Nitrous Oxide for Burn Pain Management

Overseen By Sarvesh Logsetty, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Manitoba

Must not be taking: Narcotics, IV ketamine

Disqualifiers: Respiratory disease, Cardiovascular disease, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration of dressing change sessions

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage pain for burn patients during wound care. It tests nitrous oxide, a gas often used for pain relief, to determine if it can reduce pain without the risks associated with traditional narcotics. Participants will receive either nitrous oxide or a placebo (an inactive substance) to compare effects. The trial suits adults with burns covering 5-20% of their body who are not in intensive care and can engage in trial activities. The aim is to find a safer, effective way to manage the intense pain of dressing changes for burn patients. As an Early Phase 1 trial, this research focuses on understanding how nitrous oxide works in people, offering participants the chance to be among the first to explore this potential new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that using IV ketamine or pre-injury narcotics might affect your eligibility. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that nitrous oxide is likely to be safe for humans?

Research shows that nitrous oxide, or laughing gas, is often used in medical settings like surgery and dentistry to relieve pain and reduce anxiety. Studies have found it to be generally safe and well-tolerated in controlled amounts. Some individuals might experience lightheadedness or dizziness, but serious issues are rare. Nitrous oxide has been used safely for many years in various medical procedures, indicating it could be a good option for managing pain, such as during burn wound care. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for burn pain management?

Researchers are excited about using nitrous oxide for burn pain management because it offers a fast-acting and non-invasive option. Unlike traditional pain relief methods for burns, such as opioid medications, nitrous oxide provides quick pain relief without the same risk of addiction or serious side effects. This inhalant works by altering the brain's pain perception, offering a unique mechanism that can be especially beneficial for managing intense, acute pain from burns.

What evidence suggests that nitrous oxide might be an effective treatment for burn pain management?

Research has shown that nitrous oxide, which participants in this trial may receive, can help reduce pain during burn wound care. One study with 70 adult burn patients found that nitrous oxide significantly lessened pain and anxiety during bandage changes. Another study demonstrated that a mix of nitrous oxide and oxygen was more effective than oxygen alone for treating moderate to severe pain. Additionally, nitrous oxide lowered pain scores during wound care. These findings suggest that nitrous oxide might help manage the intense pain often experienced in burn treatment. Participants in this trial may also receive a placebo for comparison. ^{5 6 7 8 9}

Who Is on the Research Team?

Sarvesh Logsetty, MD

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

This trial is for adult burn patients with 5-20% of their body surface burned, not in intensive care, able to understand English and participate in outcome measurements. It excludes those with significant heart or lung disease, pregnant women, face burns, pre-injury narcotic use, ketamine treatment during the trial or a pre-existing lung injury.

Inclusion Criteria

5-20% of my body has burn injuries.

Adults who have been admitted to the Health Sciences Centre for burn treatment.

Exclusion Criteria

Your oxygen level is below 90% when breathing normally.

I am currently in the intensive care unit.

You have been taking painkillers before getting injured (may not be allowed to participate).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nitrous oxide or placebo during burn dressing changes to evaluate pain control

Duration of dressing change sessions

Multiple visits for dressing changes

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 hour after each dressing change

What Are the Treatments Tested in This Trial?

Interventions

• Nitrous Oxide Inhalant Product
• Placebo

Trial Overview The study tests if disposable nitrous oxide canisters provide effective pain relief during burn dressing changes compared to a placebo. The goal is to find an alternative to narcotics that avoids respiratory suppression while managing intense pain.

How Is the Trial Designed?

Group I: Nitrous Oxide Inhalant Product Experimental Treatment 1 Intervention

Nitrous oxide

Group II: Placebo Placebo Group 1 Intervention

placebo comparator

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

Approved in United States as Nitrous Oxide for:

• Pain relief during medical procedures
• Anesthesia for dental and surgical procedures

Approved in European Union as Nitrous Oxide for:

• Pain relief during medical procedures
• Anesthesia for dental and surgical procedures

Approved in Canada as Nitrous Oxide for:

• Pain relief during medical procedures
• Anesthesia for dental and surgical procedures

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Published Research Related to This Trial

In a study of 70 stable adult burn patients, titrating nitrous oxide (N2O) from 30% to an ideal concentration significantly reduced pain and anxiety during burn dressing changes compared to a fixed 50% N2O treatment.

The titration method also resulted in minimal side effects and showed significant differences in vital signs, indicating a safer and more effective approach to pain management in burn care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of analgesic and anxiolytic effects of nitrous oxide in burn wound treatment: A single-blind prospective randomized controlled trial. Li, L., Pan, Q., Xu, L., et al.[2020]

The expert consensus outlines the safe and effective use of nitrous oxide and oxygen mixed inhalation for sedation and pain relief in burn surgery, based on insights from multiple expert meetings and practical experiences.

It includes comprehensive guidelines on indications, contraindications, potential side effects, and necessary training for healthcare providers to ensure optimal application of this sedation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expert consensus on the application of nitrous oxide and oxygen mixed inhalation for sedation and analgesia technology in burn surgery (2021 version)]. [2021]

A systematic review of 34 studies on recreational nitrous oxide (N2O) use highlights a concerning increase in its use and associated harms, particularly among young people, yet there is a lack of awareness about these risks.

The review calls for improved harm reduction strategies, emphasizing the need for both policy changes and service delivery improvements to better address the growing issue of N2O use and its potential dangers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Recreational Nitrous Oxide Use: Implications for Policy, Service Delivery and Individuals. Allan, J., Cameron, J., Bruno, J.[2023]

In a study involving 15 adult burned patients, the combination of nitrous oxide (N2O) and fentanyl did not significantly reduce pain during dressing changes compared to using oxygen alone.

Patients reported similar pain levels and fentanyl consumption in both the N2O group and the control group, indicating that N2O did not provide additional analgesic benefits in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of nitrous oxide on fentanyl consumption in burned patients undergoing dressing change]. Vale, AH., Videira, RL., Gomez, DS., et al.[2016]

Inhalation of nitrous oxide (N2O) from commercial sources, such as aerosol whipping cream containers and chargers, can lead to serious health risks including nerve damage, mental impairment, and even death due to hypoxemic mixtures.

The study found that these N2O products are highly concentrated and easily misused, suggesting a need for stricter regulations or discontinuation of their distribution due to their toxicity and lack of proper labeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide availability. Murray, MJ., Murray, WJ.[2019]

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 mixed with oxygen provides effective pain relief within 3 minutes and is successful in 75 to 81% of patients, making it a reliable option for managing procedure-related pain in children.

The nitrous oxide/oxygen mixture is considered safe with minimal side effects, and recent studies do not support concerns about diffusion hypoxia, reinforcing its suitability for pediatric use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analgesia using a (50/50) mixture of nitrous oxide/oxygen in children]. Carbajal, R.[2019]

Inhalation of a mixture of 65% nitrous oxide and oxygen significantly reduced pain and anxiety in burn patients during and after dressing changes, as evidenced by lower visual analogue scale (VAS) and burn specific pain anxiety scale (C-BSPAS) scores compared to the control group.

The treatment did not cause significant adverse effects and improved vital signs (heart rate, blood pressure, and oxygen saturation) during the procedure, indicating its safety and efficacy for managing discomfort in burn care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analgesic and sedative effects of inhaling a mixture of nitrous oxide and oxygen on burn patient during and after dressing change]. Li, YX., Tang, HT., Zhou, WF., et al.[2022]

Medical workers recognize a significant gap in effective pain management for children with burns during dressing changes, indicating a need for improvement in current practices.

After reviewing literature, medical staff expressed support for using 50% nitrous oxide as a pain management option for children, but they also noted that existing guidelines need to be updated to ensure its safe and effective application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical workers' cognition of using 50% nitrous oxide in children with burns: a qualitative study. Wang, HX., Li, YX., Zhou, RZ., et al.[2015]

In a study involving 15 adult burned patients, the combination of nitrous oxide (N2O) and fentanyl did not significantly reduce pain during dressing changes compared to using oxygen alone.

Patients reported similar pain levels and fentanyl consumption in both the N2O group and the control group, indicating that N2O did not provide additional analgesic benefits in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of nitrous oxide on fentanyl consumption in burned patients undergoing dressing change. do Vale, AH., Videira, RL., Gomez, DS., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3404913/

Analgesia effect of a fixed nitrous oxide/oxygen mixture on ... This article describes a study designed to test the analgesia effect of a fixed nitrous oxide/oxygen mixture on burn dressing pain.

2. withpower.com withpower.com/trial/early-phase-1-burns-9-2019-56c99

Nitrous Oxide for Burn Pain Management In a study of 70 stable adult burn patients, titrating nitrous oxide (N2O) from 30% to an ideal concentration significantly reduced pain and anxiety during burn ...

3. journals.plos.org journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0333378

Analgesic effect of diluted nitrous oxide in rehabilitation ... There is currently a lack of trials evaluating the efficacy of nitrous oxide in the treatment of pain during rehabilitation training in burn patients.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0736467919304871

Analgesic Effect of Nitrous Oxide/Oxygen Mixture for ... This study demonstrates that 65% nitrous oxide/oxygen seems to be more efficacious than oxygen in treating moderate-to-severe traumatic pain in the ED.

5. clinicalpainadvisor.com clinicalpainadvisor.com/news/during-wound-care-nitrous-oxide-reduced-pain-scores-for-burns-but-not-ulcers/

During Wound Care, Nitrous Oxide Reduced Pain Scores ... Nitrous oxide (N 2 O) was statistically significantly effective for pain reduction during burn care, according to study results published in Advances in Wound ...

6. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Nitrous-Oxide

Nitrous Oxide | N2O | CID 948 - PubChem Nitrous oxide is a colorless, sweet-tasting gas. It is also known as laughing gas. Continued breathing of the vapors may impair the decision making process.

7. adf.org.au adf.org.au/insights/nitrous-oxide/

Nitrous oxide – uses, impacts and risks Discover expert guidance on nitrous oxide uses, impacts and risks - evidence-based information, safety strategies, and professional advice ...

8. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/nitrous-oxide-laughing-gas

Nitrous Oxide (Laughing Gas): Uses, Side Effects & Safety Nitrous oxide (laughing gas) is a sedative healthcare providers use to keep you comfortable during procedures. It's a colorless, faintly sweet-smelling gas.

9. en.wikipedia.org en.wikipedia.org/wiki/Nitrous_oxide

Nitrous oxide Nitrous oxide has significant medical uses, especially in surgery and dentistry, for its anaesthetic and pain-reducing effects.