Cerebral Perfusion Pressure Using Precedex and Other Sedatives

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cerebral Perfusion Pressure Using Precedex and Other Sedatives

Conditions
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Endotracheal Intubation, Continuous IV Sedation, ICP Monitoring

Intervention / Treatment
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* Drug: Standard-of-Care plus Dexmedetomidine
* Other: Standard-of-Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard-of-Care plus Precedex<br>Subjects who are treated with dexmedetomidine (Precedex) in addition to the standard of care sedation regiment. | Drug: Standard-of-Care plus Dexmedetomidine<br>* Subjects who are treated with dexmedetomidine (Precedex) in addition to the standard of care sedation regiment<br>* Other names: Precedex;|
| Placebo Comparator: Standard-of-Care<br>Subjects who are treated with the standard of care sedation regiment only. | Other: Standard-of-Care<br>* Subjects who are treated with the standard of care sedation regiment only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline to 24 hours | 
| 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. | Baseline to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 hours | 
| 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. | Baseline to 24 hours | 
| 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. | Baseline to 24 hours |