Nitrous Oxide for Procedural Pain

(SANO-VAS Trial)

Overseen By Michelle Shabo, MD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Benzodiazepines, Opioids

Disqualifiers: Cognitive impairment, Severe B-12 deficiency, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to see if nitrous oxide during vasectomy decreases pain and anxiety, and also assess whether patients have better satisfaction when they control their own level of nitrous oxide during the procedure. If we find that patients experience less pain or anxiety with nitrous oxide, it could be suggested that self-adjusted nitrous oxide (SANO) may be a useful tool for improving experience of care during vasectomy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use benzodiazepines or opioids 'as needed' for the vasectomy.

What data supports the idea that Nitrous Oxide for Procedural Pain is an effective treatment?

The available research shows that nitrous oxide can be effective in reducing pain during certain procedures. For example, a study on adults undergoing puncture biopsy found that nitrous oxide helps relieve pain quickly. Another study found that nitrous oxide reduces the intensity of pain sensations, although it may not reduce how unpleasant the pain feels. Compared to 100% oxygen, nitrous oxide was more effective in reducing pain intensity. However, the research also indicates that its effectiveness can vary, and more data is needed to fully understand its benefits for different procedures. ^{1 2 3 4 5}

What safety data exists for nitrous oxide used for procedural pain?

Nitrous oxide, also known as laughing gas, is commonly used for its analgesic and sedative properties. Safety concerns include potential vitamin B12 deficiency, abuse liability, and risks of infertility, spontaneous abortion, blood dyscrasias, and neurologic deficits due to occupational exposure. Scavenger systems are recommended to minimize exposure. In pediatric settings, nitrous oxide is used for procedural sedation, but there is limited safety data for high-concentration use, with some studies noting adverse events and varying depths of sedation. ^{1 6 7 8 9}

Is nitrous oxide a promising drug for reducing pain during procedures?

Yes, nitrous oxide is a promising drug for reducing pain during procedures. It is appealing because it works quickly, helps with anxiety, and doesn't require needles. It has been shown to effectively reduce pain in both children and adults during various medical and dental procedures. ^{1 10 11 12 13}

Research Team

Heidi Rayala, MD, PhD

Principal Investigator

Beth Israel Deaconess Medical Center

Peter Steinberg, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Marissa Kent, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for men aged 21 to 85 scheduled for a vasectomy, who can use email and a computer, and are suitable for inhaling nitrous oxide/oxygen. It's not for those using benzodiazepines or opioids around the time of surgery, with facial hair affecting mask seal, cognitive issues preventing survey completion, or specific recent surgeries or medical conditions.

Inclusion Criteria

Scheduled for vasectomy

Access to an email and computer

You must be between 21 and 85 years old.

Exclusion Criteria

You plan to use benzodiazepines or opioids "as needed" for a vasectomy.

You have facial hair around your mouth that prevents a mask from fitting properly.

You have trouble thinking clearly and answering survey questions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (virtual or in-person)

Treatment

Participants undergo vasectomy with self-adjusted nitrous oxide for pain and anxiety management

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after vasectomy, including surveys on pain, anxiety, and satisfaction

3 months

2 surveys (electronic)

Treatment Details

Interventions

• Nitrous oxide

Trial Overview The study tests if self-administered nitrous oxide (laughing gas) during vasectomy reduces pain and anxiety compared to standard care. Participants will control their own intake of the gas to see if it improves their overall experience during the procedure.

Participant Groups

Group I: Self-adjusted nitrous oxide (SANO) Experimental Treatment 1 Intervention

All patients will receive nitrous oxide at concentrations of minimal sedation (0-50%) throughout vasectomy.

Nitrous oxide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia
• Emergency department analgesia

Approved in European Union as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia

Approved in Canada as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Findings from Research

In a study of 124 children aged 1-17 undergoing procedures in the emergency department, nitrous oxide (N2O) was used for analgesia, but pain scores showed that 34% of patients experienced significant pain (scores of 70 mm or greater) during procedures, indicating limited efficacy for very painful interventions.

Despite the pain management limitations, both parents (96% satisfaction) and staff (92% rated sedation and analgesia as adequate) reported high satisfaction with the use of N2O for procedural sedation in the emergency department.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited analgesic efficacy of nitrous oxide for painful procedures in children. Babl, FE., Oakley, E., Puspitadewi, A., et al.[2022]

Nitrous oxide (N2O) has been found to be effective in reducing pain during puncture biopsy procedures, showing a significant analgesic effect compared to controls like placebo and other sedatives, based on a review of 12 randomized controlled trials involving 1070 patients.

In addition to pain relief, N2O also significantly reduced patient anxiety and improved overall satisfaction without increasing the risk of common side effects such as nausea, headache, or dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of nitrous oxide in adults undergoing puncture biopsy: A systematic review and meta-analysis of randomized controlled trials. Wang, Z., Wang, F., Xing, Y., et al.[2023]

Nitrous oxide (N2O) is a safe and effective anesthetic and analgesic gas that can be used in various medical situations due to its low incidence of adverse effects.

It can be administered by trained medical providers or even self-administered by patients, making it a versatile option in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on nitrous oxide and its use in anesthesia practice. Zafirova, Z., Sheehan, C., Hosseinian, L.[2019]

Nitrous oxide is effective in reducing distress in children undergoing painful procedures, with 93% of patients achieving conscious sedation and 65% having no recollection of the procedure.

The treatment has minimal side effects, with 86% of patients experiencing none, and a quick recovery time of about three minutes, making it a safe option for managing pain in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nitrous oxide in alleviating pain and anxiety during painful procedures. Kanagasundaram, SA., Lane, LJ., Cavalletto, BP., et al.[2022]

In a study with 48 subjects, the use of 33% nitrous oxide and 67% oxygen significantly reduced the intensity of pain from electrical tooth pulp stimulation, but did not decrease the unpleasantness of the sensations.

The study found that 100% oxygen had no analgesic effect, highlighting the specific pain-relieving properties of nitrous oxide in dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide analgesia: a psychophysical evaluation using verbal descriptor scaling. Heft, MW., Gracely, RH., Dubner, R.[2017]

Healthcare professionals exposed to high levels of nitrous oxide (N2O) in the past faced significant reproductive risks, including congenital anomalies and reduced fertility rates, but these risks have been reduced due to occupational safety measures.

Recreational users of N2O often exceed safe exposure limits by a large margin, putting themselves at risk for similar reproductive issues, highlighting the need for increased awareness about these dangers among users, especially those who are pregnant or planning to become pregnant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide-induced reproductive risks: Should recreational nitrous oxide users worry? van Amsterdam, J., van den Brink, W.[2022]

Nitrous oxide (N2O) is an effective analgesic and sedative used in dentistry, offering benefits like rapid onset and both pain relief and anxiety reduction.

Despite its advantages, nitrous oxide can lead to vitamin B12 deficiency and has potential risks such as infertility and neurological issues, highlighting the importance of using scavenger systems to reduce occupational exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Not Available]. Liakoni, E., Liechti, ME.[2019]

A study involving 1,058 children aged 1-23 years demonstrated that nitrous oxide is a safe and effective sedation option for minor surgical procedures, with no major complications reported.

The use of nitrous oxide resulted in high patient satisfaction, with 98% of children denying pain from injections and 82% reporting mild or no procedural pain, highlighting its efficacy in reducing anxiety and discomfort during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide procedural sedation in non-fasting pediatric patients undergoing minor surgery: a 12-year experience with 1,058 patients. Pasarón, R., Burnweit, C., Zerpa, J., et al.[2018]

In a study of 762 pediatric patients aged 1 to 17 years, high-concentration nitrous oxide (70%) was found to be safe for procedural sedation, with only 8.4% experiencing mild adverse events, primarily vomiting.

The study indicated that there was no significant difference in the incidence of adverse events between nitrous oxide concentrations of 70% and 50%, and both concentrations provided effective sedation without serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-concentration nitrous oxide for procedural sedation in children: adverse events and depth of sedation. Babl, FE., Oakley, E., Seaman, C., et al.[2022]

Nitrous oxide (N2O) has been effectively used for over 170 years in dental anesthesia due to its rapid onset, analgesic, anxiolytic, and amnestic properties, making it a popular choice for procedural sedation.

While N2O is generally safe for use, it can cause irreversible inactivation of vitamin B12, which is crucial for health, and in rare cases, this can lead to serious or fatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications caused by nitrous oxide in dental sedation. Chi, SI.[2020]

Inhalation of nitrous oxide and oxygen (N2O/O2) significantly reduces perioperative pain during first-trimester termination of pregnancy, as shown in a meta-analysis of four studies involving various pain assessments.

While N2O/O2 effectively alleviates pain during the procedure, it does not impact postoperative pain or secondary effects like nausea and vomiting, indicating its focused efficacy in managing pain during the procedure itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide for pain management of first-trimester instrumental termination of pregnancy under local anaesthesia and/or minimal sedation: A systematic review and meta-analysis. Schmitt, A., Cardinale, C., Loundou, A., et al.[2022]

In a study involving 34 children undergoing laceration repair, nitrous oxide (N2O) was found to significantly reduce pain behavior compared to a placebo, especially in children under 8 years old.

No side effects were reported, indicating that N2O is a safe and effective analgesic for outpatient procedures in children, with potential for even greater efficacy at higher concentrations (40-50% N2O) that still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide analgesia in a pediatric emergency department. Gamis, AS., Knapp, JF., Glenski, JA.[2019]

In a study of 173 vascular and interventional procedures over 2 years, nitrous oxide was found to be a safe and effective analgesic, providing adequate pain relief in 74% of patients without premedication and 61% of those with premedication.

Minor complications such as nausea and vomiting were reported in a small number of patients, but these were easily managed by adjusting the nitrous oxide concentration, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide: effective analgesic for vascular and interventional procedures. Braun, SD., Miller, GA., Ford, KK., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Limited analgesic efficacy of nitrous oxide for painful procedures in children. [2022]

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

Efficacy of nitrous oxide in adults undergoing puncture biopsy: A systematic review and meta-analysis of randomized controlled trials. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Update on nitrous oxide and its use in anesthesia practice. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nitrous oxide in alleviating pain and anxiety during painful procedures. [2022]

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

Nitrous oxide analgesia: a psychophysical evaluation using verbal descriptor scaling. [2017]

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

Nitrous oxide-induced reproductive risks: Should recreational nitrous oxide users worry? [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Not Available]. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Nitrous oxide procedural sedation in non-fasting pediatric patients undergoing minor surgery: a 12-year experience with 1,058 patients. [2018]

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

High-concentration nitrous oxide for procedural sedation in children: adverse events and depth of sedation. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Complications caused by nitrous oxide in dental sedation. [2020]

11. Ireland pubmed.ncbi.nlm.nih.gov

Nitrous oxide for pain management of first-trimester instrumental termination of pregnancy under local anaesthesia and/or minimal sedation: A systematic review and meta-analysis. [2022]

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

Nitrous oxide analgesia in a pediatric emergency department. [2019]

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

Nitrous oxide: effective analgesic for vascular and interventional procedures. [2013]