Intraperitoneal Infusion of Analgesic for Postoperative Pain Management (ON-Q)

The Impact of the Continuous Infusion of Intraperitoneal Analgesics on Postoperative Pain After Minimally Invasive Hysterectomy: a Randomized Controlled Trial

The study is a prospective, double-blinded, placebo-controlled multi-center trial to measure if postoperative pain and the amount of narcotics used are reduced by a clinically significant amount in women undergoing minimally invasive hysterectomy receiving a continuous infusion of intraperitoneal (IP) local anesthetic (LA) or a continuous infusion of LA combined with an NSAID compared with a control group who receives only 0.9% normal saline.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Hysterectomy; Narcotic Use; Gynecologic Surgical Procedures
• Intervention / Treatment: Drug: Ropivacaine Infusion from ON-Q Pump; Drug: Ropivacaine + Ketorolac Infusion from ON-Q Pump; Drug: Normal Saline Infusion from ON-Q Pump

Detailed Description

• Any patient desiring minimally invasive hysterectomy will be contacted by a study team member during their visit to the MIGS (minimally invasive gynecologic surgery) clinic. The risks and benefits of participation will be explained to them. If they choose to participate they will sign the consent form at that time or if they need more time to consider participation they will sign later. They will then complete the health-related quality of life (HrQoL) questionnaire UFS-QOL* before surgery.
• Computer-generated randomization will be used to randomize patients between 3 groups:
• Group A: receiving a continuous infusion of intraperitoneal local anesthetic (LA) during 72 hours
• Group B: receiving a continuous infusion of intraperitoneal LA combined with an NSAID during 72 hours
• Group C: receiving a continuous infusion of intraperitoneal placebo during 72 hours.
• Study participants will then undergo a minimally invasive hysterectomy by one of the highly experienced minimally invasive gynecologists using a standard technique. At the conclusion of the procedure, all women will have an infusion catheter attached to an ON-Q pump inserted percutaneously into the pelvis under direct laparoscopic vision. The catheter tip will be placed in the peritoneal cavity at the vaginal vault. In order to ensure patency of the catheter tubing, a 10 mL bolus of assigned medication will be given. The ON-Q pump infusion will then provide 540 mL of assigned medication for a total of 72 hours following surgery.
• Surgical variables (length of surgery, estimated blood loss, type of analgesia and anesthesia used, concomitant procedures, uterine weight, ASA, and intraoperative complications - organ injury (bladder, bowel, vaginal laceration), EBL > 1000 cc, conversion to laparotomy, transfusion) will be recorded on a data collection sheet.
• Additional analgesia will be administered by the nursing staff in the PACU at the patient's request. The total dose of analgesia over the 72 postoperative hours will be calculated for each woman (e.g. each of the following was considered to be one dose; 1 g of paracetamol, 50 mg diclofenac, 400 mg ibuprofen, 50 mg tramadol). The total morphine equivalents per patient will also be recorded.
• All medication administered for pain as well as VAS pain scores at 1, 2, 4, 6, 24, 48, and 72 hours postoperatively will be recorded.
• Subjects will be discharged when clinically appropriate and according to our usual hospital procedure, which is usually same day discharge. Subjects staying in hospital for less than 72 hours will be given verbal and written instructions on catheter removal.
• The subjects will be given a post-operative pain diary to fill out during their 2 week recovery period including pain scores and amount of pain medication used. This diary will be collected at their first post-operative visit at around 2 weeks postoperatively. Subjects will be asked to complete the EQ-5D again during this visit. Postoperative complications will also be recorded (ICU-admission, reoperation, transfusion, DVT/PE, readmission, bowel obstruction/ileus, incision seroma/cellulitis/hematoma/separation/hernia, and cuff cellulitis/abscess/dehiscence/granulation tissue).
• Hospital (operative and pathology reports) and clinical (clinical visit notes) reports will be reviewed to compare baseline demographics, past surgical history, past medical history, comorbidities, and complications between groups.
• Pumps and syringes will be filled with study drugs depending on the assigned group to a max of 540 mL for pumps and a max of 10 mL for syringes:
• Group A: receiving a continuous infusion of intraperitoneal local anesthetic (LA) during 72 hours: 10 mL bolus of 0.2% Ropivacaine + 540 mL of 0.2% Ropivacaine at 8 mL/hour infusion
• Group B: receiving a continuous infusion of intraperitoneal LA combined with an NSAID during 72 hours: 10 mL bolus of 0.2% Ropivacaine combined with 30mg/550mL toradol + 540 mL of 0.2% Ropivacaine combined with 30mg/550mL toradol at 8 mL/hour infusion
• Group C: receiving a continuous infusion of intraperitoneal placebo during 72 hours: 10 mL bolus of 0.9% normal saline + 540 mL of 0.9% normal saline at 8 mL/hour infusion
• The IDS research pharmacist will fill the pumps for use and a member of the research team will transport the filled pumps to the hospital for the surgeries.
• Statistical Analysis: Pre-operative variables such as patient demographic and clinical information (medical and surgical history) will be recorded and compared as well as intra-operative variables such as surgical modality, length of surgery, estimated blood loss, concomitant procedures, uterine weight, ASA, and complications. Before and after their surgery, patients will complete a questionnaire regarding quality of life and pain. To combine the results of both sites, REDCap will be used to securely share de-identified data. These outcome variables will be analyzed by calculating the unadjusted and adjusted means and 95% confidence intervals using simple and multiple linear regressions.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Radwa Aly; Phone Number: 202 677 6209; Email: raly@mfa.gwu.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Medstar Washington Hospital Center
      • Contact: James Robinson, MD; Phone Number: 202-877-0526; Email: james.k.robinson@medstar.net
      • Principal Investigator: James Robinson, MD
    • Washington, District of Columbia, United States, 20037
      • Recruiting
      • The GW Medical Faculty Associates
      • Contact: Jennifer Keller, MD; Phone Number: 202-741-2524; Email: jkeller@mfa.gwu.edu
      • Principal Investigator: Jennifer Keller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Hysterectomy planned for a benign gynecologic reason (no evidence of, or concern for, malignancy in the cervix, uterus, tubes or ovaries. Benign gynecologic reasons to have a hysterectomy include fibroids, abnormal uterine bleeding, endometriosis, and pelvic pain.)
• Patient is scheduled to have surgery with a fellowship trained minimally invasive gynecologic surgeons at one of the study sites.
• Patient is planned for a robotic assisted total laparoscopic hysterectomy (RA-TLH) or a total laparoscopic hysterectomy (TLH).
• Patient is capable of informed consent.
• Patient is capable of completing the questionnaires.

Exclusion Criteria:

• Concern for malignancy
• The procedure is scheduled outside MIGS department.
• Allergy to any study related medication (i.e. Ketorolac and Ropivacaine)
• Patient is enrolled in another pain management study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ropivacaine; Subjects will receive a continuous intraperitoneal infusion of ropivacaine	Drug: Ropivacaine Infusion from ON-Q Pump; Infusion of 0.2% ropivacaine at 8 mL/hour for 72 hours; Other Names: Naropin
Experimental: Ropivacaine + Ketorolac; Subjects will receive a continuous intraperitoneal infusion of ropivacaine + ketorolac	Drug: Ropivacaine + Ketorolac Infusion from ON-Q Pump; Infusion of 0.2% ropivacaine + 30 mg ketorolac at 8 mL/hour for 72 hours; Other Names: Naropin; Toradol
Placebo Comparator: Normal Saline; Subjects will receive a continuous intraperitoneal infusion of normal saline	Drug: Normal Saline Infusion from ON-Q Pump; Infusion of 0.9% normal saline at 8 mL/hour for 72 hours; Other Names: Saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Level 1 Hour Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	1 hour postoperative
Pain Level 2 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	2 hours postoperative
Pain Level 4 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	4 hours postoperative
Pain Level 6 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	6 hours postoperative
Pain Level 24 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	24 hours postoperative
Pain Level 48 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	48 hours postoperative
Pain Level 72 Hours Postoperative	Rating from 0 "No pain sensation" to 10 "most intense pain imaginable"	72 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total dose of analgesics taken over the 72 postoperative hours	Each of the following was considered to be one dose: 1 g of paracetamol, 50 mg diclofenac, 400 mg ibuprofen, 50 mg tramadol	Within 72 hours postoperative

Collaborators and Investigators

• Sponsor: Ying Liu
• Collaborators: Avanos Medical
• Investigators: Principal Investigator: Jennifer Keller, MD, Physician

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 16, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Intraperitoneal; Ropivacaine; Pain Pump; Ketorolac Tromethamine
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Anesthetics, Local; Ketorolac; Ropivacaine
• Other Study ID Numbers: 180423

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes