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

• ClinicalTrials.gov Identifier: NCT04320082
• Recruitment Status: Active, not recruiting
• First Posted: March 24, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Claudia Spies, Charite University, Berlin, Germany

Study Description

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.

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 62 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Alteration of Blood-Brain-Barrier Permeability at Loss of Consciousness in Delirious Patients Recorded With Direct-Current Electroencephalography (ACDC)
• Actual Study Start Date: August 10, 2020
• Estimated Primary Completion Date: November 23, 2021
• Estimated Study Completion Date: June 15, 2022

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Incidence of Postoperative Delirium [ Time Frame: Patients will be follow until hospital discharge, or maximal until postoperative day 5 ]
   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.
2. Additional perioperative DC-EEG signatures: morphology, polarity (positive/negative), amplitude (µV) [ Time Frame: From the beginning of general anaesthesia to one hour after regain of consciousness ]
   Full-brain DC-EEG with 21 electrodes placed preoperatively following the 10/20-System and recording until one hour after regain of Consciousness.
3. DC-EEG signatures in young (18-30) vs. elderly (>70) patients [ Time Frame: From the beginning of general anaesthesia to one hour after regain of consciousness ]
   Full-brain DC-EEG with 21 electrodes placed preoperatively following the 10/20-System and recording until one hour after regain of consciousness
4. Analysis of pre-, intra- and postoperative blood parameters [ Time Frame: : From shortly before the beginning of general anaesthesia to maximum one hour after arrival in the recovery room ]
   Blood samples will be drawn before the start of general anesthesia, shortly after loss of consciousness and in the recovery room.
5. Peri-operative, full-brain overall EEG band power [ Time Frame: Up to the end of stay in the recovery room ]
   Full-brain EEG recording with surface Ag/AgCl electrodes Spectral analysis by Matlab Code/Lab Chart
6. Burst suppression duration [ Time Frame: During anesthesia procedure ]
   Full-brain EEG recording with surface electrodes, raw EEG analysis
7. Duration of Delirium [ Time Frame: Participants will be followed for the duration of hospital stay, or maximal until postoperative day 5 ]
   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
8. Intensive care unit length of stay [ Time Frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days ]
   The stay is measured in days.
9. Hospital length of stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ]
   The stay is measured in days.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 110 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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

Contacts and Locations

Locations

Germany

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

Berlin, Germany, 13353

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

• Study Director: Claudia Spies, MD, Prof.; Charite University, Berlin, Germany

More Information

• Responsible Party: Claudia Spies, Head of the Department of Ansthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT04320082
• Other Study ID Numbers: ACDC
• First Posted: March 24, 2020
• Last Update Posted: December 8, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Delirium; Unconsciousness; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Consciousness Disorders