Alteration of Blood-Brain-Barrier Permeability at Loss of Consciousness in Delirious Patients Recorded With Direct-Current Electroencephalography (ACDC)

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.

Study Overview

• Status: Recruiting
• Conditions: Delirium

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.

• Study Type: Observational
• Enrollment (Anticipated): 62

Contacts and Locations

• Study Contact: Name: Claudia Spies, MD. Prof.; Phone Number: +49 30 450 55 11 02; Email: claudia.spies@charite.de
• Study Contact Backup: Name: Claudia Spies, MD, Prof.; Phone Number: 49 30 450 55 11 02; Email: claudia.spies@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité - Universitätsmedizin Berlin
    • Contact: Claudia Spies, MD. Prof.
    • Sub-Investigator: Susanne Koch, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. DC-Shift (µV/sec) in the perioperative DC-EEG.	Full-brain DC-EEG with 21 electrodes placed preoperatively following the 10/20-System and recording until one hour after regain of consciousness.	From the beginning of general anaesthesia to one hour after regain of consciousness

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Delirium	Postoperative Delirium is 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.	Patients will be follow until hospital discharge, or maximal until postoperative day 5
Additional perioperative DC-EEG signatures: morphology, polarity (positive/negative), amplitude (µV)	Full-brain DC-EEG with 21 electrodes placed preoperatively following the 10/20-System and recording until one hour after regain of Consciousness.	From the beginning of general anaesthesia to one hour after regain of consciousness
DC-EEG signatures in young (18-30) vs. elderly (>70) patients	Full-brain DC-EEG with 21 electrodes placed preoperatively following the 10/20-System and recording until one hour after regain of consciousness	From the beginning of general anaesthesia to one hour after regain of consciousness
Analysis of pre-, intra- and postoperative blood parameters	Blood samples will be drawn before the start of general anesthesia, shortly after loss of consciousness and in the recovery room.	: From shortly before the beginning of general anaesthesia to maximum one hour after arrival in the recovery room
Peri-operative, full-brain overall EEG band power	Full-brain EEG recording with surface Ag/AgCl electrodes Spectral analysis by Matlab Code/Lab Chart	Up to the end of stay in the recovery room
Burst suppression duration	Full-brain EEG recording with surface electrodes, raw EEG analysis	During anesthesia procedure
Duration of Delirium	Diagnostic and Statistical Manual of Mental Disorders (DSM-V); Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Confusion Assessment Method (CAM), Chart Review	Participants will be followed for the duration of hospital stay, or maximal until postoperative day 5
Intensive care unit length of stay	The stay is measured in days.	Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
Hospital length of stay	The stay is measured in days.	Participants will be followed for the duration of hospital stay, an expected average of 7 days

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Anticipated): November 23, 2021
• Study Completion (Anticipated): June 15, 2022

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Consciousness Disorders; Unconsciousness
• Other Study ID Numbers: ACDC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No