Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00415701
• Other study ID #: DINA-KEK7406-IBAN-2006-1
• Status: Completed
• Phase: Phase 4
• First received: December 22, 2006
• Last updated: March 3, 2010
• Start date: November 2006
• Est. completion date: December 2009

Study information

• Verified date: March 2010
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Mitral Valve Insufficiency
• Mitral Valve Regurgitation
• Myocardial Ischemia

Intervention

Drug:
• Etomidate
Single induction dose of etomidate 0.2%; total dose 0.15 mg/kg
• Propofol
Single induction dose of propofol 2%; total dose 1.5 mg/kg
• Hydrocortisone
Hydrocortisone 100 mg/2 ml: day of operation 3x, POD 1 2x, POD 2 1x
• 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

Locations

Country	Name	City	State
Switzerland	Departments of Intensive Care Medicine and Anesthesiology	Bern	BE

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

References & Publications (16)

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. — View Citation

Allolio B, Stuttmann R, Fischer H, Leonhard W, Winkelmann W. Long-term etomidate and adrenocortical suppression. Lancet. 1983 Sep 10;2(8350):626. — View Citation

Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med. 2005 Mar;31(3):325-6. Epub 2005 Jan 27. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Fellows IW, Byrne AJ, Allison SP. Adrenocortical suppression with etomidate. Lancet. 1983 Jul 2;2(8340):54-5. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Lévy 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. — View Citation

Neumann R, Worek FS, Blümel 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. — View Citation

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. — View Citation

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

Weis F, Kilger E, Roozendaal B, de Quervain DJ, Lamm P, Schmidt M, Schmölz 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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of absolute and relative adrenal insufficiency		Preoperative day to postoperative day (POD) 4	No
Primary	Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU)		Induction of anesthesia to POD 2	No
Secondary	Incidence of failure to wean off cardiopulmonary bypass on first intention		intraoperatively	No
Secondary	Serum lactate		Induction of anesthesia to discharge ICU	No
Secondary	Time to extubation		Induction of anesthesia to extubation	No
Secondary	Length of stay (LOS) in the intensive care unit (ICU), intermediate care unit (IMC), and hospital		Admission to discharge: ICU, IMC, and hospital	No
Secondary	Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery		30 days	No