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Inhalational Analgesic Pregnancy: SPC section 4.6: mild skeletal teratogenic changes have been observed in pregnant rat embryos when the dam was exposed to high concentrations of nitrous oxide during organogenesis. However, no increased incidence of foetal malformation has been discovered in 8 epidemiological studies and case reports in human beings; there is no published material showing that nitrous oxide is toxic to the human foetus. Therefore there is no absolute contraindication to its use in the first 16 weeks of pregnancy. Lactation: Entonox can be used during the breast-feeding period, but should not be used during breast-feeding itself.

Nitrous Oxide (Entonox)

Brand names: Entonox, Nitronox

Nitrous oxide as Entonox is a premixed fifty-fifty nitrous oxide and oxygen gas used for short-term inhaled analgesia during painful procedures such as fracture manipulation and dressing changes.

Adult dose

Dose: Relief of pain (e.g. acute trauma, short-term relief for procedures inevitably involving pain such as wound and burn dressing, wound debridement and suturing): Entonox premixed gas, 50% nitrous oxide / 50% oxygen (section 2: oxygen 50.0% +/- 2.0%, nitrous oxide 50.0% +/- 2.0%), inhaled through a facemask or mouthpiece connected to the cylinder supply through a demand valve system, self-regulated by the patient (in nearly all cases self-administered, but it may be administered by attendant medical personnel)
Route: Inhalation via facemask or mouthpiece and demand valve
Frequency: As required, patient-regulated by the demand valve; not to be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring
The pinned product is ENTONOX MEDICINAL GAS (PL007355017, BOC Ltd), section 2: oxygen 50.0% +/- 2.0%, nitrous oxide 50.0% +/- 2.0%. Section 4.1: 'Entonox is used exclusively for the relief of pain' - acute trauma, short-term relief in dental work, procedures inevitably involving pain, normal labour, and acute surgical or medical conditions where pain relief allows an unfettered assessment. Section 4.2 (verbatim, abridged): 'Since pain is usually relieved by a concentration of 25% nitrous oxide, continued inhalation does not occur. However, should inhalation continue, light anaesthesia occurs and the mask or mouthpiece drops away as the patient relaxes, or is removed if administration has been by attendant personnel.' Section 4.2 also states 'There are no contra-indications to the use of Entonox in any age group.' (section 4.3 still lists gas-entrapment conditions). Paediatric: the SPC prints no age-specific dose, minimum age or paediatric technique, so paedDose is null. NOT PRINTED, so not written: any shorter continuous-use time limit, any onset or offset time, any minimum age for self-administration. The only printed duration limit is the 24 hours total / every 4 days limit above. Because this limit is a duration rule and not a dose, maxDose is left unset. COPD: caution in patients with known COPD or other conditions where compromised chemoreceptor sensitivity/function may be present (relatively high oxygen concentration may cause respiratory depression and increases in PaCO2). Avoid gases containing more than 21% oxygen where the patient has been exposed to lung-toxic agents such as paraquat. Scavenging should keep ambient nitrous oxide below 100 ppm. Non-flammable but strongly supports combustion; no oils or grease on the cylinder or delivery equipment.

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 gas is entrapped within a body and where its expansion might be dangerous, such as: artificial, traumatic or spontaneous pneumothorax; air embolism; decompression sickness; following a recent dive; following air encephalography; severe bullous emphysema; use during myringoplasty; gross abdominal distension
  • Patients having received recent intraocular injection of gas (such as SF6)

Side effects

  • Commonly described: euphoria, disorientation, sedation, nausea, vomiting, dizziness and generalised tingling - generally minor and rapidly reversible
  • Dizziness, light-headedness, somnolence; bloating / increased gas volume in the intestines; sense of intoxication; feeling of pressure in the middle ear
  • Respiratory depression (listed in the SPC adverse-reaction table)
  • 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 subclinical vitamin B12 deficiency
  • Confusion and addiction; generalised seizures (listed in the SPC table)
  • Nitrous oxide passes into gas-containing body spaces faster than nitrogen passes out: prolonged exposure may result in bowel distension, middle ear damage and rupture of ear drums

Interactions

  • Vitamin B12 - the nitrous oxide constituent inactivates vitamin B12
  • Methotrexate - the nitrous oxide constituent potentiates its effects on folate metabolism
  • Bleomycin, amiodarone and nitrofurantoin or similar antibiotics - higher levels of oxygen can increase the risk of pulmonary toxicity; give Entonox with caution and at levels kept as low as possible
  • Drugs with a central depressant action (e.g. opiates, benzodiazepines and other psychotropics) - risk of additive effects, pronounced sedation and depression of protecting reflexes; use under the supervision of appropriately trained personnel

Monitoring

  • 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; seek specialist haematologist advice in such cases
  • Haematological assessment should include megaloblastic change in red cells and hypersegmentation of neutrophils; neurological toxicity can occur without anaemia or macrocytosis and with B12 levels in the normal range
  • Caution in patients with known COPD or other conditions with compromised chemoreceptor sensitivity/function (respiratory depression and rise in PaCO2 possible)
  • Caution in patients with a known history of substance abuse (repeated administration may lead to addiction)
  • Scavenge waste gas to keep ambient nitrous oxide below 100 ppm in theatre and equivalent treatment rooms

Clinical monograph

How it works

Inhaled nitrous oxide produces rapid, short-lived analgesia and mild sedation through central effects including modulation of NMDA and opioid pathways, with quick onset and offset due to its low solubility.

Prescribing in practice

  • Contraindicated where trapped gas could expand, including pneumothorax, bowel obstruction and recent diving, as nitrous oxide diffuses into air-filled spaces.
  • Ensure adequate room ventilation or scavenging to limit occupational exposure for staff.
  • Prolonged or repeated exposure can inactivate vitamin B12 and cause megaloblastic anaemia and neuropathy.

Monitoring

Observe conscious level and oxygenation during use, ensuring the patient self-administers and remains rousable.

Counselling the patient

  • Breathe the gas yourself through the mouthpiece as the pain builds for best effect.
  • You may feel light-headed or tingly; this passes quickly once you stop.
  • Tell the team if you feel sick or very drowsy.

Evidence & guidelines

Entonox is an established option for procedural analgesia in UK emergency and trauma settings, valued for its rapid onset and offset.

Reference: BOC Entonox Product Information; MHRA Guidance on Entonox; SIGN 106; Rosen's Emergency Medicine 9th Ed; 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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