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PubMed1986

[Propofol in comparison with etomidate for the induction of anesthesia].

In the present study propofol and etomidate were compared with respect to the effects on the cardiovascular system and its side effects in 100 patients ASA grade I-IV. Anaesthesia was induced with 2.2 mg kg-1 body weight propofol. Supplemented with opioids and benzodiazepins the dose diminished to 1.8 mg kg-1 body weight (18.2%). In comparison with etomidate after propofol decrease in blood pressure was more marked, especially when supplemented with opioids and benzodiazepins but without supplementation these values ranged within acceptable limits. Following intubation blood pressure and heart rate after propofol increased only to the base line values contrary to etomidate. Following propofol administration smooth induction with very good ventilation was remarkable. Myocloni and anaphylactoid reactions were not seen. Pain on injection was frequent but thrombosis and phlebitis were not observed. There was a considerably lower incidence of postoperative nausea and vomiting compared with etomidate. The investigators concluded: propofol can be recommended for induction of anaesthesia as an alternative to etomidate.

Adult↗
PubMed1987

Effect of etomidate on adrenal function in rats.

Etomidate, an imidazole derived hypnotic was applied to rats in order to find out whether repeated treatment with the drug, in doses exceeding those usually given to human, does alter adrenal morphology and function in terms of corticosterone and 11 beta-hydroxyandrostenedione (an androgen of exclusively adrenal origin) production, both in vivo and in vitro. A slight, dose-related decrease of plasma corticosterone and 11 beta-hydroxyandrostenedione was observed from etomidate concentrations 0.3 resp. 1.4 mg kg-1 body weight, respectively. In vitro, corticosterone production was reduced in the groups receiving 0.7 mg of the drug or more. Morphologically, only minute lipid hyperplasia was found after the highest dose of etomidate, associated with a significant increase of relative body weight. Administration of low dose of etomidate (approx. one half of that given usually to human) led to an increase of corticosterone production, indicating the reversibility of such effect. Etomidate did not stimulate enzymic oxidation of 11 beta-hydroxysteroids to the corresponding 11-oxosteroids, as do some blockers of 11 beta-hydroxylase.

Adrenal Glands↗
PubMed1986

Preservation of cerebral metabolites by etomidate during incomplete cerebral ischemia in dogs.

Changes in cerebral high-energy phosphate stores and lactate concentration (as evidence for cerebral protection) were studied in dogs treated with etomidate during incomplete global ischemia, which was of a magnitude insufficient to abolish neuronal synaptic activity (as evidenced by electrical activity on EEG). In six dogs the effects of etomidate (5 mg X kg-1) on the rates of adenosine triphosphate (ATP) and phosphocreatine (PCr) depletion and lactate accumulation during 9 min of oligemic hypotension to 31 mmHg were compared with six untreated dogs. In the dogs treated with etomidate the cerebral energy stores of ATP and PCr and the cerebral energy charge were maintained at higher levels than in the untreated dogs, and the cerebral lactate accumulation was significantly less. This effect of etomidate is similar to that of other anesthetics (thiopental and isoflurane) in this model. The authors conclude that in circumstances of ischemia that are insufficient to abolish neuronal synaptic activity, etomidate may improve tolerance of the brain to ischemia by decreasing cerebral metabolism through its suppression of neuronal synaptic activity.

Adenosine Triphosphate↗
PubMed1986

Facilitatory action of etomidate and pentobarbital on recurrent inhibition in rat hippocampal pyramidal neurons.

Biochemical studies have shown that the non-barbiturate anesthetic etomidate can interact in a stereoselective, barbiturate-like fashion with the GABA/benzodiazepine receptor complex, enhancing both benzodiazepine and GABA binding, but its electrophysiological effects upon the mammalian CNS are largely unknown. The present investigations were designed to characterize the electrophysiological effects of etomidate on the recurrent GABAergic inhibitory pathway in the CA1 region of the rat in vitro hippocampal slice and to compare the actions of etomidate to those of pentobarbital. Electrical stimulation of the alveus elicited a biphasic hyperpolarizing response, consisting of an initial bicuculline-sensitive GABAergic IPSP. This was followed by a second component, termed the late hyperpolarizing potential (LHP), which is thought to reflect an increase in potassium conductance. Both pentobarbital (100 microM) and (+)-etomidate (10 microM) markedly increased the duration of the initial GABA-mediated IPSP, and frequently increased its amplitude as well. However, no significant effects of either of these drugs were observed on the LHP. Together with previous biochemical findings, our data suggest that the depressant effects of etomidate and barbiturates on the nervous system may reflect a common action upon a stereoselective receptor site intimately associated with bicuculline-sensitive GABA receptors and the chloride ion channel.

Action Potentials↗
PubMed1985

Pharmacokinetic data analysis of alfentanil after multiple injections and etomidate-infusion in patients undergoing orthopedic surgery.

The pharmacokinetics of Alfentanil, a new short acting analgesic, and Etomidate, a very short acting hypnotic compound, were studied in patients undergoing orthopedic surgery. Anesthesia was induced by bolus i.v. injection of Alfentanil and Etomidate, whereas the maintenance was performed by continuous infusion of Etomidate and repetitive i.v. injections of Alfentanil. The kinetics of the analgesic can be described by a two-compartment model; the elimination half-life has a mean value of 64.8 +/- 38.5 min. No cumulation of the drug was seen in spite of multiple injections. Concerning Etomidate it is not clear whether one or two compartments are needed. The mean elimination half-life is 29.4 +/- 6.2 min. The results suggest a possible shortening of the half-life of Etomidate in the presence of Alfentanil.

Adult↗
PubMed1985

[Etomidate versus methohexital for intravenous anesthesia with alfentanyl and nitrous oxide-oxygen. A double-blind study of circulatory behavior and postoperative course].

This study compared both etomidate and methohexitone for intravenous anaesthesia with alfentanil and nitrous oxide/oxygen in 2 X 20 patients scheduled for ENT-surgery, in a double blind, random fashion. Apart from the alternative use of etomidate and methohexitone the anaesthetic procedure did not differ: After a small dose of alfentanil anaesthesia was induced by a bolus dose of the hypnotic followed by a continuous infusion of the drug. In case of inadequate analgesia alfentanil was injected. This technique provided a good quality of anaesthesia and a remarkable cardiovascular stability. Critical arterial pressures or heart rates never occurred. During the operation patients receiving etomidate exhibited a moderate rise in blood pressure and a significantly lower heart rate than patients anaesthetised with methohexitone. After some 90 min of anaesthesia patients awoke on the average 7 min after the end of the operation and could be extubated at once. During the first three postoperative hours there was no difference in recovery between groups. Whereas half an hour postoperatively the capacity of immediate memory was limited to 44 bit following etomidate and 48 bit following methohexitone, i.e. to 47 and 54% of its normal capacity, there was only a minimum but significant impairment of cerebral function after 3 h. There was no difference in the need for alfentanil. The dosage of etomidate and methohexitone was lowe than that reported in the literature. It proved to be impossible for the anaesthetist to decide which drug he was using. Hence both anaesthetic techniques compare favourably with each other.

Adolescent↗
PubMed1985

Etomidate versus thiopental for induction of anesthesia.

Hemodynamic changes and side effects of anesthesia induction with etomidate or thiopental were evaluated in 83 ASA class I or II patients. Patients were randomly assigned to one of 12 groups according to pretreatment drug (fentanyl, 100 micrograms, or normal saline intravenously), induction agent (etomidate, 0.4 mg/kg, or thiopental, 4 mg/kg), and maintenance anesthetic technique (isoflurane-oxygen, isoflurane-nitrous oxide-oxygen, or fentanyl-nitrous oxide-oxygen). The purpose of this experiment, of factorial design, was to evaluate the combined effects of two or more experimental variables used simultaneously and to observe interaction effects. There were significant increases in heart rate in all groups, especially after tracheal intubation. These increases were attenuated but not eliminated by fentanyl pretreatment. Systolic arterial blood pressure increased significantly after intubation and was not affected either by fentanyl pretreatment or by the induction agent. Patients in whom anesthesia was induced with etomidate had a greater incidence of pain on injection and myoclonus and a lesser incidence of apnea than patients in whom anesthesia was induced with thiopental. Fentanyl pretreatment significantly decreased the incidence of pain on injection and myoclonus, but it increased the incidence of apnea when anesthesia was induced with etomidate. The incidence of postoperative nausea and vomiting was similar after thiopental and etomidate and was unaffected by fentanyl pretreatment. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Infusion strategies to investigate the pharmacokinetics and pharmacodynamics of hypnotic drugs: etomidate as an example.

Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized.

Adult↗
PubMed1983

The safety of etomidate: a new intravenous anaesthetic induction agent.

Etomidate is a new non-barbiturate intravenous (i.v.) anaesthetic induction agent. This paper attempts to evaluate its overall safety based on studies on its effects on the cardiovascular and respiratory systems, intraocular pressure changes, apgar scores of newborns, plasma potassium changes and times to full recovery of consciousness. During etomidate anaesthesia there was good cardiorespiratory stability, reduced intraocular pressure, high apgar scores of babies delivered by caesarian section, and rapid recovery of consciousness. Unlike thiopentone, etomidate failed to attenuate suxamethonium-induced hyperkalaemia. The two major disadvantages of etomidate are the pain during i.v. injection and the development of myoclonic muscle movements during induction of anaesthesia. It is concluded that etomidate is quite safe from the above-stated points of view and rates very high when compared with other i.v. anaesthetic agents. However, it rates low with regards to the smoothness and pleasantness of induction of anaesthesia.

Adolescent↗
PubMed1978

Multinational evaluation of etomidate for anesthesia induction. Conclusions and consequences.

An overall analysis was made of 4763 case report forms from 45 anesthesiologists who used etomidate (Hypnomidate) routinely as an induction hypnotic in a total of 4127 surgical cases or compared it to thiopental in a series of controlled studies (325 on etomidate, 311 on thiopental). Premedication was standardized only in the controlled studies, and there were no restrictions on the use of anesthetic agents or techniques. Etomidate proved to be a safe and effective induction hypnotic. Sleep was deep and long enough to allow the normal induction and maintenance procedures. Blood pressure and heart rate remained remarkably stable in the 3 study groups. The incidence of respiratory depression was higher for thiopental; anesthesiologists' acceptance of etomidate was, however, reduced by the occurrence of venous pain during injection and of associated involuntary muscle movements. It is expected that these adverse effects will be largely eliminated by using the recently introduced new formulation of etomidate shortly after fentanyl.

Adolescent↗
PubMed1978

Venous pain and involuntary muscular movements during and after administration of etomidate. A comparison of two different formulations.

Anaesthesia was induced in 209 patients with etomidate, using either the two vidal formulation, i.e. a solution of 30 mg etomidate sulphate in 20 ml phosphate buffered solution or the new formulation i.e. 5ml ampoules containing 2% etomidate base in polyethylene glycol 1000 (PEG 1000), a ready-for-use solution. Amongst patients who received the two vial formulation of etomidate (n = 105), 26 reported pain on injection as compared with six patients who received etomidate in PEG 1000 (n = 104). In the former group, involuntary muscle movements were reported in 12 patients, three of them being disturbing. In the latter group slight involuntary muscle movements occurred in 15 patients, but were never disturbing.

Adolescent↗
PubMed1978

[Comparative investigations on the influence of etomidate, thiopentone and methohexitone on the intracranial pressure of the patient (author's transl)].

Intracranial pressure was measured under the influence of the new hypnotic etomidate (Dosage: 0.15 to 0.30 mg/kg b.w.). For comparison thiopentone (Trapanal: 3 to 4.5 mg/kg) and methohexitone (Brevimytal: 1 to 1.5 mg/kg) were given. The investigations were performed on 28 neurosurgical patients, who thereafter underwent surgery. The patients already had a closed or open ventricular catheter by means of which intracranial pressure was continuously measured. Etomidate lowered intracranial pressure. This happened during induction of anaesthesia and later during neuroleptanalgesia when etomidate was again injected. The pressure fall after etomidate was similar to that seen after thiopentone. It was at the time of induction 5 and later on 3mm Hg. Methohexitone showed a somewhat smaller effect. The cerebral perfusion pressure was calculated. When etomidate was given during the course of a neuroleptanalgesia the cerebral perfusion pressure merely decreased slightly (-7 per cent). Perfusion pressure remained stable after thiopentone and methohexitone.

Adolescent↗
PubMed1978

[Effects of etomidate and thiopentone on the primarily elevated intracranial pressure (ICP) (author's transl)].

In 8 patients having primarily an increased ICP, the effects of etomidate on ICP, arterial pressure and cerebral perfusion pressure (CPP) were studied by comparison with thiopentone. The patients received no premedication or basic anaesthesia and relaxation was obtained using pancuronium bromide. Blood gas analysis was performed at regular intervals to maintain a constant level of the arterial pCO2. Under the conditions of a reduced intracranial compliance and an elevated ICP, thiopentone lowered the arterial pressure considerably in contrast to etomidate. The primarily elevated ICP was reduced by both, etomidate and thiopentone to an extent of 27 per cent for more than 10 min. The considerable decrease of arterial pressure by thiopentone caused marked lowering of CPP during more than 10 min. In the same period etomidate did not influence either arterial pressure or CPP. These results show that for the induction of anaesthesia in neurosurgical patients having a primarily increased ICP etomidate has good properties.

Adolescent↗
PubMed1982

Continuous intravenous anesthesia with etomidate for carbon dioxide laser surgery of the larynx.

Twenty-five adult patients undergoing carbon dioxide laser surgery for benign and malignant disease of the larynx were given continuous infusion of etomidate at 60 micrograms . kg-1 . min-1 for induction of anesthesia. Maintenance anesthesia was continued using one of three infusion rates: 20 micrograms . kg-1 . min-1 (n = 5), 30 micrograms . kg-1 . min-1 (n = 10), and 40 micrograms . kg-1 . min-1 (n = 10) of etomidate in air-oxygen mixture. Muscular relaxation was achieved by continuous infusion of succinylcholine, and fentanyl was used for analgesia. Continuous etomidate infusion for induction of anesthesia resulted in a significant decrease in the incidence of pain along the injection site to 8% and involuntary muscular movements to 12% compared with 35% and 44%, respectively, in a group of 25 adult patients undergoing endoscopic procedure who received intravenously a single volus injection of etomidate (0.3 mg .g kg-1). However, a prolonged recovery time was observed after 30 minutes of continuous etomidate infusion.

Adolescent↗
PubMed1983

Etomidate as a rectal induction agent. Part I. A preliminary study in rats.

Etomidate (Hypnomidate; Janssen) 1,25% in sterile water was given rectally on 100 occasions to 50 male Long-Evans rats in doses ranging from 4 mg/kg to 12 mg/kg. The onset and duration of ataxia and hypnosis (i.e. loss of righting ability) were recorded. Ataxia was observed in all rats, even at the lowest dose levels. The lowest hypnotic dose was 6 mg/kg, when 2 out of 5 rats lost their righting ability. In all 50 rats given 8 mg/kg or more hypnosis occurred within 4 minutes (range 2-4 minutes, average 3,3 minutes), from which they recovered within an average of 10,4 minutes. The duration of hypnosis and time to full recovery from ataxia were dose-dependent. The rectal hypnotic dose of etomidate in rats has been found to be approximately ten times the documented intravenous dose. No mortality was recorded despite the rectal administration of ten times the intravenous lethal dose (LD50) for rats. Histological examination of the rectal and colonic mucosa showed that etomidate 1,25% in sterile water (pH 3,5) caused no significant mucosal change, but undiluted etomidate 12,5% (pH 1,8) caused haemorrhagic necrosis. We conclude that rectal etomidate 1,25% in sterile water is an efficient, predictable, evanescent and safe method of inducing anaesthesia in rats and warrants further investigation in clinical anaesthesia in children.

Anesthesia, Rectal↗
PubMed1995

Comparison of anesthesia induced by ketamine-fentanyl combination and maintained by propofol or etomidate in New Zealand white rabbits.

Ketamine-fentanyl-propofol and ketamine-fentanyl-etomidate combinations were administered intravenously to four groups of rabbits. Each group received ketamine (30 mg/kg of body weight) and fentanyl (0.025 mg/kg) for anesthesia induction. Either propofol or etomidate was administered by an infusion pump to maintain anesthesia. The rabbit's responses to noxious stimuli were determined before anesthesia was induced and at 10-min intervals thereafter until the rabbit recovered. The effects of the anesthetic combinations on the cardiopulmonary system were measured by monitoring respiratory and heart rates, blood pressure, and arterial blood gas tensions. Etomidate infused at the rate of 0.2 or 0.1 mg/kg/min could maintain surgical anesthesia with fewer effects on the cardiopulmonary system for 40 and 30 min respectively. However, the high mortality and side effects such as hemolysis in these two groups preclude the clinical use of etomidate for anesthesia maintenance. Propofol administered intravenously at rates of 0.8 and 0.4 mg/kg/min could maintain surgical anesthesia for 40 and 30 min respectively. However, relatively severe hypotension, hypercapnia, and respiratory acidosis were associated with this drug. Recovery from the propofol infusion was very rapid. Ketamine-fentanyl-etomidate combination is not recommended for clinical anesthesia in rabbits. Ketamine-fentanyl-propofol combination at a dosage of 30-0.025-0.4 mg/kg/min can be safely used for short-term surgery.

Anesthesia, Intravenous↗
PubMed1976

A dose-response relationship for etomidate, with some observations on cumulation.

In a within-patient comparison in 30 subjects, sleep was induced before e.c.t. by different doses of etomidate or methohexitone: etomidate 0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg or methohexitone 1.5 mg/kg. The duration of hypnotic effect was assessed by recording the time of spontaneous waking and later, of recovery of normal ocular muscle tone. Doubling the dose of etomidate produced a significant increase in both sleeping time and late recovery. Compared with methohexitone 1.5 mg/kg, etomidate 0.2 mg/kg provides an equal duration of sleep, but allows faster late recovery. In eight patients in whome sleep was maintained by repeated injections of etomidate 0.1 mg/kg as required, little evidence of cumulation was seen up to 27.5 min duration of sleep.

Adult↗
PubMed2000

Etomidate-facilitated hip reduction in the emergency department

OBJECTIVE: The authors report what they believe is the first reported use of etomidate to assist in the reduction of a major joint in an outpatient setting. METHODS: The authors review the case of an elderly woman with a total hip arthroplasty who experienced four spontaneous posterior hip dislocations in a 5-month period. Etomidate was successfully used in two dislocations where previous methods had failed. RESULTS: A 68-year-old woman, who 13 months earlier had an uncomplicated total left hip replacement, was transported to the same ED on four separate occasions for a spontaneous left hip dislocation. Radiographs in each instance were significant only for a posterior dislocation of the implant articulation. The first reduction in the ED was unsuccessful and required a closed reduction in the operating theater. Seventy-two hours later the second dislocation and subsequent reduction occurred in the ED using etomidate to facilitate muscle relaxation. The patient was subsequently discharged home. Similar scenarios were replayed in the next few months. CONCLUSIONS: Muscle relaxation is the key characteristic for the reduction of dislocated major joints. The risks of respiratory depression and hemodynamic alterations with sedation are not insignificant, especially at the extremes of age. In the present case, intravenous narcotics and sedative-amnestic agents did not result in sufficient muscle relaxation. Larger or repeated doses may have resulted in undesirable or dangerous side effects. Etomidate is a useful adjunct when cardiopulmonary disease is present. The rapid onset and recovery from etomidate make it an excellent choice for facilitating the reduction of hip dislocations in elderly patients with prior total hip replacements.

Journal Article↗