Electroencephalography and Sleep Quality With Lormetazepam in the Intensive Care Unit

NCT ID: NCT06473415

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2024-12-31

Brief Summary

The goal of this clinical trial is to test the effect of continuous lormetazepam infusion on EEG patterns in critically ill patients who are given continuous infusion of lormetazepam in an intensive care unit setting. The main questions it aims to answer are:

• How does the continuous infusion of lormetazepam affect EEG readings in terms of specific patterns related to sleep quality and sedation depth?

Participants will be asked to:

• Receive continuous infusion of lormetazepam, administered as per the guidelines and judgment of the on-duty ward physician.
• Undergo up to three EEG measurements over a period of 24 hours each using the X8 Sleep Profiler RTA device. These measurements will monitor brain activity and other related signals in order to assess the sedation depth and sleep quality.
• These EEG readings will be performed after at least two hours of initiation of continuous lormetazepam infusion, potentially at different stages of their ICU stay.

There is no direct comparison group in this study. However, after initial data from the first 15 patients is collected, an interim analysis will be performed. This will help researchers understand the ability to measure sleep quality and defined EEG parameters in this setup, and if necessary, adapt the study design or measurement procedures for better outcomes.

Detailed Description

The misadjusted use of sedatives in critically ill patients, especially the state of deep sedation stages, is associated with an increased occurrence of delirium and increased hospital mortality. Drug sedation should be avoided according to current recommendations of care guidelines and should only be used in symptom-oriented therapy. However, the administration of drugs with a sedative effect profile remains necessary not only for patients for brain pressure therapy or positioning maneuvers in severe lung failure, but is often necessary to achieve a patient who is awake and at the same time stress-free. A variety of drugs from different substance classes are available for this. Given that a large proportion of intensive care patients develop an acute substantial disruption of the circadian rhythm, which very often goes hand in hand with pathological sleep and delirium, sedatives, which are often given continuously over a longer period, should support good sleep quality and the physiological sleep-wake rhythm. However, studies show that commonly used sedatives such as propofol worsen sleep quality. Especially for the group of benzodiazepines, there are indications from several studies that the application, even compared to α2-agonists such as dexmedetomidine, significantly favors the risk of delirium. Lormetazepam for intravenous use has only been approved for continuous use in intensive care patients for a few years. Initial studies document very good anxiolysis and the avoidance of over-sedation compared to midazolam. Currently, there are no published works that have systematically investigated the effects of continuous lormetazepam infusion on the EEG and sleep quality in intensive care patients. However, these data are necessary in order to take sleep quality and neuroprotection into account when selecting and dosing sedatives in the future and to avoid chronodisruption and cognitive damage. Studies from dementia research but also a few from intensive care medicine provide indications for potentially brain-protective EEG patterns, which promote the glymphatic clearance of the cerebrospinal fluid. This includes not only primarily sleep-associated characteristics such as Slow Wave Sleep (SWS) and spindle activity but also frontal gamma oscillations, which can have memory-consolidating effects. Corresponding patterns are to be investigated in this pilot study under continuous lormetazepam infusion. The study involves further investigations according to primary and secondary endpoints, including EEG measurements. These EEG measurements are already part of the current care guidelines, but have not yet been comprehensively implemented in the ICU. The objective is to use EEG measurements in the future for more precise monitoring of the sedation depth of critically ill patients. Implementing this in the study may potentially allow for more adequate sedation management by being able to immediately respond to specific EEG patterns (e.g., burst-suppression) with an adjustment of sedation.

Given the described data situation, this is initially an exploratory pilot study.

The main Hypothesis: Intensive care patients who receive a continuous lormetazepam infusion exhibit an electroencephalographically detectable REM portion of at least 20%.

The EEG measurements are carried out up to three times over 24 hours using the X8 Sleep Profiler RTA (Advanced Brain Monitoring). It is a single-channel EEG measuring device that captures up to five channels of electrophysiological signals with just three electrodes, a photoplethysmographic (PPG) signal, and detects noise as well as movement and position. The X8 system can record and store data in its internal memory. The Sleep Profiler RTA software offers a visual display of the recordings in near real-time.

The study plans to enroll 50 patients in a prospective pilot study at the Charité Mitte Campus 101i ICU ward. It will include ICU patients expected to require intensive treatment for 48 hours or longer and an expected continuous lormetazepam infusion of at least 24 hours. The indications and duration of intravenous lormetazepam therapy will be determined by the on-duty ward physician in accordance with the internal clinic standards. Episodic EEG measurements will be conducted. The patient screening takes place immediately after admission to the ICU and will be reevaluated every day for meeting inclusion criteria.

The EEG recordings will be made in periods of 24 hours and will start at least two hours after the initiation of the continuous lormetazepam infusion. An EEG-P is only considered complete if the measurement within the core measurement time was not interrupted.

Conditions

Critical Illness; Delirium; Sleep Disorders, Circadian Rhythm

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Electroencephalography

Electroencephalography using the Sleep-Profiler device

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patient capable of giving consent or additional legal guardian/authorized representative/spouse available for non-consenting patient in the intensive care unit
• An expected continuous lormetazepam therapy ≥ 24 hours
• Male and female patients aged ≥18 years
• Expected duration of intensive care treatment ≥ 48 hours
• Mechanical ventilation (invasive, NIV and/or nasal high-flow > 6h)

Exclusion Criteria

• Laboratory evidence of sedative/opiate intoxication
• Active alcohol abuse
• Brain surgery, cranial malformation
• History of sleep-related movement disorder (symptomatic restless legs syndrome)
• Allergy to electrode contact material
• History of severe cognitive impairment following a stroke
• Status post cardiopulmonary resuscitation requiring/undergoing therapeutic hypothermia
• Lack of consent for the pseudonymized disease data to be stored and passed on in the context of this clinical study
• Patient is housed in an institution on court or official order
• History of sleep-related breathing disorder
• Suspicion of hypoxic brain damage (including intracranial hemorrhages)
• Suspicion of increased intracranial pressure
• Existing power of attorney or patient's will, in which the patient fundamentally excludes participation in studies
• The patient's consent or that of the legal representative cannot be obtained in a timely manner
• Patients with a survival probability < 24h
• Narcolepsy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Alawi Luetz

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Charité - Universitätsmedizin Berlin

Mitte, State of Berlin, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Alawi Luetz, Prof.Dr.med

Role: CONTACT

alawi.luetz@charite.de

+4930450631208

Laura Hancke

Role: CONTACT

laura.hancke@charite.de

+4930450651309

Facility Contacts

Alawi Luetz, MD

Role: primary

Other Identifiers

20019702

Identifier Type: -

Identifier Source: org_study_id