Clinical trial NCT04320082: Alteration of Blood-Brain-Barrier Permeability at Loss of Consciousness in Delirious Patients Recorded With Direct-Current Electroencephalography (ACDC)
Official title: Alteration of Blood-Brain-Barrier Permeability at Loss of Consciousness in Delirious Patients Recorded With Direct-Current Electroencephalography (ACDC)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Delirium
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2020-03-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Elderly Cohort: Patients \>70 undergoing elective orthopaedic or trauma surgery under general anaesthesia.

Young cohort: Patients between 18 and 30 undergoing elective orthopaedic or trauma surgery under general anaesthesia.

Brief summary: With this trial we aim to characterize the intraoperative signatures of the Direct-Current-Electroencephalogram (DC-EEG) of elderly patients developing a PostOperative Delirium (POD) compared to patients who do not develop a POD. We hereby intend to gain a better understanding of the electrical potential at the blood-brain-barrier (measured with DC-EEG) during general anaesthesia. Second, we want to study the effect of age on the DC-EEG by comparing a younger (18-30y) to an elderly cohort (\>70). Third, we aim to couple the DC-EEG signatures to blood sample analysis in order to understand the relationship between metabolic, inflammatory and vascular reaction with the intraoperative DC-EEG.

Detailed description: In order to study the intraoperative DC-EEG signatures of elderly patients coupled with lab data to evaluate the role of the age-dependent blood-brain barrier (BBB) dysfunction in general anesthesia and its meaning in POD pathophysiology following protocol will be followed:

1. On the day of the surgery the 21 DC-EEG sintered Ag/AgCl (silver chloride) electrodes will be placed before the start of anesthesia following the 10-20-system.
2. The first blood sample will be collected via the routinely placed intravenous catheter.
3. During the induction of anesthesia special care will be given to the exact time of loss of consciousness (LOC), defined with the suppression of the lid closure reflex.
4. Markers will be set at important time points of the anesthetic care (Baseline, start of analgesia/anesthesia, LOC, intubation, beginning of surgical procedure, end of anesthesia, regain of consciousness, extubation, admission recovery room).
5. Shortly after consciousness has vanished (5-10 minutes), a second blood sample will be drawn.
6. The DC-EEG recording will last until one hour after arrival at the recovery room, during which NuDesc score will be assessed every 15 minutes.
7. A third blood sample is to be collected in the recovery room. In the five days following surgery patients will be visited in the morning and in the evening to screen delirious symptoms with the help of standardized scores (NuDesc, DSM V, DDS). If patients are staying on the intensive care unit the CAM-ICU will be used.

Blood sample analysis will include blood cells count, electrolytes, inflammatory markers, cholesterols, proteins, structural BBB markers and markers of neuronal damage.

Eligibility criteria: Inclusion Criteria:

* Patients aged \>70 years OR between 18 and 30
* Planned operation time \>1 hour
* Expected hospital treatment period of 5 days,
* Anesthesia induction, anesthesia maintenance with either Propofol or an inhalative anesthetic agent as Sevoflurane or Desflurane,
* The ability to give informed consent

Exclusion Criteria:

* Age under 18 or between 31 and 69
* Patients with a history of neurological or psychiatric disorders
* Planned neurosurgery
* Current medication of tranquilizers / antidepressants
* Isolation of patients with multi-resistant Bacteria
* Inability of the patients to speak and/or read German
* Intraoperative use of ketamine, N²O, Etomidate or Dexmedetomidine
* Participation in a prospective interventional trial

Primary outcomes:
measure: 1. DC-Shift (µV/sec) in the perioperative DC-EEG.
timeFrame: From the beginning of general anaesthesia to one hour after regain of consciousness
Secondary outcomes:
measure: Incidence of Postoperative Delirium
timeFrame: Patients will be follow until hospital discharge, or maximal until postoperative day 5
measure: Additional perioperative DC-EEG signatures: morphology, polarity (positive/negative), amplitude (µV)
timeFrame: From the beginning of general anaesthesia to one hour after regain of consciousness
measure: DC-EEG signatures in young (18-30) vs. elderly (>70) patients
timeFrame: From the beginning of general anaesthesia to one hour after regain of consciousness
measure: Analysis of pre-, intra- and postoperative blood parameters
timeFrame: : From shortly before the beginning of general anaesthesia to maximum one hour after arrival in the recovery room
measure: Peri-operative, full-brain overall EEG band power
timeFrame: Up to the end of stay in the recovery room
measure: Burst suppression duration
timeFrame: During anesthesia procedure
measure: Duration of Delirium
timeFrame: Participants will be followed for the duration of hospital stay, or maximal until postoperative day 5
measure: Intensive care unit length of stay
timeFrame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
measure: Hospital length of stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 7 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Claudia Spies, MD, Prof.
role: STUDY_DIRECTOR
References: