Methadone vs Morphine for Postoperative Pain

Overseen By Priyanka Singla, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must not be taking: Methadone, Buprenorphine, Naltrexone

Disqualifiers: Chronic pain, Pregnancy, Substance use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 72 hours

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using daily opioids or medications for opioid use disorder, you may not be eligible to participate.

What data supports the effectiveness of the drug methadone for postoperative pain?

Research shows that methadone can reduce the need for other pain medications and lower pain scores after surgery compared to other opioids. Patients who received methadone generally reported better satisfaction with their pain relief. ^{1 2 3 4 5}

Is methadone safe for managing postoperative pain compared to morphine?

Research shows that methadone can effectively reduce postoperative pain and opioid use without causing more side effects than morphine. However, there are risks like respiratory depression (slowed breathing) and arrhythmia (irregular heartbeat) that need careful consideration. ^{2 3 6 7 8}

How does the drug methadone differ from other treatments for postoperative pain?

Methadone is unique for postoperative pain management because it has a long-lasting effect and works by blocking certain pain receptors and affecting serotonin and noradrenaline levels, which can reduce the need for additional opioids after surgery. ^{1 3 4 6 9}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for patients undergoing major abdominal surgery who need pain management post-surgery. It's not suitable for those with blood clotting issues or low platelet counts, as they can't receive intrathecal morphine.

Inclusion Criteria

Ability to understand and read English

Body mass index (BMI) between 18.5 and 45

I am an adult with a health status rated between 1 to 3 by the ASA.

Exclusion Criteria

I am unable or unwilling to sign the consent form.

I have had a spinal fusion surgery.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Intrathecal Morphine or Intravenous Methadone prior to incision for pain management during major abdominal surgery

72 hours

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of pain and quality of recovery

92 days

Multiple assessments at 24, 48, 72 hours, 42 days, and 92 days

Treatment Details

Interventions

• Methadone
• Morphine

Trial Overview The study compares two pain control methods after abdominal surgery: IV methadone and IT morphine. The goal is to see if methadone, a noninvasive option, controls pain just as well without the side effects of morphine.

Participant Groups

Group I: Intravenous Methadone Experimental Treatment 1 Intervention

0.2 mg / kg Intravenous delivery prior to incision

Group II: Intrathecal Morphine Active Control 1 Intervention

250 mcg Intrathecal Injection prior to incision

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Findings from Research

In a study of 40 women undergoing lower abdominal surgery, those who received methadone reported significantly lower pain levels and required less additional pain relief compared to those who received morphine, indicating methadone's effectiveness for postoperative analgesia.

Methadone's long plasma half-life (approximately 54 hours) allows for sustained pain relief, making it a safe and effective alternative to morphine without notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative pain control with methadone following lower abdominal surgery. Richlin, DM., Reuben, SS.[2022]

In a meta-analysis of 10 studies involving 617 surgical patients, those who received methadone had significantly lower postoperative opioid consumption compared to those who received other opioids, with a mean difference of -15.22 mg in oral morphine equivalents.

Patients receiving methadone also reported lower pain scores and higher satisfaction with their pain management, although the use of methadone carries risks such as respiratory depression and arrhythmia that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis. D'Souza, RS., Gurrieri, C., Johnson, RL., et al.[2021]

Intraoperative use of methadone significantly reduced postoperative pain scores at rest and during movement for up to 72 hours after surgery, based on a meta-analysis of 13 trials involving 486 patients.

Methadone also decreased total opioid consumption in the postoperative period, leading to better patient satisfaction compared to other opioids, indicating its efficacy as a pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. Machado, FC., Vieira, JE., de Orange, FA., et al.[2023]

Intraoperative administration of methadone has been shown to effectively reduce post-operative pain and decrease the need for additional opioids after surgery, leveraging its long elimination half-life.

This review highlights the potential benefits of using methadone in surgical settings and calls for further research to optimize its clinical application in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative methadone for post-operative pain]. Uhrbrand, CG., Friesgaard, KD., Brix, LD., et al.[2021]

A single dose of methadone (0.2 mg/kg) given at the start of anesthesia significantly reduced the need for morphine after surgery, with patients using less morphine in the Postanesthesia Care Unit (0 mg vs. 7 mg) and over the first 72 hours (19 mg vs. 35 mg).

Patient satisfaction regarding pain control was high in both the methadone and fentanyl groups, indicating that methadone is an effective option for managing postoperative pain without compromising patient comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preoperative single dose of methadone for moderate-to-severely painful surgery reduces postoperative morphine consumption. Bastian, K., Buehler, PK., Slizyte, D., et al.[2020]

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

In a study of 52 cancer patients, rotating to methadone for pain management was effective, achieving adequate pain relief in 89% of patients within 3 days, particularly for those with mixed nociceptive-neuropathic pain.

The study suggests that using a fixed equianalgesic ratio of 10:1 for patients with a morphine-equivalent daily dose (MEDD) under 400 mg may be sufficient, indicating a tailored approach to opioid rotation can enhance pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone rotation for cancer pain: an observational study. Tan, C., Wong, JF., Yee, CM., et al.[2022]

In a study of 30 women undergoing abdominal hysterectomy, those who received methadone for postoperative pain management reported significantly lower pain scores and required fewer additional opioids compared to those who received morphine.

Patients in the methadone group experienced a less painful overall postoperative course, with no significant respiratory depression or excessive sedation observed in either treatment group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Chui, PT., Gin, T.[2022]

In a study involving 64 patients undergoing gynecological surgery, methadone provided superior pain relief compared to morphine on the second postoperative day.

Patients receiving methadone consumed significantly less opioid overall and experienced no serious side effects, such as respiratory depression, indicating it is a safer alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone versus morphine for postoperative pain in patients undergoing surgery for gynecological cancer: A randomized controlled clinical trial. Mercadante, S., David, F., Villari, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Postoperative pain control with methadone following lower abdominal surgery. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. [2023]

4. Denmark pubmed.ncbi.nlm.nih.gov

[Intraoperative methadone for post-operative pain]. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

A preoperative single dose of methadone for moderate-to-severely painful surgery reduces postoperative morphine consumption. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Methadone rotation for cancer pain: an observational study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Methadone versus morphine for postoperative pain in patients undergoing surgery for gynecological cancer: A randomized controlled clinical trial. [2021]