Nitrous Oxide

• Colourless gas, odourless/sweet smell
• Non-flammable but supports combustion


• Critical pressure (pressure required to liquify a gas at its critical temperature) is:
• 72bar at 36.5ºC
• 52bar at 20ºC

• Manufactured by heating ammonium nitrate to 250ºC:

NH₄NO₃ → N₂O + 2H₂O

• If temperature is not carefully controlled, contaminants can be present
• Ammonia
• Nitric acid
• Nitric Oxide
• Nitrogen
• These are irritant and, if present, can cause pulmonary oedema
• They are actively removed by passage through scrubbers, water and caustic soda

• Stored as a liquid with vapour on top
• Stored in French blue cylinders with French blue shoulders at 4,400kPa (4.4 bar)
• Should be stored vertically

• Filling ratio is the ratio of the mass of nitrous oxide in the cylinder to the mass of water the cylinder could hold
• In temperature regions the filling ratio is 0.75
• In tropical regions it is 0.67


• The pressure gauge on the cylinder is not a reliable estimate of remaining contents
• The pressure will remain constant until all of the liquid is evaporated
• After this the pressure drops rapidly as the remaining gas is removed
• The remaining content can instead be estimated by weighing the cylinder
• Knowledge of the molecular weight (44) of nitrous oxide is required to calculate the remaining amount

The phenomenon where the rise in alveolar partial pressure of nitrous oxide is disproportionately rapid when administered in high concentrations

• The concentration effect arises because the solubility of nitrous oxide in blood is 20x greater than that of nitrogen
• N₂O in the alveolus is rapidly absorbed into the bloodstream, whereas nitrogen is slow to diffuse out of the bloodstream
• Therefore:
• The alveolus decreases in volume, increasing the partial pressure of N₂O
• More gas from the airways is drawn into the alveolus to replenish the lost volume
• If this gas contains volatile anaesthetic, it will increase the concentration of the volatile agent in the alveolus


• This can be demonstrated by the wash-in curve, a graph of F_A/F_I ratio vs. time:



• It is a negative exponential curve, as the rate of change decreases with time
• The more insoluble the agent (blood:gas partition coefficient), the faster the rate of onset and the steeper the curve
• However, even though N₂O (B:G 0.47) has a greater blood:gas partition coeffecient than desflurane (B:G 0.4) it has a more rapid onset - because of the concentration effect
• Eventually all the lines will plateau at an F_A/F_I ratio of 1.0


• Limitations of this model:
• Assumes nitrous oxide is the only gas absorbed
• Assumes that 50% is absorbed from alveolus to pulmonary capillaries
• Doesn't include the effects of nitrogen leaving the body
• Assumes that the volume deficit from rapid nitrous absorption is replaced by gas of the same concentration as that initially inspired

The phenomenon whereby the speed of onset of an inhalational anaesthetic agent is increased when it is used with nitrous oxide as a carrier gas

• This is a consequence of the concentration effect
• Increases alveolar concentration of oxygen and volatile agents quickly
• Reduces induction time

• The reverse of the concentration effect
• At the end of anaesthesia, nitrous oxide/oxygen in the blood stream is replaced by air (nitrogen/oxygen)
• The volume of nitrous oxide diffusing from pulmonary capillaries to alveolus is high
• It is greater than the volume of nitrogen diffusing from alveolus to pulmonary capillaries
• As such it dilutes alveolar oxygen concentration and may cause hypoxia
• Prevented by changing inhaled gas mix to 100% oxygen

• Small reduction in tidal volume offset by small rise in respiratory rate therefore minute ventilation unchanged
• Impairs HPV at high concentration
• Depresses mucociliary flow and neutrophil chemotaxis, so may increase post-operative respiratory complications
• Blunts the ventilatory response to hypoxia/hypercapnia

• Mild, direct myocardial depression and negative inotropy
• Increase sympathetic activity via central effects; doesn't sensitise heart to catecholamines
• Therefore little overall change in the healthy patient; however for those in cardiac failure who cannot increase sympathetic drive, it will reduce cardiac output

• Exerts its effect by antagonising the NMDA receptor
• Increases CBF, CMRO₂ and ICP
• Potent analgesic
• Antagonism at NMDA receptor
• May act via potassium channels to hyperpolarise excitatory neurones
• Supraspinal activity at:
• Opioid receptors (effects partially reversed by naloxone) and GABA_A receptors in the PAG
• ɑ₂-adrenoreceptors in the locus coeruleus
• Weak anaesthetic with a MAC of 105%

• Emetogenic via:
• Action on opioid receptors
• Sympathomimetic effect
• Bowel dilatation

• Very high diffusing capacity (20x that of nitrogen) therefore diffuses into non-compliant (fixed volume) air filled cavities (e.g. middle ear, globe) causing rapid increased pressure
• Diffuses into compliant air filled cavities (bowel, pneumothorax) causing rapid increase in volume; after 4hrs breathing 66% nitrous oxide, bowel cavity expands 200%

• N₂O oxidises Co(I) to Co(II), inhibiting methionine synthetase
• This negatively impacts on production of:
• Methionine
• Thymidine
• THF
• DNA synthesis


• Exposure:
• Brief → megaloblastic changes
• Prolonged → agranulocytosis
• Recovery requires synthesis of new methionine synthetase and can be helped by taking folinic acid (source of THF)
• No effect in scavenged environments (N2O <50ppm) but in unscavenged (e.g. dental) environments can cause neurological syndromes from B₁₂ inactivation

• Teratogenic in rats although not unequivocally demonstrated in humans; still recommended to avoid in the first trimester


• Potential to administer a hypoxic mixture