Assessing the Effectiveness of Midazolam Premedication

NCT ID: NCT03325335

Last Updated: 2017-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-19
• Study Completion Date: 2017-08-15

Brief Summary

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.

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.

Conditions

Midazolam Premedication; Anxiety Preoperative; Premedication

Keywords

midazolam premedication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Midazolam premedication group (Group P)

Patients of group P were premedicated with intramuscular midazolam 0.05 mg/kg 30 minutes before surgery.

Group Type: ACTIVE_COMPARATOR

Midazolam premedication

Intervention Type: DRUG

Patients in Group P received midazolam (0.05 mg/kg, intramuscular injection) 30 minutes before induction of general anesthesia.

Remifentanil infusion

Intervention Type: DRUG

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)

Propofol infusion

Intervention Type: DRUG

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)

Control group (Group N)

Patients of group N were not premedicated with midazolam (Do not use placebo). \[Treatment of Glycopyrrolate (0.2 mg, IM) 30 minutes prior to surgery is not intervention because it is a routine practice of this center. (-\> removed from interventions)\]

Group Type: OTHER

Remifentanil infusion

Intervention Type: DRUG

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)

Propofol infusion

Intervention Type: DRUG

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)

Interventions

Midazolam premedication

Patients in Group P received midazolam (0.05 mg/kg, intramuscular injection) 30 minutes before induction of general anesthesia.

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Intramuscular midazolam; Target-controlled infusion (TCI) of remifentanil; Target-controlled infusion (TCI) of propofol

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pusan National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hyeon-Jeong Lee

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hyeon-Jeong Lee, PhD

Role: PRINCIPAL_INVESTIGATOR

Pusan National University Hospital

Locations

Pusan national university hospital

Busan, , South Korea

Countries

South Korea

Other Identifiers

1607-003-057

Identifier Type: -

Identifier Source: org_study_id