Continuous IV Sedation, Endotracheal Intubation, ICP Monitoring
Conditions
Brief summary
The purpose of this study is to examine the effects of using dexmedetomidine (Precedex) in addition to the current standard-of-care for sedation.
Detailed description
Primarily, this study seeks to explore whether there is a difference in mean arterial pressure (MAP) variability, incidence of intracranial hypertension, intracranial pressure (ICP) variability, cerebral perfusion pressure (CPP) and Cerebrovascular pressure reactivity index (PRx) in two groups of subjects. Patients must be submitted to the ICU and be endotracheally intubated and receiving mechanical ventilation with continuous IV sedation for less than 24 hours after recruitment into the study.
Interventions
DRUGStandard-of-Care plus Dexmedetomidine
Subjects who are treated with dexmedetomidine (Precedex) in addition to the standard of care sedation regiment
OTHERStandard-of-Care
Subjects who are treated with the standard of care sedation regiment only.
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to Duke University Neuro Critical Care Unit (NCCU) * Adult (18 years of age or older) * Expected Mechanical Ventilation for \>48 hours with sedation * Intraventricular catheter in situ
Exclusion criteria
* Hypersensitivity to study drugs * Prisoners * Moribund state or death expected within 24 hours * Surgery planned within 24 hours of subject enrollment * Receiving study drug, Precedex, prior to entering study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variability of Intracranial Pressure (ICP) | Baseline to 24 hours | Variability of intracranial pressure was assessed and listed as the standard deviation of all measurements within 24 hours. Variability was assessed and listed as the standard deviation of all measurements within 24 hours |
| Change in Pressure Reactivity Index (PRx) | Baseline to 24 hours | Using computational methods, the PRx was determined by calculating the correlation coefficient between 20 consecutive, time-averaged data points (60-second periods) of ICP and Arterial Blood Pressure (ABP). A positive PRx correlation suggests impaired cerebrovascular pressure reactivity, that is, passive transmission of changes in ABP to ICP. A negative PRx correlation indicates good pressure reactivity. Any change in ABP produces inverse changes in ICP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Sedative/Analgesic Used During Treatment in Patients With Secondary Brain Injury | 24 hours | Improved physiologic Response. A lower use of sedatives or analgesic during treatment would be considered an improved physiologic response. An increase in the use of sedatives or analgesic during treatment would be considered a worse physiologic response. |
| Cerebral Perfusion Pressure Changes in Patients With Secondary Brain Injury | Baseline to 24 hours | Improved physiologic Response. A higher cerebral perfusion pressure during treatment would be considered an improved physiologic response. A lower cerebral perfusion pressure during treatment would be considered a worse physiologic response. |
| Mean Arterial Blood Pressure (MAP) Variability in Patients With Secondary Brain Injury | Baseline to 24 hours | Improved physiologic Response. A lower variability of mean Arterial Blood pressure during treatment would be considered an improved physiologic response. A higher variability of mean Arterial Blood pressure during treatment would be considered a worse physiologic response. Variability was assessed and listed as the standard deviation of all measurements within 24 hours. |
Countries
United States
Participant flow
Recruitment details
89 subject signed consent, 5 subjects screen failed.
Participants by arm
| Arm | Count |
|---|---|
| Standard-of-Care Plus Precedex Standard-of-Care plus Dexmedetomidine: Subjects who are treated with dexmedetomidine (Precedex) in addition to the standard of care sedation regiment | 44 |
| Standard-of-Care Subjects who are treated with the standard of care sedation regiment only. | 40 |
| Total | 84 |
Baseline characteristics
| Characteristic | Total | Standard-of-Care | Standard-of-Care Plus Precedex |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 8 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 32 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants | 38 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 15 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 24 Participants | 32 Participants |
| Sex: Female, Male Female | 30 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Male | 54 Participants | 27 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 44 | 0 / 40 |
| serious Total, serious adverse events | 1 / 44 | 0 / 40 |
Outcome results
Primary
Change in Pressure Reactivity Index (PRx)
Using computational methods, the PRx was determined by calculating the correlation coefficient between 20 consecutive, time-averaged data points (60-second periods) of ICP and Arterial Blood Pressure (ABP). A positive PRx correlation suggests impaired cerebrovascular pressure reactivity, that is, passive transmission of changes in ABP to ICP. A negative PRx correlation indicates good pressure reactivity. Any change in ABP produces inverse changes in ICP.
Time frame: Baseline to 24 hours
Population: Everyone who completed the trial was included except for nineteen subjects had incomplete data and could not be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-of-Care Plus Precedex | Change in Pressure Reactivity Index (PRx) | .64 Pressure Reactivity Index | Standard Error 0.02 |
| Standard-of-Care | Change in Pressure Reactivity Index (PRx) | .66 Pressure Reactivity Index | Standard Error 0.02 |
p-value: 0.395t-test, 2 sided
Primary
Variability of Intracranial Pressure (ICP)
Variability of intracranial pressure was assessed and listed as the standard deviation of all measurements within 24 hours. Variability was assessed and listed as the standard deviation of all measurements within 24 hours
Time frame: Baseline to 24 hours
Population: Everyone who completed the trial was included except for fourteen subjects had incomplete data and could not be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-of-Care Plus Precedex | Variability of Intracranial Pressure (ICP) | 5.66 mmHg | Standard Error 0.63 |
| Standard-of-Care | Variability of Intracranial Pressure (ICP) | 5.61 mmHg | Standard Error 0.64 |
Secondary
Amount of Sedative/Analgesic Used During Treatment in Patients With Secondary Brain Injury
Improved physiologic Response. A lower use of sedatives or analgesic during treatment would be considered an improved physiologic response. An increase in the use of sedatives or analgesic during treatment would be considered a worse physiologic response.
Time frame: 24 hours
Population: Everyone who started the trial was included except for one subject had incomplete data and could not be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-of-Care Plus Precedex | Amount of Sedative/Analgesic Used During Treatment in Patients With Secondary Brain Injury | 155.4 mg/ml | Standard Error 23.3 |
| Standard-of-Care | Amount of Sedative/Analgesic Used During Treatment in Patients With Secondary Brain Injury | 213.1 mg/ml | Standard Error 26.3 |
Secondary
Cerebral Perfusion Pressure Changes in Patients With Secondary Brain Injury
Improved physiologic Response. A higher cerebral perfusion pressure during treatment would be considered an improved physiologic response. A lower cerebral perfusion pressure during treatment would be considered a worse physiologic response.
Time frame: Baseline to 24 hours
Population: Everyone who completed the trial was included except for fourteen subjects had incomplete data and could not be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-of-Care Plus Precedex | Cerebral Perfusion Pressure Changes in Patients With Secondary Brain Injury | 11.5 mmHg | Standard Error 0.63 |
| Standard-of-Care | Cerebral Perfusion Pressure Changes in Patients With Secondary Brain Injury | 12.3 mmHg | Standard Error 0.74 |
Secondary
Mean Arterial Blood Pressure (MAP) Variability in Patients With Secondary Brain Injury
Improved physiologic Response. A lower variability of mean Arterial Blood pressure during treatment would be considered an improved physiologic response. A higher variability of mean Arterial Blood pressure during treatment would be considered a worse physiologic response. Variability was assessed and listed as the standard deviation of all measurements within 24 hours.
Time frame: Baseline to 24 hours
Population: Everyone who started the trial was included except for seventeen subjects had incomplete data and could not be included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-of-Care Plus Precedex | Mean Arterial Blood Pressure (MAP) Variability in Patients With Secondary Brain Injury | 12.30 mmHg | Standard Error 0.73 |
| Standard-of-Care | Mean Arterial Blood Pressure (MAP) Variability in Patients With Secondary Brain Injury | 13.8 mmHg | Standard Error 1.44 |