Nitrous Oxide
N₂O · laughing gas
Inhaled anesthetic gas (analgesic/anesthetic adjuvant)
NMDA-receptor antagonism (primary) + opioid/GABA effects → analgesia + amnesia. Weak anesthetic (MAC 104%) so used as an adjuvant, not a sole agent.
Indications
- •Anesthetic adjuvant (MAC-sparing, 'second gas' effect)
- •Analgesia (dental, labor — Entonox 50:50)
- •Rapid inhalational induction adjunct
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Maintenance adjunct | 50–70% inspired (with O₂ ≥30%) | — |
Pharmacokinetics
Very low blood:gas solubility (0.47) → fast on/off. Second-gas effect + concentration effect speed induction. Minimal metabolism (exhaled unchanged).
Hemodynamic effects
Mild sympathetic stimulation; can raise PVR (avoid in pulmonary HTN).
Respiratory effects
DIFFUSION HYPOXIA on emergence — give 100% O₂ for a few minutes after discontinuing.
Side effects
- !Expands closed air spaces (pneumothorax, bowel, middle ear, intraocular gas, air embolism, ETT cuff)
- !Diffusion hypoxia
- !Megaloblastic anemia / neuropathy (methionine synthase inhibition — chronic/B12 deficiency)
- !↑ PONV
- !Teratogenic concern (1st trimester, chronic exposure)
Contraindications
- ×Pneumothorax
- ×Bowel obstruction
- ×Middle-ear/retinal (intraocular gas) surgery
- ×Air embolism
- ×Pulmonary hypertension
- ×Severe B12 deficiency
Clinical pearls
- ★MAC 104% → cannot be a sole anesthetic; it's the classic ADJUVANT (second-gas + concentration effects speed volatile uptake).
- ★N₂O is 34× more soluble than nitrogen → expands closed air-filled spaces (the #1 contraindication set).
- ★Give 100% O₂ on emergence to prevent DIFFUSION HYPOXIA; inhibits methionine synthase (B12) → avoid chronic exposure / B12-deficient patients.
Other drugs in Inhalation Agents
- Sevoflurane
Multi-site CNS depression: GABA-A potentiation, glycine receptor potentiation, NMDA + nicotinic ACh inhibition, two-pore K⁺ channel activation. Net: dose-dependent unconsciousness, amnesia, immobility, and analgesia (modest).
- Desflurane
Same multi-site mechanism as sevoflurane: GABA-A + glycine potentiation, NMDA + nicotinic ACh inhibition, K⁺ channel activation.
- Isoflurane
Volatile anesthetic. Multiple sites: potentiates GABA-A, antagonizes NMDA, activates two-pore-domain K⁺ channels, modulates glycine. Lower potency than sevoflurane but produces deeper unconsciousness per MAC. Pungent — not used for inhalation induction.
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Suggested reading
- •Stoelting & Hines, Pharmacology & Physiology in Anesthetic Practice, 6e
- •Miller's Anesthesia, 9e
