Sufentanil vs Methadone for Free Flap Reconstruction

Overseen By Angie M Plummer

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Indiana University

Must not be taking: Methadone, Opioids

Disqualifiers: Substance abuse, Liver disease, 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

Compensation: Varies

Number of Visits: 1

Duration: During surgery

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether sufentanil or methadone better manages pain during and after head and neck reconstruction surgery. Participants will receive one of these medications before their operation, and researchers will monitor their recovery and pain management afterward. Candidates include those undergoing head and neck surgery with tissue reconstruction at Indiana University Health who have no issues with opioids. As a Phase 4 trial, this research seeks to understand how these FDA-approved treatments can benefit more patients.

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 on methadone or taking more than 30mg of morphine equivalent per day.

What is the safety track record for these treatments?

A previous study found sufentanil to be generally safe for humans. Some reports mention breathing problems after surgery, but it usually helps maintain stable blood pressure during operations. Research has shown that methadone is also well-tolerated and can reduce the need for other pain-relieving drugs post-surgery. However, it may cause side effects like nausea, vomiting, and drowsiness. Both treatments have been used successfully in surgeries, indicating they can be safe options for managing pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using sufentanil and methadone for free flap reconstruction surgery because they offer potentially improved pain management strategies compared to standard opioids like morphine or fentanyl. Sufentanil is unique due to its potency and short-acting nature, which allows for precise control over pain management during and immediately after surgery. Methadone, on the other hand, is long-acting and may provide sustained pain relief with a single dose, potentially reducing the need for additional pain medications. Exploring these two options could lead to more effective and tailored approaches to managing post-surgical pain, enhancing patient recovery experiences.

What evidence suggests that this trial's treatments could be effective for pain control in head and neck surgery?

This trial will compare the effectiveness of sufentanil and methadone for managing pain in patients undergoing head and neck surgery with tissue reconstruction. Research has shown that both sufentanil and methadone can help manage post-surgical pain. Participants in this trial will receive either sufentanil or methadone. Studies have found that patients who received sufentanil reported less pain and required fewer additional pain medications. Methadone, on the other hand, has greatly reduced the need for strong painkillers after surgery, particularly in breast reconstruction and other surgeries. Both treatments aim to lessen pain and reduce the need for additional medications after surgery. These findings suggest that both drugs effectively manage pain, but they work in slightly different ways. The trial aims to determine which drug works better for head and neck surgery with tissue reconstruction. ^{1 2 3 4 6}

Who Is on the Research Team?

Gulraj S Chawla, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for patients undergoing head and neck dissection with free flap reconstruction surgery. Participants will be randomly assigned to receive either sufentanil or methadone to manage pain during and after the procedure.

Inclusion Criteria

I am either male or female.

Able and willing to provide written informed consent

I am having surgery for my head or neck with tissue reconstruction at Indiana University Health.

Exclusion Criteria

I am undergoing other surgeries in addition to the main one.

I am allergic to sufentanil or methadone.

Any contraindication to opiates, (i.e. allergy to opioids, substance use disorder) as determined by PI review and any contraindications reported by the patient

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to receive either Sufentanil or Methadone for postoperative analgesia during head and neck dissection with free flap reconstruction

During surgery

1 visit (in-person)

Postoperative Monitoring

Research staff obtain information about recovery and pain levels, monitoring for opioid side effects and pain scores

24 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Sufentanil

Trial Overview The study aims to compare the effectiveness of sufentanil infusion versus intravenous methadone in controlling postoperative pain following head and neck surgery with tissue reconstruction.

How Is the Trial Designed?

Group I: Sufentanil Experimental Treatment 1 Intervention

1\. Intravenous sufentanil starting at a dose of 0.5 mcg/kg/min hr ideal body weight (IBW) at the beginning of the case, prior to surgical incision, with a discontinuation of the infusion when the surgical microscope is removed from the patient field and the closure of the incision(s) begins. (n=64)

Group II: Methadone Experimental Treatment 1 Intervention

2\. Intravenous methadone of 0.2 mg/kg IBW up to a maximum dose of 20mg, rounded to the nearest milligram. The methadone will be given at the beginning of the case, prior to surgical incision. n=64)

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Published Research Related to This Trial

In a meta-analysis of eight randomized controlled trials involving 691 first-time mothers, sufentanil was found to significantly improve wound healing compared to remifentanil on the third and fifth postoperative days after a C-section.

While both sufentanil and remifentanil are effective for pain management, sufentanil showed a more pronounced positive effect on early wound healing, suggesting it may be the better choice for analgesia in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of sufentanil versus remifentanil on surgical site wound healing in caesarean section primiparas undergoing epidural anaesthesia: A systematic meta-analysis. Chen, J., Li, T., Pan, Z., et al.[2023]

In a study of 298 surgical patients, over 90% were already on methadone before surgery, highlighting the prevalence of chronic opioid use in this population.

Newly initiated post-operative methadone was linked to a higher risk of respiratory depression, particularly in older male patients, indicating the need for careful monitoring and management of analgesia in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative methadone prescribing and association with respiratory depression. Bova, SE., Kruer, RM., Nesbit, SA., et al.[2021]

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]

Methadone may be an effective option for postoperative pain control in children and adolescents, potentially reducing pain, opioid consumption, and the length of hospital stays, while also minimizing some side effects associated with traditional opioids.

Despite its benefits, methadone carries risks such as nausea, sedation, and QTc prolongation, highlighting the need for careful dosing protocols and further research to establish its safety and efficacy in various surgical contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What we know and what we don't know about the perioperative use of methadone in children and adolescents. Boisvert-Plante, V., Poulin-Harnois, C., Ingelmo, P., et al.[2023]

Sufentanil significantly extends the duration of spinal analgesia by about 25.4 minutes compared to fentanyl, without clinically meaningful differences in pain relief after intrathecal injection, based on a meta-analysis of 12 trials involving 881 patients.

Sufentanil may be safer for infants, as evidenced by higher Apgar scores at 5 minutes after delivery compared to fentanyl, while both drugs showed similar risks for respiratory depression and side effects like pruritus, nausea, and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sufentanil versus fentanyl for pain relief in labor involving combined spinal-epidural analgesia: a systematic review and meta-analysis of randomized controlled trials. Zhi, M., Diao, Y., Liu, S., et al.[2020]

In a study of 60 women undergoing cesarean sections, subcutaneous methadone significantly reduced pain severity and increased patient satisfaction compared to standard pain management, indicating its effectiveness as a pain reliever.

The use of subcutaneous methadone was found to be safe for post-operative pain control, suggesting it could be a beneficial option for improving maternal and neonatal health during the early postpartum period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the analgesic effect of subcutaneous methadone after cesarean section. Jabalameli, M., Kalantari, F.[2021]

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]

Intraoperative use of methadone in 74 patients undergoing congenital heart surgeries significantly reduced total opioid consumption in the first 36 hours post-surgery, with lower opioid use observed both during and after the procedure.

The study found no adverse events or negative clinical outcomes associated with methadone use, suggesting it is a safe option for managing pain in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study. Robinson, JD., Caruso, TJ., Wu, M., et al.[2021]

In a study of 45 patients recovering from major gynecologic surgery, those receiving sufentanil (either alone or with morphine) experienced a faster onset of pain relief compared to those receiving morphine alone.

While morphine provided the longest duration of pain relief, combining sufentanil with morphine resulted in a quicker analgesic effect and reduced the need for additional pain medication, with no significant adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of epidurally administered sufentanil, morphine, and sufentanil-morphine combination for postoperative analgesia. Sinatra, RS., Sevarino, FB., Chung, JH., et al.[2019]

In a study of 1,478 patients undergoing major spine surgery, 36.8% experienced respiratory depression and 79.8% had hypoxemia after receiving intravenous methadone, indicating a significant risk of respiratory issues post-surgery.

Despite the high incidence of respiratory depression, the overall in-hospital mortality rate was low at 0.14%, suggesting that while methadone can lead to mild to moderate respiratory complications, it can be managed effectively with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients. Dunn, LK., Yerra, S., Fang, S., et al.[2020]

Sufentanil is a highly potent opioid analgesic that provides effective anesthesia for major surgeries, showing better hemodynamic stability compared to other opioids and inhalational anesthetics.

While sufentanil offers rapid recovery and reduced need for postoperative analgesia, its use in epidural administration for labor pain relief shows promise but requires further research to confirm its effectiveness and role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sufentanil. A review of its pharmacological properties and therapeutic use. Monk, JP., Beresford, R., Ward, A.[2022]

Citations

1. 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, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41067267/

The Impact of Intraoperative Methadone on Perioperative ... Conclusion: Intraoperative methadone significantly reduces inpatient opioid use after undergoing autologous breast reconstruction on POD-1, POD2 ...

3. thieme-connect.de thieme-connect.de/products/ejournals/pdf/10.1055/a-2717-5119.pdf

The Impact of Intraoperative Methadone on Perioperative ... 1. Results. We identified 150 patients who underwent autologous free flap breast reconstruction during the study period, with 112 patients.

4. habcentral.habcommunity.com habcentral.habcommunity.com/article/the-impact-of-intraoperative-methadone-on-perioperative-opioid-requirements-in-autologous-free-flap-breast-reconstruction?article_title=The%20Impact%20of%20Intraoperative%20Methadone%20on%20Perioperative%20Opioid%20Requirements%20in%20Autologous%20Free%20Flap%20Breast%20Reconstruction.&article_id=6317238

Intraoperative Methadone Reduces Opioid Use in Breast ... Intraoperative methadone significantly reduces inpatient opioid use after undergoing autologous breast reconstruction on POD-1, POD2, and ...

5. joma.amegroups.org joma.amegroups.org/article/view/5707/html

a narrative review on perioperative pain levels and opiate use ... The purpose of this narrative review is to evaluate and discuss studies reporting on postoperative pain and opiate use in head and neck cancer (HNC) free flap ...

6. researchgate.net researchgate.net/profile/Hao-Huang-99/publication/390376355_Intraoperative_Methadone_A_New_Enhanced_Recovery_After_Surgery_Pathway_for_Deep_Inferior_Epigastric_Perforator_Flap_Breast_Reconstruction/links/67ec9a8949e91c0fead55c2f/Intraoperative-Methadone-A-New-Enhanced-Recovery-After-Surgery-Pathway-for-Deep-Inferior-Epigastric-Perforator-Flap-Breast-Reconstruction.pdf?origin=scientificContributions

Intraoperative Methadone The purpose of this study is to evaluate the efficacy of a weight-based intraoperative methadone regimen as part of an ERAS pathway in patients undergoing. DIEP ...