Efficacy of Propofol or Midazolam Compare to Placebo for Preoperative Medication
Condition: Elective Orthopedic Surgery
Study type: Interventional
Phase: Phase 4

Summary: 
      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):

        -  when the doctor places the mask on patient's face prior to going to sleep

        -  recall of 2 pictures

        -  on your satisfaction with the anesthesia as well as postoperative side effects in
           post-anesthesia care unit (PACU) e.g., nausea ,vomiting and sedation.
    

Detailed description: 
      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:

        -  produces comparable anxiolytic effects to midazolam when compared to placebo, but with
           less memory impairment

        -  facilitates early recovery profile

        -  improves patient's satisfaction with the induction and early recovery from anesthesia.
    

Intervention name(s): Midazolam; Propofol; Saline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication; Propofol (20mg) 2 ml IV, in the pre-op area as a premedication; Saline 2 ml IV, in the pre-op area as a premedication
Other intervention name(s): VERSED; Diprivan; Saline solution
Intervention MeSH terms: Midazolam; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: propofol; midazolam; sedative; anxiolytic; amnesic; recall; Memory; Perioperative outcomes