For ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), when surgery is not feasible, or in cases of severe biochemical disturbances, immunosuppression or mental instability, medical therapy with agents such as etomidate is indicated. We present our experience in using etomidate for a 41-year old female with EAS secondary to a malignant mediastinal paraganglioma. We were able to demonstrate that etomidate can be used effectively to control severe hypercortisolism in a lower dose than previously described.
Etomidate ; ACTH Syndrome, Ectopic

BACKGROUND: Etomidate frequently causes myoclonus. Since the myoclonus is caused by a transient disequilibrium due to etomidate exposure in the CNS, we hypothesized that a slow rate of injection of the drug may decrease the incidence of myoclonus. We conducted a prospective randomized study to compare the effect of two different types of the etomidate injection rate on the incidence and severity of myoclonus. METHODS: Fifty patients were randomly assigned to the fast-injection group (group F) or slow-injection group (group S): Group F patients received etomidate (0.3 mg/kg) over ten seconds. The same dose was administered over two minutes for group S patients. The response to the injection of etomidate was graded on a four-point scale in a blinded manner. The time to loss of consciousness (LOC) was also recorded. RESULTS: The incidence of myoclonus was significantly lower (P < 0.001) in group S patients; 84% and 28% in group F and group S patients, respectively. The myoclonus was also significantly less severe in group S patients (P < 0.001). The time to LOC was significantly longer in group S patients (106 +/- 22 sec) than that of group F patients (49 +/- 18 sec, P < 0.001). CONCLUSIONS: With same dose, a slower rate of injection resulted in a lower incidence of myoclonus and can effectively reduce myoclonus without the use of a pretreatment agent.
Etomidate ; Humans ; Incidence ; Myoclonus ; Prospective Studies ; Unconsciousness

BACKGROUND: Etomidate injection is often associated with myoclonus. Etomidate injection technique influences the incidence of myoclonus. This study was designed to clarify which of the two injection techniques—slow injection or priming with etomidate—is more effective in reducing myoclonus. METHODS: This prospective randomized controlled study was conducted on 189 surgical patients allocated to three study groups. Control group (Group C, n = 63) received 0.3 mg/kg etomidate (induction dose) over 20 s. Priming group (Group P, n = 63) received pretreatment with 0.03 mg/kg etomidate, followed after 1 min by an etomidate induction dose over 20 s. Slow injection group (Group S, n = 63) received etomidate (2 mg/ml) induction dose over 2 min. The patients were observed for occurrence and severity of myoclonus for 3 min from the start of injection of the induction dose. RESULTS: The incidence of myoclonus in Group P (38/63 [60.3%], 95% CI: 48.0–71.5) was significantly lower than in Group C (53/63 [84.1%], 95% CI: 72.9–91.3, P = 0.003) and Group S (49/63 [77.8%], 95% CI: 66.0–86.4, P = 0.034). Myoclonus of moderate or severe grade occurred in significantly more patients in Group C (68.3%) than in Group P (36.5%, P < 0.001) and Group S (50.8%, P = 0.046), but the difference between Groups P and S was not significant (P = 0.106). CONCLUSIONS: Priming is more effective than slow injection in reducing the incidence of myoclonus, but their effects on the severity of myoclonus are comparable.
Etomidate ; Humans ; Incidence ; Myoclonus* ; Prospective Studies

For ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), when surgery is not feasible, or in cases of severe biochemical disturbances, immunosuppression or mental instability, medical therapy with agents such as etomidate is indicated. We present our experience in using etomidate for a 41-year old female with EAS secondary to a malignant mediastinal paraganglioma. We were able to demonstrate that etomidate can be used effectively to control severe hypercortisolism in a lower dose than previously described.
Etomidate ; ACTH Syndrome, Ectopic ; Cushing Syndrome

BACKGROUND: Etomidate frequently induces myoclonus when administered intravenously with bolus injection during anesthetic induction. This can be bothersome for the anesthesiologist. The dose of remifentanil appropriate for preventing myoclonus without side effects was investigated. METHODS: All patients with American Society of Anesthesiologists (ASA) physical status I-III were divided into three groups (n = 33 per group) according to the pretreatment effect site concentration of remifentanil (Ultiva, Glaxo-Wellcome, Munchen, Germany) of 0, 2 or 4 ng/ml (Group N: 0 ng/ml, Group R: 2 ng/ml, Group Q: 4 ng/ml) by a target controlled infusion (TCI) system. After a 0.3 mg/kg dose of etomidate was injected intravenously for over 1 minute for anesthetic induction, myoclonus was observed. Before the etomidate injection, the patients were pretreated with remifentanil and their side effects were monitored. RESULTS: The number of patients showing myoclonus was significantly different among the groups. The incidence of myoclonus was 81%, 12% and 0% (groups N, R, and Q, respectively, P < 0.01). Side effects including bradycardia and hypotension did not occur in either Group R or Q. Chest wall rigidity occured in 45% of patients in Group Q. CONCLUSIONS: Administration with a 2 ng/ml effect site concentration of remifentanil could reduce the incidence of myoclonus caused by etomidate bolus injection without chest wall rigidity.
Bradycardia ; Etomidate ; Humans ; Hypotension ; Incidence ; Myoclonus ; Piperidines ; Thoracic Wall

BACKGROUND: Etomidate is a rapid-acting sedative/hypnotic agent with little or no cardiovascular effect and a high therapeutic index. For this reason, etomidate has been used as an anesthetic induction and maintenance agent in patients with poor cardiovascular reserve. Bispectral index (BIS), a parameter derived from electroencephalography (EEG), has been proposed as a measure of anesthetic effect and is shown to correlate with increasing sedation and loss of consciousness. To establish its utility for this purpose, it is important to determine the correlation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for etomidate. METHODS: Eighteen adult patients scheduled for elective surgery, ASA physical status I or II, were included. Etomidate was administerd until loss of consciousness (loss of verbal contact) using syringe pump with a constant rate (150 ml/h) and patients were observed until regaining consciousness as decided by prompt verbal response on command of "open your eyes". A BIS was monitored, arterial blood samples were obtained for analysis of drug concentration, and the patients were evaluated for level of sedation by the responsiveness portion of the modified observer's assessment of alertness/sedation (OAA/S) scale. RESULTS: The BIS (r = 0.86) correlated significantly with the OAA/S more than the etomidate plasma concentration (r = 0.57). The BIS values, OAA/S, and blood concentrations were 50, 1.26, and 1337 ng/ml at induction and 75, 4.6, and 236 ng/ml at awakening, respectively. CONCLUSIONS: We concluded that the BIS accurately predicted level of sedation with etomidate during anesthesia induction, but the correlation between blood concentration and level of sedation was less strong.
Adult ; Anesthesia* ; Anesthetics ; Consciousness ; Electroencephalography ; Etomidate* ; Humans ; Plasma ; Syringes ; Unconsciousness

BACKGROUND: The properties of etomidate include hemodynamic stability, minimal respiratory depression, cerebral protection, and rapid recovery. However, its drawbacks include temporary inhibition of steroid synthesis, pain on injection, thrombophlebitis, myoclonus, nausea and vomiting. This study was done to discover the incidence of complications which could be observed during induction and the relationship between these complications and the age, sex and weight of Koreans. METHODS: Induction was done by etomidate 0.3 mg/kg and vecuronium 0.1 mg/kg. Pain on injection and hiccup were checked as present or absent. Myoclonus was checked as absent, mild, or severe. RESULTS: The incidence of pain on injection, hiccup and myoclonus were 4%, 10%, and 40% (mild 28%, severe 12%) respectively. There was no association between pain on injection and hiccup or myoclonus. Hiccup and myoclonus had some association (Gamma 0.774). Logistic regression revealed that there was no association between pain on injection or hiccup, and sex, age or weight. Myoclonus had some association with age and weight. The occurrence of myoclonus could be estimated by the following equation. log[ Fj(x) / { 1 Fj(x) } ] = aj 0.061 age 0.019 weight j = 1, 2 As age or weight increased, the myoclonus was more likely to fall at the low end (i.e., absence). CONCLUSIONS: The incidences of the pain on injection, hiccup and myoclonus were 4%, 10% and 40% respectively. The hiccup and the myoclonus had some positive association. The occurrence of myoclonus decreased as age or weight increased.
Etomidate* ; Hemodynamics ; Hiccup ; Incidence ; Logistic Models ; Myoclonus ; Nausea ; Respiratory Insufficiency ; Thrombophlebitis ; Vecuronium Bromide ; Vomiting

BACKGROUND: Etomidate is a rapid acting sedative agent used for the induction of general anesthesia. One of the side effects of etomidate limiting its usage is myoclonus. This study was designed to determine whether a small dose of midazolam decreases the incidence of myoclonus after infusion of etomidate. METHODS: Eighty ASA physical status 1 or 2, 16-60 year old patients undergoing elective surgery were randomly allocated into two groups. Group 1 (n = 40) received normal saline 0.04 ml/kg and group 2 (n = 40) received midazolam 0.04 mg/kg 3 minutes before the administration of etomidate 0.3 mg/kg. We measured and compared the incidence, severity, onset time and duration of myoclonus, and blood pressure and heart rate. RESULTS: There were significant differences in the onset time and severity of myoclonus, but no significant differences in the incidence and duration of myoclonus. Systolic blood pressure was significantly higher in group 1 than group 2 at 3 minutes after pretreatment drug administration, immediatly after etomidate administration and 3 minutes after etomidate administration. CONCLUSIONS: An infusion of 0.04 mg/kg midazolam 3 minutes before etomidate decreases the severity of myoclonus and the onset of myoclonus.
Anesthesia, General ; Blood Pressure ; Etomidate* ; Heart Rate ; Humans ; Incidence ; Midazolam* ; Myoclonus*

BACKGROUND: Etomidate is used as a fast-acting hypnotic with few cardiovascular effects to induce anesthesia in patients with a poor cardiovascular reserve. The bispectral index (BIS) has been suggested to be a measure of the depth of anesthesia and correlates well with the level of consciousness. This study examined the population pharmacokinetics and pharmacodynamics of etomidate using nonlinear mixed effect (NONMEM) modeling and sigmoid Emax modeling. METHODS: Eighteen middle aged adults, with ASA physical status I or II, who were scheduled for elective surgery, were included. 0.2% etomidate was administerd at 150 ml/h until the patients lost consciousness. The patient recovered spontaneously until they regained consciousness, as determined by a verbal response. The BIS was determined and arterial blood samples were collected. The plasma concentrations were measured with high performance liquid chromatograhy (HPLC). NONMEM was used for population pharmacokinetic and sigmoid Emax model for pharmacodynamic analysis. RESULTS: The induction dose for the loss of eyelid reflexes was 0.38 mg/kg. The induction time from drug infusion to the loss of eyelash reflexes was approximately 3.5 minutes. This study took approximately 8.5 minutes from the start of drug infusion to the recovery of consciousness. The pharmacokinetic parameters were t(1/2alpha) = 1.1 min, t(1/2beta) = 1.9 min, t(1/2gamma) = 106.5 min, k(21) = 0.36 L/min, k(31) = 0.009 L/min, V(1) = 6.43 L, V(area) = 426 L, C(l) = 2.77 L/min. The pharmacodynamics were keo = 0.40 L/min, CE(50) = 1.0 microgram/mL, E(0) = 94, E(max) = 94 and gamma = 1.2. The performance error for the etomidate concentration was 0.14+/-0.99 (typical prediction) and -0.03+/-0.40 (individual prediction) and -0.09+/-1.00 and -0.001+/-0.13 for the BIS score. CONCLUSIONS: When compared with other previously published data, our pharmacokinetic parameters demonstrated a shorter half lives, a larger volume of distribution, and an increased clearance with significant interindividual differences. The pharmacodynamics showed a large interindividual variability. The reason for discrepancy might be the relatively short sampling time. However, further study will be warranted to improve the model performance in the future.
Adult ; Anesthesia ; Colon, Sigmoid ; Consciousness ; Etomidate* ; Eyelids ; Humans ; Middle Aged ; Pharmacokinetics* ; Plasma ; Reflex

BACKGROUND: Etomidate is used as a fast-acting hypnotic with few cardiovascular effects to induce anesthesia in patients with a poor cardiovascular reserve. The bispectral index (BIS) has been suggested to be a measure of the depth of anesthesia and correlates well with the level of consciousness. This study examined the population pharmacokinetics and pharmacodynamics of etomidate using nonlinear mixed effect (NONMEM) modeling and sigmoid Emax modeling. METHODS: Eighteen middle aged adults, with ASA physical status I or II, who were scheduled for elective surgery, were included. 0.2% etomidate was administerd at 150 ml/h until the patients lost consciousness. The patient recovered spontaneously until they regained consciousness, as determined by a verbal response. The BIS was determined and arterial blood samples were collected. The plasma concentrations were measured with high performance liquid chromatograhy (HPLC). NONMEM was used for population pharmacokinetic and sigmoid Emax model for pharmacodynamic analysis. RESULTS: The induction dose for the loss of eyelid reflexes was 0.38 mg/kg. The induction time from drug infusion to the loss of eyelash reflexes was approximately 3.5 minutes. This study took approximately 8.5 minutes from the start of drug infusion to the recovery of consciousness. The pharmacokinetic parameters were t(1/2alpha) = 1.1 min, t(1/2beta) = 1.9 min, t(1/2gamma) = 106.5 min, k(21) = 0.36 L/min, k(31) = 0.009 L/min, V(1) = 6.43 L, V(area) = 426 L, C(l) = 2.77 L/min. The pharmacodynamics were keo = 0.40 L/min, CE(50) = 1.0 microgram/mL, E(0) = 94, E(max) = 94 and gamma = 1.2. The performance error for the etomidate concentration was 0.14+/-0.99 (typical prediction) and -0.03+/-0.40 (individual prediction) and -0.09+/-1.00 and -0.001+/-0.13 for the BIS score. CONCLUSIONS: When compared with other previously published data, our pharmacokinetic parameters demonstrated a shorter half lives, a larger volume of distribution, and an increased clearance with significant interindividual differences. The pharmacodynamics showed a large interindividual variability. The reason for discrepancy might be the relatively short sampling time. However, further study will be warranted to improve the model performance in the future.
Adult ; Anesthesia ; Colon, Sigmoid ; Consciousness ; Etomidate* ; Eyelids ; Humans ; Middle Aged ; Pharmacokinetics* ; Plasma ; Reflex