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

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

What data supports the effectiveness of the drugs Methadone and Sufentanil for Free Flap Reconstruction?

Research shows that methadone can reduce the need for other pain medications after surgery and generally leads to lower pain scores and higher satisfaction with pain relief. Sufentanil is a strong pain reliever that provides effective anesthesia and may help with faster recovery and less need for additional pain medication after surgery. ^{1 2 3 4 5}

Is it safe to use Sufentanil and Methadone in humans?

Sufentanil is generally safe for use in humans, with some reports of postoperative respiratory depression, but it maintains stable blood pressure during surgery. Methadone is also generally safe, but it carries risks of respiratory depression and heart rhythm issues, which need careful consideration. ^{2 3 6 7 8}

How does the drug combination of Sufentanil and Methadone differ from other treatments for free flap reconstruction?

Sufentanil is a potent opioid that provides rapid onset and effective pain relief, while Methadone has a longer duration of action and can reduce the need for additional pain medication. This combination may offer a unique balance of quick pain relief and sustained analgesia, potentially improving postoperative pain management compared to using either drug alone. ^{2 3 9 10 11}

What is the purpose of this trial?

The main purpose of this study is to determine which type of medication, sufentanil or methadone, is better at controlling pain during and, more importantly, after surgery in patients undergoing a head and neck dissection with free flap or rotational tissue reconstruction. Prior to their operation, subjects will be randomized to receive either Sufentanil or Methadone. After surgery, research staff will obtain information about recovery and pain levels.

Research Team

Gulraj S Chawla, MD

Principal Investigator

Indiana University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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 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 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]

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]

References

1. England 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. [2023]

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

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

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

Sufentanil. A review of its pharmacological properties and therapeutic use. [2022]

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

Perioperative methadone prescribing and association with respiratory depression. [2021]

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

Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study. [2021]

6. Germany 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. [2020]

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

Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients. [2020]

8. India pubmed.ncbi.nlm.nih.gov

Evaluation of the analgesic effect of subcutaneous methadone after cesarean section. [2021]

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

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

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

Comparison of epidurally administered sufentanil, morphine, and sufentanil-morphine combination for postoperative analgesia. [2019]

11. France pubmed.ncbi.nlm.nih.gov

What we know and what we don't know about the perioperative use of methadone in children and adolescents. [2023]