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.



·      PCs: oil-gas, blood-gas, muscle-blood, fat-blood

·      FiN2O: conc effect, 2nd gas effect, diffusion hypoxia


Partition coefficients:


·   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


·   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 FA/FI -> rapid onset


·   N2O 1.2 cf. sevoflurane 3.1

·   Equilibration half time: 3 hours

·   Minimal accumulation during medium-long case


·   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 ↑ FA/FI N2O

Second gas effect

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

·   Concentration of remaining alveolar gas

·   Accelerated ↑FA/FI 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



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