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The purpose of this research is:
To evaluate the sedative (reduces irritability or agitation), anxiolytic (reduces anxiety), and amnesic (produces temporary lack of recall) effects of propofol or midazolam when administered for preoperative medication (before administration of drugs that will put patient to sleep) in comparison to placebo. This study is to test whether the use of the pre-anesthesia medication measurably reduces anxiety in comparison to receiving no pre-anesthesia medication prior to orthopedic procedures.
To assess the effect of propofol in comparison to placebo and midazolam on the ability to recall (memory of):
The role of anxiolytic premedication in the ambulatory surgical population is frequently debated. Anesthesiologists may consider the administration of anxiety-reducing drugs unnecessary when anxiety levels are low in outpatients presenting for minor surgery. However, the previous study reports that up to 80% of outpatients expressed a preference for a combination of anxiety-reducing and hypnotic premedication before surgery (1-4). In addition to anxiolysis, goals of anxiolytic premedication include sedation, amnesia, improved patient cooperation, and/or improved patient satisfaction. Intravenous (IV) midazolam is the most commonly used premedicant in the ambulatory setting due to its rapid onset, and short half-life (2,3,5), but its residual effects in the immediate postoperative period may contribute to postoperative sedation, as well as to delayed recovery and discharge-readiness after brief outpatient surgery. Furthermore, White et al. (6) noted that the slope of the dose-response curve for sedation was much steeper with midazolam compared with diazepam, which suggests that midazolam may possess a smaller margin of safety and greater need for careful titration to achieve the desired clinical end-point without untoward side effects.
Propofol has become the IV (intravenous) anesthetic of choice for ambulatory anesthesia because of its excellent recovery profile (7). Clinical experience with propofol in the ambulatory setting suggests that its use is associated with less residual sedation and lower incidence of postoperative nausea and vomiting (PONV) (8). However, there are some undesirable side effects associated with propofol including pain on injection, cardiovascular and respiratory depression, and occasional excitement on emergence from anesthesia (9). Practically, small doses of propofol (10-20 mg IV) have been used as an anxiolytic/sedative medication.
To date, there is only one study that has evaluated propofol versus midazolam versus placebo as premedication (10). In this study, the authors stated that propofol (0.4 mg/kg IV) had anxiolytic effects comparable in magnitude and duration to midazolam (0.04 mg/kg IV) with less memory impairment, respiratory depression and dizziness. However, they did not assess the efficacy of propofol and midazolam as a premedication on the recovery profiles and patient's satisfaction in their study. Compared to placebo and propofol, midazolam was associated with more frequent respiratory depression and significant impairment of anterograde explicit memory. Both propofol and midazolam helped relieve anxiety and lowered blood pressure (compared to baseline) but both were associated with greater dizziness scores (P<0.001, compared to placebo).
They concluded that Propofol had an anxiolytic effect comparable in magnitude and duration to that of midazolam with less memory impairment, respiratory depression and dizziness.
Propofol appears to be an economical, effective and safe alternative to midazolam for treating pre-anesthesia anxiety, and especially to be used for induction of anesthesia (10). (This sentence is not clear).
Therefore, we designed this randomized, double-blind, and placebo-controlled study to evaluate propofol as a premedication and to see if it:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propofol | Experimental | Propofol 20 mg IV (2 ml) |
|
| Midazolam | Active Comparator | Midazolam 2 mg IV (2 ml) |
|
| Saline | Placebo Comparator | Saline 2 ml |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication |
|
| Measure | Description | Time Frame |
|---|---|---|
| Scores on the Verbal Rating Scale For Anxiety | Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely nervous) | one day |
| Measure | Description | Time Frame |
|---|---|---|
| Scores on the Verbal Rating Scale For Sleepiness (Sedation) | Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely sleepiness) | one day |
| Produces Amnesia(Memory Recall) | Ability to recall (memory of): •recall of 2 pictures |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald H Wender, MD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical center | Los Angeles | California | 90048 | United States |
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Randomization assignment was generated with a 1:1:1 allocation ratio using a computer software program.
The randomization number specifying the study medication was placed in sealed envelope and given to a non-participating anesthesiologist on the day of the scheduled procedure after completing the patient's preoperative assessment.
Prior to the day of surgery, potential study patients received a packet of materials (initial patient contact letter, a HIPAA information sheet, and the IRB approved informed consent form) from their surgeon. Patients who were interested in participating in the study were asked to bring the materials to the hospital on the day of surgery.
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| ID | Title | Description |
|---|---|---|
| FG000 | Propofol | Propofol 20 mg IV (2 ml) Propofol: Propofol (20mg) 2 ml IV, in the pre-op area as a premedication |
| FG001 | Midazolam | Midazolam 2 mg IV (2 ml) Midazolam: Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication |
| FG002 | Saline | Saline 2 ml Saline: Saline 2 ml IV, in the pre-op area as a premedication |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Propofol | Propofol 20 mg IV (2 ml) Propofol: Propofol (20mg) 2 ml IV, in the pre-op area as a premedication |
| BG001 | Midazolam | Midazolam 2 mg IV (2 ml) Midazolam: Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Scores on the Verbal Rating Scale For Anxiety | Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely nervous) | Posted | Mean | Standard Deviation | Scores on a Scale (0-10) | one day |
|
up to 24 hours
The study lasted the day of the anesthesia procedure.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Propofol | Propofol 20 mg IV (2 ml) Propofol: Propofol (20mg) 2 ml IV, in the pre-op area as a premedication |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ronald H Wender | Department of Anesthesiology at Cedars-Sinai Medical Center in Los Angeles | 3104231682 | ronald.wender@cshs.org |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D015742 | Propofol |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Propofol | Drug | Propofol (20mg) 2 ml IV, in the pre-op area as a premedication |
|
|
| Saline | Drug | Saline 2 ml IV, in the pre-op area as a premedication |
|
|
| one day |
| BG002 | Saline | Saline 2 ml Saline: Saline 2 ml IV, in the pre-op area as a premedication |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg^m2 |
|
Saline 2 ml
Saline: Saline 2 ml IV, in the pre-op area as a premedication
|
|
| Secondary | Scores on the Verbal Rating Scale For Sleepiness (Sedation) | Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely sleepiness) | Posted | Mean | Standard Deviation | Scores on a Scale (0-10) | one day |
|
|
|
| Secondary | Produces Amnesia(Memory Recall) | Ability to recall (memory of): •recall of 2 pictures | Subjects who recall the picture | Posted | Number | participants | one day |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| EG001 | Midazolam | Midazolam 2 mg IV (2 ml) Midazolam: Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication | 0 | 40 | 0 | 40 |
| EG002 | Saline | Saline 2 ml Saline: Saline 2 ml IV, in the pre-op area as a premedication | 0 | 40 | 0 | 40 |
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| D006571 | Heterocyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |