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

NCT ID: NCT05057767

Last Updated: 2022-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-10
• Study Completion Date: 2022-07-31

Brief 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.

Conditions

Postoperative Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Pre-induction Group (I)

will receive intravenous midazolam premedication 2mg in a volume of 3 ml, 15 minutes before induction of anesthesia

Group Type: EXPERIMENTAL

Midazolam injection

Intervention Type: DRUG

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.

Pre-extubation Group (II)

will receive intravenous midazolam 2mg in a volume of 3 ml 30 minutes before extubation at the end of surgery

Group Type: EXPERIMENTAL

Midazolam injection

Intervention Type: DRUG

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.

Control Group (III)

will receive 3 ml normal saline 15 minutes before induction of anesthesia plus 3 ml normal saline 30 minutes before extubation at the end of surgery.

Group Type: PLACEBO_COMPARATOR

Midazolam injection

Intervention Type: DRUG

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.

Interventions

Midazolam injection

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 Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Benha University

OTHER

Sponsor Role: lead

Responsible Party

Samar Rafik Mohamed Amin

lecturer of anesthesia and surgical ICU

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Samar Rafik Mohamed Amin

Banhā, Qalyubia Governorate, Egypt

Countries

Egypt

Other Identifiers

RC-12-8-2021

Identifier Type: -

Identifier Source: org_study_id