Anesth Analg 2009; 108:238-239
© 2009 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318187ed37
CRITICAL CARE AND TRAUMA
Etomidate Infusion in the Critical Care Setting for Suppressing the Acute Phase of Cushing’s Syndrome
Ali Dabbagh, MD*,
Navid Sa’adat, MD , and
Zahra Heidari, MD
From the *Department of Anesthesia and Anesthesia Research Center; Department of Endocrinology, Taleghani Hospital and Endocrinology Research Center; and Department of Endocrinology, Taleghani Hospital, Shahid Beheshti University, M.C. Tehran, Iran.
Address correspondence to Ali Dabbagh, MD, Fellowship in Cardiac Anesthesia, Anesthesia Research Center, Shahid Beheshti University, M.C. Tehran, Iran. Address e-mail to alidabbagh{at}yahoo.com.
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Abstract
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A 17-year-old, 55 kg girl was referred to the endocrinology department of a university hospital to determine the etiology of suspected Cushing’s syndrome. The patient was treated with oral ketoconazole for 3 days, but a rapid and severe elevation in her liver function test results led to selection of IV etomidate as a therapeutic option. This approach led to decreasing levels of serum cortisol, and the patient was able to tolerate surgical adrenalectomy.
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Introduction
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Etomidate is an IV non-opioid anesthetic used for both induction and maintenance of anesthesia. Adrenocortical suppression is one of its main side effects. Prolonged sedation with etomidate is contraindicated due to the endocrine complications of the drug.
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CASE PRESENTATION
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A 17-year-old, 55 kg girl was referred to the endocrinology department of a university hospital with suspected Cushing’s syndrome, which seemed to be malignancy-related hypercortisolism. Because of the severity of her illness, diagnostic workup progressed poorly. Over a period of 2 yr, the patient had gradually developed a moon-faced appearance and facial obesity (Fig. 1), decreased body movement due to severe pain in all bones and joints, muscular mass atrophy, and cutaneous striae (Figs. 2 and 3). She was completely restricted due to decreased physical activity; she was incapacitated by the effects of osteoporosis, generalized microfractures in the skeleton, muscular mass atrophy, and pain in her spine and limbs.
The patient was scheduled for elective total adrenalectomy. Two consecutive 24-hour urine samples were collected. In the first, the urine free cortisol level was 2408 mcg in 3400 mL of urine (a normal level is up to 70 mcg in 24 h). The second sample had a urine free cortisol level of 2408 mcg in 4900 mL of urine. A dexamethasone stress test with 2 mg of the drug every 8 h for 2 days demonstrated no significant decrease in the very high level of adrenocorticotropic hormone in the serum. Abdominal, thoracic and pelvic magnetic resonance imaging, physical examination, radiograph, and ultrasonography did not reveal any specific source, whereas the dexamethasone stress test results suggested the source of the disease to be somewhere outside the hypothalamus-pituitary-adrenal axis. The physical status of the patient did not allow the pulmonologist to evaluate the tracheobronchial tree for any pulmonary source of the disease. Since the urinary metabolites of the corticosteroids were nearly 70 times normal and there was a great risk of sepsis and related morbidy, medical suppression of the steroidogenic process was proposed.
The patient was treated with oral ketoconazole for 3 days, but this therapeutic option was stopped due to a rapid and severe elevation in liver function test results. The patient’s urinary excretion of glucocorticoid metabolites was still very high. IV etomidate was selected as the last therapeutic option for the patient.
In the intensive care unit (ICU) the patient was monitored with a 2-lead electrocardiogram, pulse oximetry, and noninvasive arterial blood pressure monitoring. Because her peripheral lines were fragile, a central venous line was inserted. The patient received nothing orally for 8 h. A facemask delivered oxygen at a constant flow of 6 to 8 L/min. A sample of venous blood was taken from the central venous line to assess the level of blood cortisol.
The first dose of etomidate was then started as a bolus, which included 10 mg in slow incremental doses, beginning with 1 mg of etomidate during the first 30 min through the central line. Before each repeated etomidate dose, arterial blood pressure was measured, the arterial saturation of oxygen was rechecked, and then the drug was administered. After injection of each 1 mg of etomidate, the patient’s level of consciousness was controlled. After termination of the starting bolus dose, 2.5 mg/h of etomidate was administered through the central venous line for the next 24 h, until the patient was transferred to the operating room; meanwhile, she was continuously monitored in the ICU.
Serum cortisol levels were checked in 4 samples before surgical adrenalectomy: just before the etomidate infusion was started (1.16 mg/L), and 3 times during administration of etomidate, at 8 h after initiation of the infusion (0.42 mg/L), 16 h after initiation (0.22 mg/L), and 20 h after initiation (0.20 mg/L). The patient was transferred from the ICU to the operating room afterwards.
After bilateral surgical adrenalectomy, the patient was readmitted to the ICU for postoperative care. Over the next few days, the patient’s serum cortisol levels gradually declined and she began minimal physical activity. Within 14 days of the operation she was able to sit up and turn over. When she was able to attend to her personal hygiene, she was discharged.
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DISCUSSION
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Etomidate, an imidazole derivative, is an IV non-opioid anesthetic used for both induction and maintenance of anesthesia. Although it was widely used for sedation in critical care after its introduction, etomidate is contraindicated for prolonged sedation because it plays an inhibitory role in production of corticosteroids and mineralocorticoids, which could subsequently increase mortality.1–3
Life-threatening infections, diabetes, and a high mortality rate in surgeries are associated with chronic severe hypercortisolism. A number of oral therapeutic drugs (primarily ketoconazole, supplemented by oral metyrapone, aminoglutethimide, and at times the very potent drug mitotane) can suppress the steroidogenesis process, and thus diminish the risk associated with these complications. However, except for IV etomidate, there is no parenteral drug with the ability to rapidly and acutely slow the steroidogenesis process in such patients, either partially or fully. For this purpose, usually an ethyl alcohol formulation of etomidate is used.2–5 Among the main indications for drug therapy are preparation for surgery, occult ectopic adrenocorticotropic hormone syndrome, severe hypercortisolism, and malignancy-related hypercortisolism.4 Our patient could not tolerate the oral administration of ketoconazole and experienced a surge in liver enzymes, probably due to the drug.
Because mortality and high morbidity rates are associated with surgical adrenalectomy, etomidate infusion was started in this severely ill patient to suppress the steroidogenesis process in an acute setting. Also, partial inhibition of adrenocortical steroid biosynthesis was targeted both to minimize the patient’s exposure to etomidate and to produce an appropriate serum level of cortisol. To prepare the patient for the forthcoming surgical stress, the etomidate dose was titrated using serum levels. Total blockade of the steroidogenesis process was avoided to prevent the possible risk of future deprivation of the effects of steroids during surgical stress.
Etomidate is a very potent inhibitor of the 11a-hydroxylase and 17a-hydroxylase enzymes in the steroidogenesis process. The effect of etomidate is as strong as that of ketoconazole, the prototype of the oral medications. Due to the sedative effects of etomidate and its availability only in an IV form, the drug is used almost exclusively for acute control of hypercortisolemia.5 In one study of six patients with Cushing’s disease, etomidate was used at a dose of 0.3 mg/kg/h normalized serum levels of cortisol over a 12-h period.6 However, undiluted etomidate at a dose of 2 mg/mL has been infused through a central venous catheter lumen without any obvious problem with patient stability.2 It is obvious that the care of such patients in the perioperative setting requires strict vigilance on the part of the anesthesiologist as well as the internist.
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ACKNOWLEDGMENTS
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The authors acknowledge the kind efforts of the surgeons and the ICU staff of the Taleghani hospital.
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Footnotes
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Accepted for publication May 29, 2008.
Reprints will not be available from the authors.
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REFERENCES
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- Krakoff J, Koch CA, Calis KA, Alexander RH, Nieman LK. Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing’s syndrome. J Clin Endocrinol Metab 2001;86:4104–8[Abstract/Free Full Text]
- Johnson TN, Canada TW. Etomidate use for Cushing’s syndrome caused by an ectopic adrenocorticotropic hormone-producing tumor. Ann Pharmacother 2007;41:350–3[Abstract/Free Full Text]
- Nieman LK. Medical therapy of Cushing’s disease. Pituitary 2002;5:77–82[Medline]
- D'iez JJ, Iglesias P. Pharmacological therapy of Cushing’s syndrome: drugs and indications. Mini Rev Med Chem 2007;7:467–80[Web of Science][Medline]
- Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH. Medical management of Cushing disease. Neurosurg Focus 2007;23:E10[Medline]
- Drake WM, Perry LA, Hinds CJ, Lowe DG, Reznek RH, Besser GM. Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing’s syndrome and peritonitis. J Clin Endocrinol Metab 1998;83:3542–4[Abstract/Free Full Text]
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Abstract
Introduction
