Anaesthesia is usually induced by injecting a rapidly acting drug intravenously. The advantages of this are that it is easy, a precise dose can be given, there is a rapid onset of anaesthesia (no excitement stage) and only a syringe and needle are required. The disadvantage is that there is no control over waking - if you give too much you are in trouble.
The ideal iv anaesthetic would be reliable, quick acting, produce no excitment on induction, have no side effects, be rapidly metabolised, produce good muscle relaxation, be analgesic, non-irritant and water soluble but it is non existant!
Barbiturates, and particularly thiopentone (thiopental USAN: all the barbiturates end in al in American), have always been the drugs most commonly used, although they have recently been overtaken by propofol in human anaesthesia.
Thiopentone comes as powder
mixed with NaCO3. It is unstable when made up as aqueous solution but keeps
for three days in a fridge. It is used as 2.5% solution (pH 11) in most dogs,
1.25% in small dogs / cats, 10% in large animals.
It produces rapid anaesthesia in one circulation time. It is not analgesic,
there is some evidence that it is hyperalgesic. It is a potent respiratory depressant.
There is usually transient apnoea after an induction dose - ventilate the animal.
It produces transient depression (usually only 2- 3 minutes) of cardiac output
and blood pressure. It is only used for induction of anaesthesia (cumulation
occurs if used for maintenance (half life about 4.5 hours in dogs) - very slow
recovery).
Problems with thiopentone are largely caused by overdosage (see pharmacokinetics
above). Muscle relaxation is not always good enough for intubation unless a
premed has been given (in people they often use suxamethonium to aid intubation).
There are breed variations; greyhounds and similar dogs have a slow recovery.
Extravascular injection will cause skin necrosis (high pH, especially more concentrated
solutions) - inject lignocaine ± saline around area. Intra-arterial injection
will cause pain, necrosis and possibly convulsions, probably because the thiopentone
crystallises out and causes arterial spasm.
Propofol is not a barbiturate but is
clinically very similar to thiopentone. It comes as a white emulsion in single
use vials under nitrogen which is non irritant (but can cause mild pain in some
people, thought to be mediated by P2X receptors). Its major advantage over thiopentone
is that it is metabolised quickly in most species (except some cats) (half life
about 40 mins in dogs). Its disadvantages are mild excitatory effects (usually
front leg paddling in about 10% of dogs, although opisthotonus can occur) and
occasionally rough recovery. It can cause hallucinations in people which often
takes the form of sexual disinhibition in women! It is expensive, but coming
down in price. The vehicle contains egg yolk and coconut oil and is an ideal
growing medium for bacteria - open ampoules must be thrown away. There have
been some suspected deaths from septicaemia in dogs after using old propofol.
Wound infections are three times more likely after propofol anaesthesia - possibly
because people are tempted to use old propofol.
New derivatives of propofol which are water soluble and more potent are being
developed.
“Saffan” (“Althesin”)
is a mixture of the steroids alphaxalone and alphadalone. The
alphaxalone is thought to produce most of the anaesthesia, with the alphadolone
was originally included to help dissolve the alphaxalone. However, recent work
indicates that the alphadolone may have significant analgesic effect. It is
a good anaesthetic and is rapidly metabolised, even in cats. However, the vehicle
(polyethoxylated castor oil - "Cremaphore EL") causes massive histamine
release in dogs so it is not used in dogs (although a technique of premeding
with massive doses of antihistamines has been described - not recommended).
Cats sometimes get oedema of the paws and ears after Saffan; the incidence of
this can be reduced by injecting the drug more slowly (use a 25 SWG needle).
It is only commonly used in cats although it is a good anaesthetic in most species
except the dog. Because of its rapid metabolism it can be used for long term
anaesthesia / sedation such as intensive care situations. Recoveries can be
excitable if the cat is disturbed. Althesin used to be a popular human anaesthesic
but was withdrawn a few years ago after similar problems with the vehicle. Saffan
is the remaining stocks left after withdrawal of the human drug - when these
are used up Saffan may be withdrawn too.
A new preparation of alphaxalone dissolved in cyclodextrin and water is now
available (“Alfaxan CD”). This is also suitable for dogs and is
likely to be widely used if it compares with thiopentone or even propofol on
price.
Other steroid anaesthetics are under development (although all the candidates
so far also cause excitatory effects on recovery). They will be water soluble
to avoid the problems with the vehicle.
Ketamine is rather different from the other induction agents. It is a dissociative anaesthetic, which means (in people anyway) that the patient is conscious but not aware of what is being done to them. This may be because it is a good analgesic and completely blocks the memory! It produces no cardiovascular depression at normal doses. It acts rapidly by any route (although it is painful by im or sc injection - pH4). Its main disadvantage is that is produces no muscle relaxation and can actually cause convulsions in dogs and horses. It is used alone in cats and monkeys and combined with other drugs in other species (see below). It is also abused by some drug addicts, and although it is not (yet) a controlled drug in NZ, it should be locked up. Cats behave strangely for several hours after injection (movie). Tiletamine is a similar drug which comes premixed with zolazepam (benzodiazepine sedative).
Methohexitone is barbiturate which is similar
but shorter acting than thiopentone. It usually produces excitation on induction
and recovery - heavy premed required. It produces much more respiratory depression
than thiopentone. Its only real indication was for induction in greyhounds but
it has been overtaken by propofol. It is now difficult to obtain.
Pentobarbitone is rarely used for anaesthesia any more. It
gives a slower induction and is longer acting than thiopentone. Its main use
is for euthanasia, although it can be used for anaesthesia in sheep - faster
metabolism than most species. It is sometimes used for long term sedation in
dogs (eg, metaldehyde poisoning). Do not use euthanasia mixtures for anaesthesia
- they are not sterile.
Metomidate and the human analogue etomidate are not available in NZ and are mainly of historical interest, although etomidate
is currently undergoing a revival in veterinary anaesthesia in the USA. They
produce anaesthesia but no analgesia and are traditionally used in pigs. Etomidate
may be of advantage in sick dogs since cardiovascular depression is minimal.
Analgesic premed is required for a smooth induction, and sedative premed to
stop twitching. Etomidate has been abandoned by human anaesthesia because it
causes profound adrenocortical depression.
Thiamylal was used in the USA instead of thiopentone but is no longer available, it was clinically indistuingishable.
Laboratory animals are sometimes given these drugs in an attempt
to produce long acting anaesthesia with minimal cardiovascular depression. In
nearly every case, modern drugs properly administered would be better for the
animals and give more reliable results for the experimenter.
α chloralose produces 8 -10 hours of stable light anaesthesia
in rodents, but no analgesia. It may have a place in some situations.
Urethane is similar, but has more analgesia. It is carcinogenic.
Do not use.
Chloral hydrate in overdose will produce a state bordering
on general anaesthesia, but with no analgesia. Do not use.
Tribromoethanol has nothing to recommend it. It must be given
ip and is very irritant. It quickly decomposes to even more irritant metabolites.
It should never be used.
neuroleptanalgesics
sedative & hypnotic
α2 agonist & ketamine
benzodiazepine (midazolam) & ketamine
zolazepam & tiletamine
The sedative overcomes the increased muscle tone produced by the ketamine.
Small animals are usually killed by giving an overdose of pentobarbitone iv. Note that these solutions are not sterile. The volume involved in killing large animals this way will not fit easily into a syringe, so other drugs are sometimes added. Various toxic local anaesthetics such as cinchocaine have been used in an attempt to stop the heart; potassium chloride is sometimes used.
Premixed toxic cocktails (T61) have been used which include a muscle relaxant. These should always be given iv as there have been some cases of the muscle relaxant being absorbed before the sedative part of the mix - not a pleasant way to go.
