Optimization of Cardioprotection in Diabetic Patients Undergoing Cardiac Surgery

Myocardial Ischemia Clinical Trial

— OPT  

Official title:

Optimierung Der Kardioprotektion Durch Inhalative Anästhetika Eine Untersuchung Bei Patienten Mit Diabetes Mellitus während Off-pump Herzchirurgie

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02407626
• Other study ID #: STZ-IFA-0115
• Status: Terminated
• Phase: N/A
• First received: March 18, 2015
• Last updated: March 8, 2018
• Start date: September 2015
• Est. completion date: March 7, 2018

Study information

• Verified date: March 2018
• Source: Triemli Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the myocardial protection against perioperative ischemia comparing two standard anesthetic regimes in diabetic patients undergoing elective cardiac surgery. Half of the patients will receive volatile anesthesia while the other half will receive total intravenous anesthesia. Primary and secondary outcome parameters will be assessed after induction of anesthesia, at the end of the procedure and postoperative day 1 to 3.

Description:

Volatile anaesthetics such as Sevoflurane have shown to have a protective effect regarding myocardial ischemia in the perioperative setting - the so-called "preconditioning". However the observed response of preconditioning in clinical trials is not consistent.

An increased perioperative insulin resistance especially in diabetic patients resulting in an increased postoperative morbidity and mortality may be responsible for these findings.

In an animal model, the use of propofol that is being routinely applied for general anesthesia was associated with a change of the insulin receptor substrate via phosphorylation and thus a change of insulin resistance.

Avoiding a total intravenous anesthesia and applying a volatile anesthesia may result in an increased cardioprotective effect by a reduction of the perioperative insulin resistance.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 7, 2018
• Est. primary completion date: March 7, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:

• Diabetes

• Elective cardiac surgery

Exclusion Criteria:

• Emergency procedures

• Preop myocardial infarction

• Preop cardiac failure

• Preop renal replacement therapy

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• Propofol
Total intravenous anesthesia is a clinical standard procedure
• Sevoflurane
Volatile anesthesia is a clinical standard procedure

Locations

Country	Name	City	State
Switzerland	Triemli City Hospital	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
Triemli Hospital	University of Alberta

Country where clinical trial is conducted

Switzerland, 

References & Publications (10)

Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007 Aug 18;370(9587):575-9. — View Citation

Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003 Jun;98(6):1315-27. — View Citation

Lou PH, Lucchinetti E, Zhang L, Affolter A, Gandhi M, Zhakupova A, Hersberger M, Hornemann T, Clanachan AS, Zaugg M. Propofol (Diprivan®) and Intralipid® exacerbate insulin resistance in type-2 diabetic hearts by impairing GLUT4 trafficking. Anesth Analg. 2015 Feb;120(2):329-40. doi: 10.1213/ANE.0000000000000558. — View Citation

Lucchinetti E, Hofer C, Bestmann L, Hersberger M, Feng J, Zhu M, Furrer L, Schaub MC, Tavakoli R, Genoni M, Zollinger A, Zaugg M. Gene regulatory control of myocardial energy metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery: inhalational versus intravenous anesthetics. Anesthesiology. 2007 Mar;106(3):444-57. — View Citation

Piriou V, Mantz J, Goldfarb G, Kitakaze M, Chiari P, Paquin S, Cornu C, Lecharny JB, Aussage P, Vicaut E, Pons A, Lehot JJ. Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial. Br J Anaesth. 2007 Nov;99(5):624-31. Epub 2007 Oct 3. — View Citation

Swart MJ, De Jager WH, Kemp JT, Nel PJ, Van Staden SL, Joubert G. The effect of the metabolic syndrome on the risk and outcome of coronary artery bypass graft surgery. Cardiovasc J Afr. 2012 Aug;23(7):400-4. doi: 10.5830/CVJA-2012-055. — View Citation

Wang L, Ko KW, Lucchinetti E, Zhang L, Troxler H, Hersberger M, Omar MA, Posse de Chaves EI, Lopaschuk GD, Clanachan AS, Zaugg M. Metabolic profiling of hearts exposed to sevoflurane and propofol reveals distinct regulation of fatty acid and glucose oxidation: CD36 and pyruvate dehydrogenase as key regulators in anesthetic-induced fuel shift. Anesthesiology. 2010 Sep;113(3):541-51. doi: 10.1097/ALN.0b013e3181e2c1a1. — View Citation

Whittington RA, Virág L, Marcouiller F, Papon MA, El Khoury NB, Julien C, Morin F, Emala CW, Planel E. Propofol directly increases tau phosphorylation. PLoS One. 2011 Jan 31;6(1):e16648. doi: 10.1371/journal.pone.0016648. — View Citation

Zaugg M, Lucchinetti E, Garcia C, Pasch T, Spahn DR, Schaub MC. Anaesthetics and cardiac preconditioning. Part II. Clinical implications. Br J Anaesth. 2003 Oct;91(4):566-76. Review. — View Citation

Zaugg M, Lucchinetti E, Uecker M, Pasch T, Schaub MC. Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms. Br J Anaesth. 2003 Oct;91(4):551-65. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarker NT-proBNP	Difference between volatile anesthesia and total intravenous anesthesia	1. after induction of anesthesia 2. after chest closure 3.-5. postoperative day 1, day 2, day 3
Secondary	Receptor Substrate phosphorylization (IRS-1)/PP2A	Difference between volatile anesthesia and total intravenous anesthesia	1. beginning of cardiac surgery, 2. end of cardiac surgery
Secondary	Expression of TNF/IL1beta and microRNA (miR144, miR125b, miR208a)	Difference between volatile anesthesia and total intravenous anesthesia	1. beginning of cardiac surgery, 2. end of cardiac surgery