Background
Methods/Design
Study registration
Recruitment
Study type
Randomization
Inclusion criteria
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Age > 65 years
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Patient scheduled for elective heart surgery with the use of CPB
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Able to read and understand the research materials
Exclusion criteria
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Inability to give informed consent
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Intraoperative need for one-lung-ventilation and/or for an increased fraction of inspired oxygen (FiO2 > 50 %)
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Chronic obstructive pulmonary disease (COPD) GOLD > II
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Critical preoperative state (as defined by the requirement of inotropic support or intra-aortic balloon pump (IABP), ventricular tachycardia or ventricular fibrillation, preoperative cardiac massage, preoperative ventilation before anesthetic room, preoperative acute renal failure (anuria or oliguria < 10 ml hr−1) [25]
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Disabling neuropsychiatric diseases (dementia, schizophrenia, epilepsy or mental retardation)
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Presence of delirium at baseline as screened with the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) [26]
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Alcohol abuse: (defined as a CAGE score ≥ 2) [27]
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History of drug abuse
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History of stroke or traumatic brain injury with residuals
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Increased intracranial pressure
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Hypersensitivity to the study medications
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Risk for malignant hyperthermia
Anesthesia and intervention
Baseline assessment (Investigator I)
General anesthesia
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xenon 40–60 % in oxygen (FiO2 = 0.5–0.6) (xenon-group), or
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sevoflurane 1.0–1.4 % (FiO2 = 0.5–0.6) (sevoflurane-group)
Monitoring and hemodynamic management
Cardiopulmonary bypass
Intensive care unit treatment
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Active detection and treatment of pain
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Early mobilization
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Removal of catheters, drains, probes, etc. as soon as possible
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Timely recognition and treatment of medical problems such as stroke, infections, electrolyte imbalances, hypoxia, heart failure, hypotension, dehydration, urinary retention, etc.
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Strict avoidance of medications known to trigger POD (in particular, benzodiazepines and steroids)
Study outcomes
Primary endpoint
Secondary endpoints
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Incidence of MACCE (major adverse cardiac and cerebral events, occurring until discharge from hospital and in the first 6 postoperative months); i.e. death from any cause; perioperative myocardial infarction, requirement of surgical revisions at the coronary arteries; postoperative coronary angioplasty; and stroke. Myocardial infarction is defined as the occurrence of a new Q wave in addition to a rise of more than 10 ng ml−1 of troponin in the early postoperative period or any episode of chest pain with typical rise and fall of cardiac enzymes thereafter
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Other cerebrovascular accidents not included in MACCE (transient ischemic attacks, reversible ischemic neurologic deficit)
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Postoperative renal function (as assessed by serum creatinine and blood urea nitrogen (BUN) levels)
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Requirement for blood (product) transfusion
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Incidence of intraoperative awareness as detected by the use of a structured Brice questionnaire [41] that will be performed one day after ICU discharge
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Duration of postoperative ICU-stay and hospital stay
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Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions not included above. According to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), an adverse event (AE) will be defined as “any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.” A SAE is “any AE that is life threatening – results in death – requires patients re-hospitalization and/or prolongation of existing hospitalization – or results in patient’s disability” [44]
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Intraoperative hemodynamic and respiratory profile
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Intraoperative use of inotropic/vasoactive medication
Blood samples and laboratory parameters
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Markers of glial injury: serum protein S100β
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Hemoglobin and hematocrit
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Cardiac markers: CK-MB and troponin T-hs
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C-reactive protein (CRP), leukocyte counts, serum cytokines (interleukin (IL)-6, IL-10)
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Respiratory markers: SaO2, PaO2 PaCO2, arterial pH, bicarbonate and base excess
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Renal markers: serum creatinine and blood urea nitrogen
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Hepatic markers: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and total bilirubin
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Serum electrolytes and serum blood sugar concentration