Nitrous Oxide

Describe the pharmacology of nitrous oxide

Describe the comparative pharmacology of nitrous oxide, halothane, enflurane, isoflurane, desflurane, sevoflurane, xenon and ether

Property Nitrous Oxide
Pharmaceutics Non-flammable but supports combustion. Produced by heating ammonium nitrate to 250°C. Potential contaminants include NH3, N2, NO2, and HNO3.

Stored as a liquid, such that the gauge pressure is only accurate when all remaining N2O is in the gaseous phase.

The filling ratio is the mass of N2O in the cylinder compared to the mass of water it could hold, and is 0.75 in temperate regions, and 0.67 in warmer regions.
Molecular Weight 44
Boiling point -88°C
Critical Temperature/Pressure 36.5°C / 72 bar
SVP (at 20°C) 39,000 mmHg
Blood:gas coefficient 0.47
Oil:gas coefficient 1.4
MAC 105 (MAC awake 68)
Mechanism of Action Several different mechanisms, including:
- Stimulates dynorphin release (acts at KOP receptor)
- Positive allosteric modulator at GABAA receptor
- NMDA antagonist
Metabolism < 0.01% hepatic reduction.
Resp Diffusion hypoxia due to second gas effect. Small ↓ in VT, ↑ in RR such that MV is unchanged.
CVS ↑ SNS tone, mild myocardial depression. ↑ PVR - beware in pulmonary hypertension.
CNS Powerful analgesic when > 20%, via endorphin and enkephalin modulation, and on opioid receptors. ↑ CBF. Loss of consciousness common at 80%. 1.4x relative risk of PONV
GU Not tocolytic - useful adjuvant in GA caesarian section to reduce volatile anaesthetic use
GIT Expansion
Metabolic ↑ Homocysteine.
Toxic Effects More soluble than N2 means it will rapidly diffuse into air-filled cavities, increasing the volume of compliant cavities (PTHx, bowel), and increasing the pressure of non-compliant cavities (middle ear).

Prolonged use (> 6 hours) oxidates cobalt ion in vitamin B12, preventing its action as a cofactor for methionine synthetase, preventing DNA synthesis. This leads to:
- Megaloblastic changes in bone marrow
- Agranulocytosis
- Peripheral neuropathy
- Possible teratogenicity - avoid in early pregnancy

Greenhouse gas.


Entonox is a 50/50 mixture of nitrous oxide and oxygen, used as analgesia in labor and minor procedures.

Property Entonox (50% O2, 50% N2O)
Pharmaceutics The gases dissolve each other and behave differently than would be expected from their individual properties. This is the Poynting effect.
Critical Temperature/Pressure Pseudocritical temperature of -6°C, below which it will separate into liquid 50% N2O (with some dissolved O2), and gaseous O2. This is most likely to occur at 117 bar, and can lead to delivery of a hypoxic mixture.

Delivery of a hypoxic mix is prevented by:
- Storing cylinders horizontally (↑ area for diffusion)
- Storing cylinders at temperatures > 5°C
- Using a dip tube so that liquid 50% N2O is used before the gaseous mixture


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  3. ANZCA February/April 2006
  4. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  5. Emmanouil DE, Quock RM. Advances in Understanding the Actions of Nitrous Oxide. Anesthesia Progress. 2007;54(1):9-18. doi:10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2.
  6. Hendrickx, J., Peyton, P., Carette, R., & De Wolf, A. (2016). Inhaled anaesthetics and nitrous oxide. European Journal of Anaesthesiology, 33(9), 611–619.
  7. Brown S, Sneyd J. Nitrous oxide in modern anaesthetic practice. 2016. BJA Education, 16(3), 87–91.
Last updated 2019-07-18

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