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Inhalational Analgesic Pregnancy: Contraindicated in first trimester; used safely in labour analgesia (third trimester); avoid prolonged use

Nitrous Oxide (Entonox)

Brand names: Entonox, Nitronox

Adult dose

Dose: 50% nitrous oxide / 50% oxygen mixture via demand valve (patient-controlled)
Route: Inhalation via demand valve
Frequency: As required during procedure; effective in 30–60 seconds
Max: Continuous use limited to 30 minutes (vitamin B12 inactivation risk)
Patient-controlled via mouthpiece or mask; analgesic effect begins in 30–60 seconds; wears off within 5 minutes of stopping; no accumulation; scavenging equipment required in clinical areas

Paediatric dose

Route: Inhalation
Frequency: As required
Max: 30-minute sessions; standard 50/50 mixture
Children ≥5 years can self-administer via mouthpiece; ≥2 years with mask under supervision; widely used in paediatric ED and fracture clinics

Dose adjustments

Renal

No adjustment required

Hepatic

No adjustment required

Clinical pearls

  • Ideal for painful orthopaedic procedures: joint aspiration, fracture manipulation, wound irrigation, cast changes — rapid onset (30 seconds), rapid offset (5 minutes), self-administration prevents overdose, maintains patient cooperation and protective airway reflexes
  • Mechanism: NMDA receptor antagonist plus agonist activity at opioid, GABA, and dopamine receptors — produces analgesia, anxiolysis, and mild sedation without respiratory depression at 50/50 mixture
  • Vitamin B12 contraindication: irreversible inactivation of methionine synthase (required for myelin synthesis) — single 30-minute exposure safe in healthy patients; AVOID in known B12 deficiency, pernicious anaemia, or methotrexate users (folate already depleted)
  • Entonox expands gas-containing spaces rapidly: nitrous oxide 34× less soluble than nitrogen in blood — can rapidly enlarge a pneumothorax or air embolism; absolute contraindication in any suspected closed gas space
  • Occupational health: chronic staff exposure without scavenging causes sub-acute combined degeneration of spinal cord (B12 deficiency) — also pattern seen in nitrous oxide recreational abuse; relevant for theatre, ED, and fracture clinic staff

Contraindications

  • Vitamin B12 deficiency or pernicious anaemia (irreversible neurological damage)
  • Closed air spaces (pneumothorax, bowel obstruction, post-pneumonectomy, post-scuba diving <24 hours, middle ear surgery)
  • First trimester pregnancy
  • Severe COPD with hypoxic drive (use supplemental oxygen with caution)
  • Decreased consciousness or inability to cooperate

Side effects

  • Nausea or vomiting (~10%)
  • Dizziness
  • Euphoria
  • Transient sedation
  • Tingling of extremities
  • Occupational exposure risk (B12 inactivation with chronic staff exposure)

Interactions

  • Opioids — additive CNS depression (co-administration may be intentional for procedural sedation)
  • Vitamin B12 synthesis — inactivates methionine synthase; single exposure safe in healthy patients; risk increases with repeated exposures or pre-existing B12 deficiency

Monitoring

  • Oxygen saturation during procedure
  • Level of consciousness
  • Nausea prevention (aspiration risk)
  • B12 status if repeat exposures planned

Reference: BNFc; BNF 90; BOC Entonox Product Information; MHRA Guidance on Entonox; SIGN 106; Rosen's Emergency Medicine 9th Ed. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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