Assessing the Effectiveness of Midazolam Premedication
Condition: Midazolam Premedication; Anxiety Preoperative; Premedication
Study type: Interventional

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.
    

Intervention name(s): Midazolam premedication; Remifentanil infusion; Propofol infusion
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Patients in Group P received midazolam (0.05 mg/kg, intramuscular injection) 30 minutes before induction of general anesthesia.; 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); 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 intervention name(s): Intramuscular midazolam; Target-controlled infusion (TCI) of remifentanil; Target-controlled infusion (TCI) of propofol
Intervention MeSH terms: Midazolam; Remifentanil; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: midazolam premedication