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

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study compares two methods of dosing methadone for complex spine cases

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 methadone safe for use in managing postoperative pain?

Research shows that methadone is generally safe for managing postoperative pain, with studies indicating normal cardiovascular and respiratory status in patients. It is effective in reducing pain and opioid consumption without more adverse effects compared to other opioids. ^{1 2 3 4 5}

How is the drug methadone unique for postoperative pain management?

Methadone is unique for postoperative pain management because it is a long-acting opioid that can be administered intravenously, allowing patients to control their dosage through patient-controlled analgesia (PCA). This method can provide effective pain relief with potentially lower overall opioid consumption compared to other opioids, and it is less commonly used for this purpose, making it a novel option. ^{2 3 4 5 6}

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

Research shows that methadone can effectively reduce the need for other pain medications after surgery and generally leads to lower pain scores and higher patient satisfaction compared to other opioids. However, it is important to consider potential risks like breathing problems and heart rhythm issues. ^{1 2 4 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

My kidney function is low with high creatinine levels.

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

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

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 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]

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]

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]

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]

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]

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]

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 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Comparison of premedication with buprenorphine or methadone with meloxicam for postoperative analgesia in dogs undergoing orthopaedic surgery. [2018]

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

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

4. Italy pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

[Postoperative pain therapy with 1-methadone and metamizole. A randomized study within the scope of intravenous on-demand analgesia]. [2015]

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

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

7. Denmark pubmed.ncbi.nlm.nih.gov

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

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

Methadone Switching for Cancer Pain: A New Classification of Initiation Protocols, Based on a Critical Literature Review. [2022]