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

Instituto Mexicano del Seguro Social

Status and phase: Active, not recruiting; Phase 4

Conditions: Laparoscopic Cholecystectomy; Postoperative Nausea and Vomiting; Postoperative Pain Management; Ondansetron

Treatments: Drug: Ondansetron Intraperitoneal Lavage; Drug: Saline Intraperitoneal Lavage

Study type: Interventional

Funder types: Other

Identifiers

NCT06632184

F-CNIC-2024-097

R-2025-785-080 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups

Saline Lavage Only

Active Comparator group

Description:

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.

Treatment:

Drug: Saline Intraperitoneal Lavage

Saline Lavage With Ondansetron

Experimental group

Description:

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.

Treatment:

Drug: Ondansetron Intraperitoneal Lavage