2012A02 In relation to the pharmacokinetics of nitrous oxide, describe the significance of
partition coefficients, increasing inspired concentration, the second gas effect and diffusion hypoxia.

Oil-gas

·   N₂O 1.4 cf. sevoflurane 80

·   MAC 105%, MAC-awake 67%

·   Low potency, inadequate as a sole agent

·   Can be used as a high volume carrier gas

Blood-gas

·   N₂O 0.47 cf. N2 0.014

o 30x difference in solubility hence rate of equilibration

o Hence concentration effect, second gas effect, diffusion hypoxia (below)

o Hence expansion of closed air spaces (e.g. pneumothorax)

·   N₂O 0.47 cf. sevoflurane 0.69

o ↑Rate of rise F_A/F_I -> rapid onset

Muscle-blood

·   N₂O 1.2 cf. sevoflurane 3.1

·   Equilibration half time: 3 hours

·   Minimal accumulation during medium-long case

Fat-blood

·   N₂O 2.3 cf. sevo 48

·   Equilibration half time: 5 hours

·   Minimal accumulation during long case

Concentration effect

·   Seen only with high volume carrier gases

·   Switch from N₂/O₂ to N₂O/O₂

·   Rapid uptake N₂O from alveolus, but very slow output of N₂

·   Reduction in alveolar volume and pressure -> rapid inflow of N₂O-rich fresh gas

·   Accelerated ↑ F_A/F_I N₂O

Second gas effect

·   Rapid uptake N₂O from alveolus, but very slow output of N₂

·   Concentration of remaining alveolar gas

·   Accelerated ↑F_A/F_I volatile drug

Diffusion hypoxia

·   Reverse of the concentration effect

·   Switch from N₂O/O₂ to N₂/O₂

·   Rapid output N₂O into alveolus, but very slow uptake of N₂

·   Dilution of alveolar O₂ -> hypoxia

·   Avoided by high %O₂ during washout