Sleep Disorder (Disorder), Critical Care
Conditions
Keywords
Gamma-hydroxybutyrate, Sleep disorder, ICU, Slow-wave sleep
Brief summary
In intensive care, sleep disturbances are extremely common and represent a major source of discomfort for patients. Restorative sleep is very limited. Beyond being the primary source of discomfort reported by patients, these sleep disturbances are associated with difficulties in weaning from mechanical ventilation, an increased risk of delirium, and potentially higher mortality. Traditional treatments artificially increase the total duration of sleep but lead to disrupted sleep architecture. Gamma-hydroxybutyrate (GHB) is currently used for several sleep disorders, such as narcolepsy, due to its ability to increase restorative sleep. This medication has been used for years as a sedative in intensive care. Despite these potential benefits, the efficacy of GHB has never been evaluated for sleep disturbances in intensive care settings. This study focuses on evaluating the effectiveness of intravenous Gamma-hydroxybutyrate (GHB) in the treatment of sleep disorders in intensive care.
Detailed description
In intensive care, sleep disturbances are extremely common and represent a major source of discomfort for patients. While the total duration of sleep is minimally affected, deep slow-wave sleep (N3) is significantly underrepresented. Beyond being the primary source of discomfort reported by patients, these sleep disturbances are associated with difficulties in weaning from mechanical ventilation, an increased risk of delirium, and potentially higher mortality. Traditional treatments with benzodiazepines or propofol artificially increase the total duration of sleep but lead to disrupted sleep architecture. Gamma-hydroxybutyrate (GHB) is currently used for several sleep disorders, such as narcolepsy, due to its ability to reduce sleep onset latency, increase deep slow-wave sleep (N3), improve sleep quality, and enhance daytime alertness scores. Despite these potential benefits, the efficacy of GHB has never been evaluated for sleep disturbances in intensive care settings. This study focuses on evaluating the effectiveness of intravenous Gamma-hydroxybutyrate (GHB) in the treatment of sleep disorders in intensive care. The primary objective of this pilot study is to show that the intravenous administration of GHB improves the duration (in minutes) of deep slow-wave sleep (N3 stage) in critically ill adult patients compared to a placebo
Interventions
DRUGGHB
Administration of GHB intravenously with a induction followed by a maintenance dose for 8 hours.
DRUGPlacebo
Administration of a placebo in the form of 0.9% NaCl intravenously, with a induction followed by a maintenance infusion for 8 hours.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older 2. Hospitalized in the ICU for more than 48 hours 3. Informed consent obtained from the patient
Exclusion criteria
1. Unstable patient 2. Known allergy to Gamma-Hydroxybutyrate or any of the excipients 3. Technical impossibility of performing polysomnography 4. Childbearing or Positive pregnancy test for women of childbearing age or breastfeeding 5. Patient who has already received the study treatment 6. History of chronic alcoholism 7. Uncontrolled epilepsy despite appropriate antiepileptic treatment 8. Traumatic brain injury or neurological lesion at risk of epilepsy in the last month 9. Severe hypertension: SBP \> 180 mmHg despite antihypertensive treatment 10. Hypokalemia \< 3.5 mmol/L despite potassium supplementation 11. Bradycardia due to intra-cardiac conduction disorders 12. Obstructive sleep apnea syndrome 13. Sodium restriction: Salt intake \< 3g/24h 14. Patients with known or suspected succinic semialdehyde dehydrogenase (SSADH) deficiency, given the risk of GHB accumulation due to impaired endogenous metabolism. 15. Patients receiving barbiturates at inclusion 16. Patients receiving opioids at inclusion for non-mechanically ventilated patient 17. Patients presenting with hypernatraemia (sodium \> 145 mmol/L) or hyperchloraemia (chloride \> 110 mmol/L) at inclusion 18. Patients with hepatic impairment (Child-Pugh B or C) 19. Deep sedation defined by a RASS score \< -2 20. Presence of mental confusion: Positive CAM-ICU 21. Moribund patient or high likelihood of death within 48 hours 22. Legal protection: guardianship, curatorship, or judicial protection 23. Lack of social security or on AME (state medical aid) 24. Participation in another interventional clinical trial related to the management of sleep disorders, delirium, or sedation in the ICU.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Deep slow-wave sleep | During the night between the day of enrollment (Day0) and the next day (Day 1). | The primary endpoint is the duration (in minutes) of deep slow-wave sleep (N3 stage) based on polysomnographic recordings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep onset latency | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Total sleep time | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Duration of N1 stage | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Percentage of N1 stage | During the night between the day of enrollment (Day0) and the next day (Day 1) | — |
| Duration of N2 stage | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Percentage of N2 stage | During the night between the day of enrollment (Day0) and the next day (Day 1) | — |
| Percentage of N3 stage | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Duration of Rapid Eye Movement sleep | During the night between the day of enrollment (Day0) and the next day (Day 1). | — |
| Percentage of Rapid Eye Movement sleep | During the night between the day of enrollment (Day0) and the next day (Day 1) | — |
| Number of intra-sleep wakefulness. | During the night between the day of enrollment (Day0) and the next day (Day 1). | Intra-sleep wakefulness is defined as a period of wakefulness between sleep phases. The quantification of intra-sleep wakefulness corresponds to the number of awakenings during the night. |
| Duration of atypical sleep. | During the night between the day of enrollment (Day0) and the next day (Day 1). | Duration of atypical sleep relative to the total sleep time. Atypical sleep is defined as slow-wave sleep equivalent to N2 stage but without sleep spindles or K-complexes |
| Percentage of atypical sleep | During the night between the day of enrollment (Day0) and the next day (Day 1) | Percentage of atypical sleep relative to the total sleep time. Atypical sleep is defined as slow-wave sleep equivalent to N2 stage but without sleep spindles or K-complexes |
| Duration of pathological wakefulness | During the night between the day of enrollment (Day0) and the next day (Day 1). | Duration of pathological wakefulness relative to the total sleep time is defined as rapid eye movements and chin EMG activity associated with slow delta wave EEG activity |
| Percentage of pathological wakefulness | During the night between the day of enrollment (Day0) and the next day (Day 1) | Percentage of pathological wakefulness relative to the total sleep time is defined as rapid eye movements and chin EMG activity associated with slow delta wave EEG activity |
| Number of micro-awakenings. | During the night between the day of enrollment (Day0) and the next day (Day 1). | Micro-awakenings are defined as an abrupt change in EEG frequency (fromdelta-theta to theta-alpha) lasting 3 to 15 seconds in a patient who has been asleep for more than 10 seconds, with or without an increase in chin EMG activity during slow-wave sleep and with an activation lasting more than one second during REM sleep. |
| Sleep efficiency | During the night between the day of enrollment (Day0) and the next day (Day 1). | is defined as total sleep time relative to the sleep period (corresponding to total sleep time + intra-sleep wakefulness). |
| Self-assessment questionnaire of the quality of sleep | On the day after enrollment ( Day 1) | Questionnaire of the quality of sleep :Richard-Campbell Sleep Questionnaire. min : 0 max : 100 Higher is a better outcome |
| Hetero-evaluation questionnaire of the quality of sleep | On the day after enrollment ( Day 1) | min : 0 max : 4 Higher is a worse outcome |
| Daytime vigilance score | On the day after enrollment ( Day 1) | Karolinska Sleepiness scale min : 1 max : 9 Higher is a worse outcome |
| Average sleep latency during the Maintenance of Wakefulness Test | On the day after enrollment ( Day 1) | — |
| Analgesic consumption | From the day after enrollment (Day 1) to two days after enrollment (Day 2) | Morphine equivalent quantification of analgesic consumption (mg) over the 24 hours following the study night. |
| Participation in rehabilitation | From the day after enrollment (Day 1) to two days after enrollment (Day 2) | Assessment of rehabilitation participation by the physiotherapy team using a visual analog scale. min : 0 max : 100 Higher is a better outcome |
| Adverse event assessment | From the day of enrollment (Day 0) to the end of follow-up (Day 2) | All adverse events will be recorded during the study with special attention to potential side effects of GHB |
Countries
France
Contacts
CONTACTFlorian Blanchard, MD
Outcome results
None listed