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Nitrous oxide !

Weak anaesthetic gas but a good analgesic, combined with oxygen and other anaesthetics. It expands air-filled spaces and inactivates vitamin B12.

Updated 2026-11-01

  • Class: Inhaled anaesthetics
  • Receptor: NMDA glutamate receptor (and two-pore-domain potassium channels)
  • ATC code: N01AX13
  • WHO Model List of Essential Medicines

Also called: Dinitrogen monoxide, N2O

Mechanism of action

Nitrous oxide is a colourless gas, poorly soluble in blood, that mainly blocks the NMDA receptor and activates some two-pore-domain potassium channels; unlike halogenated agents, it barely acts on the GABA-A receptor. It is a weak anaesthetic, so it is not enough on its own for surgery, but it is a good analgesic and reduces the amount of other anaesthetics needed. Its rapid uptake concentrates a halogenated agent given at the same time and speeds induction (second gas effect).

  1. Inhaled, it equilibrates very quickly because of low solubility
  2. Blocks the NMDA receptor: analgesia and weak anaesthesia
  3. Adds to the halogenated agent (lower MAC)
  4. When stopped, it floods the alveoli and dilutes oxygen

Pharmacokinetics

Absorption
Through the lungs; very poorly soluble in blood: fast onset and recovery.
Metabolism
Practically not metabolised.
Elimination
Almost all is exhaled unchanged through the lungs.

Indications

  • Adjunct to general anaesthesia with other anaesthetics
  • Inhaled analgesia and sedation for brief procedures, mixed with oxygen

Adverse effects

Common

  • Raised intracranial blood flow and pressure
  • Raised venous tone and pulmonary vascular resistance
  • Blunted ventilatory response to hypoxia

Contraindications

  • Pneumothorax, bowel obstruction, blocked middle ear, intraocular gas bubble or intracranial air
  • Vitamin B12 deficiency, malnutrition or alcoholism (high risk of B12 toxicity)
  • Pulmonary hypertension (it worsens it)

Key interactions

Halogenated anaesthetics
Lowers the concentration needed and speeds induction (second gas effect).
Opioids
Together they usually lower blood pressure and cardiac output.

What is monitored

  • Oxygen saturation during and after use
  • Inspired oxygen concentration (always adequate)
  • With repeated exposure: blood count and signs of neuropathy

Administration and safety

  • Always mixed with enough oxygen; never as the only gas.
  • At the end, give 100% oxygen for a few minutes to prevent diffusion hypoxia.

Nursing care

  • Before: rule out pneumothorax, bowel obstruction, recent ear surgery or eye surgery with gas.
  • During and after: watch saturation and level of consciousness.
  • Ask about symptoms of B12 deficiency (tingling, weakness) and recreational use.

Pregnancy and breastfeeding

It has little effect on uterine muscle; its effect on vitamin B12 and DNA synthesis is a concern with repeated exposure, so it is kept to brief uses.

Test yourself

Think of the answer, then tap the question to see it.

Why is 100% oxygen given when nitrous oxide is stopped?

Because nitrous oxide leaves the blood quickly into the alveoli and dilutes the oxygen: diffusion hypoxia.

Why is nitrous oxide contraindicated in pneumothorax?

It enters the air space faster than nitrogen leaves, raising its volume or pressure and worsening the pneumothorax.

How does nitrous oxide cause megaloblastic anaemia?

It oxidises the cobalt of vitamin B12 and inactivates it as the cofactor of methionine synthase, which disturbs DNA synthesis.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 24 (McGraw Hill, 2023); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.