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International Observational Study on Perioperative Cognitive Trajectories (POCD Census International/PCI)

Completed
Conditions
Postoperative Cognitive Deficit (POCD)
Neurocognitive Disorders
Registration Number
NCT03540433
Lead Sponsor
Charite University, Berlin, Germany
Brief Summary

The purpose of this international, multi-centre observational study is to describe perioperative cognitive changes (pre-existing neurocognitive disorder \[NCD\], postoperative delirium \[POD\] and Postoperative Cognitive Dysfunction \[POCD\]) up to five years after elective surgery in a mixed cohort. Measurements and definitions of cognitive outcomes will be based on current consensus and used for further harmonization in future clinical studies on perioperative cognitive trajectories. This is a feasibility approach to identify an effective screening procedure and estimate loss to follow up rates for the planning of future intervention studies. Data from this trial may also serve to facilitate and implement time effective cognitive screening and risk stratification concerning postoperative cognitive decline in the anaesthesiological preoperative assessment.

Detailed Description

This international observational study on perioperative cognitive trajectories (POCD census international/PCI) has been designed as a pilot study to allow a peer reviewed process of four international test centres on measurement of perioperative acute and long-term cognitive outcome. Data from standard clinical treatment of 500 patients age ≥ 70 years scheduled for elective surgery (stratified according to preoperative assessment of frailty and monitored by intraoperative depth of anaesthesia) will be supplemented by guideline conform delirium- analgesia- and sedation screening until day 5 after surgery, I-Pad based neuropsychological testing \[Cambridge Neuropsychological Test Automated Battery - CANTAB connect\] pre-operatively, 3 months, 1- 2- and 5 years after surgery, a paper-based verbal fluency test (animal naming test from Addenbrooke's Cognitive Examination Revised (ACE-R)), a paper based test on executive function (Trailmaking Test), cognitive screening tests (Montreal Cognitive Assessment (MOCA) and Mini-Cog), and concomitant questionnaires to assess functional status, self- and by proxy rating of cognitive performance, psychological factors (depression, perioperative anxiety, stress, resilience and coping), social support, perioperative anxiety, stress, resilience and coping, as well as risk consumption of alcohol and tobacco.

A non-surgical control group of 100 study participants who are not scheduled for surgery will be followed up at the same time points as the surgical cohort for scaling of cognitive data and definition of cut off values to define significant cognitive decline.

Secondary outcome measures of this trial comprise levels and changes in molecular biomarkers involved in Alzheimer's dementia etiology sampled from spinal fluid on induction of spinal anaesthesia and sampled from blood in all patients.

Retrospective comparison collective (01/01/2017 to 01/01/2022):

A group of around 8000 surgical patients aged 65 and older at the Charité will be examined as control group. This control group is required for various questions, especially influencing factors with regard to the postoperative outcome of delirium, and aims to test the predictive ability of clinical routine data with regard to postoperative delirium. As part of the multimodality of this retrospective comparative cohort study, in cooperation with PD. Dr Scheel and in collaboration with Prof. Dr. Finke, cranial MRI scans analyzing routine data from the Institute of Neuroradiology. The subject of the investigation is initially the entire electronic routine data of the control group, including the existing cranial MRI scans.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
173
Inclusion Criteria
  • Surgical patients at Campus Virchow- Klinikum and Campus Charité Mitte
  • Aged ≥ 70 years
  • Informed consent
Exclusion Criteria
  • Manifest dementia
  • Lack of willingness to store and disseminate pseudonymized disease data as part of the clinical trial
  • Lack of readiness to participate in the follow-up examinations and contact to make an appointment
  • Placement in an institute under judicial or official orders (according to German drug Law §40 (1) 4)
  • Persons without a permanent residence or other circumstances that call into question the availability by telephone or post for postoperative examination
  • Employees of the respective study centers
  • illiteracy
  • Patients with a neuropsychiatric condition that limits the performance of neurocognitive testing
  • Patients with hearing and / or vision problems that limit the performance of neuro-cognitive testing
  • Simultaneous participation in a prospective clinical intervention study (apart from the desired parallel participation in the anaesthesiological study Praep-Go, EA1/225/19)

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Incidence of postoperative cognitive dysfunction (POCD)Up to 1 year

Neuropsychological testing

Secondary Outcome Measures
NameTimeMethod
Demographic variablesUp to five years
Blood biomarker for diagnosing dementiaUp to five years

Patients consented on blood sampling receive biomarker analysis from blood (Apolipoprotein E).

Incidence of postoperative cognitive dysfunction (POCD)Up to 5 years

Neuropsychological testing

Positive cognitive screeningUp to 5 years

Short neuropsychological testing

Cerobrospinal fluid biomarker for diagnosing dementiaUp to five years

Patients for spinal anesthesia who consented on lumbar puncture receive biomarkers analysis from spinal fluid (beta Amyloid 1-40, beta-Amyloid 1-42, beta-Amyloid Ratio (42/40\*10), phospho-TAU, Protein 14-3-3, PRPSc, TAU (Gesamt-Tau)).

Nutritional statusUp to five years

Changes in the nutritional status after elective surgery are measured by a questionnaire.

Findings of memory consultation sessionUp to five years
ComorbiditiesUp to five years

Comorbidities will be quantified by use of Charlson Comorbidity index

SarcopeniaUp to five years

The composite outcome measure "Sarcopenia" is defined by the following three criteria: 1) low muscle strength (hand grip strength), 2) low muscle quantity (calf circumference and 3) low physical performance (gait speed). Criterion (1) identifies probable sarcopenia, additional documentation of criterion (2) confirms sarcopenia diagnosis, and if all criteria (1), (2) and (3) are met, sarcopenia is considered severe.

Physical activityAt the beginning of the observation

Physical activity is evaluated by interviewing the Patient.

Sedation on the peripheral wardParticipants will be followed for the duration of hospital stay, an expected average of 7 days

Sedation is measured by Richmond Agitation Sedation Scale.

Major Neurocognitive DisorderUp to five years

Definition according to DSM-V as proposed in Evered L et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery. Br J Anaesth, Anesthesiology, Can J Anesth, Anesth Analg, J Alz Dis, acta scandinavica anaesthesiologica (Joint Publication) 2017; Accepted, In Press. We will use an I-pad based neuropsychological test battery (CANTAB connect), and cognitive screening instruments (MOCA, Mini-Cog™ and Animal naming test on verbal fluency from ACE-R) for assessment of cognitive function, MMQ and IQ-code for self- or by proxy reported cognitive concern and ADL/IADL for assessment of functional status. Mild/major Neurocognitive Disorder measured at baseline (pre-existing NCD) 3 months and 1 year (with specifier 'POCD'), 2- and 5 years after surgery

Malnutrition 1Up to five years

Malnutrition is measured by the Body mass index

Malnutrition 3Up to five years

Malnutrition is measured by weight

Arm circumferenceUp to five years

Arm circumference is measured in a standardized position and documented in centimeter.

Adherence to Mediterranean diet (MD)Up to five years

Adherence to Mediterranean diet (MD) is measured with a German Mediscore, could range from 0 to 9, with higher scores (6-9) indicating greater MD adherence.

Surgical riskParticipants will be followed up during surgery, an estimated duration of 1 hour

Surgical risk will be described by type and length of surgery and perioperative cardiac risk estimation as described in Anästh Intensivmed 2017; 58:349-364.

Anaesthesiological Risk 2Participants will be followed up during surgery, an estimated duration of 1 hour

Anaesthesiological risk will be measured by length of anesthesia

Duration of DeliriumParticipants will be followed for the duration of hospital stay, an expected average of 7 days

Duration of postoperative delirium, defined according to medical evaluation, measured in days

Mild Neurocognitive DisorderUp to five years

Definition according to DSM-V as proposed in Evered L et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery. Br J Anaesth, Anesthesiology, Can J Anesth, Anesth Analg, J Alz Dis, acta scandinavica anaesthesiologica (Joint Publication) 2017; Accepted, In Press. We will use an I-pad based neuropsychological test battery (CANTAB connect), and cognitive screening instruments (MOCA, Mini-Cog™ and Animal naming test on verbal fluency from ACE-R) for assessment of cognitive function, MMQ and IQ-code for self- or by proxy reported cognitive concern and ADL/IADL for assessment of functional status. Mild/major Neurocognitive Disorder measured at baseline (pre-existing NCD) 3 months and 1 year (with specifier 'POCD'), 2- and 5 years after surgery

Nutrition in the hospitalUp to five years

Participants will be followed for the duration of hospital stay, an expected average of 7 days

Intraoperative depth of anaesthesiaParticipants will be followed up during surgery, an estimated duration of 1 hour

Intraoperative depth of sedation will be monitored with changes in the pattern and power spectrum of EEG-raw data measured with the Masimo SedLine® brain function monitoring for Root®, Narcotrend®, BIS™ and additionally quantified by indices \[e.g. PSI or BIS-index\] and burst suppression ratio.

Intensive care unit length of stayParticipants will be followed for the duration of intensive care unit stay, an expected average of 5 days

Intensive care unit length of stay describes every day spent in an ICU bed.

Hospital length of stayParticipants will be followed for the duration of hospital stay, an expected average of 7 days

Hospital length of stay describes every day spent in an hospital.

Perioperative AnxietyUp to 5 days

Perioperative anxiety will be measured with APAIS preoperatively and the Faces Anxiety Scale (FAS) and during hospital stay.

Perception of stressUp to 5 days

Stress is measured by Perceived Stress Questionnaire 20

Level of dependencyUp to 5 years

Level of dependency will be measured with with ADL/IADL, single items concerning patients' living situation and the BSSS-17 (Berlin Social Support Scales).

MortalityUp to 5 years

The number of deaths in a given period.

LonelinessUp to five years

Loneliness is measured with the UCLA-Loneliness-Scale (3 items)

Malnutrition 2Up to five years

Malnutrition is measured by weight

Calf circumferenceUp to five years

Calf circumference is measured in a standardized position and documented in centimeter.

Anaesthesiological Risk 1At the beginning of the observation

Anaesthesiological risk will be described by American Society of Anesthesiologists Classification (ASA Class)

Incidence of postoperative deliriumUp to 5 days

Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V), CAM/CAM-ICU, Nu-DESC and Chart Review.

Living conditionsUp to five years
Dental healthUp to five years

The dental status is determined by tooth doctors

Anaesthesiological Risk 3Participants will be followed up during surgery, an estimated duration of 1 hour

Anaesthesiological risk will be measured by type of anaesthesia

Depth of sedation on the Intensive Care UnitParticipants will be followed for the duration of intensive care unit stay, an expected average of 5 days

Sedation is measured by Richmond Agitation Sedation Scale.

Agitation on the peripheral wardParticipants will be followed for the duration of hospital stay, an expected average of 7 days

Agitation describes a clinical state in which the patient may be impulsive and attempt to get out of bed, to wander, and to fall (which may lead to further injury or death) and attempt to remove IV lines, tubes, or catheters.

Severity of postoperative deliriumUp to 5 days

Postoperative delirium rate, defined according to Confusion assessment method - severity(CAM-S); Delirium Rating Scale Revised (DSR-R-98), Intensive Care Delirium Screening Checklist (ICDSC) and Nursing Delirium Screening Scale (Nu-DESC).

Quality of sleepUp to 5 years

Quality of sleep is measured by the Insomnia Severity Index.

Organ dysfunctionsUp to hospital discharge, an expected average of 7 days

Organ dysfunctions are evaluated according to the Clavien-Dindo classification of surgical complications

Plausibility check variablesUp to 5 years

Variables affecting performance of cognitive testings

Revison surgeryUp to 5 years

Surgery performed to replace or compensate for a failed implant or to correct undesirable sequelae of previous surgery.

Outpatient treatmentUp to 5 years

Treatment outside of the hospital in an associated facility for diagnosis or treatment.

Pain scale for patients able of pain self-assessmentUp to hospital discharge, an expected average of 5 days

Pain during hospital stay will be measured with the Numeric Rating Scale (NRS-V).

Pain scales for patients unable of pain self-assessmentUp to hospital discharge, an expected average of 5 days

For patients unable of pain self-assessment (e.g. ventilated patients, patients in delirious state or patients with stroke affecting language skills) observer-rated pain scales will be applied: Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT) during hospital stay.

Stress levelUp to 5 days

Stress level is measured by stress thermometer

Generalized anxietyUp to 5 days

Anxiety will be measured with the Generalized Anxiety Disorder 7-Item Scale (GAD-7)

DepressionUp to 5 years

Depression is measured by PHQ-8. Scores represent:0-5 = mild, 6-10 = moderate, 11-15 = moderately severe, 16-20 = severe depression

Routine laboratoryUp to hospital discharge, an expected average of 7 days
Quality of lifeUp to 5 years

Quality of life will be measured with the EQ-5D-5L

Postoperative electroencephalography (EEG) spectral analysis with band powerUp to seven days

Spectral analysis with band power are measured by EEG at third postoperative day and delirium dependent until postoperative day 7.

Evaluation of painUp to three months

Pain is measured with dolosys paintracker

Subjective/By proxy assessment of cognitive impairmentUp to five years
MedicationUp to 5 years

Prescribed regular drug intake from baseline at all follow ups including perioperative application of drugs, infusions and transfusions will be evaluated.

Re-admissionUp to 5 years

Hospital readmission is an episode when a patient who had been discharged from a hospital is admitted again within a specified time interval.

Motivational incongruenceUp to five years

The incongruence questionnaire (Der Inkongruenzfragebogen)

DementiaUp to 5 years

Dementia reported as clinical diagnosis based on DSM-5 criteria for major NCD either through neuropsychological evaluation at a memory clinic or as a research diagnosis based on neuropsychological test values (CANTAB/MOCA), cognitive concern (MMQ/IQCODE) and functionality (ADL/IADL).

Leisure behaviorUp to five years

Questionnaire on frequency of cognitively stimulating leisure activities

Social supportUp to five years

Social support is measured with the Berliner Social-Support Skalen BSSS-17

Living situationUp to five years

Living situation is measured with te question: How do you live?

Trial Locations

Locations (3)

Arbeitsbereich Physikalische Medizin

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Berlin, Germany

Internistische Hausarztpraxis

🇩🇪

Berlin, Germany

Department of Anesthesiology and Intensive Care Medicine Berlin (CCM/CVK), Charité - Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

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