Assessing the Effectiveness of Midazolam Premedication

October 28, 2017 updated by: Hyeon-Jeong Lee, Pusan National University Hospital

Randomized Controlled Trial Assessing the Effectiveness of Midazolam Premedication as an Anxiolytic, Analgesic, Sedative, and Hemodynamic Stabilizer

Pre-anesthetic dosing of midazolam is commonly used in many hospitals for the induction of anesthesia, but the effect is still controversial. The purpose of this study was to evaluate the effectiveness of midazolam premedication in four aspects: anxiety reduction, pain relief, sedation and hemodynamic stability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background

  • Midazolam premedication is a routine practice in many hospitals, but its efficacy remains controversial. We evaluated the effectiveness of midazolam premedication with respect to anxiety and sedation levels, hemodynamic parameters, and analgesic profiles.

Methods

  • Subjects

    • This randomized, prospective, open-label study was approved by IRB. After written informed consent, a total of 128 female patients aged between 20 and 65 years, ASA physical status Ⅰ or Ⅱ, scheduled for elective thyroidectomy were enrolled. Exclusion criteria were: central nervous system disorders, major cardiovascular disease, chronic pain disorders, peripheral neuropathy, diabetes mellitus neuropathy, nephropathy, hepatopathy, taking any medication affecting the central nervous system or heart rate, alcohol or drug abuse, pregnancy, and contraindication to midazolam premedication. Enrolled all subjects were randomly allocated to either midazolam premedication group (Group P, n=64) or control group (Group N, n=64). Patients of group P were premedicated with intramuscular glycopyrrolate 0.2mg and midazolam 0.05 mg/kg 30 minutes before surgery, while patients assigned to Group N were only received glycopyrrolate.

  • Anesthetic management

    • In the operating room, we did standard monitoring(ECG, pulse oximetry, noninvasive blood pressure, esophageal stethoscope temperature), train of four (TOF) and entropy and surgical pleth index(SPI). Target controlled infusion of propofol (4.0 μg/ml) and remifentanil (4 ng/ml) were used for induction of anesthesia based on the pharmacological models of Marsh and Minto, respectively. Intravenous rocuronium 1.0 mg/kg was administered for muscle relaxation. After intubation, propofol (3.0μg/ml) and remifentanil (2 ng/ml) were infused until incision time. 30 mg of ketorolac was administered 30 minutes before the end of the operation to control postoperative pain.

  • Assessment of response to midazolam

    • To evaluate the degree of anxiety, the Beck anxiety inventory was conducted at the preoperative day before surgery and immediately after arrival at the operating room. For analgesic profile assessment, SPI monitoring was performed in the operating room and NRS (numeric rating scale) measured in the recovery room and the general ward until the transition to oral analgesics. Also, additional medications for pain control were reviewed. Noninvasive blood pressure, heart rate, and entropy value were recorded at each measuring points in order to evaluate the hemodynamic stability and sedation level during anesthesia induction. Measuring points were initial time, prior to intubation, intubation, prior to incision and incision time. The time taken to induce anesthesia was also recorded.

  • Sample size and statistical analysis

    • In this study, sample size was determined based on Cohen's study. According to this analysis, when comparing the mean of two groups with α (significance criterion) = 0.05, β (probability of occurring type II error) = 0.2 and medium effect size (Cohen's d = 0.5), 64 subjects were needed per group.
    • After a normality test, continuous variables were analyzed with the use of an independent t-test, paired t-test, and repeated-measures ANOVA. Differences between categorical variables were calculated with the use of the chi-square test.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
128

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • American Society of Anesthesiologists physical status classification I or II
  • Scheduled for elective thyroidectomy under general anesthesia

Exclusion Criteria:

  • Central nervous system disorders
  • Major cardiovascular disease
  • Chronic pain disorders
  • Peripheral neuropathy
  • Diabetes mellitus neuropathy
  • Nephropathy
  • Hepatopathy
  • Taking any medication affecting the central nervous system or heart rate
  • Alcohol or drug abuse
  • Pregnancy
  • Contraindication to midazolam premedication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Midazolam premedication group (Group P)
Patients of group P were premedicated with intramuscular midazolam 0.05 mg/kg 30 minutes before surgery.
Drug: Midazolam premedication
Patients in Group P received midazolam (0.05 mg/kg, intramuscular injection) 30 minutes before induction of general anesthesia.
Other Names:
  • Intramuscular midazolam
Drug: Remifentanil infusion
Target controlled infusion of remifentanil (4ng/ml) was used for induction of anesthesia based on the pharmacological models of Minto. After intubation, remifentanil (2 ng/ml) was infused until incision time. (Both groups)
Other Names:
  • Target-controlled infusion (TCI) of remifentanil
Drug: Propofol infusion
Target controlled infusion of propofol (4.0 μg/ml) was used for induction of anesthesia based on the pharmacological models of Marsh. After intubation, propofol (3.0μg/ml) was infused until incision time. (Both groups)
Other Names:
  • Target-controlled infusion (TCI) of propofol
Other: Control group (Group N)
Patients of group N were not premedicated with midazolam (Do not use placebo). [Treatment of Glycopyrrolate (0.2 mg, IM) 30 minutes prior to surgery is not intervention because it is a routine practice of this center. (-> removed from interventions)]
Drug: Remifentanil infusion
Target controlled infusion of remifentanil (4ng/ml) was used for induction of anesthesia based on the pharmacological models of Minto. After intubation, remifentanil (2 ng/ml) was infused until incision time. (Both groups)
Other Names:
  • Target-controlled infusion (TCI) of remifentanil
Drug: Propofol infusion
Target controlled infusion of propofol (4.0 μg/ml) was used for induction of anesthesia based on the pharmacological models of Marsh. After intubation, propofol (3.0μg/ml) was infused until incision time. (Both groups)
Other Names:
  • Target-controlled infusion (TCI) of propofol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in degree of anxiety
Time Frame: the anesthesiologist's visit on the day before surgery and pre-induction time after randomization
Patients completed the Beck anxiety inventory (BAI) on two separate occasions, the anesthesiologist's visit on the day before surgery and pre-induction time after randomization. The BAI was a self-report questionnaire consisting of 21 questions.
the anesthesiologist's visit on the day before surgery and pre-induction time after randomization
Change in sedation level
Time Frame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Measuring the entropy value (CARESCAPE Monitor B850, GE Healthcare, Milwaukee, WI, USA).
At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Change in noninvasive blood pressure (hemodynamic parameters 1)
Time Frame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Measuring noninvasive blood pressure (CARESCAPE Monitor B850, GE Healthcare, Milwaukee, WI, USA)
At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Change in SPI value (Analgesic profile 1)
Time Frame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Measuring SPI (CARESCAPE Monitor B850, GE Healthcare, Milwaukee, WI, USA), which was calculated from the pulse oximetry wave
At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Numeric rating scale (Analgesic profile 2)
Time Frame: Postoperative period (until transition to oral analgesics, up to 12 hours)
Reviewing numeric rating scale (NRS) : 0 (No pain) ~ 10 (Worst possible pain)
Postoperative period (until transition to oral analgesics, up to 12 hours)
Analgesic requirement (Analgesic profile 3)
Time Frame: Postoperative period (until transition to oral analgesics, up to 12 hours)
Reviewing additional medications for pain control
Postoperative period (until transition to oral analgesics, up to 12 hours)
Change in heart rate (hemodynamic parameters 2)
Time Frame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Measuring heart rate (CARESCAPE Monitor B850, GE Healthcare, Milwaukee, WI, USA)
At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Procedure time of intubation
Time Frame: From the beginning of anesthesia to the completion of intubation
Total time taken for intubation was recorded
From the beginning of anesthesia to the completion of intubation
Correlation analysis between the SPI values and other parameters (heart rate, blood pressure, and entropy values)
Time Frame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Measuring SPI, noninvasive blood pressure, heart rate, and entropy values (CARESCAPE Monitor B850, GE Healthcare, Milwaukee, WI, USA)
At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pusan National University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hyeon-Jeong Lee, PhD, Pusan National University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 19, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 14, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 31, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1607-003-057

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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