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

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, but you cannot participate if you are currently using methadone or have a chronic pain condition requiring daily opioid use.

What data supports the effectiveness of the drug methadone for pain management 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 pain scores compared to other opioids. It has been found to provide longer-lasting pain relief, which can be beneficial in surgical settings. ^{1 2 3 4 5}

Is it safe to use remifentanil for pain management in craniotomy surgery?

Remifentanil is generally considered safe for use in craniotomy surgeries, as studies show it provides effective pain relief and sedation without causing excessive respiratory issues. It is well-tolerated by patients, with similar satisfaction and complication rates compared to other pain management options like fentanyl. ^{6 7 8 9 10}

How does the drug Methadone differ from Remifentanil for pain management in craniotomy surgery?

Methadone is unique because it has a longer duration of action compared to Remifentanil, which is a short-acting opioid. This means Methadone might provide more sustained pain relief after surgery, potentially reducing the need for additional pain medications. ^{6 7 8 9 11}

What is the purpose of this trial?

Postoperative pain is prevalent after intracranial surgery. Patients undergoing craniotomy are typically managed with short acting opioids to enable early and reliable post-operative neurological exam as well as avoid the risk of respiratory depression. However, a plethora of studies have shown that a majority of these patients experience moderate to severe pain in first 48 hours after surgery. Suboptimal pain control can lead to complications such as arterial hypertension and post-operative intracranial hemorrhage, and hence, increased morbidity and mortality. 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 that underwent orthopedic, abdominal, complex spine, and cardiac surgery. Similar findings have been shown in obstetric patients that underwent caesarean delivery under general anesthesia as well as patients that underwent gynecologic surgery and received IV methadone intraoperatively. In a recently published retrospective study, a single intraoperative dose of IV methadone was well tolerated with lower pain scores as well as MME (oral morphine milligram equivalents) requirements for up to 72 hours after elective intracranial surgery. IV methadone has, however, never been compared with conventional management via IV remifentanil for functional recovery in patients undergoing elective intercranial surgery. The investigator's hypothesis is that intravenous (IV) methadone is non-inferior to IV remifentanil in patients who undergo elective intracranial surgery. It offers the advantage of being a single dose noninvasive analgesic modality that may contribute to decreasing MME consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving quality of recovery after surgery.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Rediscovery of Methadone to Improve Outcomes in Pain Management. [2022]

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

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control. [2022]

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

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

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

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

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

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery. [2023]

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

Remifentanil with morphine transitional analgesia shortens neurological recovery compared to fentanyl for supratentorial craniotomy. [2022]

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

The Effects of Dexmedetomidine and Remifentanil on Hemodynamic Stability and Analgesic Requirement After Craniotomy: A Randomized Controlled Trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Postoperative condition after the use of remifentanil with a small dose of piritramide compared with a fentanyl-based protocol in patients undergoing craniotomy. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[Remifentanil for awake craniotomy]. [2018]

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

Patient satisfaction with awake craniotomy for tumor surgery: a comparison of remifentanil and fentanyl in conjunction with propofol. [2018]

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

Post-Craniotomy Pain Management: Beyond Opioids. [2018]