Pain Control and Quality of Recovery After Intravenous Methadone Versus Intrathecal Morphine in Major Abdominal Surgery

April 30, 2024 updated by: Priyanka Singla, University of Virginia

Moderate to severe postoperative pain is relatively common after major abdominal surgery. It is associated with less than optimal surgical experience, poor quality of recovery, and the development of persistent postsurgical pain. Opioids remain a significant component of postoperative pain management. Side effects of opioids used for the treatment of postoperative pain include constipation, pruritus, nausea, and vomiting. Enhanced recovery after surgery (ERAS) protocols involve the utilization of multimodal analgesia. Analgesic techniques used include epidural analgesia, nerve blocks, and Intrathecal (IT) administration of morph ne. IT morphine reduces the postoperative opioid requirement for 18-24 hours after major abdominal surgery and reduces hospital length of stay (LOS) compared with epidural analgesia. A significant number of patients who receive IT morphine still experience moderate to severe postoperative p in. Additionally, many patients refuse the invasive procedure or cannot receive IT morphine due to procedure contraindications, thrombocytopenia, and/or coagulopathy.

Intravenous (IV) methadone has a long analgesic half-life and has N-methyl-D-aspartate (NMDA) receptor antagonist and serotonin and norepinephrine reuptake inhibitor (SNRI) properties. It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in patients who underwent orthopedic, abdominal, complex spine, and cardiac surg ry. Similar findings have been shown in obstetric patients who underwent cesarean delivery under general anesthesia as well as patients who underwent gynecologic surgery. IV methadone has, however, never been compared with IT morphine as a postoperative analgesic.

The hypothesis is that intravenous (IV) methadone is non-inferior to IT morphine in patients who undergo major abdominal surg ry. It offers the advantage of being a noninvasive analgesic modality that may contribute to decreasing opioid consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving the quality of recovery after surgery.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Moderate to severe postoperative pain is relatively common after major abdominal surgery. It is associated with less than optimal surgical experience, poor quality of recovery, and the development of persistent postsurgical pain. Opioids remain a significant component of postoperative pain management. Side effects of opioids used for the treatment of postoperative pain include constipation, pruritus, nausea, and vomiting. Enhanced recovery after surgery (ERAS) protocols involve the utilization of multimodal analgesia. Analgesic techniques used include epidural analgesia, nerve blocks, and Intrathecal (IT) administration of morph ne. IT morphine reduces the postoperative opioid requirement for 18-24 hours after major abdominal surgery and reduces hospital length of stay (LOS) compared with epidural analgesia. A significant number of patients who receive IT morphine still experience moderate to severe postoperative p in. Additionally, many patients refuse the invasive procedure or cannot receive IT morphine due to procedure contraindications, thrombocytopenia, and/or coagulopathy.

Intravenous (IV) methadone has a long analgesic half-life and has N-methyl-D-aspartate (NMDA) receptor antagonist and serotonin and norepinephrine reuptake inhibitor (SNRI) properties. It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in patients who underwent orthopedic, abdominal, complex spine, and cardiac surg ry. Similar findings have been shown in obstetric patients who underwent cesarean delivery under general anesthesia as well as patients who underwent gynecologic surgery. IV methadone has, however, never been compared with IT morphine as a postoperative analgesic.

The hypothesis is that intravenous (IV) methadone is non-inferior to IT morphine in patients who undergo major abdominal surg ry. It offers the advantage of being a noninvasive analgesic modality that may contribute to decreasing opioid consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving the quality of recovery after surgery.

Study Type

Interventional

Enrollment (Estimated)

218

Phase

  • Early Phase 1

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 Backup

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908-0710
        • University of Virginia

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients with an American Society of Anesthesiologists (ASA) physiological status I-III
  • Undergoing laparotomy with midline incision
  • Body mass index (BMI) between 18.5 and 45
  • Ability to understand and read English
  • Willingness and ability to comply with scheduled visits and study procedures

Exclusion Criteria:

  • Not able or unwilling to sign consent
  • Patients undergoing ambulatory surgery or anticipated to be discharged sooner than 24 hours after surgery
  • Patients with chronic pain, requiring daily opioid use at the time of surgery, milligram morphine equivalent (MME) >60 as FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin.
  • Pregnancy
  • Patients requiring emergent surgery
  • Any contraindication to neuraxial anesthesia (coagulopathy, localized infection at the site of injection, pre-existing spinal pathology, or peripheral neuropathy)
  • length of the QT interval (QTc) >450 on the most recent preoperative electrocardiogram (EKG)
  • Prior spinal fusion
  • Active or Prior Substance Use Disorder, undergoing active treatment with Medication of Opioid Use Disorder including methadone (once daily dosing), Buprenorphine (any formulation) and Naltrexone

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: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intrathecal Morphine
250 mcg Intrathecal Injection prior to incision
Drug: Morphine
Intrathecal Morphine
Other Names:
  • Intravenous Morphine
Experimental: Intravenous Methadone
0.2 mg / kg Intravenous delivery prior to incision
Drug: Methadone
Intravenous Methadone
Other Names:
  • Intrathecal Methadone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Recovery 15 score
Time Frame: 24 hours, 48 hours, 72 hours
The Quality of Recovery-15 (QoR-15) scale is a patient-reported outcome measurement of the quality of recovery after surgery and anesthesia. The scale ranges from 0 to 150, with a higher score indicating a better quality of recovery. A score of 0 indicates extremely poor quality of recovery, while a score of 150 indicates excellent quality of recovery. The QoR-15 score can be classified into four severity classes: excellent, good, moderate, and poor recovery.
24 hours, 48 hours, 72 hours
Overall Benefits of Analgesic Score
Time Frame: 24 hours, 48 hours, 72 hours

The overall benefit of analgesic score (OBAS) is a daily survey that assesses a patient's satisfaction with analgesia, pain intensity, and adverse effects.

To compute score, add all scores in items 1-7. Range: [0 - 28]. A low score indicates high benefit

  1. Rate your current pain at rest on a scale between 0=minimal pain and 4=maximum imaginable pain
  2. Grade any distress and bother from vomiting in the past 24 hours (0=not at all to 4=very much)
  3. Grade any distress and bother from itching in the past 24 hours (0=not at all to 4=very much)
  4. Grade any distress and bother from sweating in the past 24 hours (0=not at all to 4=very much)
  5. Grade any distress and bother from freezing in the past 24 hours (0=not at all to 4=very much)
  6. Grade any distress and bother from dizziness in the past 24 hours (0=not at all to 4=very much)
  7. How satisfied are you with your pain treatment during the past 24 hours (0=not at all to 4= very much)
24 hours, 48 hours, 72 hours
morphine milligram equivalent
Time Frame: 24 hours, 48 hours, 72 hours
morphine milligram equivalent is a measurement of a given analgesic effect standardized to a milligram of morphine. In other words agent X has the same effect as Y milligrams of morphine.
24 hours, 48 hours, 72 hours
Verbal Rating Scale (VRS) pain scores
Time Frame: 24 hours, 48 hours, 72 hours

Verbal Rating Scale (VRS) pain scores use common words to grade pain intensity, such as "mild", "severe", "none", "moderate", or "very severe". The scale can have anywhere from four to 15 descriptors. For example, one scale uses five descriptors: "mild", "distressing", "horrible", "excruciating", and "discomforting". Another scale uses the following descriptors: "very severe", "never", "rarely", "sometimes", "often", "always", "poor", "fair", "good", "very good", "excellent", "not at all", "a little bit", "moderately", "quite a bit", and "extremely".

Here are some examples of how a VRS scale might work:

0: Relaxed and comfortable 1-3: Mild discomfort 4-6: Moderate pain 7-10: Severe discomfort or pain 0-0: No pain 6-8: Moderate pain 9-10: Severe pain
24 hours, 48 hours, 72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
McGill Pain questionnaire score
Time Frame: 42 days, 92 days

The McGill Pain Questionnaire (MPQ), also known as the McGill Pain Index, is a self-report questionnaire that helps patients describe the quality and intensity of their pain that assesses three components of pain experience: Sensory intensity, Emotional impact, and Cognitive evaluation of pain.

The MPQ consists of 20 categories of verbal descriptors, 78 pain-related descriptors, and six words for current pain intensity. The descriptors fall into four major groups:

Sensory: 1 to 10 Affective: 11 to 15 Evaluative: 16 Miscellaneous: 17 to 20 Each descriptor has a rank value based on its position in the word set. The sum of the rank values is the pain rating index (PRI). The maximum pain score is 78, and the higher the score, the greater the pain.

The MPQ is valid, reliable, and sensitive for measuring cancer pain.
42 days, 92 days
Verbal Rating Scale (VRS) pain scores
Time Frame: 42 days, 92 days
Verbal Rating Scale (VRS) pain scores use common words to grade pain intensity, such as "mild", "severe", "none", "moderate", or "very severe". The scale can have anywhere from four to 15 descriptors. For example, one scale uses five descriptors: "mild", "distressing", "horrible", "excruciating", and "discomforting". Another scale uses the following descriptors: "very severe", "never", "rarely", "sometimes", "often", "always", "poor", "fair", "good", "very good", "excellent", "not at all", "a little bit", "moderately", "quite a bit", and "extremely".
42 days, 92 days

Collaborators and Investigators

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

Sponsor

University of Virginia

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 (Estimated)

May 12, 2024

Primary Completion (Estimated)

May 11, 2026

Study Completion (Estimated)

May 11, 2026

Study Registration Dates

First Submitted

April 23, 2024

First Submitted That Met QC Criteria

April 23, 2024

First Posted (Actual)

April 29, 2024

Study Record Updates

Last Update Posted (Actual)

May 2, 2024

Last Update Submitted That Met QC Criteria

April 30, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSR230492

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

Yes

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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