Methadone Dosing for Postoperative Pain
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Florida
Must not be taking: Methadone, Buprenorphine
Disqualifiers: Morbid obesity, Renal failure, Liver failure, Alcohol abuse, others
No Placebo Group
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
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.
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.12345
Is methadone safe for use in managing postoperative pain?
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.35678
Research Team
CS
Christoph Seubert, MD
Principal Investigator
University of Florida
Eligibility Criteria
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.
I am between 18 and 75 years old.
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.
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Trial Timeline
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
Treatment Details
Interventions
- Methadone (Opioid Analgesic)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Aliquots of methadone titrated to apneaExperimental Treatment1 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 methadoneActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UF HealthGainesville, FL
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Who Is Running the Clinical Trial?
University of Florida
Lead Sponsor
Trials
1428
Patients Recruited
987,000+
References
Comparison of premedication with buprenorphine or methadone with meloxicam for postoperative analgesia in dogs undergoing orthopaedic surgery. [2018]To determine whether methadone, administered before orthopaedic surgery, results in improved postoperative analgesia compared to buprenorphine.
Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis. [2021]Postoperative pain is not adequately managed in greater than 40% of surgical patients and is a high priority for perioperative research. In this meta-analysis, we examined studies comparing postoperative opioid consumption and pain scores in surgical patients who received methadone by any route vs those who received another opioid by any route. Studies were identified from PubMed, Cochrane, Web of Science, EMBASE, and Scopus from January 1966 to November 2018. Pooled odds ratios were calculated for a primary outcome of postoperative opioid consumption and secondary outcomes of time-to-extubation, time-to-first postoperative analgesia request, satisfaction, hospital length-of-stay, and complications. Postoperative pain scores were assessed qualitatively. Ten studies (617 patients) were included. Postoperative opioid consumption at 24 hours was lower in the methadone group vs control (mean difference = -15.22 mg oral morphine equivalents, 95% confidence interval -27.05 to -3.38; P = 0.01). Patients in the methadone group generally reported lower postoperative pain scores in 7 of 10 studies. Meta-analysis revealed greater satisfaction scores with analgesia in the methadone group vs control (0-100 visual analog scale; mean difference = 7.16, 95% confidence interval 2.30-12.01; P = 0.004). There was no difference in time-to-extubation, time-to-first analgesia request, hospital length-of-stay, or complications (nausea, sedation, respiratory depression, and hypoxemia). The results demonstrate that surgical patients who received intraoperative methadone had lower postoperative opioid consumption, generally reported lower pain scores and experienced better satisfaction with analgesia. However, these advantages need to be weighed carefully against dangerous risks with perioperative methadone, specifically respiratory depression and arrhythmia. Future studies should explore logistics, safety, and cost effectiveness.
Postoperative pain control with methadone following lower abdominal surgery. [2022]To describe a technique for the use of methadone during and following lower abdominal surgery that integrates its pharmacokinetic and pharmacodynamic properties with the objective of postoperative analgesia; to compare methadone with morphine for postoperative pain control.
A preoperative single dose of methadone for moderate-to-severely painful surgery reduces postoperative morphine consumption. [2020]Data from patient questionnaires reveal that the intensity of postoperative pain is widely underestimated. Insufficient pain control may contribute to impaired short- and long-term outcome. Preoperative administration of methadone might potentially improve postoperative pain control due to its long pharmacological half-life.
[Postoperative pain therapy with 1-methadone and metamizole. A randomized study within the scope of intravenous on-demand analgesia]. [2015]Methadone, a potent long-acting opioid analgesic, is only seldom prescribed for postoperative pain relief in Germany. It was the aim of the present investigation to evaluate its efficacy and to establish an adequate dose range using intravenous patient-controlled analgesia (PCA), as well as to determine possible drug interactions with the antipyretic analgesic metamizol (dipyrone). 120 patients recovering from elective major abdominal, gynaecological or orthopaedic surgery under standardized balanced anaesthesia were randomly allocated to three groups to self-administer intravenous 1-methadone. Demand doses were 0.573 mg (group LD), 1.145 mg (group HD) or 0.573 mg to which 50 mg metamizol (dipyrone) were added (group LM). Infusion rate was set to 0.137 mg 1-methadone/h in every group, lockout time was 1 min. Hourly maximum dose was set to 5.95 mg 1-methadone/h. During an average PCA duration of 21 hours patients demanded mean dosages of 16.4 mg (LD), 18.7 mg (HD) or 13.4 mg (LM) 1-methadone. Although individual variation in drug consumption was high, effective pain relief was possible in all cases. Cardiovascular and respiratory status during the observation period was always normal. 88-93% of patients preferred PCA in comparison with earlier experienced conventional postoperative pain treatment. It is concluded that patients are able to control adequate drug consumption, i.e. to avoid overdosage, by adjusting demand frequency if variable demand dosages are offered. Thus 13-19 mg 1-methadone per day can be recommended as reasonable dose range for pain relief during the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)
Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. [2023]Intravenous methadone may be useful in acute and chronic pain management compared with other opioids because of its pharmacokinetic and pharmacodynamic characteristics, including the long duration of effect and ability to modulate both pain stimuli propagation and analgesic descending pathways. However, methadone is underused in pain medicine because of several misperceptions. A review of studies was performed to assess data regarding the use of methadone in perioperative pain and chronic cancer pain. The majority of studies have shown that intravenous methadone produces an effective postoperative analgesia and lowers opioid consumption in the postoperative period, without more adverse effects in comparison with other opioid analgesics, and has an interesting potential to prevent persistent postoperative pain. A minority of studies investigated the use of intravenous methadone for cancer pain management. These studies were mostly case series that showed promising activities of intravenous methadone for difficult pain conditions. There is sufficient evidence suggesting that intravenous methadone is effective in perioperative pain, while more studies are needed in patients with cancer pain.
[Intraoperative methadone for post-operative pain]. [2021]Methadone is an opioid with several desirable pharmacological features, including a long elimination half-life. Several studies have suggested that a single intraoperative dose reduces post-operative pain and opioid consumption. In this review, we summarise the current knowledge of intraoperative methadone for the treatment of post-operative pain and propose recommendations for clinical use and future research.
Methadone Switching for Cancer Pain: A New Classification of Initiation Protocols, Based on a Critical Literature Review. [2022]Background: The initiation of methadone, a known effective analgesic for cancer pain, is complex. The existing protocols are often inadequately described; therefore, a classification of literature is needed. We reviewed and classified the recent literature on methadone initiation protocols in cancer patients experiencing severe pain. Objective: To provide a new classification of initiation protocols, based on a critical literature review. Data Sources: The MEDLINE database was searched for articles published until March 25, 2021, using the terms "cancer pain," "methadone," "methadone introduction," or "methadone initiation." The search was limited to human studies, randomized controlled trials (RCTs), other clinical trials, meta-analyses, and case reports. Selected articles were assessed for initiation details (rapid or progressive), administered dose (fixed rescue dose or ad libitum), and dose calculation (fixed or progressive ratios using morphine equivalent daily dose [MEDD] for daily or unitary dose). Results: Twenty-four publications that met our inclusion criteria were analyzed. No large-scale prospective double-blind RCTs with robust design were identified. Most studies assessed relatively small numbers of patients. Eight initiation types were identified, of which three involved seven "high quality" studies: "rapid switch-fixed doses and rescue dose-progressive daily ratio," "progressive switch-fixed dose and rescue dose-progressive daily ratio," and "rapid switch-ad libitum-fixed ratio for unitary dose" protocols. This classification provides the latest information on methadone initiation protocols. The total daily dose of methadone varied largely across protocols. Conclusion: We recommend a maximal daily methadone dose of 100 mg (3 doses of 30 mg or 5 doses of 20 mg) for MEDD <500 mg, when the two "ad libitum" protocols are used. Further clinical research on this topic is warranted.