The research leading consortium to these results has received funding from the European Union Seventh Framework Programme \[FP7/2007-2013\] under grant agreement no 602461 (www.biocog.eu). The investigators will establish valid biomarkers panels (neuroimaging and molecular) for risk and clinical outcome prediction of postoperative delirium (POD)/postoperative cognitive deficit (POCD) in elective surgical patients (Age ≥ 65 years) in study centers in Berlin,Germany (data collection within 2 years after initial hospital stay) and Utrecht, The Netherlands (data collection within 1 year after initial hospital stay), thereof cerebrospinal fluid (only once on day of surgery in patients with planned spinal anesthesia/combined spinal epidural analgesia in patients, only in Berlin). A control group of ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients. The ASA II/III- control patients receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 (Utrecht) and 2 years (Berlin). To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years, ASA I and II) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa. A study group at maximum (n= 80) and is collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days).The primary endponit of this substudy is gamma amino-butyric acid concentration in CNS after 3-months (measured by MRI). A retrospective comparison group (extracting 8000 intensive care unit patient data from the patient data management system during the BioCog study period in 2016) to analyse economic effects that are caused by the implementation of quality indicators in health care. An interim-analysis is performed on the primary endpoint after 400 included patients. The resulting (multivariate) expert system is expected: 1) to support clinical decision-making in patient care, e.g. to balance the individual POD/POCD risk against the expected overall clinical outcome of an (elective) surgical intervention, 2) to allow the design of more sophisticated and hypothesis-driven clinical studies and drug trials (translational research) in the future. The latter will be possible on the basis of biomarker-based sub-grouping of patients and a better understanding of relevant pathophysiological processes. Furthermore, a state-of-the art clinical database and biobank will be created that does not yet exist worldwide. Both the expert system and the reference database/biobank will expand the leadership of the contributing academic institutions in this particular research area. In addition, the newly created biobank will become an integral part of the European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) which allows top address specific and hypothesis-driven research questions. Most notably, the developed (multivariate) expert system also has the potential for commercialization. Possible customers are: 1) physicians and hospital departments being involved in pre-surgical decision making, 2) pharmaceutical industry intending to conduct biomarker-based drug trials in POD/POCD.
Study Type
OBSERVATIONAL
Enrollment
1,054
Department of Anesthesiology and Intensive Care Medicine, CCM and CVK, Charité - Universitätsmedizin Berlin
Berlin, Germany
Department of Intensive Care Medicine, University Medical Center Utrecht
Utrecht, Netherlands
Incidence of Delirium
Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and/or as ≥ 2 cumulative points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method (CAM) and/or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score and/or patient chart review that shows descriptions of delirium.
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days
Incidence of postoperative cognitive deficit (POCD)
POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) and paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)
Time frame: Up to 3 months after the operation
Duration of Delirium
* Diagnostic and Statistical Manual of Mental Disorders (DSM-V) * Nursing Delirium Screening Scale (Nu-DESC) * Intensive Care Delirium Screening Checklist (ICDSC) * Delirium Detection Scale (DDS) * Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) * Confusion Assessment Method (CAM) * Chart Review
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Duration of subsyndromal postoperative delirium
Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for delirium.
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Incidence of subsyndromal postoperative delirium
Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for Delirium
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Intensive care unit length of stay
Time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Hospital length of stay
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Postoperative organ complications
Postoperative organ complications are classified according to Clavien - Dindo classification.
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Incidence of postoperative cognitive deficit
POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB), paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)
Time frame: 1 year, 2 years, 5 years after the operation
Socioeconomic characteristics
Study center Berlin: Health economic data according to cost of patient care (The §21 dataset (diagnoses and operation-codes). Hospital costs are calculated according to the Institute for the Hospital Remuneration System (InEK) calculation scheme to compare the refinanced costs in each cost category/cost-center segment from study center Charité. Necessity and indirect costs of medical care (outpatient visits) after hospital stay.
Time frame: 3 months, 1, 2 and 5 years after the operation
Health related quality of life
Study center Berlin: Measurement by EQ-5D
Time frame: 3 months, 1, 2 and 5 years after the operation
Barthel Index
Time frame: 3 months, 1, 2 and 5 years after the operation
Instrumental activities of daily living scale
Time frame: 3 months, 1, 2 and 5 years after the operation
Hand grip strength test
Time frame: 3 months, 1, 2 and 5 years after the operation
Malnutrition
Mini Nutritional Assessment - Short form, Serum albumin
Time frame: 3 months, 1, 2 and 5 years after the operation
Mobility
Timed up and go test
Time frame: 3 months, 1, 2 and 5 years after the operation
Neuroimaging Biomarker
Time frame: 3 months, 1, 2 and 5 years after the operation
Molecular Biomarker
Time frame: 3 months
Health related Quality of life
Study center Utrecht: Measurement by EQ-5D
Time frame: 3 months, 1 year after the operation
Socioeconomic characteristics
Study center Utrecht: Health economic data according to direct cost of patient care (inpatient and outpatient stays) and necessity and indirect costs of medical care (outpatient visits) after hospital stay.
Time frame: 3 months, 1 year after the operation
Heart rate variability
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light Levels (lux)
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Light frequencies
Time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Depression
Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Anxiety
Faces Anxiety Scale (FAS)
Time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
Electroencephalography (EEG)- Mapping
Study center Berlin: EEG with19 electrodes and hypo- and hyperventilation in physiological limits (no patients with neurological pre-existing conditions or proposed neuro-surgery)
Time frame: At time of surgery
Mortality
Time frame: 3 months, 1, 2 and 5 years after the operation
Depth of consciousness index
Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
Time frame: At time of surgery
Intraoperative cerebral oxymetry
Time frame: At time of surgery
Changes of Electroencephalography
Signals are measured by EEG Monitor and Delir Monitor software
Time frame: Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days
Depth of sedation
Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)
Time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Pain Scales
Perioperatively: Pain sensitivity questionnare; Pain Catastrophing Scale (PCS-GE)(PSQ); Numerische Rating Scale (NRS-V); Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT); Rotterdam Elderly Pain Observation Scale (REPOS); Pupillometry by Neurolight; Intraoperatively: Measurement of the nociceptive flexion reflex threshold (Dolosys Paintracker); Measurement of the pupillary dilation reflex threshold (AlgiScan); Automatic collection of the data of the medication pumps; Multiple blood analysis to measure the plasma-concentrations of anesthetics; Automatic collection of the data of the SED-Line-EEG-Monitor.
Time frame: 3 months
Quality indicators of intensive care unit
Study Center Berlin: This endpoint aims to analyse economic effects of the prospective study patients and retrospective control subjects in the intensive care unit that are caused by the implementation of quality indicators in health care.
Time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Glucosevariability
Measured by Continuous Glucose Monitoring System
Time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Frailty
Time frame: 3 months, 1, 2 and 5 years after the operation
Coagulationdisorder of the blood
Kidney marker
Time frame: 3 months
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