Comparative Efficacy of Dexamethasone - Ondansetron Versus Dexamethasone - Haloperidol in Reducing PONV

Comparative Efficacy of Dexamethasone - Ondansetron Versus Dexamethasone - Haloperidol in Reducing Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy: A Randomized Controlled Trial

Nausea and vomiting following laparoscopic cholecystectomy remain common, with occurrence rates of 40-70% during the initial 24 hours post-operation. The underlying mechanisms of postoperative nausea and vomiting engage five distinct neurotransmitter receptors. Consequently, employing a combination of antiemetics from diverse classes that target various receptors for effective prevention is advised. Ondansetron's antiemetic properties derive from its ability to inhibit serotonin receptors, whereas Haloperidol targets dopamine receptors, and Dexamethasone reduces prostaglandin production.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Cholecystectomy
• Intervention / Treatment: Drug: Ondansetron; Drug: Haloperidol

Detailed Description

Postoperative nausea and vomiting (PONV) are also known as the little problem interpreted as a seemingly less significant complication but lead to increased morbidity, longer hospital stays, increased medical costs, and diminished patient satisfaction with healthcare services. These symptoms are reported more frequently than postoperative pain, making its prevention as important as postoperative pain management. In laparoscopic cholecystectomy, the occurrence of PONV can range from 40 - 70%, which is higher than the 33 - 49% observed in other types of surgeries under general anesthesia within the first 24 hours post-procedure. The mechanism of PONV is complex, involving multiple neurotransmitters. Targeted neurotransmitter receptors in the action of antiemetic drugs include muscarinic-1-acetylcholine (M1), dopamine-2 (D2), histamine-1 (H1), 5-Hydroxytryptamine-3-serotonin (5HT3), and neurokinin1-substance P (NK1) receptors. Based on this, the prevention of postoperative nausea and vomiting is recommended using a combination of various groups of antiemetics that work on different receptors. Studies have shown that combining different antiemetic classes is more effective than using a single agent. A meta-analysis study stated that dexamethasone, ondansetron, and droperidol are the most used types of antiemetics alone or in combination. Dexamethasone with a 5HT3 antagonist such as ondansetron is the most used antiemetic combination. Another viable option includes dexamethasone with Butypherone group drugs, such as droperidol, which acts as a D2 antagonist. However, droperidol was subject to FDA black box warnings in 2003 due to its association with arrhythmias caused by QT interval prolongation. Subsequent research has suggested haloperidol, another Butypherone group drug, as a safer alternative to droperidol.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • West Java
    • Bandung, West Java, Indonesia, 40161
      • Hasan Sadikin General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing laparoscopic cholecystectomy
• aged 18 - 65 years
• ASA physical status 1 and 2
• Apfel score ≥2

Exclusion Criteria:

• a history of allergies
• routine use of antipsychotic drugs, steroids, antihistamines, and antiemetics before surgery
• cardiac rhythm disorders
• elevated liver enzyme levels (SGOT/SGPT) ≥5 times upper limit normal
• BMI ≥35 kg/m2

Dropout Criteria:

• if they experienced hypotension, defined as systolic blood pressure below 90 mmHg or mean arterial pressure (MAP) below 60 mmHg, or a decrease in systolic blood pressure and/or MAP greater than 20% from baseline for a duration exceeding two minutes, surgical procedures extending >3 hours, and any alterations in the planned surgical intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ondansetron; 19 participants in group O received 4 mg of ondansetron intravenously.	Drug: Ondansetron; 4 mg of ondansetron intravenously
Active Comparator: Haloperidol; 19 participants in group H received 1 mg of Haloperidol intravenously.	Drug: Haloperidol; 1 mg of Haloperidol intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea and Vomiting Score	Score 0 (No nausea, no vomiting); Score 1 (Nausea present, no vomiting); Score 2 (Nausea present, vomiting present); Score 3 (Vomiting >2 episodes in 30 minutes)	24 hours post-operation

Collaborators and Investigators

• Sponsor: Universitas Padjadjaran
• Investigators: Principal Investigator: Dian Mardiani, M.D, Faculty of Medicine Universitas Padjadjaran Bandung

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Anti-Dyskinesia Agents; Haloperidol; Haloperidol decanoate; Ondansetron
• Other Study ID Numbers: AN-202405.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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