Impact of Timing of Midazolam Administration on Incidence of Postoperative Nausea and Vomiting
Condition: Postoperative Nausea and Vomiting
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional

Summary: 
      Postoperative nausea and vomiting (PONV), defined as nausea and/or vomiting occurring within
      24 hours after surgery, affects between 20% and 30% of patients, As many as 70% to 80% of
      patients at high risk may be affected. The etiology of PONV is thought to be multifactorial,
      involving individual, anaesthetic and surgical risk factors. PONV results in increased
      patient discomfort and dissatisfaction and in increased costs related to length of hospital
      stay. Serious medical complications such as pulmonary aspiration, although uncommon, are also
      associated with vomiting.

      Patients with a higher risk of PONV often require a combination or multimodal approach of 2
      or more interventions for effective risk reduction. Thus, researchers have explored
      additional nontraditional antiemetics, such as midazolam, that would aid in the multimodal
      prevention of PONV.
    

Detailed description: 
      Midazolam is often administered in the perioperative period to reduce anxiety in addition to
      causing sedation and amnesia. The pharmacologic qualities allow for a rapid onset, short
      duration, and short half-life. The clinical effects of midazolam result from an agonist
      action on the γ-aminobutyric acid A (GABAA) receptor throughout the central nervous system.
      Benzodiazepines do not work directly on the GABA receptor, so there is a physiologic ceiling
      effect, which contributes to their safety and low toxicity.

      Although the exact antiemetic mechanisms remain unknown, researchers postulate that midazolam
      works on the chemoreceptor trigger zone by reducing the synthesis, release, and postsynaptic
      dopamine. It remains debatable whether midazolam reduces dopamine directly or blocks the
      reuptake of adenosine leading to an adenosine-mediated reduction of dopamine release.
      Additionally, the binding of midazolam to the GABA benzodiazepine complex may cause
      dopaminergic neuronal activity and the release of 5-hydroxytryptamine. The reduction of PONV
      may also be a secondary effect of the anxiolytic properties of benzodiazepines.

      Despite literature demonstrating the PONV benefits of midazolam in the perioperative period,
      But the timing of administration of this drug is still not well established. As it is known
      that it has half-life of about 1.5 - 2.5 hours and the controversies remain whether to
      administer this drug preoperatively or postoperatively to prevent PONV. So this comparative
      study is designed to know the better time for administration of this drug to prevent PONV and
      to improve patient satisfaction.
    

Intervention name(s): Midazolam injection
Intervention type(s): Drug
Intervention description(s): No premedication will be given to Patients in the group undergoing a standardized anesthesia protocol which include induction with thiopental (5 mg/kg) and fentanyl (1-2 μg/kg). Atracurium will be used as a muscle relaxant. After tracheal intubation, anesthesia will be maintained with isoflurane in a concentration of 0.8%-1.2%. Ventilation will be adjusted to produce normocapnia. At the end of surgery, reversal of residual neuromuscular blockade will be accomplished using i.v. atropine 20 μg/Kg and neostigmine 40 μg/kg.
Intervention MeSH terms: Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention