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Section IICoredrugs in anaesthetic practicewhich may cause upper airway irritability, coughing and breath-holding. How-
ever, despite its pungent smell it causes some bronchodilation.
Cardiovascular – its main effect is to reduce systemic vascular resistance. The result-
ing reflex tachycardia suggests that the carotid sinus reflex is preserved. It causes
only a small decrease in myocardial contractility and cardiac output. It has been
suggested that isoflurane may cause coronary steal whereby normally responsive
coronary arterioles are dilated and divert blood away from areas supplied by unre-
sponsive diseased vessels, resulting in ischaemia. However more recent work has
suggested that as long as coronary perfusion is maintained coronary steal does
not occur. In addition isofluane may have myocardial protective properties via its
effects on ATP-dependent potassium channels.
Central nervous system – of all the volatile agents isoflurane produces the best
balance of reduced cerebral oxygen requirement and minimal increase in cerebral
blood flow. At concentrations up to 1 MAC cerebral autoregulation is preserved.Metabolism
Only 0.2% is metabolized and none of the products has been linked to toxicity.Toxicity
Owing to the presence of a –CHF 2 group in its structure it may react with dry soda lime
(or baralyme) producing carbon monoxide. Reports of this relate to circle systems
that have been left with dry gas circulating over a weekend so that subsequent use of
isoflurane causes release of carbon monoxide. Enflurane and desflurane also possess
–CHF 2 groups and may react in a similar manner.Sevoflurane
Sevoflurane is a polyfluorinated isopropyl methyl ether and has the favourable com-
bination of a relatively low blood:gas partition coefficient (0.7), pleasant odour and
relatively low MAC (1.8). However during storage where the concentration of added
water is below 100 ppm it is susceptible to attack by Lewis acids at its ether and halo-
gen bonds, releasing the highly toxic hydrofluoric acid (HF). (A Lewis acid is defined
as any substance that can accept an electron pair and includes many metal oxides
but also H+;glass is a source of Lewis acids.) Hydrofluoric acid corrodes glass expos-
ing sevoflurane to further Lewis acids. As a result sevoflurane is formulated with
300 ppm of water, which acts as a Lewis acid inhibitor. In addition it is stored in poly-
thylene napthalate bottles, rather than glass. A dry formulation containing less than
130 ppm water is now available and is presented in an aluminium bottle lined with an
epoxyphenolic resin lacquer. Unlike the other volatile agents sevoflurane is achiral.Manufacture
The one pot method – all the ingrediants are added together to produce sevoflurane
and then water is added to 300 ppm.