Assessing the Effectiveness of Midazolam Premedication

Premedication Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03325335
• Other study ID #: 1607-003-057
• Status: Completed
• Phase: N/A
• First received: October 22, 2017
• Last updated: October 28, 2017
• Start date: July 19, 2016
• Est. completion date: August 15, 2017

Study information

• Verified date: October 2017
• Source: Pusan National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: August 15, 2017
• Est. primary completion date: August 14, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety Preoperative
• Midazolam Premedication
• Premedication

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Pusan national university hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Pusan National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in degree of anxiety	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
Primary	Change in sedation level	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
Primary	Change in noninvasive blood pressure (hemodynamic parameters 1)	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
Primary	Change in SPI value (Analgesic profile 1)	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
Primary	Numeric rating scale (Analgesic profile 2)	Reviewing numeric rating scale (NRS) : 0 (No pain) ~ 10 (Worst possible pain)	Postoperative period (until transition to oral analgesics, up to 12 hours)
Primary	Analgesic requirement (Analgesic profile 3)	Reviewing additional medications for pain control	Postoperative period (until transition to oral analgesics, up to 12 hours)
Primary	Change in heart rate (hemodynamic parameters 2)	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	Procedure time of intubation	Total time taken for intubation was recorded	From the beginning of anesthesia to the completion of intubation
Secondary	Correlation analysis between the SPI values and other parameters (heart rate, blood pressure, and entropy values)	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