Methadone vs Remifentanil for Pain in Craniotomy Surgery

Overseen By Lauren Dunn, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must not be taking: Methadone, Buprenorphine, Naltrexone, others

Disqualifiers: Chronic pain, Substance use disorder, others

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

Compensation: Varies

Number of Visits: 1

Duration: Surgery day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, methadone and remifentanil, to determine which better manages pain after brain surgery. The goal is to assess if a single dose of methadone can control pain as effectively as remifentanil, typically administered in smaller, repeated doses. Success with methadone might reduce the need for additional pain medications post-surgery. Individuals who have undergone brain surgery and experience pain may be suitable candidates, particularly if they have not regularly used opioids before surgery. As an Early Phase 1 trial, this research aims to understand how these treatments work in people, offering participants a chance to contribute to innovative pain management strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using methadone or have a chronic pain condition requiring daily opioid use.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both methadone and remifentanil are generally safe and effective for pain management. Studies indicate that a single dose of IV methadone during surgery is well-tolerated by patients undergoing various types of brain surgeries, with only a few side effects. Patients experienced less pain and required fewer painkillers afterward.

Research has also found remifentanil to be a safe option during surgeries, including brain surgeries, and it has been used effectively without causing major problems. This suggests that remifentanil is a good choice for controlling pain during and after surgery.

Both treatments have demonstrated strong safety records in other surgeries, making them promising options for managing pain during craniotomy surgeries. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about methadone for pain management during craniotomy surgery because it offers a unique approach compared to standard options like remifentanil. Unlike many anesthetics that require continuous titration, methadone allows for a single, pre-incision intravenous dose, which may streamline the anesthesia process and reduce the need for constant adjustments. Additionally, methadone has a longer-lasting effect, potentially providing more sustained pain relief post-surgery. This could lead to improved patient comfort and a smoother recovery process compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for postoperative pain in craniotomy surgery?

This trial will compare the effectiveness of Methadone and Remifentanil for managing pain in craniotomy surgery. Research has shown that Methadone, which participants in this trial may receive, effectively manages post-surgical pain and reduces the need for additional pain medication in various surgeries, including brain surgeries. Patients who receive Methadone report less pain and require fewer painkillers for up to 72 hours after surgery. Methadone is promising due to its long duration and ability to block certain pain signals.

In contrast, Remifentanil, another treatment option in this trial, provides quick and effective pain relief during brain surgeries. It is often used for its rapid action and ability to maintain stable conditions during the operation. Both treatments aim to manage pain effectively, but Methadone might offer longer-lasting relief. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for patients undergoing craniotomy surgery who need effective pain control post-operation. The study aims to include those who could benefit from long-lasting pain relief without the risk of respiratory depression, which is crucial after brain surgery.

Inclusion Criteria

2. Undergoing supratentorial intracranial surgery

3. American Society of Anesthesiologists (ASA) physiological status I-III

4. Body Mass Index (BMI) between 18.5 and 45

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IV methadone or IV remifentanil during craniotomy surgery

Surgery day

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for pain control and recovery quality using various scales over 72 hours post-surgery

3 days

Daily assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

5-10 days

Hospital stay until discharge

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Remifentanil

Trial Overview The trial is testing whether a single dose of IV methadone can manage pain as effectively as IV remifentanil in patients after elective intracranial surgery. It's looking at how well methadone controls pain and improves recovery compared to the standard opioid treatment.

How Is the Trial Designed?

Group I: IV Methadone Experimental Treatment 1 Intervention

0.2 mg / kg Intravenous delivery prior to incision

Group II: IV Remifentanil Active Control 1 Intervention

titratable medication, dosage determined by anesthesia care team.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

In a study of 20 patients undergoing upper abdominal surgery, intravenous methadone provided longer-lasting pain control compared to morphine, with patients in the methadone group going an average of 20.7 hours before needing additional pain relief, compared to just 6.2 hours for those on morphine.

Patients receiving methadone required significantly less total opioid (11.5 mg) over 60 hours for adequate pain relief compared to those receiving morphine (41 mg), indicating that methadone may be more effective in managing postoperative pain with lower overall dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. Gourlay, GK., Willis, RJ., Lamberty, J.[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]

Craniotomy pain is often severe and can be challenging to manage due to the need to balance effective pain relief with the risk of adverse effects from opioids, such as sedation and respiratory depression.

Non-opioid analgesics, including regional scalp blocks, paracetamol, and non-steroidal anti-inflammatory drugs, are effective for managing post-craniotomy pain and may be used in combination with newer analgesics like dexmedetomidine and ketamine, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Craniotomy Pain Management: Beyond Opioids. Dunn, LK., Naik, BI., Nemergut, EC., et al.[2018]

Patients who received a single intraoperative dose of methadone during complex spine surgery reported significantly lower weekly frequency of chronic pain at 3 months post-surgery compared to those who received hydromorphone, indicating methadone's potential for long-term pain management.

In cardiac surgery patients, those who received methadone also experienced less frequent postsurgical pain at 1 month compared to those who received fentanyl, suggesting methadone's efficacy in reducing early postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery. Murphy, GS., Avram, MJ., Greenberg, SB., et al.[2023]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37084845/

Retrospective Study of the Safety and Efficacy ... The single intraoperative dose of methadone is well tolerated by adult patients undergoing various types of intracranial surgeries, with minimal side effects.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878875023005387

Original Article Retrospective Study of the Safety and ... Methadone, with its prolonged half-life and multimodal central nervous system effects, presents a promising option for managing postcraniotomy pain. Despite its ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06810336

Pain Control and Quality of Recovery After Intravenous ... It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in ...

4. experts.llu.edu experts.llu.edu/en/publications/retrospective-study-of-the-safety-and-efficacy-of-intraoperative-

Retrospective Study of the Safety and Efficacy ... Retrospective Study of the Safety and Efficacy of Intraoperative Methadone for Pain Management in Patients Undergoing Elective Intracranial Surgery.

5. withpower.com withpower.com/trial/methadone-vs-remifentanil-for-pain-in-craniotomy-surgery-a6cb0

Methadone vs Remifentanil for Pain in Craniotomy Surgery Research shows that methadone is effective in managing postoperative pain, as it reduces the need for additional pain medication and generally results in lower ...

6. mdpi.com mdpi.com/1648-9144/59/1/28

A Retrospective Cohort Study This single-center study finds that at the time of hospital discharge, opioids are prescribed for head/neck pain in as many as seven out of ten patients after ...