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PubMed1983

Profile of etomidate. A hypnotic, anticonvulsant and brain protective compound.

A review of the hypnotic, anticonvulsant and brain protective action of etomidate in animals shows that when given as a single injection in different animal species recovery from hypnosis is quick and that the safety margin is large. In dogs a bolus or infusion produces high amplitude theta activity on the electroencephalogram (EEG). During infusion burst suppression is seen. After high doses, behaviour and EEG changes returned to normal within 3 hours. The wide spectrum of anticonvulsant activity suggests that etomidate may be useful in the treatment of status epilepticus. Studies in various animal models show that etomidate might have brain resuscitative properties. In hypoxic-ischaemic conditions etomidate has some protective effects, where its anticonvulsant action is probably important. Lowering of the cerebral metabolic rate of oxygen consumption, and reducing the rise of intracranial pressure, coupled with immobilisation and prevention of hyperactivity enables animals to resist a hypoxic insult.

Anesthesia, Intravenous↗
PubMed1983

Plasma concentrations of etomidate during an intravenous infusion over 48 hours.

Two groups of six patients who had undergone major maxillofacial surgery and who required intermittent positive pressure ventilation, analgesia and sedation for about 48 hours postoperatively were studied. Analgesia in the postoperative period was maintained by an infusion of fentanyl 0.034 micrograms/kg/minute. Sedation was maintained with an intravenous infusion of etomidate such that the patients slept but opened their eyes when addressed and obeyed commands. An assay method was developed which enabled the measurement of plasma concentration of etomidate for periods of up to 24 hours after stopping the infusion. The steady state plasma concentration associated with the technique which produced the required degree of sedation was found to be 158 micrograms/litre (SEM 36). Etomidate exhibited linear pharmacokinetics and the decrease in plasma concentration of etomidate after stopping the infusion was consistent with a three-compartment pharmacokinetic model. All the patients recovered within 1 hour of stopping the infusion. The use of results obtained from the first group of six patients enabled a dosage regimen to be calculated that used a two stage infusion. This regimen enabled a reduction in the time taken to establish the appropriate degree of sedation in the second group of six patients. The two-stage infusion technique provides a means of rapid sedation and of maintaining a suitable clinical response for the prolonged periods that may be necessary when patients are transferred to an intensive therapy unit.

Anesthesia, Intravenous↗
PubMed1984

Alfentanil in short procedures. A comparison with halothane using etomidate or methohexitone for induction of anaesthesia.

Ninety patients, premedicated with temazepam 20 mg, undergoing suction termination of pregnancy, were studied. Forty patients received alfentanil (500 micrograms), and thirty halothane (1.5%) as supplements to either etomidate or methohexitone-nitrous oxide-oxygen anaesthesia. A further 20 patients received alfentanil 250 micrograms at induction of anaesthesia with methohexitone, followed by a further 250 micrograms immediately prior to the onset of surgery. Recovery was assessed by the time patients took to open eyes on command, to giving their correct date of birth, and to performing the 'p' deletion test. Satisfactory operating conditions were not obtained with the combination of etomidate and halothane. Faster recovery was seen in patients with either etomidate or methohexitone and receiving alfentanil (p less than 0.01) Testing by the 'p' deletion test showed impaired psychomotor performance at 30 minutes after cessation of anaesthesia in all groups compared with the pre-operative scores. Side effects leading to unsatisfactory anaesthesia were more frequent in patients who had received etomidate (p less than 0.01).

Abortion, Induced↗
PubMed1984

Etomidate by infusion for neuroanaesthesia. Kinetic and dynamic interactions with nitrous oxide.

An etomidate infusion was used to anaesthetise twelve patients for spinal surgery; six (group I) with 67% nitrous oxide and six (group II) with oxygen enriched air. Anaesthesia was induced with infused etomidate at a rate of 100 micrograms/kg/minute for 10 minutes and maintained at a rate of 10 micrograms/kg/minute. Recovery was assessed as the time to opening eyes on command (t1) and the time to giving correct date of birth (t2). In group I, mean value for t1 was 37.9 minutes and t2 59.1 minutes which is significantly longer than in group II where mean value for t1 was 9.0 minutes and t2 15.1 minutes. Blood was taken for estimation of etomidate levels. In group I the maintenance level was 501 ng/ml and the plasma clearance 20.9 ml/kg/minute. In group II the maintenance level was 367 ng/ml and plasma clearance 27.3 ml/kg/minute. Etomidate infusion appears to be a suitable alternative for neuroanaesthesia when nitrous oxide is contra-indicated.

Adult↗
PubMed1984

The inhibition by etomidate of the 11 beta-hydroxylation of cortisol.

The effect of a sleep-dose of etomidate on the plasma concentrations of cortisol, 11-deoxycortisol and 17 alpha OH-progesterone was investigated in eight patients; two other patients received thiopentone. Blood samples were collected at 0, 15 and 30 min after etomidate or thiopentone when an injection of tetracosactrin was given and a final sample was collected at 60 min. The plasma cortisol response to tetracosactrin was depressed below normal in patients given etomidate, and the 11-deoxycortisol response was very high, ranging from 36.4 to 184.7 nmol/l. The two patients that received thiopentone had a normal response to all steroids. The identity of the plasma 11-deoxycortisol in two patients was confirmed by high-performance liquid chromatographic separation and quantification by both spectrophotometric and radioimmunoassay measurements. These results suggest that a single dose of etomidate inhibits 11 beta-hydroxylation of cortisol.

17-Hydroxycorticosteroids↗
PubMed1980

Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentone and etomidate.

The occurrence of phlebitis, thrombosis, and thrombophlebitis after intravenous premedication with diazepam (0.15 mg/kg) dissolved in propylene glycol (Valium) or in polyethylene glycol (Diapam) or flunitrazepam (0.0125 mg/kg), and after intravenous induction of balanced general anaesthesia with thiopentone (4.0 mg/kg) or etomidate (0.3 mg/kg) was studied on the 7th and 14th postoperative days in 115 patients undergoing short-stay varicose vein surgery. Venous complications occurred most frequently after etomidate (43% at 14 days), thiopentone (23% at 14 days), and Valium (21% at 7 days). Diapam caused fewer venous sequelae (9% at 14 days) than Valium (18% at 14 days), but the smallest number of complications were noticed after flunitrazepam (8% at 7 days and none at 14 days). Venous sequelae were more severe and more extended after thiopentone and after etomidate than those after the diazepam preparations. It is concluded that venous complications after flunitrazepam premedication were mild and infrequent and that the incidence of such complications was unacceptably high after etomidate induction.

Adult↗
PubMed1982

Cardiovascular effects of etomidate used for induction and in combination with fentanyl-pancuronium for maintenance of anaesthesia in patients with valvular heart disease.

The effects of induction of anaesthesia by etomidate 3 mg kg-1 followed by continuous infusion of etomidate 2 mg min-1, fentanyl 0.01 mg.kg-1 and pancuronium 0.1 mg.kg-1 were studied in ten patients with valvular heart disease. No haemodynamic changes were seen injection of etomidate, but after fentanyl was given there was a significant decline in cardiac index (10%), in mean arterial systemic pressure (20%), in systemic vascular resistance (14%), in left ventricular minute work index (27%) and in right ventricular minute work index (21%) compared to the control values. After supplementing with pancuronium, no further significant changes were seen. There was no significant change in the pulmonary vascular resistance during the whole study. In conclusion, it appears that etomidate is a safe intravenous agent, and is worth further study, in particular in patients with minimal cardiac reserve requiring high inspired oxygen tension.

Adult↗
PubMed1986

Effects of cortisol suppression by etomidate on changes in circulating metabolites associated with pelvic surgery.

The effects of cortisol suppression by etomidate on the changes in circulating metabolites associated with pelvic surgery were investigated in healthy female patients. The use of etomidate resulted in the inhibition of cortisol secretion for 24 h compared with a control group of patients. However, the inhibition of steroidogenesis was not associated with a significant effect on blood glucose, blood lactate and plasma nonesterified fatty acid values, although the glycaemic response to surgery was consistently less in those patients who received etomidate. Heart rate and arterial pressure were significantly decreased during surgery in the etomidate group compared with the control group, but were similar in the postoperative period when the difference in plasma cortisol between the groups was greatest. The results suggest that cortisol has only a minor role in determining changes in circulating metabolites associated with surgery.

Anesthesia, General↗
PubMed1987

In vitro effect of etomidate and thiopental on granulocyte migration.

An increased mortality has been reported during long-term etomidate infusion. Inhibition of adrenal corticosteroid synthesis has been incriminated - but other factors related to host defence cannot be excluded. Using an under-agarose assay, we investigated the effect of etomidate on in vitro granulocyte migration. Unlike thiopental (50 micrograms/ml), etomidate (4-32 micrograms/ml) did not affect either spontaneous or directed migration. Impaired granulocyte migration is an unlikely cause of morbidity during long-term etomidate infusion.

Cell Movement↗
PubMed1989

Induction and recovery characteristics of propofol, thiopental and etomidate.

Propofol, thiopental and etomidate, with 20 patients in each group, were compared for anesthesia of short duration in women undergoing termination of pregnancy, with respect to: 1: pain on injection (equally often after propofol and etomidate, but more rarely after thiopental); 2: apnea following induction (no difference); 3: involuntary muscular movements more frequent after etomidate); 4: blood pressure (larger drop after propofol); 5: heart rate (greater increase after thiopental); 6: time to eye opening on command (longer after propofol); 7: Steward score on eye opening (no difference); 8: coin counting after 15, 30 and 60 min (performance better after propofol at 15 and 30 min, producing even shorter times than preoperatively at 60 min); 9: reaction time after 15, 30 and 60 min (performance better after propofol, producing even shorter times than preoperatively at 60 min. It is concluded that the faster recovery gives propofol an advantage over thiopental and etomidate in outpatient anesthesia.

Abortion, Induced↗
PubMed1983

Enhancement of diazepam and gamma-aminobutyric acid binding by (+)etomidate and pentobarbital.

(+)Etomidate and pentobarbital enhance [3H]diazepam and [3H]gamma-aminobutyric acid [( 3H]GABA) binding to cerebral cortex membranes. Both (+)etomidate and pentobarbital increase the affinity of [3H]diazepam for its binding sites. In contrast, they increase the Bmax of both the high- and low-affinity GABA receptor sites. The enhancement of [3H]diazepam and [3H]GABA by (+)etomidate and pentobarbital is blocked by GABA antagonists. These results indicate that hypnotic drugs such as (+)etomidate and pentobarbital, which are not structurally related, modulate diazepam and GABA binding sites via similar mechanisms.

Animals↗
PubMed1983

Adrenocortical suppression in multiply injured patients: a complication of etomidate treatment.

Three patients admitted to the intensive care unit after multiple injury were observed to suffer episodes of adrenocortical insufficiency suggested by clinical manifestations and confirmed by appropriately low cortisol concentrations. This prompted a prospective study of pituitary-adrenocortical function in six multiply injured patients, three of whom showed evidence of adrenocortical suppression. The only factor common to the six patients with abnormally low adrenocortical function was an association between periods of adrenocortical suppression and intravenous infusion of etomidate; when the drug was stopped adrenocortical function was restored, and renewed administration of the drug caused further inhibition. Etomidate infusions lasting only six hours were found to cause low, flat responses to short tetracosactrin tests and grossly raised plasma concentrations of adrenocorticotrophic hormone, suggesting direct suppression of the adrenal cortex. Median plasma cortisol concentrations measured at 0900 were significantly lower and median plasma concentrations of adrenocorticotrophic hormone measured at 0900 were significantly higher in the three patients studied prospectively who were receiving etomidate infusions compared with the three patients who did not receive etomidate (p = 0.05).

Adolescent↗
PubMed1990

An evaluation of combining thiopentone and etomidate for the induction of anaesthesia.

The characteristics of three combinations of thiopentone and etomidate [in the ratios of thiopentone (mg):etomidate (mg) of 5:1, 13:1 and 25:1] have been compared with the individual agents alone for the induction of anaesthesia. The incidence of pain on injection and abnormal movements was less with the combination containing the highest ratio of thiopentone to etomidate, when compared to etomidate alone. The mixtures did not otherwise confer any advantages over the individual agents.

Adult↗
PubMed2005

Sensory and motor effects of etomidate anesthesia.

The effects of anesthesia with etomidate on the cellular mechanisms of sensory processing and sensorimotor coordination have been studied in the active electric sense of the mormyrid fish Gnathonemus petersii. Like many anesthetics, etomidate is known to potentiate GABA(A) receptors, but little is known about the effects on sensory processing at the systems level. A better understanding is necessary for experimental studies of sensory processing, in particular regarding possible effects on the dynamic structure of excitatory and inhibitory receptive fields and to improve the knowledge of the mechanisms of anesthesia in general. Etomidate slowed the electromotor discharge rhythm, probably because of feedback inhibition at the premotor level, but did not alter the structure of the electromotor command. Sensory translation through primary afferents projecting to the cerebellum-like electrosensory lobe (ELL) was not changed. However, central interneurons and projection neurons were hyperpolarized under etomidate, and their spiking activity was reduced. Although the spatial extent and the center/surround organization of sensory receptive fields were not changed, initial excitatory responses were followed by prolonged inhibition. Corollary discharge input to ELL was maintained, and the temporal sequence of excitatory and inhibitory components of this descending signal remained intact. Later inhibitory corollary discharge responses were prolonged by several hundred milliseconds. The result was that excitatory reafferent sensory input was conserved with enhanced precision of timing, whereas background activity was greatly reduced. Anti-Hebbian synaptic plasticity evoked by association of sensory and corollary discharge input was still present under anesthesia, and differences compared with the nonanesthetized condition are discussed.

Action Potentials↗
PubMed2005

Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing's disease.

BACKGROUND: Paediatric Cushing's disease (CD) is rare, but is associated with considerable morbidity and requires effective treatment. Control of hypercortisolaemia is recommended prior to definitive therapy by transsphenoidal pituitary surgery with selective adenomectomy. We describe a 6.2-year-old male with severe hypercortisolaemia and life-threatening complications of Cushing's disease. Control of cortisol with metyrapone and ketoconazole was ineffective, and due to his deteriorating condition, the decision was taken to proceed to bilateral adrenalectomy. METHODS: Low-dose IV infusion of etomidate, with dose titration according to serum cortisol levels, was administered. RESULTS: Etomidate infusion (3.0 mg/h i.v.) decreased serum cortisol from 1,250 to 250 nmol/l within 24 h. Combined etomidate and hydrocortisone therapy was maintained to provide stable serum cortisol levels within the desired range for 12 days prior to successful bilateral adrenalectomy. CONCLUSION: In our experience, etomidate was effective and safe for short-term control of severe hypercortisolaemia in a severely ill child.

Adrenalectomy↗
PubMed2006

Relative adrenal insufficiency in etomidate-naïve patients with septic shock.

A recent study reported that 77% of patients with septic shock had relative adrenal insufficiency. However, all patients were mechanically ventilated and received high-dose inotropes. In addition, at least 24% had prior exposure to etomidate, a drug known to suppress adrenal function. We studied the incidence of relative adrenal insufficiency in etomidate-naïve patients with septic shock by analysing the adrenal response to high-dose short synacthen test in 113 consecutive patients from three university-affiliated intensive care units in Australia. Patients were allocated to three groups according to severity of illness and inclusion criteria of the trial of low dose hydrocortisone supplementation using information from patient records. Of the 113 patients, 98 had septic shock (Group A). The incidence of relative adrenal insufficiency in this subpopulation was 24.5%. Eighty-one per cent of patients with septic shock were mechanically ventilated (Group B). In this group, the incidence of relative adrenal insufficiency was 27.8%. Only 38 of the 98 patients with septic shock (39%) fulfilled inclusion criteria for the steroid supplementation trial (Group C). In this group, the incidence of relative adrenal insufficiency was only 34.2%. In all groups its presence was associated with a higher mortality. We conclude that the incidence of relative adrenal insufficiency in etomidate-naive septic shock patients was lower than observed in the steroid supplementation trial. Further, in those who fulfilled inclusion criteria for the trial, the incidence of relative adrenal insufficiency was half that reported by the trial. Our observations raise concerns about the generalizability of the findings of the above trial to etomidate-naïve patients.

APACHE↗
PubMed1978

Clinical evaluation of etomidate as an induction agent.

A comparative study between Etomidate and Thiopentone was carried out on 100 healthy female patients scheduled for post-partum abdominal sterilization under epidural analgesia. Our results show Etomidate to be a safe and effective induction agent, comparable to Thiopentone in having a rapid onset of action and rapid recovery time. The pulse rates and blood pressures remained relatively stable during the use of Etomidate. However, there was a high incidence of transient respiratory upsets while causing less respiratory depression than Thiopentone. The objectionable features of Etomidate are high incidence of pain on injection and involuntary muscular activity, which account for the low anaesthetist acceptance rate.

Adult↗
PubMed1988

Fentanyl pretreatment modifies anaesthetic induction with etomidate.

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I = 2 ml normal saline; Group II = 100 micrograms of fentanyl; Group III = 250 micrograms of fentanyl; Group IV = 500 micrograms of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P less than 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P less than 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 micrograms of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

Adult↗