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

54 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug methoxyflurane for pain relief?

Research shows that methoxyflurane, when self-administered at a low dose, is a fast-acting and safe option for short-term pain relief, particularly in cancer-related procedures. ^{1 2 3 4 5}

Is methoxyflurane safe for pain relief in humans?

Methoxyflurane has been used safely for over 40 years in Australia for pain relief in both adults and children, with a well-established safety profile. Adverse effects are usually brief and mild, and serious kidney problems seen with high doses are not reported with the low doses used for pain relief. ^{6 7 8 9 10}

How does the drug methoxyflurane differ from other pain relief options for trauma?

Methoxyflurane is unique because it is an inhaled, non-opioid pain reliever that provides rapid pain relief and can be self-administered using a hand-held inhaler. Unlike other pain relief options that may require injections or intravenous administration, methoxyflurane is easy to use and has a quick onset of action, making it a convenient option for managing moderate to severe trauma pain in emergency settings. ^{6 8 9 11 12}

What is the purpose of this trial?

This study is to assess the non-inferiority of using inhaled methoxyflurane (MOF) versus intravenous conscious sedation with fentanyl and midazolam on women's perception of pain, during hysteroscopy and/or polypectomy in an outpatient setting. The researchers will determine whether the participants receiving the inhaled MOF (experimental group) achieve similar clinical effects in reduction of pain and ability to complete the procedure. Women's perception of pain will be recorded on a scale from 0 to 10 using the numeric rating scale (NRS).

Research Team

Peter S Thiel, MD MPH FRCSC

Principal Investigator

University of Saskatchewan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Concepts for treatment of postoperative pain]. [2008]

2. Germany pubmed.ncbi.nlm.nih.gov

Literature review on the use of methoxyflurane in the management of pain in cancer-related procedures. [2023]

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

A prospective time-series quality improvement trial of a standardized analgesia protocol to reduce postoperative pain among neurosurgery patients. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Effect of postoperative pain treatment on outcome-current status and future strategies. [2022]

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

Improving ambulatory surgical pain management. [2019]

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

The role of inhaled methoxyflurane in acute pain management. [2020]

7. England pubmed.ncbi.nlm.nih.gov

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. [2022]

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

Service Evaluation of Methoxyflurane Versus Standard Care for Overall Management of Patients with Pain Due to Injury. [2021]

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

Low-Dose Methoxyflurane versus Standard of Care Analgesics for Emergency Trauma Pain: A Systematic Review and Meta-Analysis of Pooled Data. [2022]

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

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis. [2022]

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

Methoxyflurane: A Review in Trauma Pain. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France. [2021]