Role of Opioids in Epidural Solutions

The Role of Epidural Opioids in Pain Management After Abdominal Surgery in Adult Patients - a Randomized Clinical Trial

It is unclear whether addition of opioids to epidural solutions for postoperative analgesia is beneficial. In this multicenter randomized double-blinded trial, we aim to test the primary hypothesis that epidural solutions containing only bupivacaine are as effective as solutions containing both bupivacaine and fentanyl in promoting analgesia in patients recovering from open abdominal surgery. We also aim to assess the incidence of epidural-induced hypotension, the difference in patient-reported opioid side-effects between the two groups. If we demonstrate no clinically important difference between the two interventions, clinicians will be able to substantially reduce the amount of opioids patients receive during their postoperative recovery, and potentially decrease the associated high incidence of opioid adverse effects in post-surgical patients.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Bupivacaine; Drug: Fentanyl

• Study Type: Interventional
• Enrollment (Anticipated): 286
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Barak Cohen, MD; Phone Number: +972-52-7360368; Email: barakc@tlvmc.gov.il
• Study Contact Backup: Name: Orr Goren, MD; Phone Number: +972-52-7360330; Email: goren.orr@gmail.com

Study Locations

• Israel
  • Tel-Aviv, Israel
    • Recruiting
    • Division of Anesthesia, Pain and Critical Care, Tel-Aviv Sourasky Medical Center
    • Contact: Barak Cohen, MD; Phone Number: +972-52-7360368; Email: barakc@tlvmc.gov.il
    • Contact: Orr Goren, MD; Phone Number: +972-52-7360330; Email: goren.orr@gmail.com
    • Principal Investigator: Barak Cohen, MD
    • Sub-Investigator: Orr Goren, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent
2. 18-85 years old
3. Undergoing open abdominal surgery (including colorectal, intestinal, gastric, pancreatic, hepatobiliary, urological, or gynecological surgery)
4. For which a clinical decision has been made to provide epidural analgesia preoperatively and extending to the post-operative period
5. Anticipated hospitalization of at least 2 nights

Exclusion Criteria:

1. Known allergy to bupivacaine or fentanyl
2. Chronic liver disease, defined as cirrhosis, portal hypertension, or variceal bleeding
3. Patients under chronic alpha-blocking agents for hypertension
4. Clinical contraindications to epidural introduction, as judged by the anesthesia provider (thrombocytopenia, un-interrupted anticoagulation, clinically-significant atrio-ventricular conduction block, etc.)
5. Pregnant women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bupivacaine; Epidural solution containing 0.1% bupivaacaine in normal saline	Drug: Bupivacaine; epidural solution containing bupivacaine 0.1% in normal saline; Other Names: Marcaine
Experimental: Bupivacaine + Fentanyl; Epidural solution containing 0.1% bupivacaine and 3 mcg/ml of fentanyl in normal saline	Drug: Bupivacaine; epidural solution containing bupivacaine 0.1% in normal saline; Other Names: Marcaine; Drug: Fentanyl; Epidural solution containing fentanyl 3 mcg/ml (in addition to bupivacaine) in normal saline; Other Names: Beatryl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative analgesia	A joint outcome of the difference in average pain score and a ratio of opioid consumption (in mg morphine equivalents) between the 2 study groups	48 postoperative hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant postoperative hypotension	Number of participants experiencing a composite of use of IV fluid boluses prescribed for hemodynamic support; sympathomimetic drugs administration; and holding or early discontinuation of the epidural infusion in order to recover blood pressure.	48 postoperative hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of gastrointestinal function	Time to first postoperative bowel movement	Throughout the postoperative hospital stay, up to 30 days
Opioid-related side effects	A composite of opioid-related side-effects as measured by the Opioid-Related Symptom Distress Scale (OR-SDS) questionnaire (higher scores represent more side-effects and related distress, scores are given on multiple dimensions)	48 postoperative hours

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Israel Society of Anesthesiologists

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: January 16, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics, Local; Fentanyl; Bupivacaine
• Other Study ID Numbers: 0489-19-TLV

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