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Patient Care

Nitrous Oxide as a Prehospital Analgesic

Your ALS ambulance is dispatched for a 22-year-old male with no past medical history who complains of a possible shoulder dislocation. Upon arrival you find an isolated anterior shoulder dislocation on the right, with no additional injuries or complaints. You want to treat the patient’s pain, but what do you choose? NSAIDs? Morphine? Maybe fentanyl? Or is there another option?

Nitrous oxide (nitrox) has been well known and studied in the prehospital environment since the 1970s, with additional studies cited in the anesthesia, obstetrics, and emergency medicine literature.1 NHTSA approved nitrox for use at the advanced emergency medicine technician (AEMT) level in 2007.2

With increasing pressure from the media and public, as well as increasing support in medical literature for reducing opiate analgesics, emergency systems are actively exploring alternatives to opiate pain medications.

Nitrox is no different.3 EMS use of nitrox as a treatment for acute pain has been explored as far back as 2014,4 and internationally—such as in Canada, France, Australia, and the United Kingdom—nitrox has been safely and effectively used for years as both a hospital and prehospital analgesic.5,6

Delivery and Action

The delivery system, as approved by the FDA, is a two-cylinder rig with a distal mixing chamber, which delivers nitrous oxide and oxygen at a fixed 1:1 mixture, under negative pressure, with a demand valve attached to a face mask.7 The safety of the device lies with the demand valve: With this system the patient is in charge of their own dose of nitrox. The patient must be able to maintain an airtight seal between the mask and their face to receive the gas. Should the patient become drowsy or unable to hold the mask, the mask will fall away, stopping the administration. An additional fail-safe within the system prevents the risk of a hypoxic mixture or delivery of pure nitrous oxide.

The analgesic effect of nitrox is due to its partial mu receptor agonist properties, while the anxiolytic effect resembles that of benzodiazepines, acting as an agonist at selected subunits of the gamma-aminobutyric acid type A (GABA-A) receptor. The anesthetic effect of nitrox may also involve actions at GABA-A receptors and possibly NMDA receptors as well.8 Peak therapeutic levels are reached within 2–5 minutes of administration, and levels fall below the therapeutic index approximately 3–5 minutes after stopping administration.8 

Indications and Contraindications

A 2003 position paper reviewed 10 studies that all concluded prehospital providers underestimate and inadequately treat pain.9 As an alternative to opiate administration, patient-administered nitrox has been found to be safe and effective in the prehospital setting.10–12 Specifically, nitrox has been shown to safely and effectively treat acute pain related to conditions such as angina, nephrolithiasis, urinary retention, burns, musculoskeletal injuries including fractures and dislocations, labor pain, and even anxiety and pain associated with pediatric IV insertion.10–13

With a patient-controlled inhaled anesthetic, the patient must have an intact mental status and be able to comprehend instructions. Additionally, due to the medication’s mechanism of action and potential to alter the senses, patients already altered due to drugs, alcohol, or psychiatric conditions are not good candidates for nitrox. Patients with maxillofacial abnormalities or facial burns also cannot use this medication, as it is administered via face mask.

Since nitrous oxide is administered via inhalation, it should not be used in instances where there is any pathologic air accumulation, such as a pneumothorax.

Nitrox also should not be used in cases of undifferentiated abdominal pain, which could present as a tender abdomen with possible rigidity or rebound tenderness, as these signs are suspicious for free air in the abdomen or intestinal wall14 —additional examples of pathologic accumulation of air.

Nitrox is also contraindicated in decompression illness and head injury, as it could result in increased intracranial pressure.15 Additionally, due to the theoretical possibility of hypoxemia in the fetus, nitrox should not be administered to pregnant patients, with the exception of those in active labor.13,14

Ambulance Ventilation

Since nitrox has a high molecular weight, the gas can build up on the floor of the transport unit. Consequently, transport units should be well ventilated to prevent both short-term intoxication and long-term cumulative exposure. In a 2008 study, after 10 minutes of nitrox use in a confined ambulance space, concentration of the gas exceeded 25 ppm, which is the recommended level for staff exposure by NIOSH.16,17 Researchers measured nitrox concentrations at three different locations during administration and found concentrations in the attendant’s chair were 400–1,500 ppm, in the bench seat 550–1,550 ppm, and in the driver’s compartment 200–500 ppm.17 

This study also found levels remained elevated in the attendant’s chair (25–65 ppm), bench seat (25–60 ppm), and driver’s compartment (10–25 ppm) despite the use of a standard ambulance exhaust fan and scavenger system.17

There is conflicting data on the effectiveness of the standard exhaust fan, scavenger system, and air-conditioning blower with open windows used to ventilate an ambulance compartment. In previous studies authors found a 98%–99% drop in nitrox concentration within the box of a modular ambulance; however, all studies have measured nitrox concentrations greater than 25 ppm despite this ventilation.17–21 

Ultimately these studies are limited in their application to current protocols, as ambulance design, exhaust fans, and scavenger systems have improved since the publication of these papers. Therefore, we recommend new studies be performed utilizing current ambulance technology before nitrox administration can be advised in the closed patient compartment of an ambulance during transport.

Take-Home Points

Nitrox is a safe and effective prehospital analgesic for acutely painful conditions. It can be used as a safe alternative to opiates and may provide better pain control in a multitude of scenarios. 

Special precautions should be taken to ensure adequate ventilation of the crew space during nitrox administration, and nitrox should not be administered during patient transport.  

The authors wish to thank Mark Merlin, DO, medical director and chief medical officer for MONOC, for his assistance with this article.


1. Thal ER, Montgomery SJ, Atkins JM, et al. Self-administered analgesia with nitrous oxide. Adjunctive aid for emergency care systems. JAMA, 1979; 242(22): 2,418–9.

2. National Highway Traffic Safety Administration. National EMS Scope of Practice Model,

3. Dart RC, Surratt HL, Cicero TJ, et al. Trends in Opioid Analgesic Abuse and Mortality in the United States. NEJM, 2015; 372: 241–8.

4. Oglesbee S, Selde W. Using Nitrous Oxide to Manage Pain. J Emerg Med Serv, 2014; 39(4).

5. Joint Royal Colleges Ambulance Liaison Committee, Ambulance Service Association. UK Ambulance Service Clinical Practice Guidelines (2006),

6. Donen N, Tweed WA, White D, et al. Pre-hospital analgesia with Entonox. Can Anaesth Soc J, 1982; 29(3): 275–9.

7. Code of Federal Regulations, Title 21, Chapter I, Subchapter H.

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9. Alonso-Serra HM, Wesley K. Prehospital pain management. Prehosp Emerg Care, 2003; 7(4): 482–8.

10. Faddy SC, Garlick SR. A systematic review of the safety of analgesia with 50% nitrous oxide: Can lay responders use analgesic gases in the prehospital setting? Emerg Med J, 2005; 22(12): 901–8.

11. Ducasse JL, Siksik G, Durand-Bechu M, et al. Nitrous oxide for early analgesia in the emergency setting: A randomized, double-blind multicenter prehospital trial. Acad Emerg Med, 2013; 20(2): 178–84.

12. Bledsoe BE, Myers J. Future trends in prehospital pain management. J Emerg Med Serv, 2003; 28(6): 68–71.

13. Rooks JP. Safety and risks of nitrous oxide labor analgesia: A review. J Midwifery Women’s Health, 2011; 56(6): 557–65.

14. Fujinaga M. Teratogenicity of nitrous oxide. Best Practice & Research Clinical Anaesthesiology, 2001 Sep; 15(3): 363–75. 

15. Moss E, McDowall DG. I.C.P. increases with 50% nitrous oxide in oxygen in severe head injuries during controlled ventilation. Br J Anaesth, 1979; 51(8): 757–61.

16. National Institute for Occupational Safety and Health. Controlling Exposures to Nitrous Oxide During Anesthetic Administration,

17. Housel FB, Murphy TG. Ambient levels of nitrous oxide in a modular ambulance. Am J Emerg Med, 2008; 26(2): 186–8.

18. Ancker K, Halldin M, Gothe CJ. Nitrous oxide analgesia during ambulance transportation. Airborne levels of nitrous oxide. Acta Anaesthesiol Scand, 1980; 24(6): 497–500.

19. Ancker K, Halldin M, Gothe CJ. Local exhaust ventilation and exposure to nitrous oxide in ambulances. Int Arch Occup Environ Health, 1990; 62(1): 27–9.

20. Schrading W, Kaplan R, Stewart R. Effect of scavenging on ambient levels of nitrous oxide in ambulances. Ann Emerg Med, 1990; 19(8): 910–3.

21. Bristow A, Giesecke A, Thal E, Atlins J. Environmental concentrations of nitrous oxide in a modular ambulance. Crit Care Med, 1986; 14(9): 815–6. 

Garrett Cavaliere, DO, NRP, is an emergency medicine resident at the University of Maryland Medical Center, Baltimore, Md., and recent graduate of Touro College of Osteopathic Medicine, Middletown, N.Y. He is also a firefighter-paramedic with Prince George's County Fire/EMS Department, Prince George's County, Md.

Janae Hohbein, DO, is a former paramedic and recent graduate of the EMS/Disaster Medicine Fellowship based in Newark, N.J. She will be returning to practice emergency medicine in Chicago.


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