Original Article
Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate
N Engl J Med 1984; 310:1415-1421May 31, 1984DOI: 10.1056/NEJM198405313102202
- Abstract
- Abstract
The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (±S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8±0.5 μg per deciliter and 0.5±1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450–dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11β-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate Inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used. (N Engl J Med 1984; 310:1415–21.)
Media in This Article
Figure 1,
Steroid Responses to Serial ACTH-Stimulation Tests in a Patient Receiving an Infusion of Etomidate.Figure 2
Effect of Etomidate on Conversion of Steroidogenic Precursors in a Mitochondrial Preparation from Rat Adrenal Glands.Article Activity
- Article
ETOMIDATE is an intravenous sedative-hypnotic that has been used for the induction and maintenance of anesthesia and for prolonged sedation of critically ill patients. The drug is administered by either bolus injection or continuous infusion1 and is characterized by a rapid onset of action and recovery,2 excellent cardiovascular stability,3 and the absence of histamine release.4 Although only recently available in the United States, etomidate has gained wide acceptance in Furope as an anesthetic for patients with cardiovascular instability5 and as a sedative for ventilator-dependent patients.6
Recently, an intensive-care unit in England reported an increased mortality rate7 associated with low levels of plasma Cortisol8 , 9 in patients receiving prolonged sedation with etomidate. To evaluate this possible drug effect further, we performed serial ACTH-stimulation tests measuring Cortisol and aldosterone in one patient receiving etomidate for continuous sedation and in four patients receiving etomidate during cardiac or vascular surgery.
Etomidate is a substituted imidazole, as is the imidazole antifungal agent ketoconazole, which has been shown to suppress cortisol production in patients.10 We have recently shown this inhibitory effect to result from a blockade of mitochondrial cytochrome P-450–dependent enzymes.11 To ascertain whether the adrenocortical suppression in patients receiving etomidate was mediated by a similar mechanism, we studied the drug's effects on steroidogenesis in rat adrenal mitochondria and intact adrenal cells and compared the results with those obtained with ketoconazole.
Methods
Studies in Patients
Prolonged Etomidate Infusion for Sedation
Case 1, a 38-year-old man with a history of alcohol abuse, was admitted to another hospital with a productive cough and a left pleural effusion. When his pulmonary function rapidly worsened, he-was intubated and transferred to the intensive-care unit at Stanford University Hospital, where a diagnosis of viral pneumonia complicated by adult respiratory-distress syndrome and hemodynamic instability was made. Sedation was a major problem early in the hospitalization, with alcohol-withdrawal syndrome superimposed on severe respiratory impairment. Initially, 2.5 to 5 mg of diazepam every three hours and 2 mg each of morphine sulfate and pancuronium hourly were required to suppress agitation and facilitate controlled mechanical ventilation. On the second day in the intensive-care unit, etomidate (Amidate, Abbott, Chicago), 2 mg per milliliter dissolved in 35 per cent (vol/vol) propylene glycol, was administered by continuous intravenous infusion. Although etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) produced effective sedation to control ventilation adequately, concern regarding propylene glycol toxicity prompted discontinuation of the infusion after 20 hours and a return to the initial sedation regimen for an additional three days (during which time a comparable degree of sedation was required). Subsequently, the patient improved and was ultimately discharged. ACTH-stimulation tests were performed before, during, and after the etomidate infusion, and plasma etomidate levels were measured during the infusion.
Etomidate for Cardiovascular Anesthesia
Pertinent clinical features of the four surgical patients studied (Cases 2 through 5) are shown in Table 1Table 1
Demographic and Drug-Dosage Data on Patients Undergoing Cardiac (Cases 2 and 3) and Vascular (Cases 4 and 5) Surgery.. The patients had normal preoperative hepatic and renal function and no evidence of adrenal or pituitary dysfunction. All patients were premedicated with an opiate and an antihistamine, and anesthesia was induced with a combination of fentanyl and etomidate. Patients undergoing cardiac surgery were maintained with fentanyl, nitrous oxide, and supplemental doses of etomidate (5 to 10 mg). Patients undergoing carotid surgery were maintained with isoflurane and nitrous oxide. After their operations, all patients received morphine sulfate for pain and diazepam for sedation. The total etomidate dose ranged from 0.2 to 0.7 mg per kilogram. ACTH-stimulation tests were performed 4 and 24 hours after the last dose of etomidate was given.Clinical Laboratory Studies
The rapid ACTH-stimulation test was performed by injecting 250 μg of synthetic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 ACTH (Cortrosyn, Organon, West Orange, N.J.), as an intravenous bolus. Cortisol levels were determined in plasma at 0, 30, and 60 minutes, with use of a specific radioimmunoassay12 after column chromatography.13 Levels of 11-deoxycortisol and ACTH were measured by specific radioimmunoassays.13 , 14 These assays were performed by the Endocrine Metabolic Center, Oakland, Calif. Normal values for this laboratory are as follows: cortisol, 5 to 25 μg per deciliter (0.1 to 0.69 μmol per liter); 1l-deoxycortisol, <0.5 μg per deciliter (<0.02 μmol per liter); and ACTH, 10 to 71 pg per milliliter (2 to 16 pmol per liter). A normal cortisol response to ACTH is a rise of at least 7 μg per deciliter (0.2 μmol per liter) above the basal cortisol level at either 30 or 60 minutes.15 Aldosterone was measured by a specific radioimmunoassay16 at 0 and 60 minutes by Endocrine Sciences Laboratory, Tarzana, Calif. Normal aldosterone.values are 3 to 16 ng per deciliter (83 to 440 pmol per liter), and the normal rise in aldosterone after ACTH stimulation in this laboratory ranges from 7 to 33 ng per deciliter (190 to 910 pmol per liter). Plasma etomidate levels were determined with a modification of a method using high-performance liquid chromatography.17
In Vitro Studies
To evaluate the effect of etomidate on enzymes in the steroidogenic pathway, a series of experiments was performed in which each steroidogenic intermediate was supplied as substrate and conversion products were assayed. Rat adrenal glands lack 17-hydroxylase activity, and the natural glucocorticoid produced is cortieostcrone, not cortisol. To estimate inhibitory potency, several concentrations of etomidate were compared with vehicle-treated controls as well as with ketoconazole. [3H]Cholesterol and [3H]11-deoxycorticoster-one ([3H]DOC) were added to a mitochondria-rich fraction because cholesterol-side-chain cleavage enzyme and 11β-hydroxylase are intramitochondrial. Intact adrenal cells were used to examine the effect of etomidate on the nonmitochohdrial enzymes 3β-hydroxysleroid dehydrogenase, Δ5-3 oxosteroid isomerase, and 21-hydroxylase.
Steroidogenesis by Rat Adrenal Mitochondrial Fractions
Mitochondria-enriched fractions were prepared from rat adrenal glands by the method of Mason et al.18 An aliquot of this mitochondrial fraction was preincubated with etomidate at concentrations of 0.5, 1.0, 5.0, and 25 μg per milliliter, with ketoconazole at a concentration of 5 μg per milliliter, or with saline (control), all at 37°C for 15 minutes under an atmosphere of 95 per cent oxygen:5 per cent carbon dioxide. One microcurie of [3H]DOC (47 Ci per millimole) or [3H]cholesterol (47 Ci per millimole) was then added to start thereaction. The incubation was continued for an additional five minutes, and the experiment was terminated by the addition of Folch reagent (chloroform:methanol, 2:1 vol/vol). After an overnight extraction and Folch wash,19 the radioactive steroid products were analyzed by reverse-phase high-performance liquid chromatography as previously described.11
Steroidogenesis by Isolated Rat Adrenal Cells
Isolated adrenal cells were prepared by collagenase digestion of adrenal glands freshly removed from male rats as previously described.10 Cells were preincubated with the study drugs or saline for 15 minutes as described above, then 1 μCi of [3H]progesterone (53 Ci per millimole) or [3H]pregnenolone (19.3 Ci per millimole) was added as substrate, and the incubation continued for 20 minutes. The experiment was terminated, and the radioactive steroid products were analyzed by high-performance liquid chromatography as described above.
Materials
Crystalline etomidate and ketoconazole were obtained from Janssen Pharmaceutica (Beerse, Belgium), standard steroids were from Steraloids (Wilton, N.H.), and Radio-labeled steroids were from Amersham (Arlington Heights, I11.).
Results
Studies In Patients
Prolonged Etomidate Infusion
The results of serial ACTH-stimulation tests in Case 1 are summarized in Figure 1Figure 1,
Steroid Responses to Serial ACTH-Stimulation Tests in a Patient Receiving an Infusion of Etomidate.. On the second day in the intensive-care unit (before etomidate), the unstimulated cortisol level was high (24 μg per deciliter [0.66 μmol per liter]), and the aldosterone level was low (1.3 ng per deciliter [36 pmol per liter]), presumably because of stress and intravenous saline administration, respectively. ACTH stimulation resulted in a doubling in the plasma cortisol level and a substantial rise in aldosterone level. On Day 3, during the etomidate infusion, the basal cortisol level was depressed to 4 μg per deciliter (0.1 μmol per liter). Results of the ACTH-stimulation test were clearly abnormal, with no incremental cortisol response and marked suppression of the aldosterone response. Although etomidate was discontinued on Day 3 after a 20-hour infusion period, the cortisol response to stimulation was still completely suppressed on Day 4 and only slightly improved on Day 5. The basal and ACTH-stimulated cortisol values on Day 7 were technically within normal limits, but markedly diminished as compared with the pre-etomidate pattern (Day 2). The aldosterone response remained suppressed through Day 7. The patient's clinical status was essentially unchanged over the five-day period during which adrenal function was assessed. In addition, there were no overt signs of acute adrenal insufficiency, as evidenced by changes in vasopressor requirements, electrolyte values, or routine blood tests.Before etomidate administration, the level of the cortisol precursor 11-deoxycortisol was appropriately low,20 and the ratio of cortisol to 11-deoxycortisol was 100 (Fig. 1). During the etomidate infusion, there was an increase in the 11-deoxycortisol level, resulting in a ratio of cortisol to 11-deoxycortisol of 0.6. After etomidate, 11-deoxycortisol levels rose dramatically and remained elevated as late as Day 7 (four days after cessation of etomidate), with ratios of cortisol to 11-deoxycortisol slowly increasing to 2.
Plasma etomidate levels ranged from 360 to 540 ng per milliliter during the 20-hour etomidate infusion—levels within the hypnotic concentration range.21 , 22 One hour after the infusion was discontinued, the plasma etomidate level had fallen to 210 ng per milliliter.
Etomidate for Cardiovascular Anesthesia
Plasma cortisol and aldosterone levels were normal before surgery in four surgical patients. After surgery, four hours after etomidate was last administered, basal plasma levels of ACTH were elevated in all four patients (Table 2Table 2
Cortisol and Aldosterone Responses to Postoperative 1–24ACTH Stimulation in Four Patients Receiving Etomidate for Induction or Maintenance of Anesthesia.). Despite this endogenous ACTH stimulus, cortisol and aldosterone values were moderately depressed. The response to exogenous ACTH stimulation was flat, with a mean (±S.D.) maximal increase for cortisol and aldosterone of only 1.8±0.5 μg per deciliter (0.05±0.01 μmol per liter) and 0.5±1.1 ng per deciliter (14±30 pmol per liter), respectively. Twenty-four hours after surgery a normal cortisol response and a probably normal aldosterone response to ACTH were seen in the two patients tested. There were no obvious signs of acute adrenal insufficiency (e.g., hypotension or hyperkalemia) in anypatient during the perioperative period.In Vitro Studies
Adrenal Mitochondrial Fractions
The ability of etomidate to inhibit steroidogenesis was first examined in a mitochondria-rich fraction, with [3H]DOC and [3H]cholesterol as substrates. The conversion of [3H]DOC substrate to [3H]corticosterone by the rat mitochondrial enzyme 11β-hydroxylase is illustrated in the lower panel of Figure 2Figure 2
Effect of Etomidate on Conversion of Steroidogenic Precursors in a Mitochondrial Preparation from Rat Adrenal Glands.. Under control conditions, mitochondria converted all available [3H]DOC to [3H]corticosterone. In contrast, the etomidate-treated mitochondria showed marked inhibition of [3H]corticosterone production and a large residual quantity of unconverted [3H]DOC substrate. The degree of inhibition was directly related to the etomidate concentration. Etomidate at 0.5 μg per milliliter (data not shown) was approximately equal to ketoconazole at 5 μg per milliliter in inhibiting 11β-hydroxylase, whereas etomidate at 5 μg per milliliter completely inhibited this enzyme.The other mitochondrial cytochrome P-450 enzyme studied, cholesterol-side-chain cleavage enzyme, was also inhibited by etomidate in a concentration-dependent manner (Fig. 2, upper panel). In the presence of excess [3H]cholesterol substrate, control mitochondria converted the [3H]cholesterol to [3H]pregnenolone, and small amounts were subsequently metabolized to form [3H]progesterone, [3H]DOC, and [3H]corticosterone. Etomidate-treated mitochondria produced these steroids from [3H]cholesterol in smaller amounts. The degree of inhibition was again directly related to the concentration of etomidate. Etomidate at 1 μg per milliliter (data not shown) was slightly less potent than ketoconazole at 5 μg per milliliter in the inhibition of cholesterol-side-chain cleavage activity, and etomidate at 5 μg per milliliter completely blocked enzyme activity.
Isolated Adrenal Cells
Isolated whole adrenal cells were used to examine the effect of etomidate on other enzyme activities in the steroidogenic pathway. When [3H]progesterone was employed as a substrate in the whole-adrenal-cell preparation (Fig. 3Figure 3
Effect of Etomidate on Conversion of Steroidogenic Precursors in Intact Rat Adrenal Cells., lower panel), etomidate did not inhibit conversion to [3H]DOC by the enzyme 21-hydroxylase. Similarly, when [3H]pregnenolone was the added substrate (Fig. 3, upper panel), conversion to [3H]progesterone by 3β-hydroxysteroid dehydrogenase and Δ5-3 oxosteroid isomerase was unaffected by etomidate. Etomidate concentrations of up to 25 μg per milliliter failed to block the conversion of either substrate to [3H]DOC (data not shown). In both experiments the expected blockade of the conversion of [3H]DOC to [3H]corticosterone by 11β-hydroxylase was again demonstrated by the accumulation of [3H]DOC in both the etomidate-treated and keto-conazole-treated cells. Under these conditions, the blockade was essentially complete at etomidate concentrations as low as 0.5 μg per milliliter.Discussion
Our study confirms previous reports that prolonged infusions of etomidate depress cortisol production.9 The findings presented clearly show that the site of the inhibition is within the adrenal gland. The serial ACTH-stimulation tests in Case 1 demonstrate a marked suppression of adrenal steroidogenesis during etomidate infusion, followed by a gradual recovery of glucocorticoid production during the four days of observation after cessation of etomidate. The aldosterone response to ACTH was suppressed even on Day 7, four days after etomidate. Similarly, there was a continued abnormal elevation of the level of 11-deoxycortisol, the immediate precursor to cortisol, suggesting a continued partial blockade of 11β-hydroxylase four days after discontinuation of the etomidate infusion. Our data suggest a more prolonged inhibition of 11β-hydroxylase than of cholesterol-side-chain cleavage enzyme. Inhibition of cholesterol-side-chain cleavage activity blocks the initial step in steroidogenesis, thereby limiting production of all subsequent intermediates in the pathway. Inhibition of this enzyme may explain the relatively low 11-deoxycortisol level on Day 3. Later, increasing levels of 11-deoxycortisol suggest diminishing blockade at the cholesterol-side-chain cleavage site, with persistent inhibition of 11βhydroxylase. We have no data on whether etomidate also inhibits the 18-hydroxylase conversion of corticosterone to aldosterone. However, both the prolonged inhibition of aldosterone responsiveness to ACTH and the fact that 18-hydroxylase is a mitochondrial cytochrome P-450–dependent enzyme suggest this possibility.
In the presence of enzyme inhibition, it is important to use a specific assay for measuring plasma cortisol because accumulation of cortisol precursors (e.g., 11-deoxycortisol) could result in falsely elevated values when less specific techniques are used. In our Case 1 for example, a falsely elevated plasma cortisol level of 36 μg per deciliter (0.99 μmol per liter) was measured on Day 4 by a conventional competitive-protein-binding assay (transcortin), as compared with levels of 18 μg of 11-deoxycortisol per deciliter (0.54 μmol per liter) and only 3 μg of cortisol per deciliter (0.08 μmol per liter) that were measured by highly specific radioimmunoassays.
In patients receiving etomidate during cardiac or vascular surgery, we found inhibitory effects on adrenal function four hours after administration of etomidate (Table 2). In a subsequent controlled study involving the use of either thiopental or etomidate for the induction of anesthesia,23 we found that the thio-pental (control) group had normal responsiveness to ACTH during the early postoperative period, with cortisol and aldosterone levels rising 20.1 ±8.1 μg per deciliter (0.554±0.22 μmol per liter) and 10.2±6.0 ng per deciliter (283± 166 pmol per liter), respectively. In the etomidate group, plasma cortisol and aldosterone levels failed to increase in response to ACTH administration. Although additional studies are needed to determine the magnitude and time course of adrenal suppression after various doses of etomidate, our case studies suggest that adrenal suppression resolved within 24 hours after a single dose of etomidate, whereas a prolonged infusion (20 hours) of etomidate produced adrenal suppression lasting at least four days.
Because etomidate has an imidazole structure, we suspected that its mechanism of steroid inhibition might be analogous to that of ketoconazole.11 Our data indicate that etomidate, like ketoconazole, blocks adrenal steroid synthesis by inhibiting the two mitochondrial cytochrome P-450–dependent enzymes in the glucocorticoid-synthetic pathway — namely, cholesterol-side-chain cleavage enzyme and 1lβ-hydroxylase. The blockade of glucocorticoid production appears limited to these two enzymes, since the in vitro experiments showed normal function of the three microsomal enzymes in the pathway. Although we did not measure sex-steroid production, we predict that the concentrations of these hormones will also be shown to be decreased, since they traverse the same initial steroidogenic pathway by means of cholesterol side-chain cleavage enzyme. Indeed, ketoconazole has been shown to inhibit testosterone production.24
In our experiments, etomidate was at least as potent as ketoconazole (on a mass basis) as an inhibitor of steroidogenesis. Although ketoconazole also binds to the glucocorticoid receptor and thereby exhibits antagonist activity at the target tissue,25 etomidate did not displace [3H]dexamethasone from glucocorticoid-receptor sites in rat kidney (data not shown). The ability of this imidazole-containing drug to inhibit mitochondrial cytochrome P-450–dependent enzymes and adrenal steroidogenesis suggests that this property may be present in other structurally related imidazole drugs. As suggested previously,10 , 11 , 24 imidazole drugs may be useful as therapeutic agents that could block steroidogenesis in Cushing's disease, hirsutism, and endocrine-dependent neoplasms (e.g., breast and prostate cancer). In addition, etomidate and other imidazole-containing drugs may inhibit hepatic cytochrome P-450 enzymes that are involved in drug metabolism and detoxification.
The clinical implications of the demonstrated effect of etomidate on steroidogenesis are unclear. Prevention of the glucocorticoid response to surgery during the perioperative period is considered a therapeutic goal by some anesthesiologists.26 On the other hand, it is well accepted that patients with adrenocortical insufficiency require glucocorticoid supplementation during surgery.27 In addition, acute adrenal failure with addisonian crisis may supervene when patients with limited adrenal reserve undergo severe stress.27 We are unaware of any reports of acute adrenal insufficiency after surgery in which etomidate has been a component of the anesthesia. Interestingly, in a patient receiving a prolonged infusion of etomidate, hypotension developed that was unresponsive to vasopressor drugs but improved with the administration of a glucocorticoid.28 Although one intensive-care unit has reported a markedly increased mortality rate in patients receiving prolonged infusions of etomidate,7 others have been unable to confirm this observation.29 Our patients did not have obvious signs of adrenal insufficiency. However, they were being carefully maintained with respect to blood pressure and fluid and electrolyte balance, so that clinical signs of adrenal insufficiency may have been masked.
In conclusion, our data suggest that the use of etomidate is followed by biochemical evidence of cortisol suppression and impaired responsiveness of both cortisol and aldosterone to exogenous ACTH. Although patients may not have overt signs of adrenal insufficiency, we believe they have inadequate adrenal reserve and may be at increased risk if complications occur. Until the clinical implications of these findings are clarified, we think that physicians should be aware of this side effect of the drug and be prepared to treat postoperative adrenal insufficiency in patients receiving the anesthetic etomidate. If the drug is used in critically ill patients, corticosteroid supplementation may be required. Further studies are necessary to ascertain whether the risks of adrenal suppression outweigh the benefits of this otherwise useful anesthetic agent.
Note added in proof: Since submission of our paper, two subsequent reports30 , 31 have described clinical signs consistent with acute adrenal insufficiency in patients who bad blunted cortisol responses to ACTH while receiving etomidate. These reports are consistent with our findings and indicate that adrenal insufficiency may follow prolonged etomidate infusion.
Supported in part by grants (GM 28825 and Al 20409) from the National Institutes of Health. Dr. Kan is the recipient of a National Research Service Award (AM 06962) from the National Institutes of Health.
We are indebted to A. Scott Connelly, M.D., for allowing us to participate in the care of bis patients; to C. Philip Larson, M.D., for his helpful review of the manuscript; to E. Price Stover for performing the glucocorticoid-receptor-binding studies; and to Virginia Gibbons for assistance in the preparation of the manuscript.
Source Information
From the Departments of Anesthesia and Medicine, Stanford University School of Medicine, Stanford, Calif. Address reprint requests to Dr. Feldman at the Division of Endocrinology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
- References
References
1
Tarnow
CrossRef | Medline2
Kay
CrossRef | Web of Science | Medline3
Criado
CrossRef | Web of Science | Medline4
Doenicke
CrossRef | Web of Science | Medline5
Gooding
CrossRef | Web of Science | Medline6
Edbrooke
CrossRef | Web of Science | Medline7
Ledingham
CrossRef | Web of Science | Medline8
Finlay
CrossRef9
Ledingham
CrossRef | Web of Science10
Pont
Web of Science | Medline11
Loose
CrossRef | Web of Science | Medline12
Abraham
CrossRef | Web of Science13
Abraham GE, Manlimos FS, Garza G. Radioimmunoassay of Steroids. In: Abraham GE, ed. Handbook of radioimmunoassay. New York: Marcel Dekker, 1977:591–656.
14
Kao
Web of Science | Medline15
Speckart
CrossRef | Web of Science | Medline16
Mayes
CrossRef | Web of Science | Medline17
Ellis
CrossRef | Web of Science | Medline18
Mason
CrossRef | Web of Science | Medline19
Folch
Web of Science | Medline20
Peterson RE. Metabolism of adrenal cortical steroids. In: Christy NP, ed. The human adrenal cortex. New York: Harper & Row. 1971:113.
21
Schüttler
Medline22
Fragen
CrossRef | Web of Science | Medline23
Wagner RL, White PF. Etomidate inhibits adrenocortieol function in surgical patients. Anesthesiology (in press).
24
Pont
CrossRef | Web of Science | Medline25
Loose
CrossRef | Web of Science | Medline26
Wood C, ed. Stress free anaesthesia: analgesia and the suppression of stress responses. London: Royal Society of Medicine, 1978.
27
Baxter JD, Tyrell JB. The adrenal cortex. In: Felig P, Baxter JD, Broadus AE, Frohman LA, eds. Endocrinology and metabolism. New York: McGraw-Hill, 1981:385–510.
28
Allolio
CrossRef | Web of Science | Medline29
Miranda
Web of Science | Medline30
Fellows
CrossRef | Web of Science | Medline31
Chee
CrossRef | Web of Science
- Citing Articles (154)
Citing Articles
1
Sivananthaperumal Shanmugasundararaj, Xiaojuan Zhou, Jens Neunzig, Rita Bernhardt, Joseph F. Cotten, Rile Ge, Keith W. Miller, Douglas E. Raines. (2013) Carboetomidate. Anesthesia & Analgesia1
2
Kurt Ruetzler, Peter Krafft, Michael Frass. Airway Management in Intensive Care Medicine. In: Benumof and Hagberg's Airway Management. Elsevier, 2013:916-954.e7.
3
Soft Drugs. In: Retrometabolic Drug Design and Targeting. John Wiley & Sons, Inc., 2012:77-258.
4
Roy Phitayakorn, Christopher R. McHenry. (2012) Perioperative considerations in patients with adrenal tumors. Journal of Surgical Oncology 106:5, 604-610
5
Ervin Pejo, Joseph F. Cotten, Elizabeth W. Kelly, Ri Le Ge, Gregory D. Cuny, Joydev K. Laha, Jifeng Liu, Xiang Jie Lin, Douglas E. Raines. (2012) In Vivo and In Vitro Pharmacological Studies of Methoxycarbonyl-Carboetomidate. Anesthesia & Analgesia 115:2, 297-304
6
Mohammad M. Ahasan, Rowan Hardy, Christopher Jones, Kirren Kaur, Dominika Nanus, Maria Juarez, Stuart A. Morgan, Zaki Hassan-Smith, Cécile Bénézech, Jorge H. Caamaño, Martin Hewison, Gareth Lavery, Elizabeth H. Rabbitt, Andrew R. Clark, Andrew Filer, Christopher D. Buckley, Karim Raza, Paul M. Stewart, Mark S. Cooper. (2012) Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells. Arthritis & Rheumatism 64:7, 2404-2413
7
C. Martin, T. Steinke, M. Bucher, C. Raspé. (2012) Perioperative Addison-Krise. Der Anaesthesist 61:6, 503-511
8
Antoine J. Cherfan, Yaseen M. Arabi, Hasan M. Al-Dorzi, Lisa P. Kenny. (2012) Advantages and Disadvantages of Etomidate Use for Intubation of Patients with Sepsis. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 32:5, 475-482
9
Martin H Iversen, Finn Økland, Eva B Thorstad, Bengt Finstad. (2012) The efficacy of Aqui-S vet. (iso-eugenol) and metomidate as anaesthetics in European eel (Anguilla anguilla L.), and their effects on animal welfare and primary and secondary stress responses. Aquaculture Researchn/a-n/a
10
J.-E. de La Coussaye, F. Adnet. (2012) Sédation et analgésie en structure d’urgence. Quelles sont les modalités de réalisation d’une sédation et/ou d’une analgésie pour l’intubation trachéale ?. Annales Françaises d'Anesthésie et de Réanimation 31:4, 313-321
11
Donglu Zhang, Oliver Flint, Lifei Wang, Ashok Gupta, Richard A. Westhouse, Weiping Zhao, Nirmala Raghavan, Janet Caceres-Cortes, Punit Marathe, Guoxiang Shen, Yueping Zhang, Alban Allentoff, Jonathan Josephs, Jinping Gan, Robert Borzilleri, W. Griffith Humphreys. (2012) Cytochrome P450 11A1 Bioactivation of a Kinase Inhibitor in Rats: Use of Radioprofiling, Modulation of Metabolism, and Adrenocortical Cell Lines to Evaluate Adrenal Toxicity. Chemical Research in Toxicology120302074331005
12
Inger Hilde Zahl, Ole Samuelsen, Anders Kiessling. (2012) Anaesthesia of farmed fish: implications for welfare. Fish Physiology and Biochemistry 38:1, 201-218
13
Lynne U. Sneddon. (2012) Clinical Anesthesia and Analgesia in Fish. Journal of Exotic Pet Medicine 21:1, 32-43
14
Nienke Molenaar, Ronald M Bijkerk, Albertus Beishuizen, Christel M Hempen, Margriet FC de Jong, Istvan Vermes, Gertjan van der Sluijs Veer, Armand RJ Girbes, AB Johan Groeneveld. (2012) Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate. Critical Care 16:4, R121
15
Boris Jung, Noemie Clavieras, Stephanie Nougaret, Nicolas Molinari, Antoine Roquilly, Moussa Cisse, Julie Carr, Gerald Chanques, Karim Asehnoune, Samir Jaber. (2012) Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis. Critical Care 16:6, R224
16
R.A. Weber, J.J. Pérez-Maceira, J.B. Peleteiro, L. García-Martín, M. Aldegunde. (2011) Effects of acute exposure to 2-phenoxyethanol, clove oil, MS-222, and metomidate on primary and secondary stress responses in Senegalese sole (Solea senegalensis Kaup 1858). Aquaculture 321:1-2, 108-112
17
Joseph F. Cotten, Ri Le Ge, Natalie Banacos, Ervin Pejo, S. Shaukat Husain, James H. Williams, Douglas E. Raines. (2011) Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats. Anesthesiology 115:4, 764-773
18
Zaki Hassan-Smith, Mark S. Cooper. (2011) Overview of the endocrine response to critical illness: How to measure it and when to treat. Best Practice & Research Clinical Endocrinology & Metabolism 25:5, 705-717
19
M.J. Hannon, M. Sherlock, C.J. Thompson. (2011) Pituitary dysfunction following traumatic brain injury or subarachnoid haemorrhage – In “Endocrine Management in the Intensive Care Unit”. Best Practice & Research Clinical Endocrinology & Metabolism 25:5, 783-798
20
Tomás B. Corcoran, Samuel Hillyard. (2011) Cardiopulmonary aspects of anaesthesia for the elderly. Best Practice & Research Clinical Anaesthesiology 25:3, 329-354
21
Y. Nyman, K. von Hofsten, C. Ritzmo, S. Eksborg, P. A. Lonnqvist. (2011) Effect of a small priming dose on myoclonic movements after intravenous anaesthesia induction with Etomidate-Lipuro in children. British Journal of Anaesthesia 107:2, 225-228
22
Chhaya V. Sharma, Simon Stacey, Paul Yate. (2011) Reducing Post-Cardiopulmonary Bypass Delirium: More Ketamine or Less Etomidate?. Journal of Cardiothoracic and Vascular Anesthesia 25:3, 581-582
23
Vanessa M. Banz, Stephan M. Jakob, Daniel Inderbitzin. (2011) Improving Outcome After Major Surgery. Anesthesia & Analgesia 112:5, 1147-1155
24
David Borsook, Lino Becerra. (2011) CNS animal fMRI in pain and analgesia. Neuroscience & Biobehavioral Reviews 35:5, 1125-1143
25
Stuart A. Forman. (2011) Clinical and Molecular Pharmacology of Etomidate. Anesthesiology 114:3, 695-707
26
Mary K. Ziejewski, Howard M. Solomon, Dinesh Stanislaus, Robert L. Clark, Tacey E. White, April R. Apostoli. (2011) The potential role for corticosterone in the induction of cleft palate in mice after treatment with a selective NK-1 receptor antagonist, casopitant (GW679769B). Birth Defects Research Part B: Developmental and Reproductive Toxicologyn/a-n/a
27
Ann E. Thompson, Rosanne Salonia. Airway Management. In: Pediatric Critical Care. Elsevier, 2011:1590-1613.
28
Joseph D. Tobias. Anesthesia Principles and Operating Room Anesthesia Regimens. In: Pediatric Critical Care. Elsevier, 2011:1625-1637.
29
Peter J. Davis, Adrian Bosenberg, Andrew Davidson, Nathalia Jimenez, Evan Kharasch, Anne M. Lynn, Stevan P. Tofovic, Susan Woelfel. Pharmacology of Pediatric Anesthesia. In: Smith's Anesthesia for Infants and Children. Elsevier, 2011:179-261.
30
Stuart A. Forman. (2010) Molecular Approaches to Improving General Anesthetics. Anesthesiology Clinics 28:4, 761-771
31
Corinne M. Hohl, Carolyn H. Kelly-Smith, Titus C. Yeung, David D. Sweet, Mary M. Doyle-Waters, Michael Schulzer. (2010) The Effect of a Bolus Dose of Etomidate on Cortisol Levels, Mortality, and Health Services Utilization: A Systematic Review. Annals of Emergency Medicine 56:2, 105-113.e5
32
Letterio B. Santamaria, Daniela Schifilliti, Domenico La Torre, Vincenzo Fodale. (2010) Drugs of anaesthesia and cancer. Surgical Oncology 19:2, 63-81
33
Zachariah Thomas, Farooq Bandali, Karen McCowen, Atul Malhotra. (2010) Drug-induced endocrine disorders in the intensive care unit. Critical Care Medicine 38, S219-S230
34
K. Reinhart, F.M. Brunkhorst, H.-G. Bone, J. Bardutzky, C.-E. Dempfle, H. Forst, P. Gastmeier, H. Gerlach, M. Gründling, S. John, W. Kern, G. Kreymann, W. Krüger, P. Kujath, G. Marggraf, J. Martin, K. Mayer, A. Meier-Hellmann, M. Oppert, C. Putensen, M. Quintel, M. Ragaller, R. Rossaint, H. Seifert, C. Spies, F. Stüber, N. Weiler, A. Weimann, K. Werdan, T. Welte. (2010) Prävention, Diagnose, Therapie und Nachsorge der Sepsis. Der Anaesthesist 59:4, 347-370
35
K. Reinhart, F.M. Brunkhorst, H.-G. Bone, J. Bardutzky, C.-E. Dempfle, H. Forst, P. Gastmeier, H. Gerlach, M. Gründling, S. John, W. Kern, G. Kreymann, W. Krüger, P. Kujath, G. Marggraf, J. Martin, K. Mayer, A. Meier-Hellmann, M. Oppert, C. Putensen, M. Quintel, M. Ragaller, R. Rossaint, H. Seifert, C. Spies, F. Stüber, N. Weiler, A. Weimann, K. Werdan, T. Welte. (2010) Prävention, Diagnose, Therapie und Nachsorge der Sepsis. Intensivmedizin und Notfallmedizin 47:3, 185-207
36
Fethi Gultop, Taylan Akkaya, Nurdan Bedirli, Haluk Gumus. (2010) Lidocaine pretreatment reduces the frequency and severity of myoclonus induced by etomidate. Journal of Anesthesia 24:2, 300-302
37
Alexander Geppert. (2010) Gleiche Therapien bei kardiogenem und septischem Schock?. Wiener klinisches Magazin 13:2, 24-29
38
Benjamin A. Kohl, Stanley Schwartz. (2010) How to Manage Perioperative Endocrine Insufficiency. Anesthesiology Clinics 28:1, 139-155
39
Joseph F. Cotten, Stuart A. Forman, Joydev K. Laha, Gregory D. Cuny, S. Shaukat Husain, Keith W. Miller, Hieu H. Nguyen, Elizabeth W. Kelly, Deirdre Stewart, Aiping Liu, Douglas E. Raines. (2010) Carboetomidate. Anesthesiology 112:3, 637-644
40
Carrie Sims, Vicente Gracias. Adrenal insufficiency in critical illness. In: Trauma, Critical Care and Surgical Emergencies. CRC Press, 2010:358-361.
41
Laura R. Hopson, Richard B. Schwartz. Pharmacologic Adjuncts to Intubation. In: Clinical Procedures in Emergency Medicine. Elsevier, 2010:99-109.
42
Paul F. White, Matthew R. Eng. Ambulatory (Outpatient) Anesthesia. In: Miller's Anesthesia. Elsevier, 2010:2419-2459.
43
Benjamin A. Kohl, Stanley Schwartz. (2009) Surgery in the Patient with Endocrine Dysfunction. Medical Clinics of North America 93:5, 1031-1047
44
A. Geppert. (2009) Einsatz von inotropen und vasopressorischen Substanzen bei der akut dekompensierten Herzinsuffizienz. Intensivmedizin und Notfallmedizin 46:6, 407-414
45
Joseph F. Cotten, S Shaukat Husain, Stuart A. Forman, Keith W. Miller, Elizabeth W. Kelly, Hieu H. Nguyen, Douglas E. Raines. (2009) Methoxycarbonyl-etomidate. Anesthesiology 111:2, 240-249
46
Talmage D. Egan. (2009) Is Anesthesiology Going Soft?. Anesthesiology 111:2, 229-230
47
Erika Atucha, Friedrich Hammerschmidt, Ilse Zolle, Werner Sieghart, Michael L. Berger. (2009) Structure–activity relationship of etomidate derivatives at the GABAA receptor: Comparison with binding to 11β-hydroxylase. Bioorganic & Medicinal Chemistry Letters 19:15, 4284-4287
48
Lukas Brander, Tobias Haltmeier, Anna Suter, Peter Studer, Daniel Inderbitzin, Daniel Candinas, Andreas Vogt, Christoph Henzen, Jukka Takala, Stephan M. Jakob. (2009) Peri-operative adrenocortical response to low-dose (1 μg) ACTH and relation to postoperative complications in patients undergoing elective abdominal surgery. Surgery 146:1, 88-99
49
Volker Wenzel, Karl H Lindner. (2009) Best pharmacological practice in prehospital intubation. The Lancet 374:9686, 267-268
50
Kevin Y. Ching, Carl R. Baum. (2009) Newer Agents for Rapid Sequence Intubation. Pediatric Emergency Care 25:3, 201-211
51
Virginie Maxime, Olivier Lesur, Djillali Annane. (2009) Adrenal Insufficiency in Septic Shock. Clinics in Chest Medicine 30:1, 17-27
52
ELÖD Z. SZABÓ, IGOR LUGINBUEHL, BRUNO BISSONNETTE. (2009) Impact of anesthetic agents on cerebrovascular physiology in children. Pediatric Anesthesia 19:2, 108-118
53
Karis L. Tekwani, Hannah F. Watts, Kathleen H. Rzechula, Rolla T. Sweis, Erik B. Kulstad. (2009) A Prospective Observational Study of the Effect of Etomidate on Septic Patient Mortality and Length of Stay. Academic Emergency Medicine 16:1, 11-14
54
ENDOCRINE AND METABOLIC ADVERSE EFFECTS OF NON-HORMONAL AND NON-METABOLIC DRUGS. In: Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier, 2009:571-691.
55
GENERAL ANESTHETICS. In: Meyler's Side Effects of Drugs Used in Anesthesia. Elsevier, 2009:1-78.
56
Angus McEwan. Anesthesia for Children Undergoing Heart Surgery. In: A Practice of Anesthesia for Infants and Children. Elsevier, 2009:331-359.
57
E. Lecarpentier, J. Pottecher. (2009) Etomidato. EMC - Anestesia-Reanimación 35:3, 1-11
58
Michael H. Catenacci, Kaira King. (2008) Severe Sepsis and Septic Shock: Improving Outcomes in the Emergency Department. Emergency Medicine Clinics of North America 26:3, 603-623
59
Lowell Clark, Catherine Preissig, Mark R. Rigby, Frank Bowyer. (2008) Endocrine Issues in the Pediatric Intensive Care Unit. Pediatric Clinics of North America 55:3, 805-833
60
Joshua R. Dusick, Christina Wang, Pejman Cohan, Ronald Swerdloff, Daniel F. Kelly. (2008) Chapter 1: pathophysiology of hypopituitarism in the setting of brain injury. Pituitary
61
Marc Vinclair, Christophe Broux, Patrice Faure, Julien Brun, Céline Genty, Claude Jacquot, Olivier Chabre, Jean-François Payen. (2008) Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Medicine 34:4, 714-719
62
Brian T. Fengler. (2008) Should etomidate be used for rapid-sequence intubation induction in critically ill septic patients?. The American Journal of Emergency Medicine 26:2, 229-232
63
Marieke Brinker, Anita C. S. Hokken-Koelega, Jan A. Hazelzet, Frank H. Jong, Wim C. J. Hop, Koen F. M. Joosten. (2008) One single dose of etomidate negatively influences adrenocortical performance for at least 24
h in children with meningococcal sepsis. Intensive Care Medicine 34:1, 163-168
64
I.D. Welters, M. Leuwer. 10 General anesthetics and therapeutic gases. Elsevier, 2008:137-151.
65
E. Lecarpentier, J. Pottecher. (2008) Étomidate. EMC - Anesthésie-Réanimation 5:3, 1-10
66
Shekhar Venkataraman, Ricardo Munoz, Cristina Candido, Selma Feldman Witchel. (2007) The hypothalamic–pituitary–adrenal axis in critical illness. Reviews in Endocrine and Metabolic Disorders 8:4, 365-373
67
Exercise and Protein Metabolism. CRC Press, 2007:23-106.
68
Kwame Asare. (2007) Diagnosis and Treatment of Adrenal Insufficiency in the Critically Ill Patient. Pharmacotherapy 27:11, 1512-1528
69
Lindy S. Klaff, Brent E. Wisse. (2007) Current Controversy Related to Glucocorticoid and Insulin Therapy in The Intensive Care Unit. Endocrine Practice 13:5, 542-549
70
Samuel Durkan, Armelle de Laforcade, Elizabeth Rozanski, John E. Rush. (2007) Suspected relative adrenal insufficiency in a critically ill cat. Journal of Veterinary Emergency and Critical Care 17:2, 197-201
71
S. Bendel, E. Ruokonen, P. Pölönen, A. Uusaro. (2007) Propofol causes more hypotension than etomidate in patients with severe aortic stenosis: a double-blind, randomized study comparing propofol and etomidate. Acta Anaesthesiologica Scandinavica 51:3, 284-289
72
Monica Langer, Biren P Modi, Michael Agus. (2006) Adrenal insufficiency in the critically ill neonate and child. Current Opinion in Pediatrics 18:4, 448-453
73
Kenneth B. Davis, Brian C. Small. (2006) Rates of cortisol increase and decrease in channel catfish and sunshine bass exposed to an acute confinement stressor. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 143:1, 134-139
74
Dušan Palić, Dawn M. Herolt, Claire B. Andreasen, Bruce W. Menzel, James A. Roth. (2006) Anesthetic efficacy of tricaine methanesulfonate, metomidate and eugenol: Effects on plasma cortisol concentration and neutrophil function in fathead minnows (Pimephales promelas Rafinesque, 1820). Aquaculture 254:1-4, 675-685
75
B. Drexler, C. Grasshoff, U. Rudolph, K. Unertl, B. Antkowiak. (2006) Die GABAA-Rezeptor-Familie. Der Anaesthesist 55:3, 287-295
76
J. M. Olmos, J. A. Amado, C. Valero, J. L. Hernandez, J. Gonzalez-Macias. (2006) Factors other than glucocorticoids are involved in the osteoblast activity decrease caused by tissue injury. Clinical Endocrinology 64:3, 280-283
77
J.P. Hinson, P.W. Raven. (2006) Effects of endocrine-disrupting chemicals on adrenal function. Best Practice & Research Clinical Endocrinology & Metabolism 20:1, 111-120
78
Joseph D. Tobias. (2006) Anesthesia: Looking Back at the Last Century and Forward to the Next. Southern Medical Journal 99:3, 320-322
79
Michael F. Roizen, Nader M. Enany. Diseases of the Endocrine System. In: Anesthesia and Uncommon Diseases. Elsevier, 2006:413-454.
80
Karen L. Johnson, Cindy Renn RN. (2006) The Hypothalamic-Pituitary-Adrenal Axis in Critical Illness. AACN Clinical Issues: Advanced Practice in Acute and Critical Care 17:1, 39-49
81
Aaron L. Zuckerberg, Myron Yaster. Anesthesia for Pediatric Orthopedic Surgery. In: Smith's Anesthesia for Infants and Children. Elsevier, 2006:737-769.
82
Peter J. Davis, Jerrold Lerman, Stevan P. Tofovic, D. Ryan Cook. Pharmacology of Pediatric Anesthesia. In: Smith's Anesthesia for Infants and Children. Elsevier, 2006:177-238.
83
William King, Brian Hooper, Stephanie Hillsgrove, Christopher Benton, David L Berlinsky. (2005) The use of clove oil, metomidate, tricaine methanesulphonate and 2-phenoxyethanol for inducing anaesthesia and their effect on the cortisol stress response in black sea bass (Centropristis striata L.). Aquaculture Research 36:14, 1442-1449
84
Pejman Cohan, Christina Wang, David L. McArthur, Shon W. Cook, Joshua R. Dusick, Bob Armin, Ronald Swerdloff, Paul Vespa, Jan Paul Muizelaar, Henry Gill Cryer, Peter D. Christenson, Daniel F. Kelly. (2005) Acute secondary adrenal insufficiency after traumatic brain injury: A prospective study*. Critical Care Medicine 33:10, 2358-2366
85
J Thomas, J Lerman. Anesthesia for Pediatric Trauma. In: Pediatric Trauma. CRC Press, 2005:147-180.
86
Brian Small, Nagaraj Chatakondi. (2005) Routine Measures of Stress Are Reduced in Mature Channel Catfish during and after AQUI-S Anesthesia and Recovery. North American Journal of Aquaculture 67:1, 72-78
87
N. Bruder, P. Ravussin. (2005) Anestesia en neurocirugía. EMC - Anestesia-Reanimación 31:4, 1-29
88
N. Bruder, P. Ravussin. (2005) Anesthésie en neurochirurgie. EMC - Anesthésie-Réanimation 2:3, 1-27
89
M. P. Yeager, P. M. Guyre, A. U. Munck. (2004) Glucocorticoid regulation of the inflammatory response to injury. Acta Anaesthesiologica Scandinavica 48:7, 799-813
90
Philip E Knapp, Seth M Arum, James C Melby. (2004) Relative adrenal insufficiency in critical illness: a review of the evidence. Current Opinion in Endocrinology & Diabetes 11:3, 147-152
91
K Davis. (2004) Physiological responses of hybrid striped bass under sedation by several anesthetics. Aquaculture 233:1-4, 531-548
92
Samir Patel. (2003) Cardiovascular Effects of Intravenous Anesthetics. International Anesthesiology Clinics 40:1, 15-33
93
M Iversen. (2003) The efficacy of metomidate, clove oil, Aqui-S™ and Benzoak® as anaesthetics in Atlantic salmon (Salmo salar L.) smolts, and their potential stress-reducing capacity. Aquaculture 221:1-4, 549-566
94
Lori K. Rothermel. (2003) Newer pharmacologic agents for procedural sedation of children in the emergency department–etomidate and propofol. Current Opinion in Pediatrics 15:2, 200-203
95
B Small. (2003) Anesthetic efficacy of metomidate and comparison of plasma cortisol responses to tricaine methanesulfonate, quinaldine and clove oil anesthetized channel catfish Ictalurus punctatus. Aquaculture 218:1-4, 177-185
96
Tl Higgins, Pg Jodka, A Farid. (2003) Pharmacologic approaches to sedation, pain relief and neuromuscular blockade in the intensive care unit. Part I: Sedation. Clinical Intensive Care 14:1-2, 1-11
97
Cooper , Mark S. , Stewart , Paul M. , . (2003) Corticosteroid Insufficiency in Acutely Ill Patients. New England Journal of Medicine 348:8, 727-734
Full Text98
M.K. Johansson, J.T. Sanderson, B-O. Lund. (2002) Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicology in Vitro 16:2, 113-121
99
KEVIN J. SULLIVAN, NIRANJAN KISSOON. (2002) Securing the child’s airway in the emergency department. Pediatric Emergency Care 18:2, 108-121
100
Charles E. Smith. (2001) Rapid-Sequence Intubation in Adults: Indications and Concerns. Clinical Pulmonary Medicine 8:3, 147-165
101
M. Fassnacht, S. Hahner, F. Beuschlein, A. Klink, M. Reincke, B. Allolio. (2000) New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. European Journal of Clinical Investigation 30:S3, 76-82
102
Joseph D. Tobias. (2000) Etomidate: Applications in pediatric critical care and pediatric anesthesiology. Pediatric Critical Care Medicine 1:2, 100-106
103
Avi A. Weinbroum, Valery Rudick, Gideon Paret, Yoram Kluger, Ron Ben Abraham. (2000) Anaesthesia and critical care considerations in nerve agent warfare trauma casualties. Resuscitation 47:2, 113-123
104
M. Bennun, B. Goldstein, Y. Finkelstein, R. Jedeikin. (2000) Continuous propofol anaesthesia for patients with myotonic dystrophy. British Journal of Anaesthesia 85:3, 407-409
105
PETER E. SOKOLOVE, DANIEL D. PRICE, PAMELA OKADA. (2000) The safety of etomidate for emergency rapid sequence intubation of pediatric patients. Pediatric Emergency Care 16:1, 18-21
106
M. W. B. Hartmannsgruber, A. Gabrielli, A. J. Layon, S. H. Rosenbaum. (2000) The Traumatic Airway: The Anesthesiologist's Role in the Emergency Room. International Anesthesiology Clinics 38:4, 87-104
107
M.C. Hinojosa Mena-Bernal, I. Fernández Martínez, M. Martín Merino, J. Crespo Pinilla. (2000) Insuficiencia suprarrenal aguda. Medicine - Programa de Formación Médica Continuada Acreditado 8:23, 1202-1207
108
(1999) Quels sont les moyens?. Réanimation Urgences 8, 64-86
109
Absalom, Pledger, Kong. (1999) Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 54:9, 861-867
110
Melanie L. Richards, Robert H. Caplan, Gary G. Wickus, Pamela J. Lambert, William A. Kisken. (1999) The rapid low-dose (1 μg) cosyntropin test in the immediate postoperative period: Results in elderly subjects after major abdominal surgery. Surgery 125:4, 431-440
111
David J Hatch. (1999) Propofol-infusion syndrome in children. The Lancet 353:9159, 1117-1118
112
Philipp Ostwald, Alfred W. Doenicke. (1998) Etomidate revisited. Current Opinion in Anaesthesiology 11:4, 391-398
113
James E. Szalados, Philip G. Boysen. (1998) Sedation in the critically ill patient. Current Opinion in Anaesthesiology 11:2, 147-155
114
A. Lisbon, M. P. Fink. (1998) Adrenal function and ruptured abdominal aortic aneurysm: keeping the hormones in check. Intensive Care Medicine 24:2, 100-101
115
(1997) Neuroanesthesia and intensive care medicine: Cerebral ischemia. Acta Anaesthesiologica Scandinavica 41, 89-99
116
Ken Kobayashi, Roy E. Weiss, Nicholas J. Vogelzang, Everett E. Vokes, Linda Janisch, Mark J. Ratain. (1996) Mineralocorticoid insufficiency due to suramin therapy. Cancer 78:11, 2411-2420
117
L.P. Jager, G.J. De Graaf, H.C.A. Widjaja-Greefkes. (1996) Screening for drug-induced alterations in the production and release of steroid hormones by porcine adrenocortical cells in vitro. Toxicology in Vitro 10:5, 595-608
118
Jørgen Søberg Petersen, Michael Shalmi, Sten Christensen, Ketil Haugan, Niels Lomholt. (1996) Comparison of the renal effects of six sedating agents in rats. Physiology & Behavior 60:3, 759-765
119
Russell T. Wall. (1996) UNUSUAL ENDOCRINE PROBLEMS. Anesthesiology Clinics of North America 14:3, 471-493
120
Ulrich Pechstein, Cornelia Cedzich, Joachim Nadstawek, Johannes Schramm. (1996) Transcranial High-frequency Repetitive Electrical Stimulation for Recording Myogenic Motor Evoked Potentials with the Patient under General Anesthesia. Neurosurgery 39:2, 335-344
121
Y Olsen. (1995) Metomidate anaesthesia in Atlantic salmon, Salmo salar, prevents plasma cortisol increase during stress. Aquaculture 134:1-2, 155-168
122
Robert A. Strickland, Michael J. Murray. (1995) Fatal metabolic acidosis in a pediatric patient receiving an infusion of propofol in the intensive care unit. Critical Care Medicine 23:2, 405-409
123
John Schou. (1994) NASOTRACHEAL VERSUS OROTRACHEAL INTUBATION - A BALANCED CONCLUSION?. Acta Anaesthesiologica Scandinavica 38:2, 192-192
124
Masahiko Shimada, Richard A. Winchurch, Sadek Beloucif, James L. Robotham. (1993) Effect of anesthesia and surgery on plasma cytokine levels. Journal of Critical Care 8:2, 109-116
125
T. A. MILLANE, E. D. BENNETT, R. M. GROUNDS. (1992) Isoflurane and propofol for long-term sedation in the intensive care unit.. Anaesthesia 47:9, 768-774
126
Marinus P. Boidin, Arie Stuurman, Wilhelm Erdmann. (1990) Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations. Pharmaceutisch Weekblad Scientific Edition 12:4, 151-153
127
C. E. HARRIS, R. M. GROUNDS, A. M. MURRAY, J. LUMLEY, D. ROYSTON, M. MORGAN. (1990) Propofol for long-term sedation in the intensive care unit A comparison with papaveretum and midazolam. Anaesthesia 45:5, 366-372
128
F. Snellen, P. Lauwers, R. Derneyere, G. Byttebier, H. Aken. (1990) The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting. Intensive Care Medicine 16:5, 312-316
129
Anneli Kojo, Paavo Honkakoski, Päivi Järvinen, Olavi Pelkonen, Matti Lang. (1989) Preferential Inhibition of Mouse Hepatic Coumarin 7-Hydroxylase by Inhibitors of Steroid Metabolizing Monooxygenases. Pharmacology & Toxicology 65:2, 104-109
130
R. Neumann, F. S. Worek, G. Blümel, G. J. Zimmermann, H. L. Fehm, U. J. Pfeiffer. (1989) Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure - beneficial effect of cortisol substitution. Acta Anaesthesiologica Scandinavica 33:5, 379-384
131
E. M. McGRADY, I. H. WRIGHT. (1989) Cardiovascular instability following bolus dose of etomidate. Anaesthesia 44:5, 404-405
132
H. Mellinghoff, G. C. Loeschcke. (1989) Anaesthesiological considerations in head injury. Neurosurgical Review 12:S1, 22-31
133
D. A. White, D. G. Smyth. (1989) Continuous infusion of propofol in dystrophia myotonica. Canadian Journal of Anaesthesia 36:2, 200-203
134
J. J. DRIESSEN, M. S. C. DIRKSEN, J. M. J. RUTTEN, F. SANTMAN, J. EGMOND, T. B. VREE. (1989) Continuous infusion of midazolam during anaesthesia and postoperative sedation after maxillofacial surgery. Acta Anaesthesiologica Scandinavica 33:2, 116-121
135
M. C. DIAGO, J. A. AMADO, M. OTERO, J. J. LOPEZ-CORDOVILLA. (1988) Anti-adrenal action of a subanaesthetic dose of etomidate. Anaesthesia 43:8, 644-645
136
A. Nilsson, M. P. Persson, P. Hartvig, V. L. Wide. (1988) Effect of total intravenous anaesthesia with midazolam/alfentanil on the adrenocortical and hyperglycaemic response to abdominal surgery. Acta Anaesthesiologica Scandinavica 32:5, 379-382
137
B. Allolio, H. M. Schulte, D. Kaulen, M. Reincke, C. Jaursch-Hancke, W. Winkelmann. (1988) Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in cushing's syndrome. Klinische Wochenschrift 66:8, 361-364
138
Suzane C. Cooper, William A. Lell. (1988) Hormonal effects of an induction dose of etomidate for patients undergoing urgent myocardial revascularization. Journal of Cardiothoracic Anesthesia 2:2, 171-176
139
Paolo Preziosi, Michele Vacca. (1988) Adrenocortical suppression and other endocrine effects of etomidate. Life Sciences 42:5, 477-489
140
M. E. Sinclair, J. W. Sear, R. J. Summerfield, A. Fisher. (1988) Alfentanil infusions on the intensive therapy unit. Intensive Care Medicine 14:1, 55-59
141
G. R. PARK, A. R. MANARA, L. MENDEL, P. E. BATEMAN. (1987) Ketamine infusion.. Anaesthesia 42:9, 980-983
142
Nagai Kunio, Miyamori Isamu, Takeda Ryoyu, Suhara Katsuko, Katagiri Masayuki. (1987) Effect of ketoconazole, etomidate and other inhibitors of steroidogenesis on cytochrome P-450sccII-catalyzed reactions. Journal of Steroid Biochemistry 28:3, 333-336
143
F. Knudsen, N. O. Klausen, A. H. Ferguson, J. O. Pedersen. (1987) In vitro effect of etomidate and thiopental on granulocyte migration. Acta Anaesthesiologica Scandinavica 31:1, 93-95
144
J. COSTA, D. RAMOS, S. MASSAVA, D. CARVALHO, D. PIGNATELLI. (1986) Etomidate and Cushing's syndrome. Anaesthesia 41:2, 211-212
145
B. Allolio, R. Stuttmann, W. Winkelmann. (1986) Missing effect of etomidate on testosterone secretion in man. Klinische Wochenschrift 64:2, 86-88
146
S. LACOUMENTA, J. L. PATERSON, M. A. MYERS, G. M. HALL. (1986) Effects of cortisol suppression by etomidate on changes in circulating metabolites associated with pelvic surgery. Acta Anaesthesiologica Scandinavica 30:1, 101-104
147
J. Descotes, J.Cl. Evreux. General anesthetics and therapeutic gases. Elsevier, 1986:97-103.
148
Patricia B. Kan, Margaret A. Hirst, David Feldman. (1985) Inhibition of steroidogenic cytochrome P-450 enzymes in rat testis by ketoconazole and related imidazole anti-fungal drugs. Journal of Steroid Biochemistry 23:6, 1023-1029
149
M. P. MEHTA, J. B. DILLMAN, B. M. SHERMAN, M. M. GHONEIM, J. H. LEMKE. (1985) Etomidate Anesthesia Inhibits the Cortisol Response to Surgical Stress. Acta Anaesthesiologica Scandinavica 29:5, 486-489
150
B. ALLOLIO, H. DÖRR, R. STUTTMANN, D. KNORR, D. ENGELHARDT, W. WINKELMANN. (1985) EFFECT OF A SINGLE BOLUS OF ETOMIDATE UPON EIGHT MAJOR CORTICOSTEROID HORMONES AND PLASMA ACTH. Clinical Endocrinology 22:3, 281-286
151
H. G. Dörr, U. Kuhnle, H. Holthausen, F. Bidlingmaier, D. Knorr. (1984) Etomidate: A selective adrenocortical 11β-hydroxylase inhibitor. Klinische Wochenschrift 62:21, 1011-1013
152
B. Allolio, R. Stuttmann, U. Leonhard, H. Fischer, W. Winkelmann. (1984) Adrenocortical suppression by a single induction dose of etomidate. Klinische Wochenschrift 62:21, 1014-1017
153
(1984) Sedation in the Intensive-care Unit. The Lancet 323:8391, 1388-1389
154
(1984) The Malignant Large-bowel Polyp— Conservative or Radical Treatment?. The Lancet 323:8391, 1387-1388
