing their brain hemispheric electrical activity from 9 +/- 1 Hz to a burst-suppressive state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Peri-operative endocrine effects of etomidate.

This study investigated the effects of etomidate on endocrine responses to anaesthesia and surgery. Patients undergoing abdominal hysterectomy received standard anaesthetics of either etomidate for induction with etomidate infusion, or thiopentone and halothane. Etomidate suppressed the secretion of cortisol and aldosterone for between 8 and 22 hours after the end of the etomidate infusion; 11-deoxycortisol secretion was not suppressed during the etomidate infusion, but rose postoperatively; 17 alpha-hydroxyprogesterone suppression also lasted only as long as the etomidate infusion. There were no effects on plasma oestradiol, ACTH, or prolactin, but growth hormone concentrations were elevated in the etomidate group. Etomidate was concluded to have influenced adrenocortical function only, where it probably inhibits 11 beta-hydroxylation, 17 alpha-hydroxylation and other intramitochondrial hydroxylation reactions. There were no clinical sequelae attributable to adrenocortical suppression. The relationship of chemical structure of etomidate and other phenylated imidazoles to inhibition of steroidogenesis is discussed.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing's syndrome and dose-response relationship in normal subjects.

To investigate the adrenostatic potential of a nonhypnotic low dose etomidate infusion, we administered 0.03 mg/kg etomidate in a bolus injection, followed by constant infusion of 0.3 mg/kg.h for 24 h to 6 patients with severe Cushing's syndrome. The dose-response relationship also was determined in 15 normal subjects. Three groups of 5 received, respectively, doses of 0.03, 0.1, and 0.3 mg/kg.h etomidate for 5 h after an initial bolus dose of 0.03 mg/kg. The response to exogenously administered ACTH [0.25 mg ACTH-(1-24)], injected after the etomidate or control infusion, was determined in all normal subjects. In the six hypercortisolemic patients, serum cortisol concentrations decreased from 1374 +/- 436 nmol/L (mean +/- SEM) to 188 +/- 91 nmol/L after 11 h of etomidate infusion and remained low until the end of the infusion. Cortisol levels returned to pretreatment concentrations by 24 h. Excretion of urinary free cortisol decreased from 1180 +/- 196 to 185 +/- 66 nmol/day. In the normal subjects, administration of etomidate led to a dose-dependent decrease in serum cortisol from about 550 to 83 nmol/L, while 11-deoxycortisol rose from low or undetectable levels up to 346 nmol/L. In response to ACTH, cortisol levels rose in inverse proportion to the etomidate dose. It was, however, significantly reduced compared to normal saline infusion even after the lowest dose. Changes in aldosterone and corticosterone concentrations were similar to those in cortisol, and 11-deoxycorticosterone changed in a pattern similar to that of 11-deoxycortisol. Two of five normal subjects reported tiredness during the highest etomidate infusion. No other side-effects were noted. We conclude that iv administered etomidate in a low nonhypnotic dose reduces serum cortisol concentrations in a dose-dependent manner in both hyper- and eucortisolemic subjects. This study suggests that etomidate at a dose of 0.1 mg/kg.h or lower may be an effective strategy for the control of severe hypercortisolemia.

Adolescent↗
PubMed1992

Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts.

The authors examined direct myocardial and coronary vascular responses to the anesthetic induction agents etomidate, ketamine, midazolam, propofol, and thiopental and compared their effects on attenuating autoregulation of coronary flow as assessed by changes in oxygen supply/demand relationships. Spontaneous heart rate, atrioventricular conduction time during atrial pacing, left ventricular pressure (LVP), coronary flow (CF), percent oxygen extraction, oxygen delivery, and myocardial oxygen consumption (MVo2) were examined in 55 isolated guinea pig hearts divided into five groups of 11 each. Hearts were perfused at constant pressure with one of the drugs administered at steady-state concentrations increasing from 0.5 microM to 1 mM. Adenosine was given to test maximal CF. At concentrations below 10 microM no significant changes were observed; beyond 50 microM for midazolam, etomidate, and propofol, and 100 microM for thiopental and ketamine, each agent caused progressive but differential decreases in heart rate, atrioventricular conduction time (leading to atrioventricular dissociation), LVP, +dLVP/dtmax, percent oxygen extraction, and MVo2. The concentrations (microM) at which +dLVP/dtmax was reduced by 50% were as follows: etomidate, 82 +/- 2 (mean +/- SEM); propofol, 91 +/- 4; midazolam, 105 +/- 8; thiopental, 156 +/- 11; and ketamine, 323 +/- 7; the rank order of potency was etomidate = propofol = midazolam greater than thiopental greater than ketamine; results were similar for LVP. At the 100 microM concentration, CF was decreased 11% +/- 2% by ketamine and 5% +/- 3% by thiopental but was increased 17% +/- 6% by etomidate, 21% +/- 5% by midazolam, and near maximally to 57% +/- 10% by propofol; MVo2 was decreased 8% +/- 4% by thiopental, 10% +/- 5% by ketamine, 19% +/- 5% by midazolam, 29% +/- 7% by etomidate, and 37% +/- 5% by propofol; oxygen delivery/MVo2 was unchanged by thiopental and ketamine but was increased 62% +/- 7% by midazolam, 71% +/- 9% by etomidate, and 150% +/- 15% by propofol. Between 100 microM and 1 mM, thiopental and ketamine did not increase CF but decreased MVo2 and percent oxygen extraction, whereas propofol maximally increased CF and decreased MVo2 and midazolam and etomidate had intermediate effects. These results indicate that on a molar basis, propofol, and less so midazolam and etomidate, depress cardiac function moderately more than thiopental and ketamine, and that propofol markedly attenuates autoregulation by causing coronary vasodilation. With doses used to induce anesthesia, propofol and thiopental appear to depress cardiac function more than ketamine or etomidate.

Adenosine↗