Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery - Full Text View

Purpose

The purpose of this study is to evaluate the effect of a single dose of etomidate for patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB) on post-CPB adrenocortical responsiveness, on requirements of hemodynamic support, and on use of intensive care resources.

Condition	Intervention	Phase
Coronary Artery Disease Mitral Valve Regurgitation	Drug: Etomidate Drug: Propofol Drug: Hydrocortisone Drug: NaCl 0.9% Other: Tetracosactin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effect of an Anesthetic Induction Dose of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Surgery

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Propofol Hydrocortisone butyrate Cosyntropin Etomidate Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:

Incidence of absolute and relative adrenal insufficiency [ Time Frame: Preoperative day to postoperative day (POD) 4 ] [ Designated as safety issue: No ]
Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU) [ Time Frame: Induction of anesthesia to POD 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of failure to wean off cardiopulmonary bypass on first intention [ Time Frame: intraoperatively ] [ Designated as safety issue: No ]
Serum lactate [ Time Frame: Induction of anesthesia to discharge ICU ] [ Designated as safety issue: No ]
Time to extubation [ Time Frame: Induction of anesthesia to extubation ] [ Designated as safety issue: No ]
Length of stay (LOS) in the intensive care unit (ICU), intermediate care unit (IMC), and hospital [ Time Frame: Admission to discharge: ICU, IMC, and hospital ] [ Designated as safety issue: No ]
Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	130
Study Start Date:	November 2006
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Etomidate as a single induction dose	Drug: Etomidate Single induction dose of etomidate 0.2%; total dose 0.15 mg/kg
Active Comparator: 2 Propofol as a single induction dose	Drug: Propofol Single induction dose of propofol 2%; total dose 1.5 mg/kg
3 Hydrocortisone substitution or placebo (50-50%) in etomidate-group	Drug: Hydrocortisone Hydrocortisone 100 mg/2 ml: day of operation 3x, POD 1 2x, POD 2 1x Drug: NaCl 0.9% NaCl 0.9% 2 ml; day of operation 3x, POD 1 2x, POD 2 1x Other: Tetracosactin Diagnostic test, Tetracosactin 250 microg iv

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients undergoing elective
- coronary artery bypass graft (primary or re-operation)
- mitral valve reconstruction/replacement for mitral valve regurgitation
Age between 18 and 80 years (extremes included)
Subject itself has signed the informed consent
No clinically relevant deviation from the laboratory's reference range of biochemistry, hematology, or urinalysis testing

Exclusion Criteria:

Participation in another ongoing interventional trial
Known adrenocortical insufficiency
Use of etomidate or propofol within 1 week preoperatively
Use of glucocorticoids within 6 month preoperatively
Known sensitivity to etomidate, propofol, or emulgator
Severe hepatic dysfunction (bilirubin > 3mg/dl)
Severe renal dysfunction (plasma creatinine > 180mikromol/l)
Sepsis, endocarditis or other chronic inflammatory disease
Manifest insulin-dependent diabetes mellitus
Positive HIV serology
Hemodynamically significant carotid stenosis requiring treatment
Serious illnesses: endocrine, neurological, psychiatric, metabolic disturbances
Pregnancy or breast-feeding female; females will be subject to pregnancy testing
Requirement of rapid sequence induction
Emergency surgery
History of asthma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00415701

Locations

Switzerland
Departments of Intensive Care Medicine and Anesthesiology
Bern, BE, Switzerland, 3010

Sponsors and Collaborators

University Hospital Inselspital, Berne

Investigators

Principal Investigator:

Stephan M Jakob, Professor

University Hospital Inselspital, Berne

More Information

Publications:

Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Levy B, Bollaert PE. Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med. 2005 Mar;31(3):388-92. Epub 2005 Feb 10.

Weis F, Kilger E, Roozendaal B, de Quervain DJ, Lamm P, Schmidt M, Schmolz M, Briegel J, Schelling G. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. J Thorac Cardiovasc Surg. 2006 Feb;131(2):277-82.

den Brinker M, Joosten KF, Liem O, de Jong FH, Hop WC, Hazelzet JA, van Dijk M, Hokken-Koelega AC. Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab. 2005 Sep;90(9):5110-7. Epub 2005 Jun 28.

Absalom A, Pledger D, Kong A. Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia. 1999 Sep;54(9):861-7.

Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med. 2005 Mar;31(3):325-6. Epub 2005 Jan 27. No abstract available.

Duthie DJ, Fraser R, Nimmo WS. Effect of induction of anaesthesia with etomidate on corticosteroid synthesis in man. Br J Anaesth. 1985 Feb;57(2):156-9.

Fellows IW, Bastow MD, Byrne AJ, Allison SP. Adrenocortical suppression in multiply injured patients: a complication of etomidate treatment. Br Med J (Clin Res Ed). 1983 Dec 17;287(6408):1835-7.

Fellows IW, Byrne AJ, Allison SP. Adrenocortical suppression with etomidate. Lancet. 1983 Jul 2;2(8340):54-5. No abstract available.

Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984 May 31;310(22):1415-21.

Allolio B, Stuttmann R, Fischer H, Leonhard W, Winkelmann W. Long-term etomidate and adrenocortical suppression. Lancet. 1983 Sep 10;2(8350):626. No abstract available.

Crozier TA, Beck D, Wuttke W, Kettler D. [Relation of the inhibition of cortisol synthesis in vivo to plasma etomidate concentrations] Anaesthesist. 1988 May;37(5):337-9. German.

Watt I, Ledingham IM. Mortality amongst multiple trauma patients admitted to an intensive therapy unit. Anaesthesia. 1984 Oct;39(10):973-81.

Kenyon CJ, McNeil LM, Fraser R. Comparison of the effects of etomidate, thiopentone and propofol on cortisol synthesis. Br J Anaesth. 1985 May;57(5):509-11.

Kilger E, Weis F, Briegel J, Frey L, Goetz AE, Reuter D, Nagy A, Schuetz A, Lamm P, Knoll A, Peter K. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Crit Care Med. 2003 Apr;31(4):1068-74.

Loisa P, Uusaro A, Ruokonen E. A single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock. Anesth Analg. 2005 Dec;101(6):1792-8.

Neumann R, Worek FS, Blumel G, Zimmermann GJ, Fehm HL, Pfeiffer UJ. Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure--beneficial effect of cortisol substitution. Acta Anaesthesiol Scand. 1989 Jul;33(5):379-84.

Responsible Party:	Stefan M Jakob, Professor, Department of Critical Care Medicine
ClinicalTrials.gov Identifier:	NCT00415701 History of Changes
Other Study ID Numbers:	DINA-KEK7406-IBAN-2006-1
Study First Received:	December 22, 2006
Last Updated:	March 3, 2010
Health Authority:	Switzerland: Ethikkommission

Keywords provided by University Hospital Inselspital, Berne:

Etomidate
Propofol
Adrenocortical Insufficiency
Hemodynamic Process
Vasoactive Agonists
Coronary Artery Bypass

Ischemic Coronary Heart Disease
Mitral valve reconstruction/replacement
Mitral valve regurgitation
Heart Valve Prosthesis
Cardiopulmonary Bypass

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Mitral Valve Insufficiency
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Heart Valve Diseases
Cosyntropin
Etomidate
Propofol
Cortisol succinate
Hydrocortisone acetate

Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Vasoconstrictor Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on May 21, 2013