Anaesthesia - inhalation drugs

halothane
isoflurane
enflurane
sevoflurane
desflurane
ether
methoxyflurane
trichloroethylene
chloroform
nitrous oxide

table of physical properties

Halothane is the most important inhalation anaesthetic in veterinary anaesthesia by a long way. It is a good general purpose anaesthetic but not a very good analgesic (use with nitrous oxide or injectable analgesic). It is also a poor muscle relaxant. It is best used as the hypnotic part of a balanced anaesthesia technique. Its side effects include:

•respiratory depression (dose dependent)
•reduced cardiac output
•vasodilatation
•sensitises heart to adrenaline
•(halothane hepatitis)
•(malignant hyperthermia in pigs)

When used alone, to provide surgical anaesthesia (ie, high doses), cardiorespiratory depression can be severe. If not enough halothane is used, the combination of halothane and adrenaline can cause tachyarrhythmias, especially in cats.

Halothane hepatitis is a cause of (unnecessary?) worry in human anaesthesia - halothane has been largely replaced by isoflurane (particularly in the USA) and may be withdrawn in the future. Hepatitis after halothane is not a problem in domestic animals but concern about operating theatre staff may cause controls on atmospheric pollution (see scavenging below).

Malignant hyperthermia occurs in some breeds of pig (and people), particularly Pietrain and some families of Landrace pigs. If the pig starts to go hot and rigid, turn off the halothane immediately and ventilate with 100% oxygen. It may also need to be hosed down with cold water. The problem is caused by a mutation of the ryanodine receptor, which controls calcium flux out of the sarcoplasmic reticulum. The definitive treatment is dantrolene (ryanodine receptor antagonist), but it is rarely available. Malignant hyperthermia can also occur in other species but is rare. Halothane is sometimes deliberately used in pigs to detect if they are carrying the MH genes (MH is also induced by stress and lowers the value of the meat). About 30% of commercial pigs in NZ have the MH gene. Pigs have been extensively studied as a model for MH in people; but little is known about it in other species.

Isoflurane is similar to halothane but gives a faster induction and recovery. Many dogs object to the smell. It is expensive, but can be useful in sick animals or where a very fast induction and recovery are required. If halothane is taken off the market, isoflurane is the obvious sucessor. It may also cause MH. Like halothane, it has little analgesic effect. Enflurane is a chemical isomer of isoflurane but often produces excitatory effects which make judgement of depth of anaesthesia difficult. It has no obvious advantages and is not often used.

Nitrous oxide (N₂O, laughing gas) has been around since the 18th century. It was used as a recreational drug until its analgesic properties were discovered. It is a weak anaesthetic although a good analgesic so it must be used with other agents. It produces a rapid induction - it equilibrates in about 10 mins. A number of problems are associated with nitrous oxide:
• diffusion hypoxia - Fink effect - the opposite of the second gas effect
• diffuses into air filled spaces - beware pneumothorax and colic
• can build up in circle systems - oxygen analyser must be used or run the system semi closed.
• depresses folate metabolism (long term use > 8 hours)
Since it is a gas, it comes in cylinders and requires pressure regulators, flow regulators etc (more equipment to break down!). However, it is well worth the bother. The main reason to use it is that its analgesic properties mean that much less halothane can be used. This either means smoother anaesthesia or faster recoveries, depending on how it is used.

New drugs

The newer agents desflurane and sevoflurane are not yet fully evaluated in animals (but give a very fast induction and recovery in man). Desflurane is very good in theory but requires special (very expensive) vaporisers. Sevoflurane has been used in horses, pigs and birds. Some paediatric anaesthetists use them for induction (takes 10 - 60 seconds) and then switch to halothane or isoflurane for maintenance. They may have their use depending on price. Sevoflurane is catching on in human anaesthesia and getting cheaper all the time.

Old drugs

Older agents include trichoroethylene which is almost obselete but worth using in some circumstances. It is a very good analgesic but a poor muscle relaxant and is best used in combination with another agent such as halothane - low dose halothane keeps the animal asleep and trichloroethylene provides the analgesia. It gives a very slow induction and recovery but good analgesia during recovery. Do not use in a closed system with soda lime - reacts to produce phosgene. (Anaesthetic or HPLC grade trichloroethylene should be used for anaesthesia; it is also one of the commonest industrial solvents but solvent grade is full of toxic impurities.)
Diethyl ether (= ether) is almost obselete and should be avoided in most circumstances. It is a good anaesthetic but very inflammable in air, and explosive in oxygen. Its vapour is heavier than air and will roll along the floor and under doors. It gives a slow induction and recovery. The only reason it is still around is that it is the only agent which can be used without supplementary oxygen as it stimulates respiration (but if oxygen is available use it). It is irritant to the airways (peroxide degradation products) - anticholinergic premed required.
Methoxyflurane is not available in NZ and is almost obselete. It gives a very slow induction and recovery, but is a very good analgesic and a good muscle relaxant so is useful for long orthopaedic ops. It is extensively metabolised releasing free fluoride ions which may cause kidney damage (particularly in combination with NSAIDs).
Chloroform used to be used in horses because it was cheap. It causes massive liver necrosis in hypoxia and is very good at sensitising the heart to adrenaline. Do not use.

copyright Massey University