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PubMed2000

Effects of propofol, etomidate, and pentobarbital on critical oxygen delivery.

OBJECTIVE: To test the hypothesis that propofol, etomidate, and pentobarbital increase critical oxygen delivery in a dose-dependent manner during progressive hemorrhage. DESIGN: Prospective, randomized laboratory investigation. SETTING: University laboratory. SUBJECTS: A total of 40 anesthetized, paralyzed, and mechanically ventilated dogs weighing 29.2+/-4.6 kg. INTERVENTIONS: Dogs were randomly assigned to be anesthetized with propofol (n = 13), etomidate (n = 13), or pentobarbital (n = 14) at either low or high dosages. At 30 mins after splenectomy, the dogs underwent progressive hemorrhage by successive withdrawals of 3-5 mL/kg arterial blood. MEASUREMENTS AND MAIN RESULTS: At each step of hemorrhage, oxygen consumption and oxygen delivery were determined. Oxygen consumption was obtained from expired gas analysis, and oxygen delivery was determined from thermodilution cardiac output and calculated arterial oxygen content. In each animal, critical oxygen delivery and critical oxygen consumption were obtained from a plot of oxygen consumption vs. oxygen delivery as the point of intersection of the two best-fit regression lines determined by a least sum of squares method. Critical oxygen extraction was obtained by dividing critical oxygen consumption by critical oxygen delivery. In the three groups, animals receiving the higher anesthetic infusion had a significantly higher critical oxygen delivery (propofol: 10.5+/-0.8 vs. 13.9+/-2.5 mL/min/m2, p < .05; etomidate: 10.1+/-0.7 vs. 13.4+/-3.0 mL/min/m2, p < .05; pentobarbital: 7.8+/-1.0 vs. 12.3+/-2.5 mL/min/m2, p < .01) attributable to a lower critical oxygen extraction ratio (propofol: 41.1+/-6.4% vs. 54.2+/-2.5%, p < .01; etomidate: 42.7+/-10.2% vs. 60.6+/-7.1%, p < .01; pentobarbital: 42.2+/-7.2% vs. 64.3+/-8.8%, p < .01). CONCLUSIONS: This study indicates that propofol, etomidate, and pentobarbital increased critical oxygen delivery in a dose-dependent manner. This effect was mainly related to a decrease in tissue oxygen extraction capabilities.

Anesthetics, Intravenous↗
PubMed2000

The safety of etomidate for emergency rapid sequence intubation of pediatric patients.

OBJECTIVE: To determine whether pediatric patients given etomidate for rapid sequence intubation (RSI) in the ED develop clinically important hypotension or adrenal insufficiency. METHODS: Retrospective review of 100 consecutive patients younger than age 10 years given etomidate for RSI in the ED at two academic medical centers. Data were abstracted from ED and in-patient medical records. Clinically important hypotension was defined as a decrease in systolic blood pressure (BP) measurement to below one standard deviation (SD) of mean normal for age. Clinically important adrenal insufficiency was defined as the need for exogenous corticosteroid replacement for suspected adrenal insufficiency at any time during hospitalization. RESULTS: BP measurements before and within 20 minutes after etomidate administration for RSI were recorded on 84 intubations (84%). The mean change in BP between pre-intubation and post-intubation measurements was a decrease of 1 mmHg (95% CI: -6 mm Hg to +7 mm Hg, P = 0.83). When expressed as a percentage of normal BP for age, the mean change in BP was a decrease of 1% (95% CI: -7% to +6%, P = 0.82). Four patients (4.8%; 95% CI: 1.3-11.7%) had a systolic BP decrease to below one SD of mean normal for age. Fourteen patients received corticosteroids during hospitalization, but none (0/99, 95% CI: 0-3.7%) for suspected adrenal insufficiency. CONCLUSIONS: We found no evidence of clinically important adrenocorticoid suppression and a low incidence of clinically important hypotension when using etomidate for emergent pediatric RSI. Because other induction agents may also result in hypotension, prospective comparison studies are needed to further evaluate the safety of etomidate in this patient population.

Adrenal Glands↗
PubMed1995

Propylene glycol toxicity caused by prolonged infusion of etomidate.

We describe a case of propylene glycol toxicity due to intravenous administration of etomidate for cerebral protection. A continuous etomidate infusion was titrated to burst suppression of the electroencephalogram during surgical resection of a large intracranial arteriovenous malformation. The etomidate formulation used (Amidate, Abbot) contains etomidate 2 mg/ml in a 35% propylene glycol vehicle. A total of 5 g/kg of the solvent was given during 12 h. Adverse effects of propylene glycol were observed including hyperosmolality with an increased osmolal gap, hemolysis, hemoglobinuria, and metabolic acidosis. Normalization of these metabolic and ionic alterations occurred after 12 h of discontinuation of the infusion. The potential toxicity of the solvent should be considered during long-term administration of etomidate.

Acidosis↗
PubMed2004

Double-blind placebo controlled study of the effects of etomidate-alfentanil anesthesia in electroconvulsive therapy.

The effect of etomidate and alfentanil on heart rate, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure was compared with etomidate and placebo during electroconvulsive therapy (ECT). We also studied the influence of alfentanil on seizure duration using both the cuff method and 2-lead electroencephalographs on the prevention of myoclonus induction by etomidate, on duration of apnea and on postictal agitation after ECT. We enrolled 21 consecutive patients in a prospective placebo-controlled, within patient blocked randomized study. Alfentanil significantly reduced heart rate, diastolic arterial pressure, and mean arterial pressure both before and after the stimulus. The increase in these variables during the convulsion was not affected, compared with placebo. Alfentanil had no effect on seizure duration. However, apnea duration was prolonged during the alfentanil sessions as compared with placebo (73 seconds). Alfentanil did not significantly reduce the occurrence of myoclonus after etomidate as compared with placebo, nor did postictal agitation after ECT appear more often with alfentanil. Alfentanil could be useful to reduce tachycardia and hypertension during ECT in high-risk patients without effects on seizure duration. Alfentanil itself has no proconvulsive effect in combination with etomidate.

Adult↗
PubMed2006

The effect of etomidate on intracranial pressure and systemic blood pressure in pediatric patients with severe traumatic brain injury.

OBJECTIVE: To evaluate the effects of single-dose etomidate in pediatric patients with intracranial hypertension after severe traumatic brain injury. METHODS: Patients admitted to the pediatric intensive care unit with severe traumatic brain injury were enrolled with the informed consent of their guardians. The experimental intervention was a single dose of etomidate 0.3 mg/kg intravenously. This dosage was administered only when enrolled patients had acute elevations of intracranial pressure (ICP) to over 20 mm Hg for over 5 minutes. ICP and mean arterial pressure (MAP) were monitored continuously. ICP and MAP values for 6 consecutive 5-minute intervals after etomidate administration were averaged for all patients and compared with baseline. RESULTS: Eight patients were enrolled. Mean ICP after etomidate administration was significantly lower than baseline ICP for each 5-minute interval (P < 0.05). The mean MAP for all patients increased from baseline during the first 5-minute interval, but this change was not statistically significant. No patient's MAP decreased below baseline at any time point. CONCLUSIONS: In pediatric patients with severe traumatic brain injury, single-dose etomidate administration resulted in statistically significant reductions in ICP and improvement in cerebral perfusion pressure without significantly altering MAP.

Adolescent↗
PubMed2004

The GABA-A beta3 subunit mediates anaesthesia induced by etomidate.

The i.v. agent etomidate exerts its anaesthetic actions through potentiation of gamma-aminobutyric acid-A receptors containing beta2 and beta3 subunits. It was recently shown that the beta2 subunit contributes to the sedative properties of etomidate, whereas the beta3 subunit is responsible for its anaesthetic properties. However, these studies evaluated anaesthetic effects in point mutation mice in which the effect of etomidate was decreased, but not abolished, at the beta2 subunit. Here we have used beta2 knockout mice to completely remove any contribution of the beta2 subunit to the effects of etomidate. Etomidate was equally anaesthetic in wildtype and knockout mice, thus further confirming that efficacy at the beta3 subunit only is sufficient to induce general anaesthesia.

Anesthesia↗
PubMed2006

Anesthesia and electroconvulsive therapy: a retrospective study comparing etomidate and propofol.

BACKGROUND: The choice of anesthetic can influence the efficacy of electroconvulsive therapy (ECT). In the UK, propofol is a popular induction agent for ECT, but is associated with higher stimulus charge, shorter seizures, and known to affect seizure threshold. Etomidate is an alternative induction agent but there are concerns over its adverse events and safety. OBJECTIVES: We examined the differences between propofol and etomidate in the real life situation of an ECT clinic by assessing their effect on (i) length of course of ECT (ie, number of treatments required to remission), (ii) adverse effects of each induction agent, (iii) the number of 'missed seizures,' and (iv) stimulus dose (charge in mC), which relates to seizure threshold. METHOD: Using a retrospective naturalistic study design, 94 patients were identified over a 36-month period in our ECT clinic, of which, 65 met the inclusion criteria. Of these, 36 had received etomidate and 29 had received propofol as induction agents throughout their course of ECT. RESULTS: Patients who received propofol had a significantly longer course of ECT, higher seizure thresholds, and increased amounts of electrical charge (mC) over their course. There were no significant differences in adverse events with either of the induction agents. CONCLUSIONS: When used for acute courses of ECT, propofol and etomidate are equally well tolerated as induction agents. Patients who received propofol had longer acute courses of ECT and, consequently, longer and costlier inpatient stays. Etomidate could be a better alternative induction agent in ECT.

Anesthetics↗
PubMed1983

Etomidate: an 'immunologically safe' anaesthetic agent.

A review of the important aspects of immunity and its disturbance by drugs is given, together with a resumé of the various immunological pathways involved in adverse anaesthetic reactions. Etomidate is unique amongst anaesthetic drugs in that it does not release plasma histamine. Between 1978 and 1982, five cases of possible reactions involving the use of etomidate were investigated. All involved only immediate widespread cutaneous flushing or urticaria, which was followed in two cases by extensive perioperative vomiting. The direct involvement of etomidate was uncertain. In 1982 two further cases were investigated which also involved hypotension. In both, suxamethonium and/or alcuronium had been used. The first case was repeated uneventfully when etomidate was used with pancuronium. The second case is as yet unresolved but the reaction was again probably caused by the muscle relaxants. The absence of severe reactions, and particularly cardiovascular effects, to etomidate leads the author to recommend its use in high risk patients, such as those with allergy or atopy and in those who have previously exhibited severe anaphylactoid responses.

Adult↗
PubMed1991

Plasma etomidate levels in mother and fetus.

The most commonly used induction agent in anaesthesia for Caesarean section is still thiopentone. The increasing incidence of Caesarean section for delivery of premature babies from a hostile environment may call in question the assumption that the dose of thiopentone received by the neonate will not cause depression in the hours following birth. Previous studies on thiopentone for Caesarean section have shown inconsistency in umbilical vein/maternal vein ratios. We have studied plasma etomidate levels in maternal and umbilical blood at the time of delivery to see whether equilibrium occurs with this agent. We were able to demonstrate an umbilical/maternal vein etomidate ratio of 0.5 (SD 0.18), with no relation to time in the range encountered. Also, the uterine artery/uterine vein etomidate ratio was 0.86 (SD 0.33), suggesting that etomidate uptake into the fetus is effectively complete. Further, in all cases the neonatal plasma etomidate levels were less than half those measured at recovery of consciousness in adults in other studies, despite a larger induction dose than is usually used.

Adult↗
PubMed1985

Basophil histamine release in asthma patients after in vitro provocation with Althesin and etomidate.

Our aim was to compare the histamine-releasing effect of etomidate and Althesin on basophil leukocytes from asthmatic patients and normal persons. Blood from eight asthmatic patients and six normal persons was tested for histamine release after in vitro provocation with etomidate and althesin. In the group of asthmatic patients there was a significantly higher histamine release after provocation with althesin than after provocation with etomidate at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was significantly higher histamine release for asthmatic patients than for normal persons after provocation with althesin at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was no difference between the asthma group and the normal group after provocation with etomidate. Data were analysed using Wilcoxon's and Mann-Whitney's rank sum tests. We conclude that asthmatic patients may risk bronchospasm during induction of anaesthesia with althesin, and that etomidate may be suitable intravenous anaesthetic for asthmatic patients.

Alfaxalone Alfadolone Mixture↗
PubMedDate not supplied

Interaction of extracellular albumin and intravenous anaesthetics, etomidate and propofol, on calcium signalling in rat airway smooth muscle cells.

It has been shown in vitro that general anaesthetics modify airway responsiveness via, at least partially, a direct inhibitory effect on calcium signalling in airway smooth muscle cells. However, in vivo, these anaesthetic compounds bind serum proteins. We have investigated the effect of exposure to extracellular albumin of freshly isolated airway smooth muscle cells on the propofol- and etomidate-induced inhibitory effect on calcium signalling. [Ca2+]i was measured by microspectrofluorimetry in rat isolated tracheal smooth muscle cells using the fluorescent dye indo-1. Propofol (3 x 10(-4) M) and etomidate (10(-4) M) were the lowest 'effective' concentrations that altered the [Ca2+]i response. This alteration consisted of a decrease in both the amplitude of the [Ca2+]i peak (from 358 +/- 13 nM to 65 +/- 15 and 108 +/- 27 nM for propofol and etomidate, respectively) and the percentage of responding cells (from 80% to 37 and 25% respectively) in response to the low concentration of ACh and a decrease in the Ca2+ oscillation frequency (from 9.9 +/- 0.3 min(-1) to 4.7 +/- 0.4 and 6.9 +/- 0.4 min(-1), respectively) in response to the high concentration of ACh. Increasing the concentration of albumin reduced the inhibitory effect of etomidate and propofol on the [Ca2+]i response to ACh. When extracellular albumin concentration was kept constant (20 g/L), increasing the concentration of etomidate by one log restored its inhibitory effect on the calcium signal. This study indicates that increasing the concentration of extracellular albumin reduces the inhibitory effect of intravenous anaesthetics on calcium signalling in airway smooth muscle cells. This report suggests that, in extrapolating in vitro dose-response relationships to those from in vivo conditions, the effect of the concentration of extracellular protein can be estimated.

Acetylcholine↗
PubMed2007

Etomidate reduces initiation of backpropagating dendritic action potentials: implications for sensory processing and synaptic plasticity during anesthesia.

Anesthetics may induce specific changes that alter the balance of activity within neural networks. Here we describe the effects of the GABA(A) receptor potentiating anesthetic etomidate on sensory processing, studied in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in vitro. Previous studies have shown that the ELL integrates sensory input and removes predictable features by comparing reafferent sensory signals with a descending electromotor command-driven corollary signal that arrives in part through parallel fiber synapses with the apical dendrites of GABAergic interneurons. These synapses show spike timing-dependent depression when presynaptic activation is associated with postsynaptic backpropagating dendritic action potentials. Under etomidate, almost all neurons become tonically hyperpolarized. The threshold for action potential initiation increased for both synaptic activation and direct intracellular depolarization. Synaptically evoked inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and prolonged. Current source density analysis showed that backpropagation of action potentials through the apical dendritic arborization in the molecular layer was reduced but could be restored by increasing stimulus strength. These effects of etomidate were blocked by bicuculline or picrotoxin. It is concluded that etomidate affects both tonic and phasic inhibitory conductances at GABA(A) receptors and that increased shunting inhibition at the level of the proximal dendrites also contributes to increasing the threshold for action potential backpropagation. When stimulus strength is sufficient to evoke backpropagation, repetitive association of synaptic excitation with postsynaptic action potential initiation still results in synaptic depression, showing that etomidate does not interfere with the molecular mechanism underlying plastic modulation.

Action Potentials↗
PubMed2006

Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department: an observational cohort study.

OBJECTIVES: To describe and analyze the intubating conditions and hemodynamic effects of etomidate in patients undergoing rapid sequence intubation (RSI) in the emergency department. METHODS: The authors conducted a prospective observational study of all patients who received etomidate for induction of RSI over a 42-month period in a large tertiary care teaching hospital. Intubating conditions were determined by the emergency physician for both sedation and paralysis and for technical difficulty using a five-point Likert scale. Hemodynamic effects were evaluated before, after, and every five minutes for 15 minutes following administration of etomidate. RESULTS: Etomidate was used for induction of RSI in 522 patients, all of whom were included in the final efficacy analysis, while 491 were included in the analysis of hemodynamics. Lidocaine and fentanyl were used as pretreatment in 65.1% and 26.1% of patients, respectively, while succinylcholine was the paralytic in 94.3% of intubations. Sedation and paralysis were rated as excellent or good in 88.1% and 8.8% of patients, respectively, while technical difficulty was very easy or easy in 60.7% and 19.0% of patients, respectively. Mean (+/- SD) baseline systolic blood pressure (sBP), diastolic blood pressure (dBP), and heart rate were found to be 132.7 (+/- 35.4) mm Hg, 69.5 (+/- 21.2) mm Hg, and 96.1 (+/- 26.2) bpm, respectively. Overall, there was a clinically insignificant elevation in sBP (p < 0.0001), dBP (p = 0.0002), and heart rate (p < 0.0001) immediately postintubation. Elevations in sBP persisted at five minutes (p = 0.0230) and ten minutes (p = 0.0254) postintubation. Diastolic blood pressure and heart rate returned to baseline at five minutes after intubation and remained stable throughout the 15-minute postintubation assessment period. In the subgroup of 80 patients with a preintubation sBP < 100 mm Hg, there was a 12.1-mm Hg elevation in sBP (p < 0.0001) and a 7.3-mm Hg elevation in dBP (p = 0.0001) immediately postintubation. This elevation persisted throughout the 15-minute postintubation assessment period. CONCLUSIONS: Etomidate appears to provide appropriate intubating conditions in a heterogeneous group of patients undergoing RSI in the emergency department. Hemodynamic stability appears to be present following administration of this agent, even in patients with low pre-RSI blood pressure. This attribute must be weighed against potential adverse effects of this agent, including adrenal suppression.

Adult↗
PubMed1984

Inhibition by etomidate of steroidogenesis in isolated bovine adrenal cells.

Adverse side effects of the anaesthetic etomidate have been indirectly linked with inhibition of adrenocorticoid synthesis. The present in vitro study has shown that this is a direct effect and indicated which biosynthetic reactions are affected by etomidate. Isolated bovine adrenocortical cells were incubated with and without 10(-8)M ACTH and with increasing doses of etomidate (0-625 ng/ml). ACTH-stimulated cortisol synthesis was significantly inhibited by a concentration of etomidate (25 ng/ml), which is much less than therapeutic plasma levels (100-500 ng/ml). Both basal and ACTH stimulated synthesis of cortisol, progesterone, 17 alpha hydroxyprogesterone and corticosterone were inhibited by 625 ng etomidate/ml whereas deoxycorticosterone output was more than doubled with this dose of anaesthetic. These observations suggest that etomidate inhibits mitochondrial cytochrome P450-dependent hydroxylation reactions in the adrenal steroidogenic pathway.

Adrenal Cortex↗
PubMed1984

Etomidate suppresses adrenocortical function by inhibition of 11 beta-hydroxylation.

We studied the effect of short term infusion of the imidazole-derived anesthetic agent etomidate on plasma concentrations of ACTH, cortisol, and the cortisol-precursors 11-desoxycortisol and 17-hydroxyprogesterone. During the infusion of etomidate, a significant increase in the peripheral concentration of ACTH occurred, while plasma cortisol concentrations decreased. After the end of the infusion, cortisol concentrations further decreased, while the concentrations of desoxycortisol and 17-hydroxyprogesterone increased. Furthermore, in in vitro experiments with isolated rat pituitary and adrenal cells, etomidate did not affect corticotropin-releasing hormone-induced ACTH secretion from pituitary cells, whereas ACTH-stimulated corticosterone secretion from adrenal cells was inhibited by addition of etomidate in concentrations which occur in plasma during and after infusion of the drug. These results lead to the conclusion that etomidate inhibits adrenal 11 beta-hydroxylation.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome.

Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications.

Acute Kidney Injury↗
PubMed1993

A comparison of the cerebral protective effects of etomidate, thiopental, and isoflurane in a model of forebrain ischemia in the rat.

We evaluated the effect of etomidate, thiopental, and isoflurane on ischemic neuronal injury in rats. Control group animals received 1.2% isoflurane. The animals in the etomidate and thiopental groups received an infusion of either etomidate or thiopental until electroencephalographic (EEG) burst-suppression was attained. In the fourth group, the isoflurane concentration was increased to 3% (sufficient to produce EEG burst-suppression). Forebrain ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension for 10 min. Three days after ischemia, two blinded observers evaluated neuronal injury in coronal brain sections stained with hematoxylin and eosin. Injury to the ventral CA1 of the hippocampus was less in the etomidate group than in the control group. Injury to the entorhinal cortex was less in the thiopental group than in the control group. Histopathologic outcome in animals anesthetized with 1.2% isoflurane and 3% isoflurane was not different. Although these data indicate that etomidate and thiopental might reduce ischemic injury in some structures, the magnitude of the protective effects observed was small.

Animals↗
PubMed1994

A comparison of two formulations for etomidate, 2-hydroxypropyl-beta-cyclodextrin (HPCD) and propylene glycol.

The unphysiologic osmolality of commercial preparations of etomidate dissolved in propylene glycol has limited its use as a drug to induce anesthesia. We wanted to determine whether hydroxypropyl-beta-cyclodextrin (HPCD) is a more suitable solvent than propylene glycol by comparing pharmacokinetics, pharmacodynamics, and side effects of etomidate preparations in each solvent. Twenty-four healthy, male volunteers, randomly assigned to either the male volunteers, randomly assigned to either the HPCD or the propylene glycol group received etomidate, 0.3 mg/kg, dissolved in one of the two test solvents. We recorded arterial blood pressure, heart rate, electrocardiogram, electroencephalogram, pain on injection, myoclonic movements, and venous sequelae. Systolic and diastolic blood pressure and heart rate were similar in both groups. Frequency and severity of pain on injection differed significantly between groups. In the propylene glycol group, five subjects suffered venous sequelae: in three, thrombophlebitis resolved after 5 days; in one, after 10 days; and in the other, after 12 days. In the HPCD group, only one subject suffered severe pain on injection and none had venous sequelae. We conclude that HPCD may be superior to propylene glycol as a solvent for etomidate. HPCD is associated with less pain, less thrombophlebitis, and no hemolysis without clinically important alteration of pharmacokinetics or pharmacodynamics of etomidate.

2-Hydroxypropyl-beta-cyclodextrin↗