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Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Primary Purpose

Coronary Artery Disease, Mitral Valve Regurgitation

Status
Completed
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Etomidate
Propofol
Hydrocortisone
NaCl 0.9%
Tetracosactin
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Departments of Intensive Care Medicine and Anesthesiology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Other

Arm Label

1

2

3

Arm Description

Etomidate as a single induction dose

Propofol as a single induction dose

Hydrocortisone substitution or placebo (50-50%) in etomidate-group

Outcomes

Primary Outcome Measures

Incidence of absolute and relative adrenal insufficiency
Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU)

Secondary Outcome Measures

Incidence of failure to wean off cardiopulmonary bypass on first intention
Serum lactate
Time to extubation
Length of stay (LOS) in the intensive care unit (ICU), intermediate care unit (IMC), and hospital
Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery

Full Information

First Posted
December 22, 2006
Last Updated
March 3, 2010
Sponsor
Insel Gruppe AG, University Hospital Bern
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1. Study Identification

Unique Protocol Identification Number
NCT00415701
Brief Title
Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery
Official Title
Effect of an Anesthetic Induction Dose of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
March 2010
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Insel Gruppe AG, University Hospital Bern

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Mitral Valve Regurgitation
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Etomidate as a single induction dose
Arm Title
2
Arm Type
Active Comparator
Arm Description
Propofol as a single induction dose
Arm Title
3
Arm Type
Other
Arm Description
Hydrocortisone substitution or placebo (50-50%) in etomidate-group
Intervention Type
Drug
Intervention Name(s)
Etomidate
Intervention Description
Single induction dose of etomidate 0.2%; total dose 0.15 mg/kg
Intervention Type
Drug
Intervention Name(s)
Propofol
Intervention Description
Single induction dose of propofol 2%; total dose 1.5 mg/kg
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
Hydrocortisone 100 mg/2 ml: day of operation 3x, POD 1 2x, POD 2 1x
Intervention Type
Drug
Intervention Name(s)
NaCl 0.9%
Intervention Description
NaCl 0.9% 2 ml; day of operation 3x, POD 1 2x, POD 2 1x
Intervention Type
Other
Intervention Name(s)
Tetracosactin
Intervention Description
Diagnostic test, Tetracosactin 250 microg iv
Primary Outcome Measure Information:
Title
Incidence of absolute and relative adrenal insufficiency
Time Frame
Preoperative day to postoperative day (POD) 4
Title
Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU)
Time Frame
Induction of anesthesia to POD 2
Secondary Outcome Measure Information:
Title
Incidence of failure to wean off cardiopulmonary bypass on first intention
Time Frame
intraoperatively
Title
Serum lactate
Time Frame
Induction of anesthesia to discharge ICU
Title
Time to extubation
Time Frame
Induction of anesthesia to extubation
Title
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
Title
Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan M Jakob, Professor
Organizational Affiliation
Insel Gruppe AG, University Hospital Bern
Official's Role
Principal Investigator
Facility Information:
Facility Name
Departments of Intensive Care Medicine and Anesthesiology
City
Bern
State/Province
BE
ZIP/Postal Code
3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
15703896
Citation
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.
Results Reference
background
PubMed Identifier
16434254
Citation
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.
Results Reference
background
PubMed Identifier
15985474
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. doi: 10.1210/jc.2005-1107. Epub 2005 Jun 28.
Results Reference
background
PubMed Identifier
10460557
Citation
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.
Results Reference
background
PubMed Identifier
15750800
Citation
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.
Results Reference
background
PubMed Identifier
2982387
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. doi: 10.1093/bja/57.2.156.
Results Reference
background
PubMed Identifier
6322902
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. doi: 10.1136/bmj.287.6408.1835.
Results Reference
background
PubMed Identifier
6134923
Citation
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.
Results Reference
background
PubMed Identifier
6325910
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. doi: 10.1056/NEJM198405313102202.
Results Reference
background
PubMed Identifier
6136774
Citation
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.
Results Reference
background
PubMed Identifier
3261141
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.
Results Reference
background
PubMed Identifier
6496912
Citation
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.
Results Reference
background
PubMed Identifier
2986663
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. doi: 10.1093/bja/57.5.509.
Results Reference
background
PubMed Identifier
12682474
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. doi: 10.1097/01.CCM.0000059646.89546.98.
Results Reference
background
PubMed Identifier
16301260
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):1792-1798. doi: 10.1213/01.ANE.0000184042.91452.48.
Results Reference
background
PubMed Identifier
2572134
Citation
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.
Results Reference
background
PubMed Identifier
26914224
Citation
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.
Results Reference
derived

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Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

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