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PubMed1979

Comparison of the cardiopulmonary effects of etomidate and thiamylal in dogs.

The cardiopulmonary effects of etomidate, a nonbarbiturate, short-acting, IV anesthetic, were compared and contrasted with those of thiamylal sodium in chronically instrumented conscious dogs. Etomidate, when administered IV at dosages of 1.5 and 3.0 mg/kg of body weight, produced anesthesia lasting from 8 +/- 5 and 21 +/- 9 minutes, respectively. Heart rate, aortic blood pressure, left ventricular peak pressure, left ventricular end diastolic pressure, left ventricular contractile force, and myocardial oxygen consumption were unchanged after administration of either dose of etomidate; however, the dosage of 1.5 mg/kg produced significant (P less than 0.05) increases in respiratory rate and decreases in tidal volume. The minute volume remained unchanged from base-line values. Significant (P less than 0.05) decreases in tidal volume, arterial pH, and partial pressure of oxygen were produced, and minute volume remained unchanged when 3.0 mg of etomidate/kg of body weight was administered. Thiamylal sodium (8.0 mg/kg of body weight; given IV) produced anesthesia lasting for 14 +/- 5 minutes. Significant increases (P less than 0.05) in heart rate, arterial blood pressure, left ventricular peak pressure, and myocardial oxygen consumption were observed after IV administration. Left ventricular contractility was significantly (P less than 0.05) decreased. Respiratory rate was not significantly (P less than 0.05) affected by thiamylal although tidal volume and minute volume were decreased. These respiratory alterations resulted in significant (P less than 0.05) increases in the arterial partial pressure of carbon dioxide and decreases in pH and the partial pressure of oxygen. On the basis of cardiopulmonary function, etomidate offered rapid, safe, short duration anesthesia superior to that of thiamylal sodium.

Animals↗
PubMed1984

[Effect of etomidate and thiopental on ACTH and cortisol levels in serum. A prospective controlled comparative study in healthy probands].

A prospective controlled trial was carried out to determine the influence of etomidate and thiopentone on serum levels of cortisol and plasma levels of adrenocorticotrophic hormone (ACTH). There were two groups of nine healthy male volunteers: one group was given 0.3 mg/kg body wt. etomidate and the other 4 mg/kg body wt. thiopentone intravenously as a bolus. The hormone levels were measured before and every 30 min after injection of the anaesthetic over a period of 5 h. After thiopentone, cortisol levels dropped from a mean value of 13.2 micrograms/dl to a minimum of 9.0 micrograms/dl after 90 min and fluctuated between 9.2 and 10.9 micrograms/dl until the end of the experiment. Etomidate induced a more pronounced decrease in cortisol levels (from the 90th min the differences to the levels after thiopentone were statistically significant) from 13.9 micrograms/dl to a minimum of 5.0 micrograms/dl after 150 min. After 300 min cortisol levels had recovered only to 7.7 micrograms/dl. Plasma levels of ACTH were also different in the two groups. After thiopentone they decreased from 26.1 pg/ml to 18.2 pg/ml after 30 min, then increased to 30 pg/ml after 300 min. After etomidate, ACTH levels were as high at 30 min as before the injection and increased continuously to 67.1 pg/ml by the end of the experiment; from the 150th min on, the differences to the ACTH levels after thiopentone were statistically significant. We conclude from these hormone levels that a single intravenous bolus injection of thiopentone induces a slight but statistically significant and ACTH-independent decrease in adrenal cortisol secretion in healthy volunteers not stressed by an operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1977

Total intravenous anesthesia with etomidate. III. Some observations in adults.

An investigation was undertaken to determine the dosage of etomidate required to maintain sleep in adults undergoing surgery under regional local anesthesia. Premedication of diazepam 10 mg and atropine 0.5 mg was given, and sleep was induced and maintained by intermittent intravenous injections of etomidate 0.1/mg/kg, given whenever the patient would open his eyes on request. A mean overall dose of etomidate 17.4 microgram/kg/min. was required to maintain sleep, but great individual variation occurred, with older patients requiring less drug. The investigation was discontinued after 18 patients because of the frequency and intensity of side-effects, particularly pain and myoclonia, which caused the technique to be abandoned in two cases. It is considered unlikely that etomidate will prove to be the hypnotic of choice for a totally intravenous anesthetic technique in adults because of the high incidence of myoclonia after prolonged administration. In several patients uncontrollable muscle movements persisted for many minutes after complete recovery of consciousness.

Adolescent↗
PubMed1983

[Etomidate in Intralipid. A solution for pain-free injection].

A new formula for solution of etomidate has been studied. Like other lipophilic drugs etomidate may be dissolved in a non-irritating oil emulsion and used for intravenous injection. Etomidate in Intralipid was compared as induction agent with etomidate in glycolic solution (Hypnomidate) and with methohexitone (Brietal). No pain on injection occurred when etomidate/Intralipid was used.

Animals↗
PubMed1981

[A clinical study on the use of etomidate for induction and maintenance of anaesthesia (author's transl)].

The action of etomidate, a short-acting non-barbiturate hypnotic agent, was studied in three groups of patients. Used alone for induction it did not significantly alter either the pulse rate or the diastolic blood pressure. Systolic blood pressure fell slightly, but became stable after 2 minutes. The pH of the arterial blood was not significantly altered. pO2 and pCO2 showed changes indicative of respiratory depression during induction (group 1). Etomidate combined with fentanyl caused a moderate, significant fall in both diastolic and systolic blood pressure, but did not affect the pulse rate (group 2). In view of its inconsiderable haemodynamic effects etomidate can be regarded as a safe agent for induction. In doses of 10-20 micrograms/kilogramme bodyweight/minute infusions of etomidate (combined with fentanyl and muscle relaxants) provide adequate basal narcosis for most routine surgical operations. It cannot, however, be considered the anaesthetic of choice for major abdominal surgery which requires deep analgesia and full muscular relaxation (group 3).

Adult↗
PubMed1983

A pharmacokinetically designed etomidate infusion regimen for hypnosis.

An etomidate infusion regimen for hypnosis as part of balanced, totally intravenous anesthesia was designed to maintain plasma etomidate concentrations above the awakening concentration of 300 ng/ml while avoiding dose-related side effects. The etomidate infusion regimen of 0.1 mg/kg/min for 3 min, 0.02 mg/kg/min for 27 min, and 0.01 mg/kg/min for the remainder of the anesthesia was used together with intravenous bolus doses of fentanyl, droperidol, and pancuronium. This was evaluated in 11 patients and the kinetics of etomidate were reexamined. The anesthetic technique seemed clinically satisfactory for the infusion periods of 30-109 min. The average time and plasma concentration at the end of the infusion was 59.5 min and 583 ng/ml, at awakening was 9.3 min and 307 ng/ml, and at alertness was 19.5 min and 227 ng/ml. The main difference between the kinetics observed in the present study and those of previous studies is in the elimination clearance. The average plasma elimination clearance of the present study was 1210 ml/min and the whole-blood clearance was estimated to be 1357 ml/min, giving an apparent hepatic extraction ratio of approximately 0.90. The negative correlation of patient mass and elimination clearance normalized for body mass suggests that the terminal infusion should not be adjusted to body mass.

Adult↗
PubMed1981

Plasma protein binding of etomidate in different age groups and in patients with chronic respiratory insufficiency.

Plasma protein binding of etomidate, an intravenous anesthetic agent of basic nature, has been studied in healthy subjects of different age groups and in patients with chronic respiratory insufficiency. No differences were detected in the plasma protein binding of etomidate between young children and young adults, but elderly subjects exhibited decreased binding. Low levels of serum albumin may account in part for this decreased binding, but differences in the amount of etomidate bound per mol of albumin and in affinity constants for the binding were also apparent between young adults and elderly individuals. Although plasma protein binding of etomidate may also be decreased in patients with chronic respiratory insufficiency, further studies are needed to clarify this point.

Adult↗
PubMed1981

[The influence on the cardiovascular system of etomidate infusion anaesthesia combined with fentanyl/nitrous oxide (author's transl)].

Blood pressure and heart rate after the application of etomidate, soluble in alcohol 70% (a ml approximately or equal to 125 mg) and supplemented by fentanyl under controlled respiration with N2O/O2 as an continuous infusion for anaesthesia has been investigated during surgery. After the administration of fentanyl/etomidate (Hypnomidate)/succinylcholine the patients were intubated. Then the infusion of etomidate began with 1.5-2 mg/min for ten minutes, whereafter the dose was reduced to 0.15-0.25 mg/min. The continuous infusion of etomidate was stopped about 20 minutes before the end of the operation. The influence on the cardiovascular system during the whole operation was very minimal. The anaesthesia could be handled without any problems. Therefore the application of etomidate as a continuous infusion in combination with fentanyl and nitrous oxide 66% seems to be an effective technique of intravenous anaesthesia.

Adult↗
PubMed1980

[Etomidate and suxamethonium. The duration of relaxation and pseudocholinesterase activity. A clinical experimental study (author's transl)].

In ten health volunteers general anaesthesia was induced with etomidate (0.3 mg per kg body weight) and continued with NWO/O2 inhalation. Together with etomidate, suxamethonium (1.5 mg per kg body weight) was given simultaneously and the same dose reinjected as soon as the original muscle tone had returned completely. At equal intervals after the first and second injection the pseudocholinesterase was spectrophotometrically measured. No significant alteration of the enzyme activity was detectable at any time. Etomidate therefore does not inhibit the pseudocholinesterase. The two phases of relaxation were registered with the "finger-twitch" method and their duration compared. Etomidate did not prolong the time of relaxation after suxamethonium.

Adult↗
PubMed1980

[The influence of etomidate and thiopentone on the intracranial pressure elevated by nitrous oxide (author's transl)].

Intracranial pressure (ICP), arterial blood pressure (BP) and the calculated cerebral perfusion pressure (CPP) were investigated under standard conditions in 14 patients with severe brain injury. The influence of etomidate 0.3 mg/kg in comparison with thiopentone 6.0 mg/mg was evaluated both in patients with primarily elevated ICP (group I) and with an increase of ICP produced by nitrous oxide in oxygen (group II). In both groups of patients a marked ICP reduction (42%/26%) was produced by etomidate as well as by thiopentone. Whereas the reduction of CPP caused by thiopentone was enhanced by a moderate fall in BP, no influence on either BP or CPP was observed with etomidate. A regular fall in BP by about 10-15% was observed under nitrous oxide in oxygen alone, subsequently reducing the CPP by about 25%. These results emphasize the importance of the actions and interactions of different combinations of anesthetics in patients with acute brain injury in the prevention of further brain ischaemia. We believe that etomidate like thiopentone has brain protective properties in patients with cerebral hypoxia and must therefore be considered as an important therapeutic agent in such patients.

Blood Pressure↗
PubMed1980

Hypothermia and etomidate. Electroencephalographic aspects.

Etomidate 0.3 mg/kg was injected in 30 seconds to patients submitted to coronary surgery under ECC (output = 2.4 l/min/m2) and moderate hypothermia (29 degrees). The effect of this injection on the EEG was investigated in 3 patients by the traditional EEG monitoring (bipolar fronto-parietal derivation) as well as in 12 patients by the Berg-Fourier spectral analysis. At 29 degrees C etomidate induces an EEG depression in the form of burst suppression periods of 3 to 10 seconds lasting for about 4 minutes. After etomidate injection, the electric activity measured between 0.5 Hz and 32 Hz in 7 patients remained for 4.5 minutes (+/- 1.5 min.) lower than 20% of the value noted prior to the injection. The significance of this important EEG decrease as well as the possible protective effect of etomidate against cerebral anoxia are discussed.

Anesthesia, Intravenous↗
PubMed1997

Cortisol suppression in cats after induction of anesthesia with etomidate, compared with ketamine-diazepam combination.

OBJECTIVE: To evaluate duration and magnitude of adrenocortical function suppression after administration of etomidate to cats. ANIMALS: 15 purpose-bred, healthy cats. PROCEDURE: Cats were allotted to 2 groups. Anesthesia was induced with etomidate (ET, 2 mg/kg of body weight, i.v.; n = 8) or a mixture (KD, n = 7) of ketamine (5 mg/kg; i.v) and diazepam (0.25 mg/kg, i.v.). Anesthesia was maintained with halothane in all cats for 2 hours. ACTH gel (2.2 U/kg, i.m.) was administered 30 minutes after anesthesia induction. Blood samples for cortisol assay were taken before anesthesia induction (T -30), and before (T0) and at 30, 60, 120, 180, 300, and 420 minutes after ACTH administration. Anesthesia was discontinued after the T120 sample was obtained. RESULTS: After anesthesia induction, median (interquartile range [Q1-Q3]) cortisol values were significantly lower in the ET group (4 [3 to 4] micrograms/dl) at T0, compared with T -30 values and with T0 values in the KD group (5 [3 to 9] micrograms/dl). After ACTH administration, cortisol values in the ET group continued to decrease two- to threefold below T -30 values and remained decreased over the 2-hour anesthesia period. After ACTH administration, cortisol values increased twofold for 2 hours in the KD group, compared with T -30 values. One hour after anesthesia recovery, cortisol values in the ET group (3 [2 to 3] micrograms/dl) remained significantly lower than values in the KD group (9 [7 to 11] micrograms/dl) and preanesthesia values. By T300, both groups had cortisol concentration near 7 micrograms/dl, similar to preanesthesia values. CONCLUSION: Induction of anesthesia with etomidate caused suppression of adrenocortical function during 2 hours of halothane anesthesia and 1 hour of recovery in cats. Cortisol concentration did not return to baseline until after 2 additional hours. CLINICAL RELEVANCE: Results from these healthy cats suggest profound suppression of important stress hormones after anesthesia induction with etomidate, use of which could put critically ill cats at further risk.

Anesthesia↗
PubMed1999

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs.

PURPOSE: The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. METHOD: The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). RESULTS: Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. CONCLUSION: On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol.

Journal Article↗
PubMed1976

Effect of dose and premedication on induction complications with etomidate.

The induction characteristics of etomidate, a new i.v. hypnotic agent, were studied in 400 patients. Two hundred were premedicated with atropine and anaesthesia was induced with 0.2, 0.25, 0.3 or 0.35 mg/kg of etomidate. The remainder received one of four standard premedications and anaesthesia was induced with etomidate 0.3 mg/kg. Involuntary muscle movements occurred in more than 60% of patients receiving atropine alone. The frequency was reduced in the second group, but remained unacceptable in over 8% of patients. The incidence of other excitatory phenomena, such as cough and hiccup, was 10% approximately. Cardiovascular changes were minimal and no serious allergic phenomena were observed. Nausea and vomiting occurred after surgery in up to 30% of patients and was unrelated to the dose of etomidate or to premedication. Pain on injection occurred in up to 80% of patients when the drug was injected into small peripheral veins and occurred in more than 7% when using more normal veins.

Adult↗
PubMed1998

Etomidate revisited.

The major advantage of etomidate is its lack of cardiovascular side effects. In addition, etomidate is supposed to be neuroprotective. The side effects of etomidate include adrenal suppression and myocloni. A review of the recent literature on etomidate, its clinical use, its side effects and its mechanism of action was performed. Among others, major recent advances include a new drug preparation devoid of propylene glycol and its side effects, a new pretreatment technique that may reduce the incidence of myocloni, and the identification of its site of action in the central nervous system.

Journal Article↗
PubMed1975

[Neurophysiological investigation of the central nervous action of the hypnotic agent etomidate in cats (author's transl)].

1. The action of etomidate (0.125-4.0 mg/kg) injected intravenously or into the right atrium (time of injection about 1 sec) was investigated in cats under different central nervous conditions. 2. In decerebrate unanaesthetized animals and in lightly anaesthetized (pentobarbitone) animals with an intact CNS etomidate (0.25-4 mg/kg i.v.) caused a decrease of the spontaneous lumbar fusimotor activity and a strong depression of the fusimotor pinnareflex. Partly a reversal of this reflex from excitation to inhibition was observed. The effects occurred within 20 sec after the injection and lasted for 5-70 min, showing a clear non-linear relationship with the injected dose. 3. In encephale isole preparations etomidate (0.125-1 mg/kg injected intra-right atrially) caused distinct changes of the spontaneous EEB (decrease of frequency, increase of amplitude, occurrence of steeper waves) and a depression of the arousal reactions in the EEB following different stimuli (acoustic stimuli and different stimuli in the area of the face and eyes). These effects occurred within 8 sec after the injection and lasted up to 40 min, dependent upon the injected dose. 4. The character and the principal similarity of the results observed in decerebrate animals and in animals with intact CNS suggest that a considerable part of the action of etomidate consists of a depression of the activity and reactivity of the brain stem reticular formation.

Benzyl Compounds↗
PubMed1989

Etomidate infusions for the control of refractory status epilepticus.

Etomidate was used in eight patients to control status epilepticus which had been refractory to previous anticonvulsant therapy. Cortical activity was measured using a Cerebral Function Analysing Monitor and etomidate administered to achieve a 5 microV mean amplitude, avoiding burst suppression if possible with obliteration of any paroxysmal increase in amplitude. Neuromuscular blockade facilitated endotracheal intubation and mechanical ventilation, and corticosteroid replacement was provided. Rapid control of seizure activity, with cardiovascular stability, was obtained in all cases. Initially the mean infusion rate of etomidate required to achieve adequate suppression of cortical activity was 25 micrograms kg-1 min-1, but several patients exhibited tachyphylaxis. Weaning from the infusion presented difficulties in four patients due to recurring seizures. Adrenocortical function returned to normal within 96 hrs of stopping the infusion. At six month follow up, two patients had died, and two patients had significant reduction in cerebral function compared with their pre-morbid state.

Adult↗
PubMed1977

The effects of etomidate on arterial pressure, pulse rate and preganglionic sympathetic activity in cats.

We have studied the effects of etomidate on preganglionic cervical sympathetic activity, arterial pressure, and pulse rate. Normal and baroreceptor-denervated animals were studied. On the basis of findings it is concluded that etomidate exerts a minimal direct depressant action on the cardiovascular system. A profound depression of sympathetic tone was observed in spite of unaffected arterial pressure. Etomidate was also shown to possess a mild vagolytic action.

Animals↗