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.

 

List:

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

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

 

Partition coefficients:

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 FA/FI -> 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

 

↑FiN2O:

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