Nitrous oxide (medication)

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"Gas and air" redirects here. For the 1923 film, see Gas and Air (film).
Nitrous oxide
Entonox CD cylinder and giving set
Clinical data
Trade namesEntonox, Nitronox, others
ATC code
Pharmacokinetic data
Onset of action30 seconds[1]
Duration of action1 minute[1]
Identifiers
  • Nitrous oxide
JSmol)
  • [N-]=[N+]=O
  • InChI=1S/N2O/c1-2-3
  • Key:GQPLMRYTRLFLPF-UHFFFAOYSA-N

Nitrous oxide is an inhaled gas used as a

medications for anesthesia.[2] Common uses include during childbirth, following trauma, and as part of end-of-life care.[2] Onset of effect is typically within half a minute, and the effect lasts for about a minute.[1]

There are few side effects, other than

numbness may occur.[2] It should always be given with at least 21% oxygen.[2] It is not recommended in people with a bowel obstruction or pneumothorax.[2] Use in the early part of pregnancy is not recommended.[1] It is possible to continue breastfeeding following use.[3]

Nitrous oxide was discovered between 1772 and 1793 and used for anesthesia in 1844.

developing countries.[7][8]

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;[1] 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.[1] It is effective in managing pain during labor and delivery.[9]

Nitrous oxide is more soluble than oxygen and nitrogen, so 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[1])[10][11] and characterised by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly.[citation needed
]

When used in combination with other anesthetics gases, nitrous oxide causes a dose dependent increased respiratory rate and decreased tidal volumes, the net effect is a lower minute ventilation. Like volatile anesthetics, it increases cerebral blood flow and intracranial pressure. However, contrary to volatile anesthetics, it leads to an increase in cerebral metabolic rate of oxygen.[12][13]

Contraindications

N2O should not be used in patients with bowel obstruction, pneumothorax, or middle ear or sinus disease,[1] or who have had a recent intraocular injection of gas[14] and should also not be used on any patient who has been scuba diving within the preceding 24 hours[15] or in violently disturbed psychiatric patients.[16] There are also clinical cautions in place for the first two trimesters of pregnancy and in patients with decreased levels of consciousness.[1]

Composition

The gas is a mixture of half nitrous oxide (N2O) and half oxygen (O2).[1][16] The ability to combine N2O and oxygen at high pressure while remaining in the gaseous form is caused by the Poynting effect (after John Henry Poynting, an English physicist).[1]

The Poynting effect involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporisation of the liquid to form a gaseous O2/N2O mixture.[1]

Inhalation of pure N2O over a continued period would

deprive the patient of oxygen,[17] but the 50% oxygen content prevents this from occurring. The two gases will separate at low temperatures (<4 °C
), which would permit administration of hypoxic mixtures. Therefore, it is not given from a cold cylinder without being shaken (usually by cylinder inversion) to remix the gases.

  • Distinct blue and white cap of an Entonox cylinder
    Distinct blue and white cap of an Entonox cylinder
  • Typical Schrader valve attachment, making the gas usable only with demand based giving sets
    Typical Schrader valve attachment, making the gas usable only with demand based giving sets

Administration

The gas is self-administered through a

anaesthetist for administration. The 50% oxygen in Entonox ensures the person will have sufficient oxygen in their alveoli and conducting airways for a short period of apnea to be safe.[citation needed
]

Mechanism of action

Main article: Nitrous oxide § Mechanism of action

The pharmacological

euphoriant effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents.[18][21] In addition to its effects on ion channels, N
2O may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties.[21]
Nitrous oxide is 30 to 40 times more soluble than nitrogen.

History

Administration of nitrous oxide, 1870[22]

Pure N2O was first used as a medical analgesic in December 1844, when

Hartford.[23][24]

Its debut as a generally accepted method, however, came in 1863, when

New Haven and New York City.[25]

The first devices used in dentistry to administer the gas consisted of a simple breathing bag made of rubber cloth.[26]

Breathing the pure gas often caused

asphyxiation. Eventually practitioners became aware of the need to provide at least 21% oxygen content in the gas (the same percentage as in air).[24] In 1911, the anaesthetist Arthur Ernest Guedel first described the use of self-administration of a nitrous oxide and oxygen mix. It was not until 1961 that the first paper was published by Michael Tunstall and others, describing the administration of a pre-mixed 50:50 nitrous oxide and oxygen mix, which led to the commercialisation of the product.[24]

In 1970, Peter Baskett recognised that pre-mixed nitrous oxide and oxygen mix could have an important part to play in the provision of pre-hospital pain relief management, provided by ambulance personnel. Baskett contacted the Chief Ambulance Officer for the Gloucestershire Ambulance Brigade, Alan Withnell, to suggest this idea. This gained traction when Baskett negotiated with the British Oxygen Company, the availability of pre-mixed nitrous oxide and oxygen mix apparatus for training. Regular training sessions began at Frenchay Hospital (Bristol) and a pilot study was run in Gloucestershire (in which ambulances were crewed by a driver and one of the new highly trained ambulance men), the results of this trial were published in 1970.[27]

Today the nitrous oxide is administered in hospitals by a

nitrous oxide mixed with oxygen.[citation needed
]

The machine used in dentistry is much simpler, and is meant to be used by the patient in a fully conscious state. The gas is delivered through a

demand-valve inhaler over the nose, which will only release gas when the patient inhales through it.[citation needed
]

Society and culture

Nitronox was a registered trademark of

the BOC Group between 1966 and 1999,[28] and was reregistered by Hs Tm Inc since 2005[citation needed] It is also colloquially known as "gas and air" in the United Kingdom.[29]

Research

Investigational trials show potential for antidepressant applications of N2O, especially for treatment-resistant forms of depression, and it is rapid-acting.[30][31][32][33]

References

  1. ^ a b c d e f g h i j k l m n "Anaesthesia UK : Entonox". www.frca.co.uk. 26 January 2009. Archived from the original on 31 October 2007. Retrieved 15 December 2016.
  2. ^
    ISBN 9789241547659
    .
  3. ^ "Nitrous Oxide use while Breastfeeding". Drugs.com. Archived from the original on 21 December 2016. Retrieved 15 December 2016.
  4. ISBN 9780313080579. Archived
    from the original on 2016-12-20.
  5. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  6. ISBN 9780857111562
    .
  7. ISBN 9781444333466. Archived
    from the original on 2016-12-20.
  8. ISBN 92-4-140101-X
    .
  9. PMID 22419342
    .
  10. PMID 33407845
    .
  11. PMID 4865545
    .
  12. PMID 30725698. NBK537013
    .
  13. PMID 30422517. NBK532922
    .
  14. ^ "Entonox: The essential guide" (PDF). BOC online. Retrieved 2023-12-24.
  15. ^ Komesaroff D (1998). "Oxygen administration in diving accidents". South Pacific Underwater Medicine Society Journal. 28 (3 Supplement).
  16. ^
    ISBN 978-1-84690-060-0. Archived
    (PDF) from the original on 2011-06-05.
  17. ^ "Breathing Nitrous Oxide". Nitrous Oxide Supplies. Archived from the original on 2009-02-16.
  18. ^
    S2CID 4684919
    .
  19. PMID 9822732
    .
  20. S2CID 7762447
    .
  21. ^
    PMID 17352529
    .
  22. ^ Thomas FR (1870). "Manual of the discovery, manufacture, and administration of nitrous oxide, or laughing gas in its relations to dental or minor surgical operations, and particularly for the painless extraction of teeth". Philadelphia : S.S. White. Retrieved 17 December 2018.
  23. PMID 21433572. Archived from the original
    on 2012-12-23.
  24. ^ a b c "History of Entonox". BOC Gases. Archived from the original on 2009-07-05. Retrieved 2009-04-11.
  25. ISBN 978-0-471-89980-8
    . Retrieved 21 April 2010.
  26. S2CID 71117361
    .
  27. PMID 5440577
    .
  28. ^ "NITRONOX Trademark Information". trademarkia. Archived from the original on 2017-09-10. Retrieved 2017-07-11.
  29. ^ "Entonox (gas and air)". Baby Centre. Archived from the original on 2006-11-11.
  30. PMID 25577164
    .
  31. PMID 26423481
    .
  32. S2CID 235381316
    .
  33. ^ Mozes A (2021-06-10). "'Laughing Gas' May Help Tough-to-Treat Depression". WebMD. Retrieved 2021-06-15.

Further reading

External links
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