Clinical trial NCT02407626: Optimization of Cardioprotection in Diabetic Patients Undergoing Cardiac Surgery
Official title: Optimierung Der Kardioprotektion Durch Inhalative Anästhetika Eine Untersuchung Bei Patienten Mit Diabetes Mellitus während Off-pump Herzchirurgie
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Myocardial Ischemia
Keywords: ischemia
cardiac surgery
volatile anesthetic
total intravenous anesthesia
Lead sponsor: Triemli Hospital
Sponsor class: OTHER
Collaborators: name: University of Alberta
First posted: 2015-04-03
Enrollment: 2
Sex: MALE
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Diabetes
* Elective cardiac surgery

Exclusion Criteria:

* Emergency procedures
* Preop myocardial infarction
* Preop cardiac failure
* Preop renal replacement therapy

Primary outcomes:
measure: Biomarker NT-proBNP
timeFrame: 1. after induction of anesthesia 2. after chest closure 3.-5. postoperative day 1, day 2, day 3
Secondary outcomes:
measure: Receptor Substrate phosphorylization (IRS-1)/PP2A
timeFrame: 1. beginning of cardiac surgery, 2. end of cardiac surgery
measure: Expression of TNF/IL1beta and microRNA (miR144, miR125b, miR208a)
timeFrame: 1. beginning of cardiac surgery, 2. end of cardiac surgery
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Triemli City Hospital
Study officials:
affiliation: Institute of Anesthesiology and Intensive Care Medicine Triemli City Hospital Zurich
name: Andreas Zollinger, MD
role: STUDY_CHAIR
References:
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. doi: 10.1097/00000542-200306000-00004.
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. doi: 10.1097/00000542-200703000-00008.
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. doi: 10.1093/bja/aem264. Epub 2007 Oct 3.
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. doi: 10.1093/bja/aeg205.
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. doi: 10.1093/bja/aeg206.
citation: 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. doi: 10.1016/S0140-6736(07)61296-3.
citation: Lou PH, Lucchinetti E, Zhang L, Affolter A, Gandhi M, Zhakupova A, Hersberger M, Hornemann T, Clanachan AS, Zaugg M. Propofol (Diprivan(R)) and Intralipid(R) 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.
citation: Whittington RA, Virag 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.
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.
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.