A Randomized, Placebo-controlled Trial of Nitrous Oxide During In-office Bladder Botox Injections

This study will assess if a 50:50 nitrous oxide and oxygen mixture can lower pain in women undergoing in-office bladder onabotulinumtoxinA (Botox) injections. Many people report pain during this procedure, and pain is a common reason not to repeat the procedure. Nitrous oxide is a fast-acting inhaled analgesic that is used commonly in the office setting.

This randomized controlled trial will compare nitrous oxide/oxygen plus standard care with sham mask plus standard care. Participants assigned to the nitrous oxide group will receive nitrous oxide via the Pro-Nox device during the procedure. Both, participants assigned to the nitrous oxide group and the standard care alone group, will receive the usual lidocaine instilled in the bladder for at least 15 minutes.

The study will measure participants overall pain during the procedure. It will also assess peak pain, overall anxiety, satisfaction, willingness to repeat, interest in using nitrous oxide in future bladder Botox procedures, and side effects. Nitrous oxide is expected to wear off within minutes, allowing participants to leave the clinic without restrictions.

This research study would be first randomized-controlled trial to evaluate nitrous oxide for pain management during this common in-office procedure.

• Pro-Nox Nitrous Oxide/Oxygen Delivery System (Drug), also known as Pro-Nox, Nitrous oxide/oxygen 50:50 mixture, Nitrous oxide/oxygen, Nitrous, Nitrous oxide, Nitrous oxide analgesia: The Pro-Nox system delivers a fixed 50:50 mixture of nitrous oxide and oxygen for patient self-administered inhaled analgesia. Participants will self-administer nitrous oxide throughout the in-office bladder Botox procedure.
• Standard Care for Bladder Botox Injection (Drug), also known as Intravesical lidocaine, Lidocaine, Standard care, Standard analgesia, Local analgesia: Standard care includes intravesical instilled 1-2% lidocaine with a dwell time of at least 15 minutes before the procedure.
• Sham Mask (Other), also known as Placebo, Room Air: The Sham Mask will involve that participant using the same mask as that of the Nitrous Oxide group, but connected to a Pro-Nox system that is turned completely off. They will therefore receive room air through the mask.

Primary outcomes

• Overall Pain (10-point NRS) [At least 3 minutes after completion of the procedure.]: Patient self-reported overall pain during the procedure on an 11-point numeric rating scale.

Secondary outcomes

• Peak Pain (10-point NRS) [At least 3 minutes after completion of the procedure.]: Patient self-reported peak pain during the procedure on an 11-point numeric rating scale.
• Peak Pain Timing [At least 3 minutes after completion of the procedure.]: Patient self-reported timing of peak pain during the procedure, as it corresponds to different steps during the procedure.
• Overall Anxiety (10-point NRS) [At least 3 minutes after completion of the procedure.]: Patient self-reported overall anxiety during the procedure on an 11-point numeric rating scale.
• Satisfaction with Pain Management (10-point NRS) [At least 3 minutes after completion of the procedure.]: Patient self-reported satisfaction with pain management during the procedure on an 11-point numeric rating scale.
• Willingness to Repeat (5-point Likert) [At least 3 minutes after completion of the procedure.]: Patient self-reported willingness to repeat under similar pain and anxiety management conditions, on a 5-point Likert scale.

Other outcomes

• Nitrous Interest (5-point Likert) [At least 3 minutes after completion of the procedure.]: Patient self-reported interest in use of nitrous oxide for pain and anxiety management in a future procedure, on a 5-point Likert scale.
• Adverse Effects [Immediately following the procedure. Completed by performing surgeon.]: Physician reported adverse events encountered peri-operatively.
• Blinding Assessment [At least 3 minutes after completion of the procedure.]: Patient self-reported perceived treatment assignment (nitrous oxide/oxygen vs sham mask), recorded as nitrous oxide, sham mask, or unsure.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Adult women ≥18 years old scheduled for in-office intradetrusor botulinum toxin injection and able to consent.

Exclusion Criteria:

* Known/suspected vitamin B12 or folate deficiency or high-risk state (e.g., pernicious anemia, malabsorption, post-bariatric or strict vegan without supplementation)
* currently pregnant
* severe/unstable pulmonary disease or baseline hypoxemia requiring supplemental home oxygen
* eye or ear surgery in the last six weeks
* trapped-air conditions (e.g., untreated pneumothorax, bowel obstruction)
* severe active otitis/sinus disease
* inability to follow directions
* history of adverse reaction to nitrous oxide