Peritoneal Lavage Using Saline or Saline With Ondansetron for Pain Control After Laparoscopic Cholecystectomy (PLUSO)

December 8, 2025 updated by: Francisco Aguilar Espinosa, Instituto Mexicano del Seguro Social

Pilot Comparative Study on the Efficacy of Multimodal Management With Peritoneal Lavage Using Saline Solution Versus Saline Solution With Ondansetron in Laparoscopic Cholecystectomy

Brief Summary Background: Laparoscopic cholecystectomy is a common procedure where postoperative pain and nausea/vomiting (PONV) remain significant issues, impairing recovery. Standardized multimodal analgesia (e.g., PROSPECT guidelines) is effective for pain, but PONV incidence stays high. Preliminary evidence suggests that adding ondansetron to the standard intraperitoneal saline lavage could provide additional analgesic and antiemetic benefits by blocking peripheral 5-HT3 receptors at the trauma site.

Objective: This pilot study aims to evaluate if intraperitoneal lavage with saline + 8mg ondansetron reduces the total burden of postoperative pain over the first 24 hours (Area Under the Curve of the Visual Analog Scale, AUC-VAS/24h) compared to saline lavage alone, within a standardized multimodal protocol.

Methods: This is a phase IV, pilot, randomized, controlled, triple-blind clinical trial. 40 adult patients (ASA I-II) undergoing elective laparoscopic cholecystectomy for symptomatic cholelithiasis (Nassar Grade I-II difficulty) will be randomly assigned (1:1) to:

Control Group: 500 ml of 0.9% saline intraperitoneal lavage.

Intervention Group: 500 ml of 0.9% saline + 8 mg ondansetron intraperitoneal lavage.

The lavage is performed for 5 minutes at the end of surgery, followed by complete aspiration. All patients receive a strict multimodal perioperative protocol, including pre-incisional port site infiltration with bupivacaine 0.75%, standardized anesthesia, and postoperative analgesics. The use of intravenous ondansetron is prohibited to avoid confounding.

Primary Outcome: Total postoperative pain burden (AUC-VAS/24h). Secondary Outcomes (Exploratory): PONV incidence; time to first rescue analgesia; rescue analgesic consumption (buprenorphine); postoperative sleep quality (Richards-Campbell Sleep Questionnaire); safety and adverse events.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. Study Rationale and Background Postoperative pain and PONV are prevalent after laparoscopic cholecystectomy, leading to patient discomfort, prolonged hospitalization, and increased resource use. The PROSPECT guidelines recommend a multimodal approach, including intraperitoneal saline lavage, to mitigate pain by diluting irritants and reducing acidosis. However, even with this approach, PONV rates remain high (30-50%).

    Ondansetron, a 5-HT3 antagonist, is a established antiemetic. Emerging evidence indicates a peripheral analgesic mechanism via blocking 5-HT3 receptors on nociceptive neurons, inhibiting neuropeptide release, and potential local anesthetic effects. Administering it intraperitoneally targets the site of surgical trauma. A previous study (Abdelaziz et al., 2021) using 4mg showed promise, but it had a small sample size and was not integrated into a strict, modern multimodal protocol. This pilot study addresses this gap by testing an 8mg dose within a rigorous, standardized PROSPECT-aligned protocol, using the AUC-VAS/24h to comprehensively capture the pain burden.

  2. Overall Study Design and Methodology This is a single-center, prospective, phase IV, randomized, controlled, triple-blind, parallel-group pilot study, designed and reported according to CONSORT guidelines for pilot trials.

    Blinding (Triple):

    Patients are unaware of their assignment.

    Care Providers & Outcome Assessors: Surgeons, anesthesiologists, nurses, and research interns collecting data are all blinded.

    Data Analyst: The statistician performs the initial analysis on coded data (Group A/B) before unblinding.

    Randomization: A computer-generated sequence using permuted blocks (sizes 4 and 6), stratified by sex and ASA status (I vs. II), will allocate patients 1:1. Allocation is concealed using sequentially numbered, opaque, sealed envelopes. A designated "blinding coordination nurse" opens the envelope, prepares the identical-looking study solution, and labels it only with a code (A or B).

  3. Standardization of Procedures A strict, standardized perioperative protocol is mandated for all participants to minimize variability.

    Preoperative:

    Dexamethasone 8mg IV (antiemetic), antibiotic prophylaxis.

    Intraoperative:

    Anesthesia: Standardized induction (Midazolam 0.02-0.03 mg/kg, Fentanyl 2-4 mcg/kg, Propofol 1-2 mg/kg, Cisatracurium 0.15 mg/kg) and maintenance (Sevoflurano 1-1.5 MAC). Multimodal analgesia: Acetaminophen 1g IV and Diclofenac 75mg IV.

    Surgery: Pneumoperitoneum pressure strictly maintained at 10-12 mmHg. Four-port technique with identical placement. Pre-incisional infiltration of all port sites with Bupivacaine 0.75% (up to 20 ml total). Critical view of safety dissection. Active and complete aspiration of pneumoperitoneum at closure.

    Intervention: The assigned solution (500ml) is instilled into the peritoneal cavity for 5 minutes with the patient in a 20° Trendelenburg position, followed by complete aspiration.

    Postoperative:

    Scheduled analgesics: Acetaminophen 1g (every 8 hours) and Diclofenac 75mg IV (every 12 hours).

    Rescue Analgesia: Buprenorphine 75mcg SC is administered only upon patient request AND a pain score ≥50mm on the VAS or ≥6 on the Faces Pain Scale-Revised (FPS-R).

    Rescue Antiemesis: Metoclopramida 10mg IV is permitted for PONV. The use of intravenous ondansetron is prohibited during the entire perioperative period to avoid confounding the intervention's effects.

  4. Objectives and Endpoints as a Pilot Study As a pilot trial, its primary goal is to assess feasibility, refine procedures, and obtain preliminary estimates of effect and variability to power a future definitive trial. The primary outcome, AUC-VAS/24h, integrates pain intensity and duration, providing a robust measure of the "total pain burden." All secondary outcomes (PONV, rescue analgesia consumption, sleep quality) are explicitly exploratory and hypothesis-generating.
  5. Safety and Monitoring The safety of intraperitoneal saline lavage and ondansetron is well-established. The combination presents minimal anticipated risk. All adverse events and postoperative complications will be actively monitored and recorded for the first 24 hours and up to 30 days post-surgery. An interim analysis for safety and efficacy will be conducted after 50% recruitment (n=20). Any serious adverse events will be reported promptly to the Institutional Ethics Committee.
  6. Significance This is the first study to evaluate the combination of standard saline lavage with 8mg of intraperitoneal ondansetron within a rigorously standardized, PROSPECT-aligned, multimodal protocol. Using a triple-blind pilot design and a comprehensive primary endpoint, it will generate high-quality preliminary evidence on this simple, low-cost intervention's efficacy and safety in a Mexican population. The results will determine the feasibility and inform the design of a larger, definitive multicenter randomized controlled trial.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44190
        • General Hospital No. 89 of the Mexican Social Security Institute (IMSS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Eligible participants will be adult patients scheduled for elective laparoscopic cholecystectomy at the study site. To ensure a homogeneous sample appropriate for this pilot trial, strict inclusion and exclusion criteria have been defined.

Inclusion criteria

Patients meeting all the following criteria will be considered for enrollment:

  1. Aged between 18 and 60 years.
  2. American Society of Anesthesiologist (ASA) physical status classification I or II.
  3. Scheduled for elective laparoscopic cholecystectomy due to symptomatic cholelithiasis, resolved choledocholithiasis post-endoscopic retrograde cholangiopancreatography (ERCP), or gallbladder polyp.
  4. Placement of a ¾-inch Penrose drain in the subhepatic cavity as part of the standardized surgical technique, to allow evacuation of residual CO2, residual lavage fluid, and close monitoring for possible postoperative bleeding or bile leakage.
  5. Intraoperative surgical difficulty assessed as Grade I, II or III according to the Nassar scale
  6. Ability to provide written, informed consent

Exclusion Criteria

Patients presenting with any of the following will be excluded:

  1. Confirmed pregnancy or lactation
  2. Intraoperative findings of Nassar Grade IV, suspected gallbladder cancer, scleroatrophic gallbladder, or cirrhosis

5. Use of NSAIDs within 24 hours prior to surgery, or chronic use of NSAIDs, opioids, immunosuppressants, chemotherapy, or anticoagulants.

6. Known allergies to ondansetron, acetaminophen, diclofenac sodium, buprenorphine or tramadol

7. Significant cardiac disease (e.g., heart failure, arrhythmias, pacemaker dependency)

8. Obesity Grade IV (Body Mass Index ≥ 50 kg/m2)

9. History of recurrent vertigo or motion sickness

Elimination Criteria

Patients who meet inclusion criteria but experience the following intraoperative events will be eliminated from the final per-protocol analysis: significant bleeding or bile duct injury requiring re-intervention, conversion to open surgery, or a total operative time exceeding 80 minutes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Saline Lavage Only
Participants in this arm will receive intraoperative peritoneal lavage with 500 mL of 0.9% saline solution for 5 minutes at the end of laparoscopic cholecystectomy. The solution will be fully aspirated before abdominal closure. The solution will remain in the peritoneal cavity for 5 minutes and then be completely aspirated before closure. All participants will also receive standard multimodal analgesia including paracetamol, diclofenac, and local wound infiltration with bupivacaine.
Drug: Saline Intraperitoneal Lavage
At the end of elective laparoscopic cholecystectomy, a peritoneal lavage will be performed using 500 mL of 0.9% saline solution (normal saline). The solution will be maintained in the peritoneal cavity for 5 minutes and then fully aspirated before surgical closure. This intervention serves as the comparator to assess the added effect of ondansetron in the experimental group.
Other Names:
  • normal saline
  • 0.9% Sodium Chloride
  • Saline Solution
Experimental: Saline Lavage With Ondansetron
Participants in this arm will undergo peritoneal lavage with 500 mL of 0.9% saline solution combined with 8 mg of ondansetron, administered intraperitoneally at the end of elective laparoscopic cholecystectomy. The solution will remain in the peritoneal cavity for 5 minutes and then be completely aspirated before closure. All participants will also receive standard multimodal analgesia including paracetamol, diclofenac, and local wound infiltration with bupivacaine.
Drug: Ondansetron Intraperitoneal Lavage
A single dose of 8 mg of ondansetron diluted in 500 mL of 0.9% saline solution will be administered as an intraperitoneal lavage at the end of elective laparoscopic cholecystectomy. The solution will remain in the abdominal cavity for 5 minutes and then be fully aspirated before surgical closure. This intervention aims to evaluate the local analgesic and antiemetic effects of ondansetron when used via the peritoneal route.
Other Names:
  • Zofran
  • 0.9% Sodium Chloride
  • Ondansetron

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Total Pain Burden as Measured by the Area Under the Curve (AUC) of Visual Analog Scale (VAS) Scores Over the First 24 Postoperative Hours
Time Frame: 0, 2, 6, 12, and 24 hours postoperatively
The primary outcome is the total burden of postoperative pain, quantified as the Area Under the Curve (AUC) of serial Visual Analog Scale (VAS) scores measured at 0, 2, 6, 12, and 24 hours after surgery. The AUC is calculated using the trapezoidal rule, which integrates both the intensity and duration of pain into a single composite measure (units: mm*hour). This provides a more comprehensive assessment of the patient's pain experience over the critical first postoperative day than isolated time-point measurements. A lower AUC indicates superior pain control.
0, 2, 6, 12, and 24 hours postoperatively

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Postoperative Nausea and Vomiting (PONV)
Time Frame: 0, 2, 6, 12, and 24 hours postoperatively
The presence and number of postoperative nausea and vomiting (PONV)
0, 2, 6, 12, and 24 hours postoperatively
Use of Rescue Analgesia Within 24 Hours Postoperatively
Time Frame: 0 to 24 hours postoperatively
The proportion of patients requiring rescue analgesia (buprenorphine 75 mcg subcutaneously) will be recorded. The time to first dose and the total number of doses will also be analyzed.
0 to 24 hours postoperatively
Postoperative Sleep Quality Assessed by the Richards-Campbell Sleep Questionnaire
Time Frame: Night of surgery to morning after surgery
Sleep quality will be evaluated using the Richards-Campbell Sleep Questionnaire, which includes six visual analog items rated from 0 to 100. A higher score indicates better sleep. The total average score will be calculated for each participant.
Night of surgery to morning after surgery
Incidence of Adverse Events Possibly Related to Intraperitoneal Ondansetron
Time Frame: 0 to 24 hours postoperatively
Any unexpected clinical signs, symptoms, or laboratory abnormalities that could be associated with the intraperitoneal use of ondansetron will be recorded and evaluated by the study team.
0 to 24 hours postoperatively

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Postoperative Nausea and Vomiting (PONV) within 24 hours after surgery
Time Frame: Evaluations will be conducted at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours postoperatively.
This outcome measures the incidence of postoperative nausea and vomiting (PONV) within the first 24 hours following laparoscopic cholecystectomy. Nausea and vomiting will be assessed using a standardized scoring system, and the frequency of PONV will be compared between the two intervention groups (ondansetron with bicarbonate versus ondansetron with saline). The goal is to determine if the formulation with bicarbonate is more effective in reducing PONV compared to the saline formulation
Evaluations will be conducted at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours postoperatively.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto Mexicano del Seguro Social

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Centro de investigación y asistencia en tecnología y diseño del estado de Jalisco A,C

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Francisco Aguilar Espinosa, Dr., Instituto Mexicano del Seguro Social

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 5, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 8, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • F-CNIC-2024-097 (Instituto Mexicano del Seguro Social (IMSS))
  • R-2025-785-080 (Other Identifier: Instituto Mexicano del Seguro Social (IMSS))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The decision to share individual participant data (IPD) has not yet been finalized. Data sharing will depend on the outcomes of the pilot study, ethical considerations, and institutional policies. Any future data sharing will ensure patient confidentiality and comply with regulatory standards.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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