Sevoflurane or Isoflurane: Which One to Use and Why

B S A V C 2008
Sam McMillan, VTS(Anaesthesia), DAVN(Med), RVN
The Royal Veterinary College
North Mymms, Hatfield, Hertfordshire

Sevoflurane and isoflurane are both from the halogenated ether group of
inhalational anaesthetic agents and both agents are indicated for the induction
and maintenance of general anaesthesia. Isoflurane is currently licensed in the
UK for use in dogs, cats, horses, ornamental birds, reptiles and small mammals
including rabbits, whilst sevoflurane is still currently only licensed for use in dogs.
Both isoflurane and sevoflurane cause similar side effects including dose-
dependent depression of the central nervous system, respiratory depression,
depression of body temperature regulating centers, hypotension, vasodilation,
myocardial depression and muscle relaxation. Both agents can cause a reduction
in cerebral metabolic rate whilst also causing vasodilation and therefore a
potential increase in cerebral pressure. This should be closely monitored in
patients with head trauma and/or cerebral disease, and it may be necessary to
ventilate them to ensure carbon dioxide levels are kept at an appropriate level to
prevent a further rise in cerebral pressure. One study has demonstrated that a
group of dogs had less respiratory depression with sevoflurane when given
equipotent doses of sevoflurane and isoflurane. No studies have demonstrated
one agent to be superior to the other in terms of overall side effects.
As a guide the minimum alveolar concentration (MAC) for isoflurane is
approximately 1.3% in the dog and 1.6% in the cat. This is considerably lower than
the MAC of sevoflurane at approximately 2.4% in both species. When you consider
that surgical anaesthesia is normally achieved at 1.5 times MAC it becomes clear
that a considerably higher vaporiser setting will be required when using
sevoflurane compared to if the same patient were anaesthetised using isoflurane.
This means that proportionally more sevoflurane will be used to ensure the patient
remains at an adequate depth for surgery. In real terms if using the same fresh
gas flow rate more sevoflurane will be used, making it a less economical option.
The blood-gas solubility of sevoflurane is lower than that of isoflurane. This
difference is not as great as the difference between isoflurane and halothane.
However, the lower the blood-gas solubility, the more rapidly the agent achieves an
effect in the brain and in turn the quicker the drug is released from the brain. This
means that induction and recovery should be more rapid with sevoflurane as
compared to isoflurane and that changes in vaporiser setting should provide a
more rapid change in anaesthetic depth. This rapid change in depth in response to
a change in the inspired anaesthetic concentration could indeed be an advantage
of sevoflurane, especially in critical patients whose vital statistics and anaesthetic
depth can be closely monitored by a competent anaesthetist. However, if the
patient cannot be monitored closely or a trained anaesthetist is not at hand to
respond to changes in anaesthetic depth then this drug should be used with
respect. Unfamiliarity with this agent and monitoring that is not thorough enough
can often lead to the patient becoming 'too deep' very quickly and to a tendency to
have the animal anaesthetised slightly 'deeper' than is ideal. This can give rise to
problems as there are few margins for error when patients become overdosed
especially when they are critically ill. Remember 'there are no such things as safe
anaesthetic drugs only safe anaesthetists!' It is worth noting that the onset of, and
indeed recovery from, side effects will also be seen more quickly with the use of
sevoflurane compared with isoflurane.
Other factors will also contribute to the recovery from anaesthesia and changes
in anaesthetic depth. These include the other drugs used concurrently in the
anaesthesia protocol, the patient's body fat ratio, the patient's disease state and
the overall metabolism of the patient. For example a patient with a very high
metabolism will quickly recover from either inhalant agent and the blood-gas
solubility becomes less of an influencing factor. In the author's opinion the
recovery from sevoflurane compared to isoflurane in a clinical situation is
generally only a few minutes faster and often does not make a dramatic difference
to recovery, especially in healthy patients.
Both sevoflurane and isoflurane are mainly eliminated from the body through
respiration following the cessation of anaesthesia and in both cases there is only
a small percentage of the drug metabolised by the liver and then excreted by the
kidneys.
The lower blood-gas solubility makes sevoflurane an ideal choice for masked
induction as the onset of anaesthesia will be faster than that seen with isoflurane.
In addition isoflurane has a marked and pungent smell and can be an airway
irritant when used for induction of anaesthesia using chambers and masks. For
this reason it is generally less well tolerated than the odourless inhalant agent
sevoflurane. Sevoflurane does not appear to cause airway irritation.
Sevoflurane is relatively expensive compared to isoflurane currently; although, as
the demand from the veterinary market rises, especially following the gradual
withdrawal of halothane, the cost could potentially fall making it more affordable
and comparable in cost to the cheaper agent isoflurane. It should be noted that
sevoflurane can be made more cost effective by using a low-flow anaesthetic
technique; although this requires careful monitoring and more monitoring
equipment. This is also true of isoflurane, so if used on a like-for-like basis
sevoflurane is still considerably more expensive. It should be noted that using low-
flow anaesthesia reduces the rate at which the vaporiser setting affects the
inhaled levels of anaesthetic gas, thus negating some of sevofluranes advantages
over isoflurane.
Sevoflurane has been demonstrated to produce 1,1,3,3,3-pentafluoro-2-
(fluoromethoxy)propene, also known as compound A when it interacts with soda
lime. Compound A has been shown to cause nephrotoxicity in rats; however, the
mechanism of this is unknown and this finding has not been demonstrated in
dogs. The concentration of compound A increases in a circle system, with
increasing sevoflurane levels and decreasing fresh gas flow rates, and for this
reason the manufacturer's data sheet advises avoiding long-duration, low-flow
anaesthesia with sevoflurane.
Conclusion

Whilst the development and licensing of sevoflurane for the veterinary market
obviously may have some benefits in the anaesthesia of critical patients, due to
the more rapid change in anaesthetic depth, isoflurane is still the licensed drug
for many species and should be considered under the VMD regulations and under
the prescribing cascade. As sevoflurane becomes more affordable and
potentially may be licensed for a greater variety of species it could be a valuable
addition to veterinary anaesthesia. Currently in dogs it provides the option of
masked induction of anaesthesia, providing rapid onset of anaesthesia.
 There is also no doubt that sevoflurane will give a small percentage increase in
recovery times and faster changes in anaesthetic depth than isoflurane but the
actual clinical relevance of this is not clear. Rapid recovery may certainly be of
benefit but rapid does not necessarily equal smooth, which in many cases is just
as important; there are other factors besides the inhalant agent that will affect
this, notably sedative premedicants and analgesia. It should at this point be noted
that a balanced anaesthetic isn't just about the inhalant and induction agents.
Despite the given advantages of sevoflurane isoflurane should not be
discounted as a valuable resource in small animal anaesthesia; despite the
pungent smell and irritability to airways if used for masked induction, it causes no
problems in this area when used for maintenance of anaesthesia. The difference
in blood-gas solubility is not so vastly great that it will make a huge difference in
healthy patients undergoing routine surgery. However, the author accepts that for
critical canine cases sevoflurane may be advantageous providing the anaesthetist
is experienced in its use.
References
1.  Flecknall P, Waterman-Pearson A. Pain management in animals. London: WB Saunders, 2000.

2.  Lumb W, Jones E, et al. Lumb & Jones' veterinary anesthesia (third edition). Philadelphia: Lippincott
Williams & Wilkins, 1996.

3.  McKelvey D, Hollingshead KW. Veterinary anesthesia and analgesia (third edition). St Louis: Mosby,
2003.

4.  Muir W, Hubbell J, et al. Handbook of veterinary anesthesia (fourth edition). St Louis: Mosby, 2007.

5.  Welsh E. Anaesthesia for veterinary nurses. Oxford: Blackwell Publishing, 2003.

S I
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Sam McMillan, VTS(Anaesthesia) DAVN(Med) RVN

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The Royal Veterinary College
Hatfield, Hertfordshire, UK

URL: http://www.vin.com/doc/?id=3862826 (http://www.vin.com/doc/?id=3862826)