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Inhalation anaesthetic / analgesic Pregnancy: SPC section 4.6: Mild skeletal teratogenic changes have been observed in pregnant rat embryos when the dam has been exposed to high concentrations of nitrous oxide during the period of organogenesis. However, no increased incidence of foetal malformation has been discovered in various epidemiological studies and case reports in human beings. There is no published material which shows that nitrous oxide is toxic to the human foetus. Therefore, there is no absolute contra-indication to its use in the first 16 weeks of pregnancy. Medical Nitrous Oxide can be used during lactation. The current UK work place exposure limit (WEL) for nitrous oxide is 100ppm (8 hour time weighted average reference period). In obstetrical anaesthesia the proportion of nitrous oxide should be less than 70% with oxygen greater than 30% for anaesthesia (section 4.4).

Nitrous oxide

Brand names: Entonox (50% N2O / 50% O2)

Nitrous oxide is an inhaled gas used as a weak anaesthetic adjunct and as an analgesic, including in a fixed nitrous oxide/oxygen mixture for procedural pain and in labour.

Adult dose

Dose: Inhalation anaesthetic, or analgesia where rapid-onset powerful short-term relief of severe pain is required (adults, including the elderly): for respiratory use at nitrous oxide concentrations of 79% or less. Never give with less than 21% oxygen.
Route: Inhalation (respiratory use)
Frequency: No repeat-dose schedule is printed; do not use for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring
Max: 79% nitrous oxide (SPC section 4.2: 'concentrations of 79% or less'); in anaesthesia at altitude, in the presence of disorders affecting oxygenation and in obstetrical anaesthesia the nitrous oxide proportion should be less than 70% with oxygen greater than 30% (section 4.4)
The pinned product is MEDICAL NITROUS OXIDE (PL159290004, Air Liquide Ltd), composition 'Nitrous Oxide Ph. Eur. 100%' supplied in gas cylinders - section 4.1: 'As an inhalation anaesthetic. As an analgesic where rapid-onset powerful short-term relief of severe pain is required.' NOT COVERED: the page also lists Entonox (50% nitrous oxide / 50% oxygen premix); this SPC is for the 100% medical gas and prints NO 50/50 premix regimen and no self-administered demand-valve technique - nothing is written for Entonox. SECTION 4.2 (sentence breaks added to the PDF text): 'Use in adults, including the elderly and children. For respiratory use at concentrations of 79% or less. Medical Nitrous Oxide should not be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring.' Section 4.4: 'Nitrous oxide should never be given with less than 21% oxygen.' and 'At altitude, in the presence of disorders affecting oxygenation and in obstetrical anaesthesia the proportion of nitrous oxide should be less than 70% with oxygen greater than 30% for anaesthesia.' CONSISTENCY CHECK (this SPC replaces the previously held manufacturer's SPC): 79% nitrous oxide leaves 21% for oxygen, which equals the SPC's own minimum, and the lower 70% limit applies only to the three stated situations - the SPC's figures do not conflict. The SPC prints no separate analgesic concentration and no separate anaesthetic concentration; the 79% figure is the only concentration limit printed. Analgesia (section 4.4): self-administration should be preferred to allow assessment of the level of consciousness; attentive monitoring is required with concomitant CNS depressants, in particular opiates and benzodiazepines. After a nitrous oxide/oxygen anaesthetic, withdrawal of the mask leads to 'diffusion hypoxia', counteracted by giving 100% oxygen for a few minutes when nitrous oxide is stopped (section 4.4). Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and equivalent treatment room levels to below 100 ppm ambient nitrous oxide (sections 4.2, 4.4). CHILDREN: section 4.2 prints the 79% figure under the combined heading 'adults, including the elderly and children'; no separate paediatric figure or age band is printed, so no paediatric block is written. Section 4.4 paediatric population: nitrous oxide may in rare cases cause respiratory depression in the neonate - check the neonate when it is used around childbirth. Use a children's formulary / specialist advice for anyone under 18.

Dose adjustments

Renal

No renal dose adjustment is printed in the retrieved SPC sections (4.2-4.4).

Hepatic

No hepatic dose adjustment is printed in the retrieved SPC sections (4.2-4.4).

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Any condition where air is entrapped within the body and where its expansion might be dangerous, such as: head injuries with impairment of consciousness; maxillofacial injuries; pneumothorax (artificial, traumatic or spontaneous); air embolism; decompression sickness and following a recent dive / recent underwater dive; following air encephalography; severe bullous emphysema; during middle ear, inner ear and sinus surgery; gross abdominal distension (e.g. intestinal obstruction); if air has been injected into the epidural space to determine the placement of the needle for epidural anaesthesia
  • Heavily sedated patients
  • Recent intraocular injection of gas (such as SF6, C3F8, C2F6) - as long as an intraocular gas bubble persists and at least for 3 months

Side effects

  • Commonly described: euphoria, disorientation, sedation, nausea, vomiting, dizziness and generalised tingling - generally minor and rapidly reversible
  • Post-operative nausea and vomiting - reported in approximately 15% of patients
  • Prolonged or frequent use (including heavy occupational exposure and addiction): megaloblastic anaemia; agranulocytosis after prolonged administration; myeloneuropathy and subacute combined degeneration of the spinal cord
  • Neurological toxicity after a single exposure for anaesthesia in patients with undiagnosed sub-clinical vitamin B12 deficiency
  • Nitrous oxide passes into all gas-containing spaces in the body faster than nitrogen passes out: prolonged anaesthesia may result in bowel distension, middle ear damage and rupture of ear drums
  • Addiction to nitrous oxide has been reported; may be sought and abused for recreational use because of its euphoric effects (section 4.4)
  • Severe vision impairment caused by expansion of an intraocular gas
  • Increase of intracranial pressure observed in some patients with intracranial disorders (section 4.4)
  • Diffusion hypoxia when nitrous oxide is stopped at the end of anaesthesia (counteracted by 100% oxygen for a few minutes)
  • Respiratory depression in the neonate in rare cases (section 4.4)

Interactions

  • Vitamin B12 - nitrous oxide causes inactivation of vitamin B12 (a co-factor of methionine synthase), interfering with folate metabolism
  • Intraocular gas (SF6, C3F8, C2F6) - nitrous oxide in patients with a persisting intraocular gas bubble, or injected less than 3 months before, can cause severe vision impairment from expansion of the intraocular gas
  • Opiates, benzodiazepines and other CNS depressant drugs - increased risk of deep sedation; attentive monitoring required (section 4.4)

Monitoring

  • Do not use as an analgesic or anaesthetic agent for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring; seek specialist advice from a haematologist in such cases
  • Haematological assessment should include megaloblastic change in red blood cells and hypersegmentation of neutrophils; neurological toxicity can occur without anaemia or macrocytosis and with B12 levels in the normal range
  • Consider assessing vitamin B12 levels before nitrous oxide anaesthesia in people with risk factors for B12 deficiency (the elderly, alcoholic patients, anaemia, atrophic gastritis, vegetarian diet, or recent use of medications that interfere with vitamin B12 and/or folate metabolism); vitamin B12 supplements should be given with repeated and prolonged administration
  • Never give with less than 21% oxygen
  • Monitor intracranial pressure closely in patients at risk of intracranial hypertension
  • Attentive monitoring is required in analgesia in patients taking CNS depressant drugs, in particular opiates and benzodiazepines (deep sedation)
  • Check the neonate for respiratory depression when nitrous oxide is used around childbirth
  • Scavenge waste gas to keep ambient nitrous oxide below 100 ppm in theatre and equivalent treatment rooms

Clinical monograph

How it works

Its analgesic and anaesthetic effects are mediated largely through antagonism of NMDA glutamate receptors, with additional opioid and other neuromodulatory actions.

Prescribing in practice

  • It diffuses into air-filled spaces and must be avoided where expansion is dangerous, such as pneumothorax, bowel obstruction, recent intraocular gas, or air embolism.
  • Prolonged or repeated exposure inactivates vitamin B12, impairing folate metabolism and causing megaloblastic changes and, rarely, neurological harm.
  • When discontinued, give supplemental oxygen to avoid diffusion hypoxia.

Monitoring

Monitor oxygenation and conscious level during use, and consider vitamin B12 status with prolonged or frequent exposure.

Counselling the patient

  • You may feel light-headed, drowsy, or nauseated while breathing the gas; these effects pass quickly afterwards.
  • Tell the team if you have had recent eye surgery involving gas, or any condition with trapped air.

Evidence & guidelines

Use reflects established anaesthetic and procedural analgesia practice; consult current prescribing references and the SPC.

Reference: AAGBI; MHRA; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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