Using Nitrous Oxide to Manage Pain

Nitrous oxide has emerged as a medication closely in line with the tenets of modern prehospital medicine: evidence-based and noninvasive. It’s a medical gas that possesses both sedative and analgesic properties, and has been used extensively in hospitals and clinics worldwide for many years. Nitrous oxide use is becoming more commonplace in the prehospital setting due to advances in delivery systems and numerous well-documented studies supporting its efficacy of use.

Nitrous oxide is an analgesic well-suited for short scene times and rescue environments because the route of administration is inhalation. Situations where time is of the essence are plentiful in EMS, such as acute myocardial infarctions (where the goal is to initiate reperfusion within 90 minutes of EMS activation), severe burns or musculoskeletal injuries. Nitrous oxide may also be used for short-term treatment of minor to moderate pain, or as a bridge to IV narcotics when ineffectual.

The gas itself is inexpensive, although delivery systems for nitrous oxide remain costly. Modern production consists of heating plentiful ammonium nitrate in a thermal decomposition process. Like any medication, nitrous oxide has specific contraindications, and providers need to carefully consider certain adverse effects. The mechanism of action is well understood, delivering a predictable and quick-acting therapy patients can self-administer.

International Usage
Credit for discovering nitrous oxide goes to English scientist Joseph Priestley, who found it–as well as oxygen–through his work isolating gasses in 1793. It was considered a novelty for many years before being used medically, and the moniker “laughing gas” sticks around to this day. Medicinal use of the gas has spanned more than 150 years, and nitrous oxide has now become the most commonly used inhaled anesthetic.1 Extensively studied in the prehospital environment since the 1970s, inhaled nitrous oxide falls into the advanced EMT (AEMT) category of medications, based on the National EMS Scope of Practice Model.2,3

The gas is now widely used among international EMS agencies, including France, Canada, Australia and the United Kingdom.4—6 Outside the United States, the predominant nitrous oxide delivery system is Entonox–which uses a mixture of 50% nitrous oxide and 50% oxygen inside a single cylinder. The U.S. Food and Drug Administration (FDA) prohibits single-cylinder nitrous oxide, and requires nitrous oxide and oxygen be housed in separate cylinders.7 The two gasses are blended in a mixing chamber preceding the demand valve, such as in the Nitronox field unit. Regardless of delivery method, in the U.S., Europe and Australia, nitrous oxide is always administered to the patient in a 1:1 (50/50) ratio with oxygen.7,8

Neural Mechanism of Action
When a patient inhales nitrous oxide, the gas molecules are readily taken into the blood stream from the lungs. It’s thought to provide sedation in a similar manner as other inhaled anesthetic gases by stabilizing the neurons in the brain to prevent action potentials. Nitrous oxide provides pain relief by acting as a partial agonist at the opioid receptors, and is generally unmetabolized, excreted by the lungs unchanged. The peak effect is quickly reached within 2—5 minutes, and its duration of action is about the same.

Central nervous system side effects of nitrous oxide include lightheadedness, headache, dizziness, confusion, nausea and vomiting (especially when use is prolonged or combined with other analgesic agents), as well as euphoria. This feel-good effect contributes to its well-known abuse potential. As many as 20% of medical and dental students have admitted to trying nitrous oxide recreationally.9

Perhaps the most common way of recreationally inhaling nitrous oxide is through household products where the gas is used as a propellant, like a can of whipped cream. This popular method has led to the term “whippits.”

Symptoms of nitrous oxide abuse typically begin with hypersensitivity in the hands and feet, progressing to loss of sensation, motor weakness and neuromotor deficits with long-term exposure. The pathophysiology is speculated to be related to nitrous oxide’s proclivity to inactivate Vitamin B12 and inhibit methionine synthase, an enzyme essential to the synthesis of DNA.10

Repeated occupational exposure may lead to problems with fertility and increased rates of spontaneous abortion in women, meriting an FDA pregnancy class C medication rating. Thus, nitrous oxide should be avoided in the first two trimesters of pregnancy.10 The medication is, however, still used frequently in the labor and delivery setting to augment labor pain without any recorded adverse effects.11

Neatly Packaged Delivery Systems
The goals behind prehospital anesthetic gas delivery are fourfold:

1. The gas is accurately delivered by blending it with oxygen;
2. Patients must be able to breathe through the apparatus;
3. Safety mechanisms are integrated in case of malfunction; and
4. It must be packaged in a compact delivery system engineered for robust field use.

Pressure regulators work on the physics principle such that pressure equals force divided by area. The demand valve is operated by negative pressure and therefore requires an airtight seal between the mask and the patient’s face. The patient seals the mask to their face with one hand, and takes slow, deep breaths to self-administer the medication to the desired level of analgesia. Should the patient become drowsy, the mask naturally falls away from their face, stopping the administration.

The Nitronox Field Unit, an FDA 510(k) registered medical device, is comprised of two hoses, a small nitrous oxide cylinder, demand valve and a mixing device. It connects to your existing oxygen supply. The other hose has a mask and demand valve and mask attached for patient self-administration. The device is preset to deliver nitrous oxide and oxygen at a 1:1 mixture–neither the patient nor providers are able to adjust the ratio, eliminating the risk of delivering a hypoxic mixture. Should the oxygen line depressurize for any reason, the device can’t deliver nitrous oxide. An oxygen failsafe mechanism is built in to avoid administration of pure nitrous oxide, which would suffocate the patient.

In the prehospital setting, adequate pain control is not often provided because providers underestimate patients’ needs. Providers may be inadequately assessing patients for pain, and they’re often negatively biased after having encounters with patients seeking to abuse drugs or those who exaggerate their level of pain. This often results in patients being undermedicated, if medicated at all.12

Every patient encounter includes an assessment for the presence and severity of pain; serial assessments and appropriate patient documentation are paramount in order to gauge efficacy before and after analgesic administration. Pain assessment tools include the mnemonic OPQRSTU, 0—10 scale, or the qualitative verbal rating scale (none, mild, moderate, severe or unbearable).11

Nitrous oxide is a good alternative to opioid analgesia because it takes the provider’s subjective choice in dosage out of the equation. Patients typically like the medication because they’re able to administer it themselves, it provides a significant reduction in pain and anxiety, and it doesn’t require an IV.

Nitrous oxide has been used effectively in cases of chest pain secondary to infarction and angina, acute urinary retention, kidney stones, severe burns, fractures, dislocations and other forms of musculoskeletal trauma. It’s also proven effective among the pediatric population, including use as sedation and analgesia prior to IV cannulation. Nitrous oxide can also be used safely during childbirth to treat labor pain.11

Nitrous oxide should only be used by patients who have the ability and capacity to understand how to perform self-administration. Nitrous oxide can lead to changes in mental status and shouldn’t be used if the patient’s mental state is altered due to drugs, alcohol or psychiatric conditions. It also can’t be used by patients with an anatomic pathology that would interfere with self-administration, such as maxillofacial trauma or facial burns.

Because nitrous oxide is inhaled, it shouldn’t be used when there might be air in places that are pathologic. This includes chest trauma, both blunt and penetrating–due to the risk of pneumothorax–and abdominal pain that’s undifferentiated, where there’s risk of air in the bowel wall, gall bladder wall, or free air in the abdomen itself. Nitrous oxide use is also contraindicated in decompression illness, such as an air embolism and “the bends.” Nitrous oxide increases cerebral blood flow, and therefore should be avoided in head injury to prevent increased intracranial pressure.13

In a review of available literature, a meta-analysis study suggested nitrous use is an effective analgesia in the treatment of a wide variety of injuries, and prehospital providers can safely administer the medication with a success rate similar to that achieved with IV opiate medications. The study also suggested there were minimal side effects associated with the treatment, such as hypotension and oxygen desaturation, which weren’t attributed to the nitrous.8

Special Considerations
When used during transport, providers must take into consideration that the gas is heavier than air and can therefore build up on the floor of the unit. Administration should take place in a well-ventilated environment; otherwise it could present risks to caregivers, through both short-term intoxication and long-term cumulative exposure. Some agencies prohibit nitrous oxide use inside the ambulance due to the exposure risk, opting to only use it outdoors, on scene or inside the patient’s home.

Scavenger systems that use local exhaust ventilation to collect and remove exhaled and overflow waste gas from the patient’s oropharynx and nasopharynx can be used to vent gas out of an ambulance; however, a recent study showed that even when using a scavenger system and an exhaust fan inside the patient compartment, ambient levels of nitrous oxide are still difficult to control.14

In the study, after 10 minutes of nitrous oxide use during a simulated transport, concentration of the gas in the patient care area exceeded the 25 ppm level recommended by the National Institute of Occupational Safety and Health and remained elevated at 65 ppm throughout the duration of transport.14

Research has shown that nitrous oxide can be safely and effectively employed in the prehospital environment. Its mechanism of action is well understood, and nitrous oxide is in the national scope of practice model for AEMTs. It has sedative and analgesic effects similar to that of opiates; however, nitrous oxide doesn’t require IV cannulation and can be self-administered. Advances in delivery systems have enabled the medical gas to emerge out of the hospital and clinic environment, where it resided exclusively until the late 1970s.

Like any medication, nitrous oxide has contraindications and limitations to its use. There’s also the potential for abuse, and providers need to consider methods to minimize unintended exposure. There are several published studies for providers to ponder while developing a clinical practice guideline that includes medical gas therapy. Once the hurdle of acquiring a delivery system is out of the way, nitrous oxide is an effective, inexpensive medicinal adjunct for pain control.

 1. Emmanouil DE, Quock RM. Advances in understanding the actions of nitrous oxide. Anesth Prog. 2007;54(1):9—18.
 2. Thal ER, Montgomery SJ, Atkins JM, et al. Self-administered analgesia with nitrous oxide. Adjunctive aid for emergency care systems. JAMA. 1979;242(22)2418—2419.
 3. National Highway Traffic Safety Administration. (2007). National EMS Scope of Practice Model. Retrieved Dec. 31, 2013, from
 4. 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—184.
 5. Donen N, Tweed WA, White D, et al. Pre-hospital analgesia with Entonox. Can Anaesth Soc J. 1982;29(3):275—279.
 6. Joint Royal Colleges Ambulance Liaison Committee. (2006). UK ambulance service clinical practice guidelines. Retrieved Dec. 31, 2013, from
 7. Bledsoe BE, Myers J. Future trends in prehospital pain management. JEMS. 2003;28(6):68—71.
 8. 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—908.
  9. Rosenberg H, Orkin FK, Springstead J. Abuse of nitrous oxide. Anesth Analg. 1979;58(2):104—106.
10. Brodsky JB, Cohen EN. Adverse effects of nitrous oxide. Med Toxicol. 1986;1(5):362—374.
11. Rooks JP. Safety and risks of nitrous oxide labor analgesia: A review. J Midwifery Women’s Health. 2011;56(6):557—565.
12. Alonso-Serra HM, Wesley K. Prehospital pain management. Prehosp Emerg Care. 2003;7(4):482—488.
13. 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—761.
14. Housel FB, Murphy TG. Ambient levels of nitrous oxide in a modular ambulance. Am J Emerg Med. 2008;26(2):186—188.

Table 1: Indications and contraindications for nitrous oxide use



Chest pain secondary to angina

Altered mental status

Acute myocardial infarction

Acute intoxication or drug use

Kidney stones

Psychiatric exacerbation

Urinary retention

Facial trauma or burns


Maxillofacial abnormalities

Fractures, dislocation or musculoskeletal trauma

Blunt or penetrating
chest trauma

Ability to self-administer medication

Undifferentiated abdominal pain (due to potential free air in the abdomen)

Ability to understand provider’s instruction

Respiratory distress

Bridge to IV analgesia

Status-post retina surgery

Labor pain during childbirth

Pregnancy (except
during delivery)

Pain control and sedation during pediatric IV starts

Head injuries

Fear of needles in low/moderate acuity conditions

Diving injuries such as decompression illness


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