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. doi: 10.1111/acem.12072.


Objectives: Although 50% nitrous oxide (N(2) O) and oxygen is a widely used treatment, its efficacy had never been evaluated in the prehospital setting. The objective of this study was to demonstrate the efficacy of premixed N(2) O and oxygen in patients with out-of-hospital moderate traumatic acute pain.

Methods: This prospective, randomized, multicenter, double-blind trial enrolled patients with acute moderate pain (numeric rating scale [NRS] score between 4 and 6 out of 10) caused by trauma. Patients were assigned to receive either 50/50 N(2) O and oxygen 9 L/min (N(2) O group) or medical air (MA) 9 L/min (MA group), in ambulances from two nurse-staffed fire department centers. After the first 15 minutes, every patient received N(2) O and oxygen. The primary endpoint was pain relief at 15 minutes (T15), defined as a NRS ≤ 3 of 10. The NRS was measured every 5 minutes. Secondary endpoints were treatment safety and adverse events, time to analgesia, and patient and investigator satisfaction with analgesia.

Results: Sixty patients were included with no differences between groups in age (median = 34 years, interquartile range [IQR] = 23 to 53 years), sex (37 males, 66%), and initial median NRS of 6 (IQR = 5 to 6). At T15, 67% of the patients in the N(2) O group had an NRS score of 3 or lower versus 27% of those in the MA group (delta = 40%, 95% confidence interval [CI] = 17% to 63%; p < 0.001). The median pain scores were lower in the N(2) O group at T15, 2 (IQR = 1 to 4) versus 5 (IQR = 3 to 6). There was a difference at 5 minutes that persisted at all subsequent time points. Four patients (one in the N(2) O group) experienced adverse events (nausea) during the protocol.

Conclusions: This study demonstrates the efficacy of N(2) O for the treatment of pain from acute trauma in adults in the prehospital setting.

Trial registration: NCT01356745.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Pain / therapy*
  • Adult
  • Aged
  • Analgesia / adverse effects
  • Analgesia / methods*
  • Double-Blind Method
  • Emergency Service, Hospital
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitrous Oxide / adverse effects
  • Nitrous Oxide / therapeutic use*
  • Oxygen / adverse effects
  • Oxygen / therapeutic use*
  • Pain Management / methods*
  • Pain Measurement
  • Patient Satisfaction
  • Prospective Studies
  • Treatment Outcome


  • Nitrous Oxide
  • Oxygen

Associated data