Clinical trial NCT03325335: Assessing the Effectiveness of Midazolam Premedication
Official title: Randomized Controlled Trial Assessing the Effectiveness of Midazolam Premedication as an Anxiolytic, Analgesic, Sedative, and Hemodynamic Stabilizer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Midazolam Premedication
Anxiety Preoperative
Premedication
Keywords: midazolam premedication
Lead sponsor: Pusan National University Hospital
Sponsor class: OTHER
First posted: 2017-10-30
Enrollment: 128
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in degree of anxiety
timeFrame: the anesthesiologist's visit on the day before surgery and pre-induction time after randomization
measure: Change in sedation level
timeFrame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
measure: Change in noninvasive blood pressure (hemodynamic parameters 1)
timeFrame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
measure: Change in SPI value (Analgesic profile 1)
timeFrame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
measure: Numeric rating scale (Analgesic profile 2)
timeFrame: Postoperative period (until transition to oral analgesics, up to 12 hours)
measure: Analgesic requirement (Analgesic profile 3)
timeFrame: Postoperative period (until transition to oral analgesics, up to 12 hours)
measure: Change in heart rate (hemodynamic parameters 2)
timeFrame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Secondary outcomes:
measure: Procedure time of intubation
timeFrame: From the beginning of anesthesia to the completion of intubation
measure: Correlation analysis between the SPI values and other parameters (heart rate, blood pressure, and entropy values)
timeFrame: At the time of pre-induction (initial), prior to intubation, intubation, prior to incision, and surgical incision
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Pusan national university hospital
Study officials:
affiliation: Pusan National University Hospital
name: Hyeon-Jeong Lee, PhD
role: PRINCIPAL_INVESTIGATOR
References: