Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Effect of an Anesthetic Induction Dose of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Mitral Valve Regurgitation
• Intervention / Treatment: Drug: Etomidate; Drug: Propofol; Drug: Hydrocortisone; Drug: NaCl 0.9%; Other: Tetracosactin

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of absolute and relative adrenal insufficiency	Preoperative day to postoperative day (POD) 4
Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU)	Induction of anesthesia to POD 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of failure to wean off cardiopulmonary bypass on first intention	intraoperatively
Serum lactate	Induction of anesthesia to discharge ICU
Time to extubation	Induction of anesthesia to extubation
Length of stay (LOS) in the intensive care unit (ICU), intermediate care unit (IMC), and hospital	Admission to discharge: ICU, IMC, and hospital
Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery	30 days

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Stephan M Jakob, Professor, University Hospital Inselspital, Berne

Publications and helpful links

General 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. doi: 10.1007/s00134-004-2550-8. 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. doi: 10.1016/j.jtcvs.2005.07.063.
• 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. doi: 10.1210/jc.2005-1107. 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. doi: 10.1046/j.1365-2044.1999.01003.x.
• Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med. 2005 Mar;31(3):325-6. doi: 10.1007/s00134-005-2560-1. 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. doi: 10.1093/bja/57.2.156.
• 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. doi: 10.1136/bmj.287.6408.1835.
• Fellows IW, Byrne AJ, Allison SP. Adrenocortical suppression with etomidate. Lancet. 1983 Jul 2;2(8340):54-5. doi: 10.1016/s0140-6736(83)90043-0. 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. doi: 10.1056/NEJM198405313102202.
• Allolio B, Stuttmann R, Fischer H, Leonhard W, Winkelmann W. Long-term etomidate and adrenocortical suppression. Lancet. 1983 Sep 10;2(8350):626. doi: 10.1016/s0140-6736(83)90710-9. 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. doi: 10.1111/j.1365-2044.1984.tb08885.x.
• 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. doi: 10.1093/bja/57.5.509.
• 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. doi: 10.1097/01.CCM.0000059646.89546.98.
• 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):1792-1798. doi: 10.1213/01.ANE.0000184042.91452.48.
• 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. doi: 10.1111/j.1399-6576.1989.tb02927.x.
• Basciani RM, Rindlisbacher A, Begert E, Brander L, Jakob SM, Etter R, Carrel T, Eberle B. Anaesthetic induction with etomidate in cardiac surgery: A randomised controlled trial. Eur J Anaesthesiol. 2016 Jun;33(6):417-24. doi: 10.1097/EJA.0000000000000434.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 22, 2006
• First Submitted That Met QC Criteria: December 22, 2006
• First Posted (Estimate): December 25, 2006

Study Record Updates

• Last Update Posted (Estimate): March 4, 2010
• Last Update Submitted That Met QC Criteria: March 3, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Propofol; Cardiopulmonary Bypass; Coronary Artery Bypass; Etomidate; Heart Valve Prosthesis; Adrenocortical Insufficiency; Hemodynamic Process; Vasoactive Agonists; Ischemic Coronary Heart Disease; Mitral valve reconstruction/replacement; Mitral valve regurgitation
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Valve Diseases; Coronary Disease; Coronary Artery Disease; Mitral Valve Insufficiency; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hypnotics and Sedatives; Propofol; Hydrocortisone; Etomidate; Cosyntropin
• Other Study ID Numbers: DINA-KEK7406-IBAN-2006-1