Delirium, Postoperative Cognitive Deficit (POCD)
Conditions
Keywords
Neuroprotection
Brief summary
The drug Dexmedetomidine will be investigated in 72 patients (men and women) undergoing elective cardiac or abdominal surgery. The study medication will be administered perioperatively by intravenous infusion continuously (at the longest 48 h) to prevent/reduce the rate of Delirium and the incidence of postoperative cognitive deficit (POCD). A non-surgical control group of 15 ASA II/III- patients from Berlin and surrounding area is collected for measuring the learning experience during the cognitive testings. The participants are matched on age, education, and gender to the study patients. Cognitive testings are performed in patients of the study group (n= 72) and the control group (n= 15) to evaluate deficits in their cognitive areas (POCD (Postoperative cognitive deficit)) at three different time points up to three months.
Interventions
DRUGDexmedetomidine (Dexdor®)
Dexmedetomidine (Dexdor 100 micrograms/ml concentrate for solution for infusion)
DRUG0.9% Sodium Chloride
Solution for infusion: Sodium Chloride : 9.0 g/l; Each ml contains 9 mg sodium chloride mmol/l : Na+ : 154. Cl-: 154.
Sponsors
Claudia Spies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study Group: Inclusion Criteria: 1. Patients aged ≥ 60 years 2. Male and female patients undergoing elective cardiac (elective CABG-surgery without valve surgery with left ventricular ejection fraction ≥ 30%) or pancreatic or hepatic or gastric or intestinal surgery of both Campus Charité Mitte and Campus Virchow - Klinikum, Charité - Universitätsmedizin Berlin 3. Offered patient information and written consent by the patient (according to German Drug Law § 40 (1) 3b) 4. Premedication only with benzodiazepines 5. Pain therapy during the operation with regional procedures and/or Sufentanil/Fentanyl 6. Anesthesia in cardio surgery according to Heart-Lung-Apparatus 7. Anesthesia with hypnotic agent Propofol 8. Pain therapy after operation according to S3-Guideline 9. Postoperative medication for anxiolysis only with benzodiazepines
Exclusion criteria
1. Known drug intolerance/allergy: dexmedetomidine or to other ingredients 2. Lacking willingness to save and hand out pseudonymised data within the clinical trial 3. Accommodation in an institution due to an official or judicial order (according to AMG §40 (1) 4) 4. Employee of the Charité - Universitätsmedizin Berlin CVK/CCM 5. Illiteracy 6. Inability to speak and/or read German 7. Minimal mental status examination (MMSE) \< 24 8. Severe hearing loss or visual impairment 9. Acute brain injury 10. Intracranial haemorrhage within one year before participation in the study 11. Manifest psychiatric disease 12. Known illicit substance abuse 13. Acute intoxication 14. For women: Pregnancy or positive pregnancy test within the preoperative screening 15. Homeless or other circumstances, where the patient would not be reachable by telephone or postal services for the 3-months follow up 16. Participation in another interventional clinical trial according to the German Drug Law at time of inclusion and during the trial 17. Acute circulatory failure at time of randomisation (severe hypotension with mean arterial pressure \< 55 mmHg despite vasopressors or optimal preload) 18. AV-conduction-block II or III (unless pacemaker installed) 19. Severe bradycardia (heart-rate \< 50 bpm, preoperative, permanent) 20. Spinal cord injury with known autonomic dysregulation 21. Preoperative acute cerebrovascular event with neurologic residues 22. Liver insufficiency (Child C cirrhosis, MELD Score \> 17) 23. Application of Remifentanil during the operation 24. Deep sedation (RASS, -4 to -5) 25. Administration of Clonidine during administration of the study drug 26. Additional administration of Dexmedetomidine within 3 months after study inclusion Control Group: Inclusion Criteria: 1. Patients aged ≥ 60 years of European descent (Caucasian) 2. Male or female patients with ASA II+III 3. ASA II+III-patients, for which no operation is planned within the next year 4. No operation in the last half year before study inclusion 5. Offered patient information and written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative delirium | Until the 5th postoperative day | Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) or the Confusion Assessment Method (CAM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of delirium in the intensive care unit | Until the 14th postoperative day/discharge | Duration of intensive care unit-delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) |
| Severity of anxiety | Up to three months | Severity of anxiety measured with the Faces Anxiety Scale (FAS) |
| Management of sedation | Until the 5th postoperative day | Management of sedation measured by the Richmond Agitation Sedation Scale (RASS) |
| Management of vigilance | Until the 5th postoperative day | Management of Vigilance measured by Glasgow Coma Scale (GCS) |
| Management of analgesia and pain levels | Up to three months | Management of analgesia and pain levels measured by Numeric Rating Scale - Visualized (NRS-V), the Faces Pain Scale - Revised (FPS-R), the Behavioral Pain Scale (BPS) or the Behavioral Pain Scale for Non-Intubated (BPS-NI) |
| Relevant medication | Until the 5th postoperative day | — |
| Severity of illness | Up to 14 postoperative days | Severity of illness measured by Sequential Organ Failure Assessment (SOFA-Score), Simplified Acute Physiology Score (SAPS II) and the Acute Physiology and Chronic Health Evaluation (APACHE II) |
| Mechanical ventilation/weaning failure | Until the 5th postoperative day | — |
| Intraoperative cerebral oxymetry | At time of surgery | — |
| Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®) | At time of surgery | — |
| Determination of blood levels | Change from baseline complete blood count performance (Sysmex®) and acetylcholinesterase-analysis at third postoperative day | Complete blood count performance (Sysmex®) and acetylcholinesterase-analysis |
| Incidence of subsyndromal delirium and severity of postoperative delirium | Until the 14th postoperative day/discharge | Incidence of Subsyndromal Delirium (SSD) and severity of postoperative Delirium measured with the Intensive Care Delirium Screening Checklist (ICDSC) |
| Organ dysfunctions | Up to three months | — |
| Infections | Up to three months | Infections according to surgical site infections (SSI) and according to the US Centers for Disease Control and Preventions (CDC). |
| ICU length of stay | Participants will be followed for the duration of intensive care stay, an expected average of 2 days | — |
| Hospital length of stay | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | Discharge criteria have to be met according to Post Anaesthetic Discharge Scoring System (PADSS) for monitoring patients discharge. |
| Quality of life | Up to three months | Quality of life is measured by EQ-5D (EuroQol Group), a measure generating a single index value for health status with considerable potential for use in health care evaluation |
| Incidence of postoperative cognitive dysfunction | Up to three months | Incidence of postoperative cognitive dysfunction (POCD) is measured by Cambridge Neuropsychological Test Automated Battery (CANTAB®) and Mini Mental State Examination (MMSE) including subjective memory feeling (Item 10 of the Geriatric Depression Scale (for already included patients the retrospective follow up by telephone interview)), including limitations in daily activities (EQ-5D) |
| Mortality | Up to three months | — |
| Sleep quality | Up to three months | — |
| Photomotor reflex | At time of surgery | — |
| Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography | At time of surgery | Hemodynamic aparemters are measured in patients for elective CABG surgery |
| Cortisol-analysis | Up to three months | — |
Countries
Germany
Outcome results
None listed