Methadone Dosing for Postoperative Pain

Overseen By Regina Knudsen, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Methadone, Buprenorphine

Disqualifiers: Morbid obesity, Renal failure, Liver failure, Alcohol abuse, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: Immediate perioperative period

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to use methadone, an opioid medication, for managing pain after complex spine surgeries. Researchers compare two methods of administering methadone to determine which provides better pain relief. One method uses a standard dose, while the other adjusts the dose based on breathing response. Individuals scheduled for multilevel spine surgery with hardware and without a history of drug or alcohol abuse may qualify for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings in pain management.

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 using methadone or buprenorphine.

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

Research has shown that methadone is generally safe and effective for managing post-surgical pain. Studies have found that patients receiving methadone often report less pain. In one study, patients given methadone expressed greater satisfaction with their pain relief compared to those who did not receive it.

Methadone is administered during surgery to help control pain afterward, typically as a single dose while the patient is under anesthesia. This method provides good pain relief with few side effects. Common side effects, such as nausea and vomiting, are usually mild.

Overall, using methadone during surgery appears to be a safe option for many patients when administered by a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the methadone dosing methods being studied for postoperative pain management due to their potential to enhance effectiveness and precision. Unlike standard methadone dosing, which typically involves a fixed dose, one investigational method uses incremental aliquots titrated to achieve a specific respiratory rate, allowing for a more tailored approach to each patient's needs. This method could lead to more effective pain management by minimizing under- or overdosing and improving overall patient outcomes. Additionally, by carefully adjusting doses to achieve a target state, this approach might reduce side effects associated with traditional opioid dosing.

What evidence suggests that this trial's methadone dosing methods could be effective for postoperative pain?

Research has shown that using methadone during surgery can help manage postoperative pain. In this trial, participants will receive either a standard methadone dose or incremental aliquots titrated to apnea. Studies have found that administering a single dose of methadone while a patient is under anesthesia can reduce the need for additional painkillers later. This approach may lead to less opioid use after surgery, enhancing patient safety. Early data in children suggests that methadone provides effective pain relief without major side effects. In complex spine surgeries, these findings indicate methadone could be a valuable component of pain management plans. ^{3 4 6 7 8}

Who Is on the Research Team?

Christoph Seubert, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-75 undergoing complex spine surgery with fusion and instrumentation, who consent to participate. It's not for those using methadone or buprenorphine, severely obese people, those with chronic kidney or liver failure, a history of substance abuse, certain heart conditions (prolonged QTc), very high surgical risk (ASA IV/V), or spine issues due to tumor, infection, or trauma.

Inclusion Criteria

I am having spine surgery with hardware and fusion at multiple levels.

Patients must consent to participate and sign the IRB-approved informed consent prior to beginning any study specific procedures.

Exclusion Criteria

I have liver failure due to cirrhosis or a severe liver episode.

I have a spine condition due to a tumor, infection, or injury.

My kidney function is low with high creatinine levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive methadone dosing during spine surgery, either standard dosing or titrated to apnea

Immediate perioperative period

1 visit (in-person, during surgery)

Post-operative Monitoring

Participants are monitored for opioid requirements and respiratory status post-surgery

72 hours

Continuous monitoring (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview The study compares two ways of giving methadone during complex spine surgeries: the standard dosing method versus titrated doses based on the patient's breathing response. The goal is to see which method better manages postoperative pain.

How Is the Trial Designed?

Group I: Aliquots of methadone titrated to apnea Experimental Treatment 1 Intervention

Receive incremental aliquots of methadone up to 0.5 mg/Kg based on ideal body weight titrated to apnea. Each subject will receive a 5-10 mg loading dose then aliquots of 5mg each, given at 3 to 5 minute time intervals. The practitioner will continue to coach patient to take deep breaths. After reaching the apnea threshold as determined by respiratory rate less than 8 breaths/min, induction of general anesthesia and intubation will proceed.

Group II: Standard dosing of methadone Active Control 1 Intervention

Receive 0.2 mg/kg based on ideal body weight of methadone after the intubation and before positioning.

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 Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study of 120 patients recovering from major surgery, intravenous patient-controlled analgesia (PCA) with methadone provided effective pain relief, with patients self-administering an average of 13-19 mg of methadone over 21 hours.

The study found that patients preferred PCA over traditional pain management methods, and there were no significant cardiovascular or respiratory issues, indicating that methadone can be safely used for postoperative pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative pain therapy with 1-methadone and metamizole. A randomized study within the scope of intravenous on-demand analgesia]. Lehmann, KA., Abu-Shibika, M., Horrichs-Haermeyer, G.[2015]

A review of 24 studies on methadone initiation protocols for cancer pain revealed eight different types of protocols, with three being supported by high-quality studies, indicating a need for standardized approaches in clinical practice.

The analysis suggests a maximum daily methadone dose of 100 mg for patients with a morphine equivalent daily dose (MEDD) of less than 500 mg when using certain 'ad libitum' protocols, highlighting the importance of careful dosing in methadone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone Switching for Cancer Pain: A New Classification of Initiation Protocols, Based on a Critical Literature Review. Treillet, E., Giet, O., Picard, S., et al.[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]

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]

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]

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 study involving 38 dogs undergoing orthopedic surgery, methadone provided significantly better pain relief compared to buprenorphine, as indicated by lower pain scores and reduced need for additional analgesia.

Both methadone and buprenorphine effectively sedated the dogs, but methadone resulted in superior postoperative analgesia for up to 8 hours, highlighting its efficacy as a pain management option in veterinary orthopedic procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of premedication with buprenorphine or methadone with meloxicam for postoperative analgesia in dogs undergoing orthopaedic surgery. Hunt, JR., Attenburrow, PM., Slingsby, LS., et al.[2018]

Citations

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Intraoperative methadone for postoperative pain management It has been suggested that methadone, when given as a single bolus while under anesthesia, provides good postoperative analgesia and is associated with minimal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07092475

The Impact of Intraoperative Methadone on Postoperative ... This is a single-institution, randomized controlled trial to assess the effectiveness of intraoperative methadone on postoperative opioid use, ...

3. reporter.nih.gov reporter.nih.gov/project-details/10990745

sadhasivam, senthilkumar - NIH RePORTER Our preliminary data in children undergoing CS with car- dio-pulmonary bypass (CPB) reveal opioid-sparing and safe postoperative analgesia with methadone. We ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089947225001066

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

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07222072

Methadone to Reduce Chronic Opioid Use After Major ... If acute postoperative pain is reduced, the development of chronic pain may also decrease, as well as the need for long-term opioid therapy, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31613867/

a systematic review and meta-analysis Patients in the methadone group generally reported lower postoperative pain scores in 7 of 10 studies. Meta-analysis revealed greater satisfaction scores with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772609625000425

Intraoperative methadone for postoperative pain in adult ... This study hypothesised that methadone would provide superior postoperative pain relief and reduced opioid consumption compared with fentanyl.

8. bjaopen.org bjaopen.org/article/S2772-6096(23)00098-9/fulltext

Clinical effectiveness and safety of intraoperative ... Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse ...