Clinical trial NCT00356746: Inflammatory Response During Anesthesia and Surgery
Official title: A Prospective, Randomized Trial to Study the Effects of Different Anesthetic Agents on the Perioperative Immune Response
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Inflammatory Response Syndrome
Myocardial Ischemia
Keywords: Perioperative inflammatory response
General anesthesia
Toll-Like Receptors
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: European Association of Cardiothoracic Anaesthesiologists
First posted: 2006-07-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: specific surgical patients receiving general anesthesia of university teaching hospital

Brief summary: The purpose of this study is to investigate the effects of total intravenous anesthesia versus volatile anesthesia on the perioperative inflammatory response during and after major surgery.

Detailed description: Patients undergoing major surgical procedures, in particular those undergoing cardiac surgery, develop a severe inflammatory response in up to 50% of cases leading to increased mortality and morbidity. The inflammatory response depends on the surgical procedure and on patient related factors like genetic predisposition and co morbidities. However, in vitro studies showed that the type and duration of general anaesthesia also influences the extent of perioperative inflammation.

Comparison: total intravenous anesthesia by propofol is compared to volatile anesthesia by isoflurane with respect to development of perioperative inflammatory response.

The IRAS study is a single centre study, executed in the University Medical Centre Utrecht, The Netherlands. Four different patient groups are included. 1) Patients undergoing coronary artery bypass grafting (CABG) with use of cardiopulmonary bypass (CPB), 2) patients undergoing aorta aneurysm repair via endovascular approach and 3) via conventional open procedure, and 4) patients undergoing surgery for replacement of implantable cardioverter defibrillator (ICD).

The IRAS is a prospective, randomized clinical trial. Patients are randomly assigned to a intravenous or a balanced anaesthesia technique. Peripheral blood samples are drawn before, during and up to 72h after surgery.

Eligibility criteria: Inclusion Criteria:

* Patients older than 18 years and planned for elective Coronary Artery Bypass Grafting (CABG), aorta surgery or Implantable Cardioverter Defibrillator (ICD) replacement

Exclusion Criteria:

* Emergency operations
* Patients undergoing combined or re-do procedures
* Patients who are diagnosed with or undergoing treatment for a steroid or hormone disorder, excluding diabetes
* Patients suffering from chronic inflammatory diseases
* Patients suffering form current infections
* Patients currently treated with steroids
* Patients undergoing treatment or care for a malignancy
* Patients participating in another study that may interfere with the endpoints of the IRAS trial

Primary outcomes:
measure: Perioperative inflammatory response through measurement of expression and responsiveness of Toll-like Receptor (TLR) 2 and 4 of monocytes from full blood samples.
timeFrame: 72 hours
Secondary outcomes:
measure: Parameters of systemic haemodynamics
timeFrame: 72 hours
measure: Need of vasoactive medication to develop predefined haemodynamic goals
timeFrame: 72 hours
measure: Biochemical parameter of myocardial ischaemia and infarction (Troponin-I), measured immediately before and after surgery, 24 hr and 72hr after surgery
timeFrame: 72 hours
measure: Serious adverse events assessed 3 days after surgery, at discharge, 30 days and one year after surgery
timeFrame: 1 year
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Division of Perioperative Care and Emergency Medicine, Department of Anesthesiology
Study officials:
affiliation: University Medical Centre Utrecht, The Netherlands
name: Cor J Kalkman, Prof MD PhD
role: STUDY_CHAIR
affiliation: University Medical Centre Utrecht, The Netherlands
name: Wolfgang F Buhre, MD PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Utrecht, The Netherlands
name: Gerard Pasterkamp, Prof MD PhD
role: STUDY_DIRECTOR
References:
citation: de Kleijn D, Pasterkamp G. Toll-like receptors in cardiovascular diseases. Cardiovasc Res. 2003 Oct 15;60(1):58-67. doi: 10.1016/s0008-6363(03)00348-1.
citation: de Rossi LW, Brueckmann M, Rex S, Barderschneider M, Buhre W, Rossaint R. Xenon and isoflurane differentially modulate lipopolysaccharide-induced activation of the nuclear transcription factor KB and production of tumor necrosis factor-alpha and interleukin-6 in monocytes. Anesth Analg. 2004 Apr;98(4):1007-1012. doi: 10.1213/01.ANE.0000106860.27791.44.
citation: Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner GA, Bauer M. Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology. 1998 Nov;89(5):1218-27. doi: 10.1097/00000542-199811000-00023.
citation: Flier S, Concepcion AN, Versteeg D, Kappen TH, Hoefer IE, de Lange DW, Pasterkamp G, Buhre WF. Monocyte hyporesponsiveness and Toll-like receptor expression profiles in coronary artery bypass grafting and its clinical implications for postoperative inflammatory response and pneumonia: An observational cohort study. Eur J Anaesthesiol. 2015 Mar;32(3):177-88. doi: 10.1097/EJA.0000000000000184.
citation: Flier S, Post J, Concepcion AN, Kappen TH, Kalkman CJ, Buhre WF. Influence of propofol-opioid vs isoflurane-opioid anaesthesia on postoperative troponin release in patients undergoing coronary artery bypass grafting. Br J Anaesth. 2010 Aug;105(2):122-30. doi: 10.1093/bja/aeq111. Epub 2010 Jun 23.