MedPath

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

Early Phase 1
Recruiting
Conditions
Pain, Postoperative
Interventions
Registration Number
NCT06387303
Lead Sponsor
University of Virginia
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
40
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, MME >60 as the FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin.

  • Pregnant Women

  • Patients requiring emergent surgery

  • Contraindications to neuraxial anesthesia including:

    • Coagulopathy
    • localized infection at the site of injection
    • pre-existing spinal pathology, specifically defined as active radiculopathy, severe central canal stenosis in the lumbar region, or an acute fracture in the lumbar region
  • 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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intrathecal MorphineMorphine250 mcg Intrathecal Injection prior to incision
Intravenous MethadoneMethadone0.2 mg / kg Intravenous delivery prior to incision
Primary Outcome Measures
NameTimeMethod
Quality of Recovery 15 score24 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.

morphine milligram equivalent24 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.

Numeric Rating Scale pain scores (NRS)24 hours, 48 hours, 72 hours

The numeric rating scale (NRS) is a pain screening tool commonly used to assess pain severity at a given moment in time. It uses a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable."

Overall Benefits of Analgesic Score24 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)

Secondary Outcome Measures
NameTimeMethod
McGill Pain questionnaire score42 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.

Numeric Rating Pain Score (NRS)42 days, 92 days

The numeric rating scale (NRS) is a pain screening tool commonly used to assess pain severity at a given moment. It uses a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable."

Trial Locations

Locations (1)

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

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