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SGEM#60: Nitrous Oxide It’s a Gas, Gas, Gas

SGEM#60: Nitrous Oxide It’s a Gas, Gas, Gas

Podcast Link: SGEM60
Date:  January 22, 2014

Guest Skeptic: Dr. Josh Williams

Case Scenario: You are working at “The Hut” (Ski Patrol Hut) and a 46yo snowboarder comes in after falling. He has an obvious deformity of his right wrist. He is neurovascularly intact but in a moderate pain. It is 45 minutes transfer from the ski hill to the emergency department.

Questions:  How does nitrous oxide compare to medical air for prehospital treatment of adults with moderate traumatic acute pain?

Slide30Background: On the surface N2O has a lot of the properties we’d like to see in a prehospital analgesic. From studies with children, we know it’s safe, non-invasive (doesn’t require IV access), has a rapid onset and offset, effective and reversible. However, there is a paucity of high-quality studies looking at adults in the emergency department setting.

Reference: Ducassé JL et al (2013). Nitrous oxide for early analgesia in the emergency setting: a randomized, double-blind multicenter prehospital trial. Acad Emerg Med. 2013 Feb;20(2):178-84.

  • Population: Prospective, randomized, double-blind, multicenter controlled trial of 60 adult French patients who suffered moderate (self-rated pain of 4-6 out of 10) acute pain as a result of traumatic injury. Exclusion criteria included contraindications to premixed 50% N20 and oxygen such as intracranial hypertension, unconsciousness, pneumothorax, recent eye surgery and other disorders involving accumulation of gas in closed body spaces such as emphysema, intestinal ileus, sinusitis, or facial trauma. Other exclusion criteria included lack of a nurse in the fire service team, analgesic medication within 6-hours, pregnancy, or inclusion in another trial. Patients not transported to the reference hospital were not included.
  • Intervention: 50% nitrous oxide at 9L/min
  • Comparison: Medical air at 9L/min
  • Outcome: The primary outcome measure was the percentage of patients with pain relief (numeric pain score of 3 or less) at 15 minutes. Secondary outcomes assessed included safety and adverse events, time to analgesia, and patient and investigator satisfaction with analgesia.

Authors Conclusions“Nitrous oxide is an efficacious means of prehospital analgesia for moderate traumatic acute pain.”

Quality Checklist:

  1. The study population included or focused on those in the ED. NO
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias).Yes
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants were unaware of group allocation. Yes
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete. Yes
  10. All patient-important outcomes were considered. Yes
  11. Treatment effect was large enough and precise enough to be clinically significant. Yes

Results: After 15 minutes of N20 versus placebo, 67% of patients in the N20 group reported a numeric pain score of 3 or lower compared to 27% of those in the medical air group. The median pain scores were also lower in the N20 group after 15 minutes of treatment (pain score 2 versus 5). Only one patient in the N20 group described an adverse event.

Screen Shot 2014-01-22 at 7.22.43 AMBEEM Commentary: This was a randomized, double-blind multicenter trial with good methodology, which showed significant results (reduced pain score of 67% in the treatment group versus 27% in the control [95% CI 17% to 63%, p < 0.001]). The authors do not provide absolute numbers, a 2×2 contingency table, or any estimate of number needed to treat (NNT), but BEEM did these calculations on your behalf. The NNT with nitrous oxide to obtain a pain score of three or less within 15-minutes in a patient who otherwise would not have obtained this pain score is 3 (95% CI 1.6-8.6).

Two details are particularly important. First, this was a study of efficacy only, so although there is commentary on adverse effects, the study was not designed to assess safety. Second, this was a trial in the prehospital setting and we should not generalise these results to the ED based on this study alone.

Further research is required in the ED setting, particularly for safety before use of N20 in the ED is standard of care. Nonetheless, there is promise for use of this agent without waiting for IV access, with an agent that demonstrates no adverse hemodynamic changes, few adverse effects, and can be easily titrated.

The Bottom Line: Though not ready for widespread and routine ED application, N20 shows promise as an analgesic for moderate traumatic acute pain.

Case Resolution: You recognize the patient is in pain. He is provided with 50% nitrous oxide, splinted and transferred. Within 15 minutes his pain has decreased significantly. He arrives at the emergency department 45 minutes later feeling more comfortable and xray confirms a distal radius fracture.

Screen Shot 2014-01-22 at 7.41.33 AMClinical Application: If futures studies demonstrate safety and efficiency, N20 could be added to analgesic options in the prehospital setting.

What do I tell my patients? We do not have access to nitrous oxide (laughing gas) in the adult ED, although many children’s hospitals are using it. Early research in adults indicates that nitrous oxide could be an effective and safe strategy to acutely reduce pain without an IV, but we need to study this medication a bit more. Your dentist’s chair is still the likeliest place you’ll experience laughing gas.

KEENER KONTEST: Last weeks winner was Dr. James Huffman from Calgary Alberta. He knew that Dr. Peter Safar had been nominated three times for a Nobel Prize in Medicine but never won for his development of CPR.

Listen to the SGEM podcast to hear the keener question. If you know the answer send an email to with Keener Kontest in the subject line. The first person with the correct answer will win a cool skeptical prize.

BEEM Conferences: SteelBEEM, SweetBEEM and PrairieBEEM

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

  • Chris Cresswell

    Hi guys. I think you need to be careful stating: “Though not ready for widespread and routine ED application, N20 shows promise as an analgesic for moderate traumatic acute pain.” Naive listeners/readers will think that N2O is not an acceptable ED treatment yet. In fact nitrous has a wealth of safety data from anaesthetics and widespread ED.

    We need to keep these things in perspective and not get lost in the academic analysis of one paper.

    Otherwise, love your work

    Chris Cresswell
    Emergency Physician
    New Zealand.

    • admin

      Thanks for the feedback. Glad you like the SGEM. I am going to ask Josh who was the primary reviewer on the paper to respond to your concerns. Keep listening and keep the dialog going.

    • Josh Williams

      Hi Craig,

      Thanks for the comment. I think you may be overstating things when you say the is a “wealth of safety data” on N2O, though I would support there is a wealth of experience with the drug in both the hospital and pre-hospital setting. I’m unaware of any ED-based, well-performed, adequately powered studies looking at the safety of N2O in this setting. If it’s out there and I’m ignorant, I’d love the reference!

      I think N2O is likely an acceptable ED treatment in the right setting ie. experienced provider, adequate monitoring and personnel, etc, etc, and I believe it’s probably used more commonly where you practice (judging from where much of the literature comes from). Where I practice, the only place I see this used is in the pre-hospital setting (paramedics and ski patrol), and I’ve never seen a serious safety issue in those hands.

      I’m looking forward to the day that I can unequivocally support N2O in the ED setting, but until I see that good safety data, it’s difficult to make that recommendation.