Anaes · Volatile & inhalational agents

Nitrous oxide

Also known as N2O · Laughing gas · Entonox (50:50 with oxygen) · Non-halogenated inorganic anaesthetic gas · MAC 105 percent gas

Nitrous oxide (N2O) is the only non-halogenated inorganic inhalational agent and a weak anaesthetic but potent analgesic adjunct. Its MAC of 105 percent is the highest of any agent, so a full MAC cannot be achieved at atmospheric pressure and it is used as an adjunct, never a sole maintenance agent. Its very low blood-gas partition coefficient of 0.47 gives rapid uptake and elimination, and when co-administered with a potent volatile the rapid N2O uptake produces the concentration effect and second gas effect, accelerating the rise of the companion agent (Korman, 2023). N2O is 34 times more blood-soluble than nitrogen, so it diffuses into closed gas-containing spaces faster than nitrogen can leave, expanding pneumothoraces, obstructed bowel, the middle ear and venous air emboli (Almujaiwel, 2026). Diffusion hypoxia can occur on emergence as N2O rapidly leaves the blood. N2O is minimally metabolised and does not trigger malignant hyperthermia, but it inactivates vitamin B12 and methionine synthase, causing subacute combined degeneration and megaloblastic anaemia, particularly with chronic recreational use (Li, 2026; Tikaria, 2026; Brasfield, 2026). The methionine-synthase block raises homocysteine and thrombotic risk (Serrano, 2026). N2O is a potent greenhouse gas with a global-warming potential around 273 and is ozone-depleting, requiring scavenging (Kayak, 2026). Its clinical uses include labour analgesia as Entonox (Kichili, 2026). Use is declining due to environmental and B12/homocysteine concerns.