Dexmedetomidine Versus Propofol in the Medical Intensive Care Unit (MICU)

Study Overview
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Brief Summary
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This is a randomized controlled trial to compare propofol to dexmedetomidine for prolonged sedation (> 24 hours) in critically ill patients who require mechanical ventilation.

Detailed Description
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Mechanically ventilated critically ill patients are routinely given sedative and analgesic medications to relieve pain and anxiety associated with intubation, mechanical ventilation, and critical care in general. While integral in minimizing discomfort, these medications may increase mechanical ventilation time, the duration of intensive care unit (ICU) stay, ICU complications (e.g. delirium, ventilator associated pneumonia, venous thromboembolism), the morbidity associated with critical illness, and patient mortality. This study compares two sedative medications that have been used in patients who require a mechanical ventilator. Enrolled patients will be randomly assigned to receive propofol or dexmedetomidine for sedation while they require ventilatory support. All patients will also receive the pain medication fentanyl as needed.

Official Title
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A Double-blinded Randomized Controlled Trial of Dexmedetomidine Versus Propofol for Sedation in Mechanically Ventilated Medical Intensive Care Unit Patients.

Conditions
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Mechanical Ventilation, Critical Illness

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Propofol
* Drug: Fentanyl
* Drug: Midazolam
* Behavioral: Physical and Occupational Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years old mechanically ventilated through endotracheal tube anticipated need for ventilation > 48 hours requiring sedative/analgesic medication Exclusion Criteria: on mechanical ventilator > 96 hours primary neurologic disease post cardiac arrest do not speak English (assessment only English language validated) pregnancy or lactation active myocardial ischemia second or third degree heart block pancreatitis elevated serum triglycerides (> 400 mg/dL)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexmedetomidine<br>Patients in this arm will receive continuous dexmedetomidine infusion (0.2 - 1.5 mcg/kg/hour) titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first. | Drug: Dexmedetomidine<br>* continuous IV infusion 0.2 - 1.5 ucg/kg/hour titrated to target RASS<br>* Other names: Precedex;Drug: Fentanyl<br>* 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale<br>Drug: Midazolam<br>* 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS>+2)<br>* Other names: Versed;Behavioral: Physical and Occupational Therapy<br>* Daily therapy sessions targeting range of motion, strength, and mobility<br>|
| Active Comparator: Propofol<br>Patients in this arm will receive propofol (5 - 50 mcg/kg/min) for sedation, titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first. | Drug: Propofol<br>* continuous IV infusion (5 - 50 ucg/kg/min) titrated to target RASS<br>* Other names: Diprivan;Drug: Fentanyl<br>* 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale<br>Drug: Midazolam<br>* 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS>+2)<br>* Other names: Versed;Behavioral: Physical and Occupational Therapy<br>* Daily therapy sessions targeting range of motion, strength, and mobility<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Days With Delirium | delirium assessment using CAM-ICU | daily up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score | Richmond Agitation Sedation Scale (RASS). This is a validated scale that measures level of sedation. The scale ranges from -5 to +4. -5 refers to a state where one is unarousable, +4 refers to a state where one is combative. The median and inter-quartile range over all daily assessments will be provided. | Daily up to day 28 | 
| Number of Patients Completing Mobility Milestones | Milestones: sitting upright independently, standing independently, transfer to chair, marching in place, ambulating independently | Daily through day 28 | 
| Days on Ventilator |  | 60 days from enrollment | 
| Days in ICU |  | 60 days from enollment | 
| Mortality |  | 28 days from enrollment | 
| Number of Participants With ICU Complications |  | daily through day 28 | 
| Number of Patients Requiring Fentanyl |  | during infusion of study medication up to day 28 | 
| Number of Patients Requiring Midazolam |  | during infusion of study medication through day 28 | 
| Days in Hospital |  | 60 days from enrollment | 
| Number of Patients Completing Activities of Daily Living | activities of daily living: eating, bathing, dressing, grooming, toileting | daily through day 28 | 
| Number of Adverse Medication Effects |  | duration of infusion of study medication up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypnotics and Sedatives, Respiration, Artificial, Ventilators, Mechanical, Critical care, Intensive care, Physical therapy, Occupational therapy, Sedative medications