Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

NCT00415701 | Completed Phase 4

• 1 other identifier: DINA-KEK7406-IBAN-2006-1
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (3)

1

EXPERIMENTAL

Etomidate as a single induction dose

Drug: Etomidate

2

ACTIVE COMPARATOR

Propofol as a single induction dose

Drug: Propofol

3

OTHER

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

Drug: Hydrocortisone; Drug: NaCl 0.9%; Other: Tetracosactin

Interventions

Etomidate DRUG

Single induction dose of etomidate 0.2%; total dose 0.15 mg/kg

1

Propofol DRUG

Single induction dose of propofol 2%; total dose 1.5 mg/kg

2

Hydrocortisone DRUG

Hydrocortisone 100 mg/2 ml: day of operation 3x, POD 1 2x, POD 2 1x

3

NaCl 0.9% DRUG

NaCl 0.9% 2 ml; day of operation 3x, POD 1 2x, POD 2 1x

3

Tetracosactin OTHER

Diagnostic test, Tetracosactin 250 microg iv

3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Departments of Intensive Care Medicine and Anesthesiology

Bern, Canton of Bern, 3010, Switzerland

Location

Related Publications (17)

• 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.

  PMID: 15703896 BACKGROUND

• 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.

  PMID: 16434254 BACKGROUND

• 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.

  PMID: 15985474 BACKGROUND

• 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.

  PMID: 10460557 BACKGROUND

• 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.

  PMID: 15750800 BACKGROUND

• 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.

  PMID: 2982387 BACKGROUND

• 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.

  PMID: 6322902 BACKGROUND

• 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.

  PMID: 6134923 BACKGROUND

• 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.

  PMID: 6325910 BACKGROUND

• 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.

  PMID: 6136774 BACKGROUND

• 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.

  PMID: 3261141 BACKGROUND

• 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.

  PMID: 6496912 BACKGROUND

• 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.

  PMID: 2986663 BACKGROUND

• 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.

  PMID: 12682474 BACKGROUND

• 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.

  PMID: 16301260 BACKGROUND

• 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.

  PMID: 2572134 BACKGROUND

• 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.

  PMID: 26914224 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Mitral Valve Insufficiency; Addison Disease

Interventions

Etomidate; Propofol; Hydrocortisone; Sodium Chloride; Cosyntropin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Heart Valve Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Adrenocorticotropic Hormone; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Stephan M Jakob, Professor

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 22, 2006
• First Posted: December 25, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: March 4, 2010

Record last verified: 2010-03

Locations

CH (1)