Critical Illness, Respiratory Failure, Sleep Deprivation, Sleep Disorders, Circadian Rhythm
Conditions
Keywords
Critical illness, Sleep, Polysomnography, Respiratory failure, Circadian rhythm, Sedation
Brief summary
The goal of this project is to determine whether the sleep and circadian rhythms of critically ill patients undergoing mechanical ventilation can be improved through practical strategies that can be employed at the bedside.
Detailed description
Nearly 1 million patients develop respiratory failure annually in the United States; yet, the sleep of patients undergoing mechanical ventilation has received little attention. This project is designed to characterize sleep and circadian rhythmicity in critically ill patients and to explore the efficacy of a non-pharmacological intervention to improve sleep and normalize circadian phase. The study will examine the effect of a protocol employing noise reduction and enforcement of a robust light-dark cycle on sleep quality and circadian rhythmicity. A secondary analysis will examine the relationship between delirium and sleep disruption and loss of circadian rhythmicity. Circadian rhythmicity will be characterized through the measurement of urinary 6-sulfatoxymelatonin levels at frequent intervals, while sleep will be assessed using continuous polysomnography.
Interventions
BEHAVIORALSleep and circadian rhythm promotion
This multifaceted intervention attempts to enhance sleep and circadian rhythmicity through improved scheduling of nursing procedures, enforcement of a day/night routine, increased light exposure during the day, and decreased light and sound exposure during the night. The intervention began the morning after enrollment and enforced a specific period of enhanced light exposure from 9:00 a.m. to noon. The initial target of 5,000 lux administered by light box (Sunsation, SunBox Co.) was reduced to 400-700 lux after the first 10 subjects were enrolled in the study.
BEHAVIORALUsual care
Usual care.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Brian Gehlbach
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Receiving mechanical ventilation and intravenous sedation
Exclusion criteria
* Debilitating central nervous system disease or degenerative disorder * Active seizures * Persistent coma * Renal failure requiring dialysis * Expected to be extubated within 24 hours * Currently receiving neuromuscular blocker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circadian Timing | Day 1 to Day 3 | The magnitude of the phase change in 6-sulfatoxymelatonin excretion between Day 1 and Day 3 will be compared between the intervention and usual care groups. This is done by comparing, for each group, the timing of the best-fit maximum on Day 1 with the timing of the best-fit maximum on Day 3. The result is expressed in hours. A positive value represents a phase advance from Day 1 to Day 3 (e.g. an earlier occurrence of maximum excretion on Day 3 when compared with Day 1), while a negative value represents a phase delay from Day 1 to Day 3 (e.g. a later occurrence of maximum excretion on Day 3 when compared with Day 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normal Circadian Timing | Day 3 | The percentage of subjects who exhibit normal circadian timing of 6-sulfatoxymelatonin excretion on Day 3 will be compared between the intervention and usual care groups. |
| Circadian Amplitude | Day 3 | The amplitude (e.g. one half the value from peak to trough of the fitted cosine curve) of the circadian rhythm of 6-sulfatoxymelatonin on Day 3 will be compared between the usual care and intervention groups. |
| Spectral Edge Frequency 95% | Day 2 | The difference between the polysomnographically derived daytime and nocturnal spectral edge frequency 95% parameter will be used as a measure of increased diurnal sleep/wake activity. This parameter will be compared between the usual care and intervention groups. |
| Delirium | Day 3 | The percentage of patients who are delirious at the conclusion at the study will be compared between the intervention and usual care groups. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the medical intensive care units of the University of Chicago and the University of Iowa Hospitals and Clinics.
Pre-assignment details
Two subjects who acutely developed exclusion criteria were withdrawn from the study after enrollment and prior to the performance of any study-related procedures. These subjects were not analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Sleep Promotion Protocol Behavioral: sleep and circadian rhythm promotion including timed light exposure.
Sleep and circadian rhythm promotion: This multifaceted intervention will attempt to enhance sleep and circadian rhythmicity through improved scheduling of nursing procedures, enforcement of a day/night routine, increased light exposure during the day, and decreased light and sound exposure during the night. Supplemental bright lights and eyeshades and noise cancelling headphones may also be employed. | 6 |
| Usual Care Behavioral: usual care.
Usual care: Usual care. | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Subjects With Paired 24hr Collections | Day 1 urinary profile incomplete | 0 | 1 |
| Subjects With Paired 24hr Collections | Day 3 urinary profile not available | 5 | 5 |
Baseline characteristics
| Characteristic | Sleep Promotion Protocol | Total | Usual Care |
|---|---|---|---|
| Acute Physiology and Chronic Health Evaluation II score | 25.5 units on a scale STANDARD_DEVIATION 2.5 | 25 units on a scale STANDARD_DEVIATION 5.3 | 24.4 units on a scale STANDARD_DEVIATION 2 |
| Age, Continuous | 67.2 years STANDARD_DEVIATION 10.4 | 63.7 years STANDARD_DEVIATION 9.7 | 59.6 years STANDARD_DEVIATION 7.7 |
| Average peak creatinine during study period | 2.0 mg per deciliter STANDARD_DEVIATION 0.6 | 1.9 mg per deciliter STANDARD_DEVIATION 1.3 | 1.8 mg per deciliter STANDARD_DEVIATION 0.5 |
| Benzodiazepines during study period | 0 Participants | 3 Participants | 3 Participants |
| Body mass index | 25.0 kg per meters squared | 26.4 kg per meters squared | 27.4 kg per meters squared |
| Dexmedetomidine during study period | 0 Participants | 1 Participants | 1 Participants |
| Mechanically ventilated during study period | 6 Participants | 11 Participants | 5 Participants |
| Opioids during study period | 6 Participants | 11 Participants | 5 Participants |
| Propofol during study period | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment United States | 6 participants | 11 participants | 5 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
| Total urinary 6-sulfatoxymelatonin excretion on day 1 (micrograms) | 14.5 micrograms STANDARD_DEVIATION 4.7 | 17.2 micrograms STANDARD_DEVIATION 14.5 | 20.4 micrograms STANDARD_DEVIATION 8.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 11 | 2 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Circadian Timing
The magnitude of the phase change in 6-sulfatoxymelatonin excretion between Day 1 and Day 3 will be compared between the intervention and usual care groups. This is done by comparing, for each group, the timing of the best-fit maximum on Day 1 with the timing of the best-fit maximum on Day 3. The result is expressed in hours. A positive value represents a phase advance from Day 1 to Day 3 (e.g. an earlier occurrence of maximum excretion on Day 3 when compared with Day 1), while a negative value represents a phase delay from Day 1 to Day 3 (e.g. a later occurrence of maximum excretion on Day 3 when compared with Day 1).
Time frame: Day 1 to Day 3
Population: Subjects with 24-hour 6-sulfatoxymelatonin excretion profiles from both Day 1 and Day 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sleep Promotion Protocol | Circadian Timing | 3.6 hours |
| Usual Care | Circadian Timing | -2.4 hours |
Comparison: Nonlinear regression using the least-squares approach was used to fit a single 24-hour cosine curve to all normalized data in each group on each day of 24-hour urine collection. Model parameters of acrophase and amplitude and their standard errors were derived from these curves. Using the extra sum-of-squares F test, the null hypothesis that model parameters of amplitude and phase were the same on Day 1 and Day 3 was tested for the Usual Care group.p-value: 0.37Extra sum-of-squares F test
Comparison: Nonlinear regression using the least-squares approach was used to fit a single 24-hour cosine curve to all normalized data in each group on each day of 24-hour urine collection. Model parameters of acrophase and amplitude and their standard errors were derived from these curves. Using the extra sum-of-squares F test, the null hypothesis that model parameters of amplitude and phase were the same on Day 1 and Day 3 was tested for the Sleep promotion group.p-value: 0.0074Extra sum-of-squares F test
Secondary
Circadian Amplitude
The amplitude (e.g. one half the value from peak to trough of the fitted cosine curve) of the circadian rhythm of 6-sulfatoxymelatonin on Day 3 will be compared between the usual care and intervention groups.
Time frame: Day 3
Population: Subjects with 24-hour 6-sulfatoxymelatonin excretion profiles from both Day 1 and Day 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sleep Promotion Protocol | Circadian Amplitude | 36.6 percent of 24-hour mean 6-sulfatoxymelat | Standard Deviation 14.5 |
| Usual Care | Circadian Amplitude | 11.0 percent of 24-hour mean 6-sulfatoxymelat | Standard Deviation 17.7 |
Comparison: Nonlinear regression using the least-squares approach was used to fit a single 24-hour cosine curve to all normalized data in each group on each day of 24-hour urine collection. This resulted in 4 separate best-fit curves. The model parameter of amplitude was derived from the best-fit curves.p-value: 0.03t-test, 2 sided
Secondary
Delirium
The percentage of patients who are delirious at the conclusion at the study will be compared between the intervention and usual care groups.
Time frame: Day 3
Population: Subjects still on study in the ICU on Day 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sleep Promotion Protocol | Delirium | 2 Participants |
| Usual Care | Delirium | 2 Participants |
Secondary
Normal Circadian Timing
The percentage of subjects who exhibit normal circadian timing of 6-sulfatoxymelatonin excretion on Day 3 will be compared between the intervention and usual care groups.
Time frame: Day 3
Population: Subjects with 24-hour 6-sulfatoxymelatonin excretion profiles from both Day 1 and Day 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sleep Promotion Protocol | Normal Circadian Timing | 3 Participants |
| Usual Care | Normal Circadian Timing | 1 Participants |
p-value: 0.55Fisher Exact
Secondary
Spectral Edge Frequency 95%
The difference between the polysomnographically derived daytime and nocturnal spectral edge frequency 95% parameter will be used as a measure of increased diurnal sleep/wake activity. This parameter will be compared between the usual care and intervention groups.
Time frame: Day 2
Population: Polysomnography was not conducted on any participants due to logistical constraints.