Impact of Timing of Midazolam Administration on Incidence of Postoperative Nausea and Vomiting

Impact of Timing of Midazolam Administration on Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Gynecological Surgery; a Randomized Double-blinded Controlled Study

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.

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.

Inclusion Criteria:

• Female patients
• aged twenty to sixty years old
• The American Society of Anesthesiologists (ASA) physical status classification grade I or II
• Scheduled for laparoscopic gynecological surgeries under general anesthesia.

Exclusion Criteria:

• Patients who have gastrointestinal disorders,
• histories of PONV after a previous surgery,
• Renal or liver dysfunction,
• history of motion sickness,
• Have received any opioid, steroid, or antiemetic medication in the 24hs before surgery, and
• Pregnant or menstruating women.