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PubMed1992

An assessment of the cerebral protective effects of etomidate in a model of incomplete forebrain ischemia in the rat.

The cerebral protective effects of etomidate were evaluated in a model of incomplete forebrain ischemia. Fourteen Wistar-Kyoto rats were anesthetized with halothane. After preparation, the rats were alloted to either the control group (halothane anesthesia, n = 7) or the etomidate group (n = 7). In the etomidate group, immediately before and during the period of ischemia, the animals received etomidate in sufficient concentration to achieve electroencephalogram burst suppression (loading dose, 7.5 mg/kg; infusion, 0.3-0.5 mg/kg/min). Both groups were subjected to a 10-minute ischemic insult accomplished by bilateral carotid artery occlusion and simultaneous hypotension (mean arterial pressure, 35 mm Hg). Histological evaluation of the brain was performed after a 4-day recovery period. Injury was evaluated in coronal brain sections in five structures: neocortex, striatum, reticular nucleus of the thalamus, and the CA1 and CA3 areas of the hippocampus. The location of the sections in the rostral-caudal axis was chosen to encompass anterior areas within the core of the ischemic territory as well as more posterior regions within the anticipated "watershed" zone between the occluded anterior and the intact posterior circulations. In the animals that received etomidate, statistically significant (P less than 0.05) reduction in the severity of the ischemic injury was observed in the CA3 area and in the ventral portion of the CA1 area of the hippocampus in the more posterior sections. There was an apparent trend toward protection in other structures in both rostral and caudal sections, but these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury.

An investigation was performed to compare the cerebral protective properties of etomidate, isoflurane, and thiopental. In separate groups of spontaneously hypertensive rats, etomidate, isoflurane, or thiopental was administered to achieve and maintain burst-suppression of the electroencephalogram (3-5 bursts/min) for the duration of the experiment. A fourth group received 1.2 minimal alveolar concentration halothane. All groups underwent 3 hours of middle cerebral artery occlusion and then 2 hours of reperfusion. Thereafter, the animals were killed and the volume of injured brain was determined by staining with 2,3,5-triphenyltetrazolium. Physiological parameters did not differ among the four groups during the investigation, with the exception that hemolysis occurred in the etomidate group (free hemoglobin levels, approximately 0.4 g.dl-1). The volume of injured brain in the thiopental group (56 +/- 10 mm3) was significantly smaller than that in the halothane control group (99 +/- 13 mm3). The volumes of injured brain in the etomidate and isoflurane groups (145 +/- 11 mm3 and 139 +/- 14 mm3, respectively) were significantly larger than those in the control and thiopental groups. We speculate that the apparently detrimental effect of etomidate may be the result of the binding of nitric oxide of cerebral endothelial origin by the iron component of free hemoglobin. Intracranial pressure was not recorded, and in the isoflurane group, there may have been adverse effects on cerebral perfusion pressure associated with vasodilation caused by high concentrations of isoflurane. The results are consistent with a protective effect by barbiturates.

Anesthesia, General↗
PubMed2002

Etomidate for procedural sedation in the emergency department.

STUDY OBJECTIVE: To review our experience with etomidate in nonintubated patients in the emergency department. DESIGN: A 2-year retrospective chart review of consecutive patients receiving etomidate for sedation. SETTING: Emergency department of a university-based teaching hospital. PATIENTS: Forty-eight patients who underwent painful procedures in the emergency department. MEASUREMENTS AND MAIN RESULTS: Demographics, dosing information, recovery times, and adverse events were abstracted using a standardized data collection form. Forty-eight nonintubated patients were sedated with etomidate. Mean age was 34 years (range 6-80 yrs); 38 were men and 10 women; two were children. The mean initial dose of etomidate was 13 mg. Adverse events occurred in 11 (21%) patients. None sustained any substantial morbidity as indicated by need for intubation, prolonged emergency department stay, or hospital admission. CONCLUSION: Although controversial, etomidate holds promise as a potent sedative agent for patients undergoing painful procedures in the emergency department. A large prospective evaluation is needed to document the performance and complications of this agent.

Adolescent↗
PubMed1991

Facilitation of spike-wave activity by the hypnotic etomidate in a rat model for absence epilepsy.

The epileptogenic effect of the short-acting hypnotic agent etomidate was investigated in WAG/Rij rats. Animals of this inbred strain show spontaneous spike-wave discharges and are regarded as a model for absence epilepsy. A dose-dependent increase in the total amount of spike-wave activity was found, when etomidate was injected intraperitoneally in doses of 1, 2.5, 5 and 10 mg/kg. At a dose of 10 mg/kg, spike-wave activity appeared almost uninterruptedly. Beginning with a dose of 5 mg/kg, the morphology of the spike-wave complexes changed after the administration of the drug; spike frequency decreased dose dependently from about 8 till about 4 Hz at 10 mg/kg. During spike-wave activity, animals were motionless and, certainly at 10 mg/kg of etomidate, were unresponsive to stimuli. For surgical anesthesia, a still higher dose of etomidate is necessary (20 mg/kg). It is concluded that etomidate facilitates the generation of spike-wave activity in rats with spontaneous absence seizures, presumably through its GABA-mimetic action.

Action Potentials↗
PubMed1996

Do etomidate and propofol influence oxygen radical production of neutrophils?

The effects of etomidate in an alcoholic vehicle and in a lipid-emulsion as well as those of propofol on N-formyl-methionyl-leucyl-phenylalanine (FMLP-) and zymosan-induced oxygen radical production of neutrophils were examined and compared with the effects of their respective vehicles. Furthermore free-radical scavenging capacities of these medications were investigated. The dose-response effects of etomidate, propofol and their respective vehicles on neutrophil function were tested by FMLP- and zymosan-induced chemiluminescence of neutrophils and, in addition, in a cell-free chemiluminescence system. Effects of commercial preparations of etomidate were generally not drug-specific but due to the vehicles and/or to unphysiologic osmolality values. Propofol impaired chemiluminescence of neutrophils in a drug-specific manner, even in the therapeutic concentration range. Free-radical scavenging contributed to this depression of chemiluminescence of neutrophils by propofol. Different composition of the lipid-emulsions of etomidate and propofol resulted in either a stimulation or suppression of chemiluminescence of neutrophils. Propofol but not etomidate impairs chemiluminescence of neutrophils drug-specifically. Besides a potential interaction with the neutrophils, free-radical scavenging accounts for this suppression.

Etomidate↗
PubMed1976

Clinical use of etomidate.

Etomidate and methohexital were administered for induction of anesthesia in 45 patients who had to undergo open heart surgery. The anesthesia technique was otherwise standardised. Measurements of blood pressure and heart rate were obtained during a period of ten minutes after injection of the induction agent, and in a selected group of 16 patients cardiac index and stroke volume index were obtained by impedance cardiography. In the group of 45 patients, blood pressure one minute after induction was unchanged with Etomidate, but decreased (-6%) with methohexital. During intubation, important variations of systolic blood pressure occurred, specially with Etomidate (+ 36%) and less with methohexital (+ 21%). Heart rate increased in both groups during intubation (+ 41%) and returned towards starting value after ten minutes. In the group of 16 patients, cardiac index varied with Etomidate, decreasing during intubation (- 21%), increasing to + 32% and then returning to starting value afterwards. Heart rate increased with intubation (+ 39%) and was still somewhat elevated at ten minutes. Stroke volume index decreased with intubation (- 36%) and was still lower than the initial value at ten minutes (- 14%). With methohexital, cardiac index variations were less pronounced (+ 11%). Cardiac index was lower than the initial value at ten minutes (- 14%). Stroke volume index decreased with intubation (- 36%) and was still lower than the initial value at ten minutes (- 14%). This was compensated by an increase in heart rate. These measurements made during induction reflect the complex interaction of drug administration and technical manipulations. Blood pressure lowering one minute after the injection of methohexital can be ascribed to vasodilatation and myocardial depression. The important blood pressure and cardiac index variations observed with Etomidate are probably due to the short action and the lack of analgesic properties of this agent.

Adult↗
PubMedDate not supplied

[Cardiovascular effects of induction doses of the intravenous anesthetics, propofol, etomidate and thiopentone].

After reviewing the results of published comparative studies by numerous authors we have noticed that propofol, among the other intravenous anesthetics, has the strongest cardiovascular effects. The aim of this study was to compare the cardiovascular effects of induction doses of propofol, etomidate and thiopentone. A total of 165 female patients were randomly divided into three groups, and each one received a different anesthetic agent: propofol 2.5 mg/kg (n = 58), etomidate 0.3 mg/kg (n = 54) or thiopentone 5 mg/kg (n = 53). the patients were scheduled for abortion (gravidity up to 12 weeks of gestation) in out-patient conditions. Indirect registration of systolic and diastolic blood pressure and palpatory registration of radial pulse was performed: on admittance, immediately before the induction of anaesthesia and 2, 5 and 10 min thereafter. Following the administration of induction dose of propofol, a significantly greater decrease of systolic and diastolic blood pressure was observed then after the administration of etomidate or thiopentone. Slowing down of radial pulse was also more marked in propofol, then in etomidate or thiopentone group. The results of our study had shown that the induction dose of propofol had stronger effects on cardiovascular system, compared to the induction doses of etomidate or thiopentone.

Anesthesia, Intravenous↗
PubMed1999

Effects of thiopental, ketamine, etomidate, propofol and midazolam on the production of adrenomedullin and endothelin-1 in vascular smooth muscle cells.

Endothelin-1 (ET-1) and adrenomedullin (AM) are potent vasoconstrictive and vasodilative peptides. Vascular smooth muscle cells are one of the major producing tissues of these peptides. We investigated effect of thiopental, ketamine, etomidate, midazolam and propofol on the production of ET-1 and AM in cultured rat aorta vascular smooth muscle cells. Rat cultured vascular smooth muscle cells are used and the dose-dependent effect (10(-8)-10(-4) M) of thiopental, ketamine, etomidate, midazolam, and propofol on the production of ET-1 and AM was examined. The concentration of these peptides in the culture medium were measured by radioimmunoassay. Ketamine, etomidate, propofol and midazolam, but not thiopental, decreased the production of ET-1 at a concentration of 10(-4) M and the effect of midazolam is the most potent. Thiopental and etomidate produced small but significant increases in the production of AM at a concentration of 10(-4) M. Ketamine did not affect the production, but propofol and midazolam decreased the production at 10(-4) M and 10(-5) M, respectively. These results suggest that thiopental, ketamine, etomidate, propofol and midazolam differentially affect the production of ET-1 and AM in rat vascular smooth muscle cells.

Adrenomedullin↗
PubMed2000

Cardiovascular responses to propofol and etomidate in long-term instrumented rhesus monkeys (Macaca mulatta).

BACKGROUND AND PURPOSE: Cardiac and arterial responses to prescribed doses of propofol and etomidate in rhesus monkeys were compared. METHODS: Intravenously administered induction doses of propofol (2 mg/kg of body weight) or etomidate (1 mg/kg) followed by continuous intravenous infusions of propofol (200 microg/kg/min) or etomidate (100 microg/kg/min) were administered. Left ventricular and right atrial access catheters were implanted for long-term use, along with a transit-time flow probe on the ascending aorta, and pericardial electrocardiogram leads. A dual sensor 3-F micromanometer was used to measure left ventricular pressure and aortic pressure, and an active redirectional transit-time probe measured aortic flow. Noordergraaf's four-element model was used to estimate total peripheral resistance and systemic arterial compliance. RESULTS: Significant (P < 0.01) decreases in mean arterial pressure, heart rate, and myocardial contractility were accompanied by an increase in systemic arterial compliance associated with propofol and etomidate. Only minimal changes in left ventricular diastolic pressure, cardiac output, stroke volume, and total peripheral resistance were found for both drugs. The changes associated with propofol are comparable to results in human beings, whereas the changes associated with etomidate did not agree with results of published human studies. CONCLUSION: The significant cardiovascular alterations associated with both agents were attributed to reductions in heart rate, although the possibility exists that negative inotropic effects may have had a role.

Anesthetics, Intravenous↗
PubMed2005

[Effect of etomidate on hemodynamics in elderly and shock patients during general anesthesia induction].

OBJECTIVE: To investigate the effect of etomidate on the hemodynamics in elderly and shock patients during general anesthesia induction. METHODS: Totally 100 elderly patients or patients with hemorrhagic shock (ASA II -III ) undergoing surgery were studied. Anesthesia was induced with 4 microg/kg of fentanyl, 0.1 mg/kg of vecuronium and 0.2-0.3 mg/kg of etomidate, and the mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), stroke index (SI), cardiac output (CO), cardiac index (CI), cardiac acceleration index (ACI), left cardiac work (LCW), and left cardiac work index (LCWI) were recorded using thoracic electrical bioimpedance (TEB) hemodynamic monitoring system before induction and at 1, 2 and 3 min after etomidate injection as well as at 3 min after intubation. RESULTS: After etomidate injection, MAP, HR, SV, SI, CO, CI, ACI, LCW and LCWI were decreased significantly as compared with those before induction (P<0.05). MAP, HR, CO, CI and ACI at 3 min after intubation were higher than those before induction (P<0.05), and the other indices resumed the baseline level. The amplitudes of such changes in the recorded indices was below 20% of the baseline level in the course of anesthesia induction. CONCLUSION: Cardiovascular hemodynamics may vary slightly during the course of induction with etomidate, which is an ideal drug for anesthesia induction for elderly or shock patients with unstable hemodynamics.

Abdomen↗
PubMedDate not supplied

[Comparative study of propofol with thiopental and etomidate in anesthetic induction].

Anesthetic characteristics were studied in three homogeneous groups of twenty patients ASA I who underwent intravenous anesthetic induction with propofol 2 mg/kg; thiopental 5 mg/kg; or etomidate 0.3 mg/kg. The unconsciousness time was similar in the three groups, whereas awaking time and time of response and orientation were longer after thiopental and etomidate than after propofol. Intravenous injection of the three anesthetic agents was followed by a decrease in systolic and diastolic arterial pressure. Heart rate increased after thiopental and etomidate and had only slight fluctuations after propofol. After tracheal intubation there was a significant increase in systolic and diastolic arterial pressure and heart rate in thiopental and etomidate group. These changes were minimal after propofol. The highest number of complications occurred after etomidate.

Adult↗
PubMed1991

The influence of etomidate upon cerebral metabolites after complete brain ischaemia in the rat.

The influence of etomidate on post-ischaemic cerebral metabolism was examined in 1-year-old male Wistar rats. Ten rats were randomly allocated to each of three groups. Group 1 animals received etomidate for 60 min without undergoing cerebral ischaemia. In Group 2, there was a 60-min recovery period following 15 min of complete cerebral ischaemia. Etomidate was administered to Group 3 animals after 15 min of ischaemia. At the end of the study period, the brains were frozen in situ using liquid nitrogen. The cortex was then biochemically analysed. Considering glycolysis as well as the citric-acid cycle, the pattern of metabolite changes with etomidate application was almost identical to the pattern of spontaneous recovery. The content of energy-rich phosphates was reduced when Groups 2 and 3 were compared with the non-ischaemia group, indicating previous depletion of energy reserves of brain tissue. However, the energy charge as a parameter of energy balance had already been returned to normal values. We conclude that post-ischaemic application of etomidate has no favourable effect on recovery after complete cerebral ischaemia in the rat.

Animals↗
PubMed1990

Activation of epileptogenic activities by etomidate in electrocorticoencephalography (ECoG) during operation for epilepsy.

Epileptic surgery is a radical and ablative treatment for medically refractory epilepsy. Electrocorticoencephalography (ECoG) obtained by subdural strip electrodes should always be used during operation for precise localization of epileptic focus and mapping the extent of its involvement. But difficulties and ambiguities exist when the patient's ECoG is suppressed, either owing to the anticonvulsant used, being at the stage of posterictal period, or the effects of anesthetics during operation. Then, intentional activation of epileptogenic activity should be performed to locate the pathological focus in order to accomplish a successful surgical treatment. Etomidate has been considered as an abnormal electroencephalogram (EEG) activator and its use is not recommended in patients with epilepsy. But lesser dose of etomidate as an activator for ECoG has not been investigated. The study reported here established that etomidate as an hypnotic has not only anesthetic properties but, paradoxically, also activates epileptogenic activity. With the latter pharmacologic characteristic, etomidate can be used to deliberately activate the spikes of the potentially epileptogenic tissue, the delineation and localization of which may help the surgeon determine to what extent the pathological cortex be resected in surgical treatment of a refractory epilepsy. The current recommended dosage of etomidate at veterans General Hospital-Taipei for ECoG in epileptic surgery is 0.1-0.15 mg/kg/iv.

Adolescent↗
PubMed1978

[Effect of etomidate on cerebral blood flow and oxygen metabolism in man].

The effects of Etomidate on cerebral blood flow (C.B.F.) and cerebral oxygen consumption (C.02 C.) were studied in 13 patients in a neuroradiology department. Induction of anaesthesia was ensured using a standard dose of 15 mg of Etomidate, followed by a constant rate infusion (2.8 mg/kg/hour). Seven subjects were considered to be normal whilst six were suffering from tumour pathology. Under the influence of Etomidate, C.B.F. in the normal subjects decreased by 34 p. 100 and C.02 C. by 46.7 p. 100. The relationship between C.B.F. and arterial PC01 was studied under the influence of Etomidate: cerebral vasoactivity to C02 was maintained. A special study was made of focal changes in flow in patients with tumour pathology. Under the influence of Etomidate, there were zones of adaptation of flow, indicative of vasoparalysis situated opposite the tumour.

Anesthesia, General↗
PubMed1978

[Constant flow anesthesia using a combination of etomidate and fentanyl].

In 35 orthopaedic surgery patients (33 adults and 2 children), anaesthesia was obtained using an association of etomidate and fentanyl. Induction was obtained by injection from a syringe of a mixture of etomidate and fentanyl in an average dose of 21 mg for etomidate and 0,08 mg for fentanyl. Anaesthesia was maintained by constant dose of etomidate was 1.29 mg/kg/h and 4.96 microgram/kg/h for fentanyl. The mixture used for both induction and maintenance contained 1.3 mg of etomidate and 5 mg of fentanyl per ml. The results, value, indications and contraindications of this technique are described.

Adolescent↗
PubMed1986

The role of ascorbic acid in etomidate toxicity.

Etomidate, a short-acting hypnotic used in anaesthesia, has been shown to block steroidogenesis in man. The free imidazole radical in etomidate binds to cytochrome P450. Serious side-effects of etomidate have only been observed in guinea-pigs and in man, both species relying for restoration of ascorbic acid pools upon resynthesis and upon the daily dietary intake of vitamin C. It has been shown that ascorbic acid and not ACTH can increase serum cortisol concentration during etomidate infusion. Ascorbic acid even restores the ACTH/cortisol ratio to pre-operative values. It is therefore suggested that etomidate blocks ascorbic acid metabolism. Resynthesis of ascorbic acid cannot occur because of the blockade of cytochrome P450. Depletion of the ascorbic acid pool would then cause inhibition of steroidogenesis. This is the case in man and probably also in the guinea-pig. All other species can synthesize their own ascorbic acid from alpha ketogluconic acid.

Adrenal Glands↗
PubMed1988

[Myocardial metabolism as affected by propofol in geriatric patients. A comparison with etomidate].

This study was designed to compare the effects of propofol and etomidate on myocardial metabolism in elderly patients without clinical manifestations of heart failure or coronary artery disease. Twenty geriatric patients (age 65-82 years) scheduled to undergo elective major upper-abdominal surgery were studied and randomly allocated to two equal groups (propofol and etomidate). All patients were premedicated with piritramide, 7.5 mg, and promethazine, 25 mg, intramuscularly 1 h before arrival in the anesthesia room. Ten patients received propofol (1.5 mg/kg) for induction of anesthesia, followed by 10-min infusion of an induction dose; thereafter, anesthesia was maintained with a continuous infusion of 0.1 mg/kg per min. Ten patients received etomidate, 18 mg, for induction, followed by 2.4 mg/min for maintenance. Vecuronium was used for neuromuscular blockade. Cardiovascular dynamics were recorded while the patients were awake, 1-2 min after induction during apnoea, and 1, 5 and 30 min after tracheal intubation without surgical stimulation. Coronary blood flow (argon wash-in technique with sampling of blood from the coronary sinus), myocardial oxygen consumption and myocardial uptake of glucose, free fatty acids and lactate were determined in the awake state and 5 and 30 min after intubation. Arterial plasma concentrations of propofol (high-pressure liquid chromatography with fluorescence detection) and etomidate (gas chromatography) were measured every 5 min throughout the investigation period, which lasted 45 min. Overall mean plasma concentrations of propofol were 3.69 +/- 0.16 micrograms/ml and of etomidate 1.1 +/- 0.16 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

[Induction of anesthesia using propofol in comparison with etomidate].

Etomidate and propofol were compared for induction of anesthesia in a controlled study, including 24 male patients (ASA groups I and II). Following oral premedication with lormetazepam, the patients received propofol (2.5 mg kg-1; n = 12) or etomidate (0.3 mg kg-1; n = 12) over 60 s. For statistical analysis of the cardiovascular data (blood pressure and heart rate) four blocks were set up: A, baseline value including atropine dosage; B, value after induction of anesthesia; C, value after administration of halothane and vecuronium before intubation; D, value after intubation. The blood pressure fell slightly on administration of propofol while the heart rate remained nearly unchanged. Etomidate was associated with unacceptably high increases in blood pressure and heart rate. Myoclonia occurred in seven patients after etomidate and in two patients after propofol. A smoother mask ventilation was rated as a further advantage of propofol. Because of the unfavorable cardiovascular profile, the occurrence of myoclonia and poor mask ventilation, etomidate proved to be unsuitable for induction of anesthesia unless supplemented by an opioid and/or benzodiazepine. The high incidence of pain upon injection was considered to be a disadvantage of propofol.

Adolescent↗