Myocardial Injury and Postoperative Complications
Myocardial Injury and Postoperative Complications
To determine whether perioperative myocardial injury is associated with adverse outcome in
 patients scheduled for major abdominal surgery.
Study design

 The MICOLON study is a prospective, single-centre, observational cohort study on the
 association between 5th generation high sensitive cardiac troponin T levels and non-cardiac
 outcome after major abdominal surgery in patients at risk for coronary artery disease.

 Patient eligibility

 Patients are eligible to enter the study if they are scheduled to undergo elective major
 abdominal surgery with an expected postoperative mortality rate >3%, are aged 45 years or
 older and have at least one of the following major cardiac risk factors: diabetes mellitus,
 peripheral artery disease (i.e. intermittent claudication or history of vascular surgery
 except arteriovenous shunt and vein stripping procedures), history of hospitalization for
 congestive heart failure, history of myocardial infarction, stable angina pectoris, history
 of coronary artery bypass grafting or percutaneous coronary angioplasty, renal insufficiency
 (defined as preoperative creatinine >150 μmol/L), history of cerebral vascular event, aortic
 valve stenosis (defined as aortic valve area <1 cm2), atrial fibrillation, moderate or poor
 left ventricular function (defined as left ventricular ejection fraction <55%), or two of the
 following minor risk factors for coronary artery disease: age >70 years, hypertension,
 hypercholesterolemia, history of transient ischemic attack, chronic obstructive pulmonary
 disease, smoking or low functional capacity (capable of physical activity of 4 metabolic
 equivalents or less). Patients are excluded from study participation if they have no signed
 informed consent.

 Study procedure

 Patients eligible for the study are identified at the outpatient preoperative anesthesiology
 clinic. Patients are examined and screened for cardiac risk factors by an anesthesiology
 resident or a dedicated screening nurse. Results of preoperative laboratory tests, data on
 patient characteristics and preoperative use of cardiovascular drugs (i.e. statin,
 ß--blocker, platelet inhibitor, calcium antagonists, angiotensin-converting enzyme inhibitor
 and angiotensine receptor blocker) were noted. Prior to any study procedure written informed
 consent is obtained from all patients. During the study period blood is collected for plasma
 troponin T measurements after induction of general anesthesia (baseline) and on the 1st, 3rd
 and 7th postoperative day. All plasma samples are frozen and stored at -20°C at the
 hospital's laboratory until analysis. Cardiac troponin T batch analysis is performed every 3
 weeks with the use of 5th generation Elecsys Troponin T high sensitive assay on an automated
 Cobas 6000 platform (Roche Diagnostics, Germany). The limit of detection of this high
 sensitive assay was determined at 3 ng/L with a 99th percentile upper reference limit of 14
 ng/L. In addition, plasma creatinine levels are measured in each sample with an enzymatic
 method on the same automated platform (Roche Diagnostics, Germany). An estimated glomerular
 filtration rate is calculated from plasma creatinine values using the Modification of Diet in
 Renal Disease formula. During the entire study period daily routine quality control samples
 for troponin and creatinine ensure comparable patient data across different reagent lots.
 After analysis the samples are stored at -80°C.

 Surgical procedures are performed under general anesthesia or a combination of general and
 epidural anesthesia. Anesthesia management is left to the discretion of the attending
 anesthesiologist. According to hospital protocol, patients scheduled for gastric-esophageal,
 pancreatic or hepatic surgery and patients aged ≥80 or with an American Association of
 Anesthesiologists physical status classification system ≥3 will be admitted to an intensive
 care unit postoperatively for at least 24 hours. To improve postoperative recovery all
 patients are treated according to the current Enhanced Recovery After Surgery guidelines.

 During the postoperative period research personnel performs patient visits, reviews medical
 charts and notes complications. At thirty days after surgery troponin results are reported to
 the researchers and a follow-up telephone interview is performed if patients are discharged
 from the hospital at that time. Patients will be asked if a medical complication has occurred
 since their discharge from the hospital. If so, medical details are retrieved from their
 treating physicians. Information from routine postoperative clinic visits is used if patients
 can not be reached by telephone. Noted endpoints are judged by an event committee, that is
 blinded for troponin results.

 Endpoint definition

 Primary parameter of the study is postoperative myocardial injury at day 1, 3 or 7. Secondary
 parameters are met by the occurrence of any of the following non-cardiac events within 30
 days after surgery: mortality - defined as death without cardiovascular origin; sepsis -
 defined as systemic inflammatory response syndrome (SIRS) in response to a proven or
 suspected microbial infection; pneumonia - defined as purulent sputum or isolation of a
 pathogen from sputum culture or blood culture and clinical symptoms (e.g. dyspnea, fever,
 cough) or a consolidation or pleural effusion on chest radiograph; respiratory failure -
 defined as non-cardiac hypoxia or hypercapnia leading to ICU (re)admission for respiratory
 support (e.g. (non)invasive ventilation or high concentration oxygen therapy); anastomotic
 dehiscence - defined as presence of luminal contents through drain or wound site causing
 local inflammation or SIRS, or leak detected on imaging studies in combination with clinical
 signs of SIRS; intestinal ischemia - defined as signs of superficial or transmural bowel
 ischemia on imaging studies and clinical symptoms (e.g. abdominal pain or tenderness) or
 SIRS; wound infection - purulent drainage from superficial incision or deliberate opening of
 superficial incision by surgeon and clinical signs of local inflammation (e.g. pain,
 tenderness, swelling, redness); bleeding - defined as abnormal postoperative bleeding needing
 surgical (i.e. re-operation) or endovascular (i.e. coiling) treatment. Other study parameters
 were length of hospital stay and in-hospital mortality.
Inclusion Criteria:

 -  Patients > 45 years of age with 1 or more major cardiovascular risk factors:
 Congestive heart failure, peripheral artery disease (intermittent claudication,
 history of vascular surgery etc), diabetes mellitus type I or II, coronary artery
 disease (history of myocardial infarction, stable angina pectoris, history of ischemia
 or coronary artery disease on cardiac tests (electrocardiogram, scintigraphy,
 echocardiogram, coronary angiogram etc), cerebrovascular accident, renal insufficiency
 (creatinine > 150umol/l), aortic valve stenosis (valve area < 1 cm2) OR 2 or more
 minor cardiovascular risk factors: Age > 70, hypertension, high cholesterol, low
 functional capacity (4 metabolic equivalents or less), transient ischemic attack,
 chronic obstructive pulmonary disease AND undergoing abdominal surgery with an
 expected 30-day mortality rate > 2-3%: colorectal, gastric, pancreatic and liver
 surgery.

 Exclusion Criteria:

 -  Age < 45 years of age, not scheduled for higher risk abdominal surgery, low
 cardiovascular risk profile.