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.
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.
Study Type
OBSERVATIONAL
Enrollment
50
Electroencephalography using the Sleep-Profiler device
Charité - Universitätsmedizin Berlin
Mitte, State of Berlin, Germany
RECRUITINGREM portion (%) during nocturnal sleep
Main Hypothesis: Intensive care patients who receive a continuous Lormetazepam infusion exhibit an electroencephalographically detectable REM portion of at least 20% during the nocturnal sleeping period bewetween 22:00 to 06:00.
Time frame: through study completion per patient, an average of 3 days
Total sleep time attributed to stages N2, N3 or rapid eye movement (REM) sleep during the noctural period i.e., between the hours of 22:00 and 06:00
Total high qualitiy sleep time during nocturnal period, (sum REM,N2,N3; minutes)
Time frame: through study completion per patient, an average of 3 days
Total minutes of all stages of sleep (including N1, AN3, NREM hypertonia) during the awake period i.e., between the hours of 06:00 and 22:00.
Total sleep time during awake period, (minutes)
Time frame: through study completion per patient, an average of 3 days
Total and % time atypical N3 sleep (AN3) i.e. polymorphic delta or or sepsis associated encephalopathy
Total sleep time in atypical N3 (minutes; %)
Time frame: through study completion per patient, an average of 3 days
Gamma oscillations
Hz)
Time frame: through study completion per patient, an average of 3 days
Theta-Gamma Coupling
(TGC, Modulation Index)
Time frame: through study completion per patient, an average of 3 days
Polymorphic Delta/Theta Ratio
(DTR, %)
Time frame: through study completion per patient, an average of 3 days
Slow Wave Sleep (SWS) Characteristics
This outcome measure will aggregate the characteristics of Slow Wave Sleep (SWS) by reporting the total duration (in minutes) and the average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of SWS.
Time frame: through study completion per patient, an average of 3 days
Pathological N3-Slow Wave Sleep Characteristics
This outcome measure will aggregate the characteristics of Pathological N3-Slow Wave Sleep by reporting the total duration (in minutes) and the average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of N3-Slow Wave Sleep.
Time frame: through study completion per patient, an average of 3 days
Sleep Spindle Characteristics
This outcome measure will aggregate the characteristics of sleep spindles by reporting the total occurrence (number per minute/hour), average frequency (in Hz), and total duration (in minutes) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of sleep spindles.
Time frame: through study completion per patient, an average of 3 days
Pseudo Spindle Characteristics supression and/or medications
This outcome measure will aggregate the characteristics of pseudo spindles by reporting the total duration (in minutes attributed to burst suppression and/or medications), average frequency (in Hz), and total occurrence (number per minute/hour) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of pseudo spindles.
Time frame: through study completion per patient, an average of 3 days
K-Complex Characteristics
This outcome measure will aggregate the characteristics of K-complexes by reporting the total occurrence (number per minute/hour) and average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of K-complexes.
Time frame: through study completion per patient, an average of 3 days
Burst-Suppression
(Supression Index,%)
Time frame: through study completion per patient, an average of 3 days
Total sleep time
(minutes)
Time frame: through study completion per patient, an average of 3 days
Sleep latency
(SOL, minutes)
Time frame: through study completion per patient, an average of 3 days
Nocturnal sleep efficiency (%)
(Total sleep duration/8 hours) x 100
Time frame: through study completion per patient, an average of 3 days
Eye movements during sleep
(number)
Time frame: through study completion per patient, an average of 3 days
REM latency
(minutes)
Time frame: through study completion per patient, an average of 3 days
REM-Sleep-Pressure-Index
(RSPI, %)
Time frame: through study completion per patient, an average of 3 days
Delirium incidence in intensive care unit measured with the Confusion Assessment Method
CAM-ICU
Time frame: through study completion per patient, an average of 3 days
Delirium severity in intensive care unit measured with the Intensive Care Delirium Screening Checklist
(ICDSC)
Time frame: through study completion per patient, an average of 3 days
Sedation depth: Richmond Agitation Sedation Scale
The Richmond Agitation Sedation Scale (RASS) ranges from -5 to +4, with lower scores indicating deeper sedation and higher scores indicating greater agitation. The scale includes +4 (combative), +3 (very agitated), +2 (agitated), +1 (restless), 0 (alert and calm), -1 (drowsy), -2 (light sedation), -3 (moderate sedation), -4 (deep sedation), and -5 (unarousable). Higher scores indicate worse outcomes in terms of agitation(RASS)
Time frame: through study completion per patient, an average of 3 days
Analgesia level: Numeric Rating Scale Visualized (NRS-V) or Faces Pain Scale Revised (FAS-R) Behavioural Pain Scale (BPS) or Behavioural Pain Scale for non-intubated patients (BPS-NI)
The analgesia level will be assessed using the Numeric Rating Scale Visualized (NRS-V), Faces Pain Scale Revised (FAS-R), Behavioural Pain Scale (BPS), or Behavioural Pain Scale for non-intubated patients (BPS-NI). The NRS-V ranges from 0 (no pain) to 10 (worst pain imaginable). The FAS-R uses facial expressions to represent pain levels from 0 (no pain) to 10 (worst pain imaginable). The BPS scores range from 3 (no pain) to 12 (severe pain) based on facial expression, upper limb movements, and compliance with ventilation. The BPS-NI scores range from 3 (no pain) to 12 (severe pain) based on facial expression, upper limb movements, and vocalization. Higher scores indicate worse pain outcomes.
Time frame: through study completion per patient, an average of 3 days
Total amount of intravenously administered opioids per ICU treatment day
type, cumulative dose
Time frame: through study completion per patient, an average of 3 days
Total amount of administered neuroleptics per ICU treatment day
type, cumulative dose
Time frame: through study completion per patient, an average of 3 days
Duration of invasive and non-invasive ventilation
intubated, nasal highflow, NIV-mask
Time frame: through study completion per patient, an average of 3 days
Intensive care duration at the center
days
Time frame: through study completion, an average of 1 year
Hospital treatment duration at the center
days
Time frame: through study completion, an average of 1 year
Sepsis/Septic Shock
Sepsis/Septic Shock
Time frame: through study completion per patient, an average of 3 days
Sequential Organ Failure Assessment
The Sequential Organ Failure Assessment (SOFA) Score assesses organ function and predicts outcomes in critically ill patients. The score ranges from 0 to 24, with higher scores indicating greater organ dysfunction. It evaluates six organ systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological. Each system is scored from 0 (normal function) to 4 (high degree of dysfunction). Higher SOFA scores are associated with worse patient outcomes (SOFA).
Time frame: through study completion per patient, an average of 3 days
Simplified Acute Physiology Score
The Simplified Acute Physiology Score II (SAPS II) is used to assess the severity of disease for patients admitted to intensive care units. The score ranges from 0 to 163, with higher scores indicating a higher risk of mortality. SAPS II includes 17 variables: 12 physiological variables, age, type of admission (scheduled surgical, unscheduled surgical, medical), and three underlying disease variables (AIDS, hematologic malignancy, metastatic cancer). Higher SAPS II scores correspond to worse patient outcomes (SAPSII).
Time frame: through study completion per patient, an average of 3 days
Therapeutic Intervention Scoring System
The Therapeutic Intervention Scoring System (TISS) measures the intensity of medical and nursing care required by ICU patients. The score ranges from 0 to 78, with higher scores indicating more intensive care. TISS evaluates various therapeutic interventions, including cardiovascular, renal, respiratory, and neurological support, as well as monitoring, medication, and hygiene procedures. Higher TISS scores reflect a greater need for medical and nursing interventions (TISS).
Time frame: through study completion per patient, an average of 3 days
Acute Physiological And Chronic Health Evaluation
The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is used to measure the severity of disease in ICU patients. The score ranges from 0 to 71, with higher scores indicating more severe disease and higher risk of mortality. APACHE II includes the evaluation of 12 physiological variables, age, and chronic health status. Higher APACHE II scores are associated with worse patient outcomes (APACHE II).
Time frame: through study completion per patient, an average of 3 days
Age
(years)
Time frame: through study completion per patient, an average of 3 days
Gender
(m/f/d)
Time frame: through study completion per patient, an average of 3 days
Fever
yes/no, days)
Time frame: through study completion per patient, an average of 3 days
Respiratory insufficiency/Asthma (yes/no)
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Cardiac arrest/Cardiac decompensation
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Pneumonia
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Urinary tract infection
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Exacerbated COPD
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Hypervolemia
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Meningitis
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Pancreatitis
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Cirrhosis
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Kidney insufficiency
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Thrombocytopenia
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Leukocytosis
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Leukopenia
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Hypotonia
(yes/no)
Time frame: through study completion per patient, an average of 3 days
Death
(yes/no)
Time frame: through study completion per patient, an average of 3 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.