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Assessing the Effectiveness of Midazolam Premedication

Not Applicable
Completed
Conditions
Midazolam Premedication
Anxiety Preoperative
Premedication
Interventions
Registration Number
NCT03325335
Lead Sponsor
Pusan National University Hospital
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
128
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Midazolam premedication group (Group P)Midazolam premedicationPatients of group P were premedicated with intramuscular midazolam 0.05 mg/kg 30 minutes before surgery.
Midazolam premedication group (Group P)Remifentanil infusionPatients of group P were premedicated with intramuscular midazolam 0.05 mg/kg 30 minutes before surgery.
Control group (Group N)Remifentanil infusionPatients of group N were not premedicated with midazolam (Do not use placebo). \[Treatment of Glycopyrrolate (0.2 mg, IM) 30 minutes prior to surgery is not intervention because it is a routine practice of this center. (-\> removed from interventions)\]
Control group (Group N)Propofol infusionPatients of group N were not premedicated with midazolam (Do not use placebo). \[Treatment of Glycopyrrolate (0.2 mg, IM) 30 minutes prior to surgery is not intervention because it is a routine practice of this center. (-\> removed from interventions)\]
Midazolam premedication group (Group P)Propofol infusionPatients of group P were premedicated with intramuscular midazolam 0.05 mg/kg 30 minutes before surgery.
Primary Outcome Measures
NameTimeMethod
Change in noninvasive blood pressure (hemodynamic parameters 1)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)

Change in SPI value (Analgesic profile 1)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

Analgesic requirement (Analgesic profile 3)Postoperative period (until transition to oral analgesics, up to 12 hours)

Reviewing additional medications for pain control

Change in degree of anxietythe 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.

Change in sedation levelAt 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).

Change in heart rate (hemodynamic parameters 2)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)

Numeric rating scale (Analgesic profile 2)Postoperative period (until transition to oral analgesics, up to 12 hours)

Reviewing numeric rating scale (NRS) : 0 (No pain) \~ 10 (Worst possible pain)

Secondary Outcome Measures
NameTimeMethod
Procedure time of intubationFrom the beginning of anesthesia to the completion of intubation

Total time taken for intubation was recorded

Correlation analysis between the SPI values and other parameters (heart rate, blood pressure, and entropy values)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)

Trial Locations

Locations (1)

Pusan national university hospital

🇰🇷

Busan, Korea, Republic of

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