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8 General anaesthetic agentsof methionine, thymidine, tetrahydrofolate and DNA. Methionine synthetase also
appears to be directly inhibited by N 2 O.Exposure of only a few hours may result in
megaloblastic changes in bone marrow but more prolonged exposure (i.e. days) may
result in agranulocytosis. Recovery is governed by synthesis (taking a few days) of
new methionine synthase, but may be helped by the administration of folinic acid,
which provides a different source of tetrahydrofolate.
Inaproperly scavenged environment where N 2 Oconcentrations are less than 50
ppm there is no effect on DNA synthesis. However, in unscavenged dental surgeries
where large amounts are used, chronic exposure may result in neurological syn-
dromes that resemble subacute combined degeneration of the cord, as a result of
chronic vitamin B 12 inactivation.
Inexperimental conditions N 2 Ohas been shown to be teratogenic to rats but this
effect is prevented by folinic acid. While this has never been unequivocally demon-
strated in humans, N 2 Oisoften not used in the first trimester when anaesthesia is
required.Entonox
Entonox is a 50:50 mixture of N 2 Oand O 2. The two gases effectively dissolve into
each other and do not behave in a way that would be predicted from their individual
properties. This phenomenon is called the Poynting effect.Uses
Entonox is widely used for analgesia during labour and other painful procedures.Storage
Entonox is stored as a gas in French blue cylinders (G = 3200 litres; J = 6400 litres)
with white and blue checked shoulders at 137 bar. It separates into its constituent
parts below its pseudo-critical temperature, which is about –7◦Cand is most likely
to occur at 117 bar. Higher or lower pressures reduce the likelihood of separation.
When delivered via pipeline at 4.1 bar the pseudo-critical temperature is less than
–30◦C. If a cylinder is used following separation, the inspired gas will initially produce
little analgesia as it contains mainly O 2 , but as the cylinder empties the mixture will
become progressively potent and hypoxic as it approaches 100% N 2 O.Isoflurane
This halogenated ethyl methyl ether is a structural isomer of enflurane. It is widely
used to maintain anaesthesia. Its physical properties are summarized in Table8.7.Effects
Respiratory – isoflurane depresses ventilation more than halothane but less
than enflurane. Minute volume is decreased while respiratory rate and PaCO 2
are increased. It is rarely used to induce anaesthesia due to its pungent smell,