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Efficacy of Propofol or Midazolam Compare to Placebo for Preoperative Medication

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01976845
Recruitment Status : Completed
First Posted : November 6, 2013
Results First Posted : March 14, 2016
Last Update Posted : March 14, 2016
Sponsor:
Information provided by (Responsible Party):
Ronald Wender, Cedars-Sinai Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Elective Orthopedic Surgery Drug: Midazolam Drug: Propofol Drug: Saline Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Propofol or Midazolam Versus Placebo for Preoperative Medication in Patients Undergoing Elective Orthopedic Surgery
Study Start Date : November 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: Propofol
Propofol 20 mg IV (2 ml)
Drug: Propofol
Propofol (20mg) 2 ml IV, in the pre-op area as a premedication
Other Name: Diprivan

Active Comparator: Midazolam
Midazolam 2 mg IV (2 ml)
Drug: Midazolam
Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication
Other Name: VERSED

Placebo Comparator: Saline
Saline 2 ml
Drug: Saline
Saline 2 ml IV, in the pre-op area as a premedication
Other Name: Saline solution




Primary Outcome Measures :
  1. Scores on the Verbal Rating Scale For Anxiety [ Time Frame: one day ]
    Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely nervous)


Secondary Outcome Measures :
  1. Scores on the Verbal Rating Scale For Sleepiness (Sedation) [ Time Frame: one day ]
    Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely sleepiness)

  2. Produces Amnesia(Memory Recall) [ Time Frame: one day ]

    Ability to recall (memory of):

    •recall of 2 pictures




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willingness and ability to sign an informed consent document
  • No allergies to midazolam or propofol
  • 18 - 70 years of age
  • American Society of Anesthesiologists (ASA) Class I-III adults of either sex

Exclusion Criteria:

  • Patients with known allergy, hypersensitivity or contraindications to midazolam, propofol, anesthetic or analgesic medications
  • Patients with clinically-significant medical conditions, such as brain, heart, kidney, endocrine, or liver diseases
  • Pregnant or lactating women
  • Subjects with a history of alcohol or drug abuse within the past 3 months
  • Patients chronically using sedative, anxiolytic drugs prior to the surgery
  • Morbid obesity (BMI >40 kg/m2)
  • Patients who are agitated or confused prior to receiving the drug ( verbal rating scale [VRS] greater then 6)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01976845


Locations
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United States, California
Cedars Sinai Medical center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
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Principal Investigator: Ronald H Wender, MD Cedars-Sinai Medical Center

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Responsible Party: Ronald Wender, Chairman, Department of anesthesiology, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01976845    
Other Study ID Numbers: Pro00025204
First Posted: November 6, 2013    Key Record Dates
Results First Posted: March 14, 2016
Last Update Posted: March 14, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Ronald Wender, Cedars-Sinai Medical Center:
propofol
midazolam
sedative
anxiolytic
amnesic
recall
Memory
Perioperative outcomes
Additional relevant MeSH terms:
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Midazolam
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action