Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)

Phase 4CompletedNCT02096068

Claudia Spies78 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Delirium Postoperative Cognitive Deficit (POCD)

Interventions

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

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 Exclusion Criteria 1. Minimal mental status examination (MMSE) \< 24 2. Missing informed consent for saving and hand out pseudonymous data 3. Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing 4. Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing 5. Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and other substances, which limit the conduction of the neurocognitive testing

Outcomes

Primary Outcomes

Incidence of postoperative delirium

Incidence of postoperative delirium measured with the Confusion Assessment Method for the ICU (CAM-ICU) or the Confusion Assessment Method (CAM)

Time frame: Until the 5th postoperative day

Secondary Outcomes

Incidence of subsyndromal delirium and severity of postoperative delirium

Incidence of Subsyndromal Delirium (SSD) and severity of postoperative Delirium measured with the Intensive Care Delirium Screening Checklist (ICDSC)

Time frame: Until the 14th postoperative day/discharge

Duration of delirium in the intensive care unit

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)

Time frame: Until the 14th postoperative day/discharge

Severity of anxiety

Severity of anxiety measured with the Faces Anxiety Scale (FAS)

Time frame: Up to three months

Management of sedation

Management of sedation measured by the Richmond Agitation Sedation Scale (RASS)

Time frame: Until the 5th postoperative day

Management of vigilance

Management of Vigilance measured by Glasgow Coma Scale (GCS)

Time frame: Until the 5th postoperative day

Management of analgesia and pain levels

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)

Time frame: Up to three months

Relevant medication

Time frame: Until the 5th postoperative day

Severity of illness

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)

Time frame: Up to 14 postoperative days

Mechanical ventilation/weaning failure

Time frame: Until the 5th postoperative day

Intraoperative cerebral oxymetry

Time frame: At time of surgery

Processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)

Time frame: At time of surgery

Determination of blood levels

Complete blood count performance (Sysmex®) and acetylcholinesterase-analysis

Time frame: Change from baseline complete blood count performance (Sysmex®) and acetylcholinesterase-analysis at third postoperative day

Cortisol-analysis

Time frame: Up to three months

Organ dysfunctions

Time frame: Up to three months

Infections

Infections according to surgical site infections (SSI) and according to the US Centers for Disease Control and Preventions (CDC).

Time frame: Up to three months

ICU length of stay

Time frame: Participants will be followed for the duration of intensive care stay, an expected average of 2 days

Hospital length of stay

Discharge criteria have to be met according to Post Anaesthetic Discharge Scoring System (PADSS) for monitoring patients discharge.

Time frame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Quality of life

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

Time frame: Up to three months

Incidence of postoperative cognitive dysfunction

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)

Time frame: Up to three months

Mortality

Time frame: Up to three months

Sleep quality

Time frame: Up to three months

Photomotor reflex

Time frame: At time of surgery

Changes of hemodynamic parameters in the intraoperative transesophageal echocardiography

Hemodynamic aparemters are measured in patients for elective CABG surgery

Time frame: At time of surgery

Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes