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Section IICoredrugs in anaesthetic practiceThe model described in Figure8.8is limited in numerous ways (N 2 Oisthe only
gas absorbed and the effects of N 2 leaving the body are not included), but it does
serve to illustrate the mechanism by which the concentration effect is thought to
occur. In addition it illustrates the second gas effect. It assumes that half the N 2 Oin
the alveoli is absorbed into the pulmonary capillaries, the volume deficit of which is
made good by augmented ventilation which has the same fractional composition as
the initial alveolar gas.The second gas effect
The second gas effect is a direct result of the concentration effect. Oxygen plus or
minus volatile agents used alongside high concentrations of N 2 Owill be concen-
trated by the rapid uptake of N 2 Oand augmented alveolar ventilation. This leads
to increased concentrations of oxygen and volatile agents resulting in a reduced
induction time.Diffusion hypoxia
Atthe end of anaesthesia when N 2 O/O 2 is replaced by air (N 2 /O 2 ) the reverse of the
second gas effect is seen. The volume of N 2 Oentering the alveolus will be greater
than the volume of N 2 entering the pulmonary capillaries resulting in a dilution of
all alveolar gases. Most volatile anaesthetics end by changing N 2 O/O 2 to 100% O 2
which prevents diffusion hypoxia.
Inaddition to the effects seen across the alveolar membrane, N 2 Owill cause a
rapid expansion of any air filled space (pneumothorax, vascular air embolus and
intestinal lumen).Toxicity
The cobalt ion present in vitamin B 12 is oxidized by N 2 Osothat it is unable to act
as the cofactor for methionine synthase (Figure8.9). The result is reduced synthesisVit amin B 12N 2 OMethionine SynthetaseCo(I)Folinic acidHomocysteine methyl THF methionine THFCo(II)Activates InhibitsFigure 8.9.N 2 O inhibits methionine synthetase by oxidizing cobalt (Co(I)). THF,
tetrahydrofolate.