Methoxyflurane for Pain Relief

Overseen By Darrien D Rattray, MD FRCSC

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Dr. John A. Thiel Medical Professional Corporation

Must not be taking: Fentanyl, Midazolam

Disqualifiers: Submucosal fibroids, Sleep apnea, others

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether inhaled methoxyflurane, a type of pain relief medication, is as effective as the usual IV sedation with fentanyl and midazolam for managing pain during certain outpatient gynecological procedures. The main goal is to determine if women experience similar pain relief and can complete their procedures using the inhaled method. Women needing a hysteroscopy due to abnormal or postmenopausal bleeding might be suitable candidates. Participants should not have conditions like sleep apnea or a history of severe liver or kidney issues. As an unphased trial, this study allows participants to contribute to innovative pain management research that could benefit future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that methoxyflurane is generally safe for pain relief, effectively easing pain without causing kidney or liver issues. No reports link its use to serious side effects, such as hospitalization or death. Methoxyflurane is already approved in Europe for treating moderate-to-severe pain from injuries.

Studies indicate that the intravenous drugs fentanyl and midazolam are safe when used together for sedation. This combination helps individuals relax and feel less anxious during procedures. No major safety concerns have been reported, making them well-tolerated for sedation.

In summary, both methoxyflurane and the fentanyl-midazolam combination have demonstrated good safety records in previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Methoxyflurane is unique because it offers pain relief through inhalation, using a simple device known as the "green whistle." Unlike standard options like intravenous opioids, methoxyflurane provides rapid analgesia without the need for injections or IV lines. Researchers are excited because this method allows for quick, on-the-spot pain management, which could be especially beneficial in emergency settings or situations where traditional IV access is challenging. Additionally, its non-invasive nature may reduce the risk of complications associated with intravenous treatments.

What evidence suggests that methoxyflurane might be an effective treatment for pain relief during hysteroscopy and/or polypectomy?

Research has shown that inhaled methoxyflurane, which participants in this trial may receive, provides quick and effective pain relief. One study found that almost half of the participants experienced relief after just 1 to 5 breaths. Methoxyflurane acts quickly, often easing pain within 3 to 5 minutes, and has significantly lowered pain levels compared to placebo treatments. In this trial, another group of participants will receive intravenous sedatives such as fentanyl and midazolam, which increase relaxation and reduce anxiety during procedures. These sedatives work together to make procedures more comfortable by lowering awareness and pain. ^{2 6 7 8 9}

Who Is on the Research Team?

Peter S Thiel, MD MPH FRCSC

Principal Investigator

University of Saskatchewan

Are You a Good Fit for This Trial?

This trial is for women needing a hysteroscopy due to abnormal or postmenopausal bleeding. It's not for those with conditions preventing hysteroscopy, large fibroids, allergies to fentanyl/midazolam, BMI over 42, issues with IV sedation like sleep apnea, no consent given, history of malignant hyperthermia or significant kidney/liver disease.

Inclusion Criteria

I have had bleeding after menopause that needed a special exam.

I need a procedure to examine my uterus due to abnormal bleeding.

Exclusion Criteria

BMI > 42

Uterine or patient characteristics that preclude hysteroscopy

Past allergic reaction to fentanyl or midazolam

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either inhaled methoxyflurane or intravenous sedation during hysteroscopy and/or polypectomy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain assessment and procedure acceptability

1 hour

1 visit (in-person)

Post-procedure Monitoring

Participants are observed for any immediate adverse effects and time to discharge is recorded

1 hour

What Are the Treatments Tested in This Trial?

Interventions

• Intravenous Sedatives with or Without Analgesia
• Methoxyflurane

Trial Overview The study compares inhaled methoxyflurane (MOF) against IV conscious sedation using fentanyl and midazolam during outpatient hysteroscopies. The goal is to see if MOF can similarly reduce pain without compromising the procedure's success.

How Is the Trial Designed?

Group I: IV Sedation Active Control 1 Intervention

Patients will receive 1 microgram/kg fentanyl and 1 - 3 mg midazolam intravenously as per the normal intravenous sedation protocol

Group II: Methoxyflurane Active Control 1 Intervention

Patients will receive three inhalations from the green whistle loaded with methoxyflurane

Group III: IV saline Placebo Group 1 Intervention

Patients in the Methoxyflurane group will receive intravenous saline administered from the same syringes as those in the fentanyl and midazolam group

Group IV: Inhaled saline Placebo Group 1 Intervention

Patients in the Intravenous sedation group will receive three inhalations of saline from a placebo loaded green whistle

Who Is Running the Clinical Trial?

Dr. John A. Thiel Medical Professional Corporation

Lead Sponsor

Trials

2

Recruited

110+

Published Research Related to This Trial

A study conducted in two hospital emergency departments in France found that nurses experienced very low levels of occupational exposure to methoxyflurane, with a median concentration of only 0.017 ppm during 8-hour shifts, which is nearly 900 times lower than the maximum exposure limit of 15 ppm.

There was no correlation between the number of methoxyflurane applications administered and the exposure levels measured, suggesting that the use of this inhaled analgesic is safe for healthcare providers in terms of occupational exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France. Frangos, J., Belbachir, A., Dautheville, S., et al.[2021]

A standardized analgesia protocol implemented over 10 months significantly reduced postoperative pain among neurosurgery patients, with a 32% reduction in pain scores on the first postoperative day, indicating improved pain management practices.

The protocol not only lowered pain levels but also enhanced safety, as evidenced by a significant decrease in naloxone doses administered, suggesting fewer instances of opioid-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective time-series quality improvement trial of a standardized analgesia protocol to reduce postoperative pain among neurosurgery patients. Titsworth, WL., Abram, J., Guin, P., et al.[2022]

Citations

1. nature.com nature.com/articles/s41415-023-5889-3

Effectiveness and safety of dentist-led conscious sedation ... Conclusion In this evaluation, the synergistic effects of fentanyl and midazolam resulted in enhanced sedation, anxiolysis and intraoperative ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0007091223006943

Pharmacological agents for procedural sedation and ... Compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK551685/

Procedural Sedation - StatPearls - NCBI Bookshelf Procedural sedation and analgesia commonly involve combining a short-acting benzodiazepine, such as midazolam, with an opioid, such as fentanyl.

4. synapse.koreamed.org synapse.koreamed.org/articles/1095591

Administration order of midazolam/fentanyl for moderate ... This study revealed a 29% reduction in midazolam dosage when low-dose fentanyl opioid was administered first, further demonstrating a ...

5. jamanetwork.com jamanetwork.com/journals/jamapediatrics/fullarticle/204423

Sedation and Analgesia for Pediatric Fracture Reduction in ... Conclusions Ketamine-midazolam seems to be more effective and have fewer adverse events than fentanyl-midazolam or propofol-fentanyl. Data on other forms of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6036533/

Lidocaine-Midazolam-Fentanyl Combination in Controlling ... Findings of the present study showed that adding IV lidocaine to IV midazolam + fentanyl drug combination does not provide additional analgesia in sedation for ...

7. jkms.org jkms.org/DOIx.php?id=10.3346/jkms.2019.34.e21

Efficacy and safety of fentanyl in combination with ... Fentanyl combined with midazolam is safe and more effective than midazolam alone for sedation therapy in mechanically ventilated children.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0885392498000244

Stability of Midazolam and Fentanyl in Infusion Solutions When midazolam and fentanyl are combined, both agents are apparently more than 90% stable for up to 3 hr at room temperature, but the stability of this ...

9. uptodate.com uptodate.com/contents/sedative-analgesia-in-ventilated-adults-management-strategies-agent-selection-monitoring-and-withdrawal/print

Sedative-analgesia in ventilated adults: Management ... Midazolam plus fentanyl maintained sedation level goals better, decreased the dose of the primary agent, added analgesia, and did not ...