Midazolam Versus Dexamethasone-ondansetron in Preventing Postoperative Nausea-vomiting for Laparoscopic Surgeries

A Comparison of Midazolam Versus Dexamethasone-ondansetron in Preventing Postoperative Nausea-vomiting in High Risk Patients Undergoing Laparoscopic Surgeries

Postoperative nausea and vomiting(PONV) affects 11 to 60 % of patients undergoing surgery and is a major cause of postoperative morbidity. Risk factors include female gender, non smokers, postoperative use of opioids and a past history of PONV. The simplified Apfel risk score is used to identify patients at risk for PONV. PONV prophylaxis is provided intraoperatively to patients with 2 or more risk factors. In spite of numerous drugs available, control of PONV remains a difficult task. Midazolam is a commonly used drug perioperatively for its anxiolytic and sedative properties. It decreases analgesic requirement and has also been found to have an antiemetic effect. This present study is designed to compare the prophylactic use of iv midazolam with a commonly used combination of dexamethasone-ondansetron in high risk patients (as defined by the modified Apfel score) undergoing laparoscopic surgeries.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone, ondansetron; Drug: Normal saline, Midazolam

Detailed Description

After Institutional Ethical Committee approval and written informed consent, 120 adult patients will be recruited for the study if they satisfy the inclusion and exclusion criteria as mentioned later. Consent will be obtained from the patients themselves. Standard protocol for administration of anaesthesia will be followed in all patients which is briefly described. All patients will receive general anaesthesia and will be induced with Propofol titrated to effect. Intraoperatively, isoflurane will be used as maintenance agent and vecuronium or atracurium as non depolarizing muscle relaxant. For analgesia, patients will receive intraoperative fentanyl.

For the purpose of the study, patients will be randomized into two groups depending upon a computer generated randomized sheet. Group A will receive 8mg of dexamethasone i.v. after anaesthesia induction and 4 mg of ondansetron i.v. 30 minutes prior to the end of surgery. Patients in Group B will be administered 2 mg of midazolam i.v. 30 minutes prior to the end of surgery. Time to achieve Post anaesthesia discharge score( PADSS) of ≥9 will be noted. Patients will be asked to report any incidence of nausea, retching or vomiting for the first 24 hours after surgery. The incidence of PONV and the amount of rescue antiemetic received will be noted at 2 hours and at 24 hours postoperatively. PONV will be scored based on the PONV Impact Scale score questionnaire (mentioned in the proforma)12. Rescue antiemetics will be administered in case the patient complains of PONV in accordance with American society of anesthesiologists (ASA) guidelines. The first line of rescue in Group A will be 10 mg of iv metaclopromide. Antihistaminics will be the second line of rescue antiemetic. In group B the first line of antiemetic will be 4 mg of ondansetron i.v. 10 mg of iv metaclopromide will be second line of rescue drug.

Study period : It is estimated that the study will be completed within one year Sample size Assuming a reduction in 45 % in the incidence of PONV, with α error of 0.05 and β of 0.02, we would require 60 patients in each group i.e. a total of 120 patients.13 Intervention: For administration of PONV prophylaxis, patients will be randomized into two groups depending upon a computer generated randomized sheet. Group A will receive 8mg of dexamethasone i.v. after anaesthesia induction and 4 mg of ondansetron i.v. 30 minutes prior to the end of surgery. Patients in Group B will be administered 2 mg of midazolam i.v. 30 minutes prior to the end of surgery.

Monitoring and assessment: Patients will be monitored 24 hours post operatively. Any complaints of nausea and/vomiting will be noted and rescue antiemetic will be administered as per the guidelines

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients more than 18 years of age
• Patients belonging to ASA-PS (American society of anesthesiologists Physical status) 1 or 2
• Patients with 2 or more risk factors for developing PONV undergoing laparoscopic surgeries

Exclusion Criteria:

• Anticipated difficult airway
• Obesity (body mass index >30 kg.m2),
• Pregnancy
• Patients with ASA - PS more than 2
• Consumption of an agent with anti-emetic properties within 24 h prior to commencement of the study.
• Known hypersensitivity to midazolam, ondansetron or dexamethasone
• Patients not giving consent.
• Patients with psychiatric illness or mental retardation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Dexamethasone-ondansetron	Drug: Dexamethasone, ondansetron; 8mg of dexamethasone i.v. after anaesthesia induction and 4 mg of ondansetron i.v. 30 minutes prior to the end of surgery.
Experimental: Group B; Midazolam	Drug: Normal saline, Midazolam; 2 cc normal saline i.v. after anaesthesia induction.2 mg of injection midazolam intravenous 30 minutes prior to the end of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative nausea vomiting	the incidence of postoperative nausea and/or vomiting within first 24 hours postoperatively	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue antiemetic	The amount of antiemetic used within the first 24 hours.	24 hours
Time to achieve PADSS>9	Time taken to achieve a Post anaesthesia discharge score of ≥9	1 hour
Incidence of PON, POV, PONV at 2 hours and PON and POV at 24		24 hours

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Kelika Prakash, DM, Institute of liver and Biliary Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: June 2, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Postoperative Nausea and Vomiting; Ondansetron; Dexamethasone; Midazolam; Laparoscopy; High risk
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antipruritics; Dexamethasone; Midazolam; Ondansetron
• Other Study ID Numbers: PONV prophylaxis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No