Nitrous oxide (medication)

Nitrous oxide, sold under the brand name Entonox among others, is an inhaled gas used as a pain medication and together with other medications for anesthesia. Common uses include childbirth, following trauma, and as part of end-of-life care. The onset of effect is typically within half a minute and lasts for about a minute.

There are few side effects, other than vomiting, with short-term use. With long-term use anemia or numbness may occur. It should always be given with at least 21% oxygen. It is not recommended in people with bowel obstruction or pneumothorax. Use in the early part of pregnancy is not recommended. Breastfeeding can occur following use.

Nitrous oxide was discovered between 1772 and 1793 and used for anesthesia in 1844. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. It often comes as a 50/50 mixture with oxygen. Devices with a demand valve are available for self-administration. Setup and maintenance are relatively expensive for developing countries.

Medical uses

Nitrous oxide (N2O) is itself active (does not require any changes in the body to become active), and so has an onset in roughly the lung–brain circulation time. This gives it a peak action 30 seconds after the start of administration; Entonox should thus be used accordingly, i.e. inhalation should start 30 seconds before a contraction becomes painful in labour. It is removed from the body unchanged via the lungs and does not accumulate under normal conditions, explaining the rapid offset of around 60 seconds. It is effective in managing pain during labor and delivery.

Nitrous oxide is more soluble than oxygen and nitrogen, so it will tend to diffuse into any air spaces within the body. This makes it dangerous to use in patients with pneumothorax or those who have recently been scuba diving, and there are cautions over its use with any bowel obstruction.

Its analgesic effect is strong (equivalent to 15 mg of subcutaneous route morphine and characterized by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly.


N2O should not be used in patients with bowel obstruction, pneumothorax, middle ear or sinus disease, and should also not be used on any patient who has been scuba diving within the preceding 24 hours or in violently disturbed psychiatric patients. There are also clinical cautions in place for the first two trimesters of pregnancy and in patients with decreased levels of consciousness.


The gas is a mixture of half nitrous oxide (N2O or laughing gas) and half oxygen (O2). The ability to combine N2O (nitrous oxide is the common name; dinitrogen monoxide, systematic name) and oxygen at high pressure while remaining in the gaseous form is caused by the Poynting effect (after John Henry Poynting, an English physicist).

The Poynting effect involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporization of the liquid to form a gaseous O2/N2O mixture.

Inhalation of pure N2O over a continued period would deprive the patient of oxygen, but the 50% oxygen content prevents this from occurring. The two gases will separate at low temperatures (<4 °C), which would permit the administration of hypoxic mixtures. Therefore, it is not given from a cold cylinder without being shaken (usually by cylinder inversion) to remix the gases.


Investigational trials show potential for antidepressant applications of N2O, especially for treatment-resistant forms of depression, and it is rapid-acting