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

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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?

Background: 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:

The study population included or focused on those in the ED. NO
The patients were adequately randomized. Yes
The randomization process was concealed. Yes
The patients were analyzed in the groups to which they were randomized. Yes
The study patients were recruited consecutively (i.e. no selection bias).Yes
The patients in both groups were similar with respect to prognostic factors. Yes
All participants were unaware of group allocation. Yes
All groups were treated equally except for the intervention. Yes
Follow-up was complete. Yes
All patient-important outcomes were considered. Yes
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.

BEEM 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.

Clinical 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 TheSGEM@gmail.com with Keener Kontest in the subject line. The first person with the correct answer will win a cool skeptical prize.

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