Comparative Study of Hemodynamic Changes Caused by Diazepam and Midazolam During Third Molar Surgery
Condition: Anxiety
Study type: Interventional
Phase: Phase 4

Summary: 
      Objective: The aim of the present study was to compare hemodynamic changes using 7.5 mg of
      midazolam and 10.0 mg of diazepam during the surgical removal of symmetrically positioned
      third molars.

      Study design: A prospective, randomized, double-blind, clinical trial was carried out
      involving 120 patients divided in three groups: Group 1 (diazepam and placebo), Group 2
      (midazolam and placebo) and Group 3 (diazepam and midazolam). Each subject underwent two
      surgeries on separate occasions under local anesthesia.
    

Detailed description: 
      Study design A double-blind, randomized, crossover, clinical trial with a split-mouth design
      was carried out. This study received approval from the Human Research Ethics Committee of the
      institution at which it was carried out (process number: 001.0.097.000-08) and was conducted
      in compliance with the Consolidated Standards of Reporting Trials (CONSORT) statement. All
      patients signed a statement of informed consent agreeing to participate in the study.

      Sample size and pilot study The sample size was estimated using the a computational program.
      Thirty patients were submitted to third molar surgeries in a pilot study to determine the
      sample size. This step was necessary due to the lack of similar studies in the literature.
      Calculations were performed with specific programs taking into consideration the variables, a
      95% confidence interval, 80% test power and 5% error. At the end of the study, 120 patients
      were analyzed (40 in each group), totaling 240 surgeries.

      Sample selection One hundred twenty eight individuals between 18 and 40 years of age were
      selected for participation in the present study and submission to maxillary and mandibular
      third molar extractions bilaterally at the Department of Oral-Maxillofacial Surgery. Each
      patient was to be submitted to two surgeries. The third molars (maxillary or mandibular)
      needed to have the same degree of impaction on both sides.

      Three groups were formed: Group A received diazepam and placebo, Group B received midazolam
      and placebo and Group C received midazolam and diazepam. For the purposes of randomization
      and blinding of the surgeon and researcher in charge of analyzing the results, the groups
      were renominated Groups 1, 2 and 3. The randomization procedure was carried out by a
      researcher who was not directly involved in the surgeries or evaluations. Sequentially
      numbered, sealed, opaque envelopes were used, each containing a combination of substances and
      the side to be submitted to the first surgery. For each patient, the researcher opened an
      envelope, informed the main investigator and surgeon of the side to be operated, and
      administered the substance to the patient. The second surgery was performed on the
      contralateral side with the administration of the second substance. Blinding was performed to
      avoid awareness regarding what substance was administered in each surgery. For such, the
      pills were fabricated with the same outer color and a standardized size at the Pernambuco
      Pharmaceutical Laboratory (Brazil) and were packaged in recipients with the same color. The
      recipients were denominated 1, 2 and 3.

      Surgical procedures and medications As the patients were classified as healthy, no
      prophylactic use of antibiotics was performed prior to surgery for the prevention of
      bacterial endocarditis, as recommended by the American Heart Association. All patients rinsed
      their mouths with 0.12% chlorhexidine for one minute prior to surgery to reduce the bacterial
      population in the oral cavity. Moreover, all patients were instructed to take two 4-mg pills
      of dexamethasone one hour prior to surgery. The use of a corticosteroid in the preoperative
      period minimizes the occurrence of postoperative swelling and reduces the risk of trismus.13
      The substances (diazepam, midazolam and placebo) were administered orally 45 minutes prior to
      the surgical procedure. As the substances were masked, neither the surgeon nor the patient
      was aware of what substance was given (double-blind study).
    

Intervention name(s): 7.5 mg Midazolam; 10 mg diazepam
Intervention type(s): Drug; Drug
Intervention description(s): 7.5 mg midazolam 45 minutes before surgery; 10 mg midazolam 45 minutes before surgery
Intervention MeSH terms: Midazolam; Diazepam
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Third Molar; Anty-anxiety drugs; hemodynamic; Benzodiazepines