Microsoft word - anaesthesia - released jan 2006.doc
T H E U N I V E R S I T Y O F M E L B O U R N E A N I M A L W E L F A R E C O M M I T T E E G U I D E L I N E S F O R G E N E R A L A N A E S T H E S I A A N D A N A L G E S I A O F C O M M O N L A B O R A T O R Y A N I M A L S I n t r o d u c t i o n
Anaesthesia means without ('an') feeling ('aesthesia') and general anaesthetic agents are drugs
which typically produce a progressive central nervous system depression with loss of
sensation when introduced into the circulation.
In line with the requirements of the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (2004) the use of local or general anaesthetics, analgesics or
tranquillisers must be appropriate to the species and should at least parallel their use in
current medical or veterinary practice. Anaesthesia and surgery must be performed by
competent staff with appropriate training and experience. There must also be adequate
monitoring of the depth of anaesthesia and respiratory depression. Adequate monitoring,
treatment and care, including analgesia of post-operative animals, must be provided, and
investigators must ensure that they are fully informed of the condition of the animals at all
times. Alleviation of pain or distress must always take precedence over continuing or
finishing a procedure that is under way.
G u i d e l i n e s G e n e r a l A n a e s t h e s i a
(i) injectable - administered using a needle and syringe by the intraperitoneal (ip),
subcutaneous (sc), intramuscular (im), or intravenous (iv) routes. Agents are
classified as barbiturates, narcotics, sedatives - hypnotics (sleep inducing agents),
(ii) inhalants - administered by the open/semi-open or closed/semi-closed methods.
Examples of inhalant anaesthetics are methoxyflurane, halothane and isoflurane.
Depending on the agent, anaesthetics are given individually or in combination.
Guidelines for General Anaesthesia and Analgesia Endorsed UMAWC meeting 4/05
• species/strain, weight, sex and age of the animal
• anticipated duration of the procedure and whether it is to be recovery or not
• appropriateness for the procedure, including possible interaction with other
• availability of the equipment required to administer agent(s)
• reliability of the anaesthetic agent to produce a steady-state between
anaesthesia/analgesia, muscle relaxation and optimum physiological function.
Inhalants can be used for induction and maintenance of anaesthesia. Alternatively,
anaesthesia may be induced by an injectable agent and maintained by a gaseous agent.
Inhalants have the advantage of being rapidly eliminated from the system, mostly via the
lung, which allows rapid recovery. They are particularly useful for long procedures and
avoid the need for repeated doses of injectable agents which can be cumulative. When used
with an appropriate vaporiser and oxygen delivery system, a means of assisted respiration is
always available in an emergency. (Refer to Appendix I for some recommended anaesthetic
choices in the common laboratory animals ie rabbits and rodents.)
Pre and Post-Operative Care of Animals Undergoing Procedures
In addition to the requirement for choosing the right anaesthetic for the procedure, proper
consideration must be given to pre- and post-operative care, including by non-
1. Pre-operative
• Before any procedure is undertaken, animals must be checked for health. Note
especially any signs of respiratory disease or discharge. It is important to use
healthy animals which have been obtained from a reliable source.
• While it is generally recommended that food intake be reduced or withdrawn
before a procedure (to allow for emptying of stomach contents distally and
reduction in the risk of asphyxiation by regurgitation) this is not considered
necessary/advisable in the case of rabbits and rodents.
• Animal(s) should be transferred (in their cage/s) to a comfortable corner of the
research laboratory for a 2-4 hour conditioning period, and observed.
• Immediately before administration of any premedication drug(s) eg atropine,
animals should be weighed, and the premedication and anaesthetic drug doses
Guidelines for General Anaesthesia and Analgesia
• The next step is to administer the pre-medication agent(s) and a tranquilliser.
Rarely used in rats and mice they can be useful in larger laboratory animals such
as the guinea pig or rabbit to reduce bronchial secretions and reduce the risk of
cardiac depression. It should be remembered, however, that because of the
presence of serum atropinase in a high proportion of rabbits, response to this drug
may be variable. To overcome this problem, administer atropine sc every 30
minutes. In general, premedication agents help to calm the animal, reduce the
calculated anaesthetic dose required, and provide a smooth induction.
• Administer the anaesthetic 20–30 minutes after administration of the
premedication agent(s). Where a volatile anaesthetic is to be given, use an
anaesthetic mask to deliver the agent. In the case of rabbits or larger animals,
intubation may be used, but only by people who are expert in the technique.
• At this point, consideration should be given to the administration of pre-emptive
analgesia ie the administration of an analgesic agent before a surgical
intervention. Pre-emptive analgesia is thought to block pain pathways during
surgical procedures and reduce pain experienced in the post operative period.
Long acting non-steroidal anti-inflammatory agents and/or opiates may be used.
Monitoring throughout the period of anaesthesia
The following items should be monitored throughout an anaesthetic procedure:
• pedal reflex (NOTE that this reflex is not particularly reliable in rodents), tail
pinch reflex (rats and mice) or ear pinch reflex (rabbits, guinea pigs), as well as
• body temperature (animals must be kept warm throughout the procedure eg use a
thermostatically-controlled heating pad or cover small rodents with bubble wrap)
• heart/pulse rate, tissue colour, capillary bed refill time
• (if possible) also EEG (or EKG) activity, pO2 and blood pressure.
The use of neuromuscular blocking agents must have specific approval from the
AEC. These agents, which induce immobilisation through muscle paralysis, must
always be used in conjunction with a general anaesthetic. The use of a neuromuscular
blocking agent alone is not acceptable. The neuromuscular blocking agent should
not be given until an adequate depth of general anaesthesia has been achieved.
Extreme care must be taken to ensure that anaesthesia and loss of consciousness is
Guidelines for General Anaesthesia and Analgesia
maintained for as long as the procedure takes and until the neuromuscular blocking
agent wears off. The animal will need to be artificially ventilated and the following
• sudden changes in heart rate or arterial blood pressure with the application of
• pupil size (this can be confounded by premedication with atropine which dilates
• end tidal pCO2 (which should be no greater than 4.7%) and direct arterial pCO2.
3. Post-operative
• Place the animal on its side, head extended, in a clean, dry, warm (30 °C) box on
shredded paper free of any dangerous objects which could lead to
asphyxiation/injury (eg sawdust, water containers or other material which might
act as a noose) in a quiet warm room away from strong light and in a position
where recovery can be monitored. Ensure that animals do not become
• Where an endotracheal tube has been used, it should be removed very gently as
soon as the swallowing reflex returns. Watch for any sign of regurgitation and if
necessary reposition the head to a level below that of the rest of the body so that
• Restrict access to food and water until full recovery has taken place. When
recovery is several hours, animals should be turned carefully every 20 minutes or
so to avoid fluid congestion in the lungs.
• Provide warm fluid replacement by injection, ie. Na lactate, Hartmans solution or
0.9% (w/v) ie normal saline sc or ip. Give approximately 3–5% of the animals’
pre-anaesthetic body weight in ml, eg 1–1.5 ml for a 30 g mouse.
• Provide post-operative nursing, antibiotics and analgesia as necessary (see
Appendices II and III). Once animals have fully recovered, continue to monitor
progress for a further 24–48 hours. Observation of surgical wounds is essential
• Clinical records must be kept and made available to all staff involved. Duties of
staff must be clearly defined and ways of dealing with emergencies established.
Animals found to be in a severe state of pain or distress which cannot be
alleviated promptly must be euthanased immediately.
Guidelines for General Anaesthesia and Analgesia
Further Information can be found in ‘Careful How You Hold Me - an insight into caring for
laboratory animals’ CD ROM University of Melbourne, 1999.
R e f e r e n c e s
Flecknell, P. A. Laboratory Animal Anaesthesia. 2nd edition Academic Press, London
Hau, J & Van Hoosier, G.L Handbook of Laboratory Animal Science Vol 1 Essential
Hillyer, E.V and Quesenberry, K.E (eds) Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery. W.B. Saunders Company, Philadelphia (1997)
Guidelines for General Anaesthesia and Analgesia
APPENDIX I A N A E S T H E T I C A G E N T S
As a general rule, the smaller the species the more rapid the metabolic rate and therefore a
requirement for a slightly higher anaesthetic dose rate than larger species. When calculating
anaesthetic doses, make allowance for the weight of the bowel contents in animals with a
large caecum. In the case of the guinea pig or rabbit, the weight of the bowel contents can be
up to 20% of the animal's real body weight. To be quite safe, lower dosages should be
administered initially with incremental (ie one third of the original calculated dose) top-up
doses given every half hour or so to maintain anaesthesia. Alternatively, animals should be
Monitor body temperature and maintain at 37-38 °C for rabbits and rodents. Use a
thermostatically-controlled heating pad, or cover animals in bubble wrap.
RATS AND MICE Premedication Agent Injectable Agents Comments atropine
Protects heart from vagal stimulation, bradycardia, and possible cardiac arrest induced by surgery or drugs such as xylazine.
Guidelines for General Anaesthesia and Analgesia
RATS AND MICE Anaesthetic Choices Injectable Agent/s Dose/Method Comments
∗xylazine.HCl* ketamine.HCl ketamine (as above)
prolonged sleep times (especially in rats) of up to 2
medetomidine* Ciba-Geigy) 1 mg/kg ip or sc. This helps reverse any drop in blood pressure and respiratory depression, but it also removes any relaxation and analgesia provided by these drugs.
Guidelines for General Anaesthesia and Analgesia
RATS AND MICE Anaesthetic Choices Injectable Agent/s Dose/Method Comments pentobarbitone
∗alphaxalone 9.0 /alphadolone 3.0 mg/ml methohexitone Na RATS AND MICE Anaesthetic Choices Inhalants Dose/Method Comments methoxyflurane
very small jar. Invert the test tube or jar onto the bench top when not in use.
Guidelines for General Anaesthesia and Analgesia
halothane (Halothane, isoflurane (Forthrane, GUINEA PIGS Premedication Injectable Agent Dose/Route Comments atropine
(guinea pigs have relatively narrow airways) and protect heart from vagal stimulation ie bradycardia and possible cardiac arrest Give diazepam 10–15 mins after atropine to sedate the animal.
diazepam
sedation but no analgesia. Good for sedation for minor non-invasive procedures. If used as a premedication to injectable anaesthesia, dose should be reduced. After a further 10–15 mins, administer one of the following anaesthetic choices.
Guidelines for General Anaesthesia and Analgesia
GUINEA PIGS Anaesthetic Choices Injectable Agent Dose/Route Comments *xylazine ketamine Parnell; Ketapex, Apex; Ketavet, Delvet: 100 mg/ml)
*medetomidine
medetomidine can be reversed with atipamezole at
ketamine
pressure and respiratory depression, but also removes the relaxation and analgesia provided by these drugs.
Guidelines for General Anaesthesia and Analgesia
GUINEA PIGS Anaesthetic Choices Injectable Agent Dose/Route Comments urethane (Merck)
Long duration (about 3 hours), non-recovery only. Solution needs to be freshly made up on the day and may be carcinogenic to the handler.
GUINEA PIGS Anaesthetic Choices Inhalant Gaseous Agent Dose/Route Comments methoxyflurane halothane (Halothane,
In O2 using a vaporiser as Can induce hypotension
isoflurane (Forthrane,
Guinea pigs are difficult to intubate but can be successfully maintained on a face mask
Guidelines for General Anaesthesia and Analgesia
Premedication Injectable Agent Dose/Route Comments atropine
bronchial secretions Follow with diazepam after 10–15 mins to sedate the animal.
diazepam
atropine. After 10–15 mins, administer one of the suggested anaesthetic choices.
Acepromazine
2 mg/ml (ACP, Delvet; Promex, Apex Laboratories)
Anaesthetic Choices Injectable Agent Dose Rate Comments
∗xylazine ketamine Parnell; Ketapex, Apex; Ketavet, Delvet:
Guidelines for General Anaesthesia and Analgesia
Anaesthetic Choices Injectable Agent Dose Rate Comments alphaxalone 9 mg/ml /alphadolone 3 mg/ml propofol
by maintenance on gas as for guinea pigs. Intubation is difficult in rabbits and requires practice. A close-fitting face mask can be used to maintain anaesthesia. Because of the risk of laryngeal spasm, induction using gaseous anaesthesia in rabbits is generally not recommended.
medetomidine*
minutes. Domitor can be reversed with Atipamezole (Antisedan, Ciba Geigy) 1mg/kg ip or sc.
Guidelines for General Anaesthesia and Analgesia
Anaesthetic Choices Inhalant Gaseous Agent Dose/Route Comments halothane (Halothane,
In O2 using a vaporiser as Can induce hypotension
rabbits is generally not recommended. Anaesthesia
isoflurane (Forthrane,
and maintained using a gaseous agent. . Intubation is difficult in rabbits and requires practice. A close-fitting face mask can be used to maintain anaesthesia.
Guidelines for General Anaesthesia and Analgesia
APPENDIX II A N A L G E S I A
For any surgical procedure, a pain management plan appropriate for the procedures and the
species must be developed, implemented and reviewed if necessary (Australian Code of
Practice, 3.3.25) Analgesia is best given at the time of, or just after, induction of anaesthesia
and before any procedure commences. Pre-emptive analgesia greatly reduces recovery time
and the need for post-operative analgesic administration. There are two maincategories of
analgesics: non-steroidal anti-inflammatory agents and opiates. They can be used alone or in
combination. There are several drugs in each category with different durations of action.
Choice of analgesic should be made carefully, taking into account the aim of the experiment
and the advice of the AEC. The following table provides a number of species-dependent
Analgesic Drug RATS MICE Alternatives
Guidelines for General Anaesthesia and Analgesia
APPENDIX III A N T I B I O T I C S
Always use aseptic technique for all surgical procedures to minimise the risk of infection.
Antibiotic RATS MICE Alternatives OTHER SPECIES
For other species or for information about other anaesthetics/analgesics, refer to resources
listed under References and contact your department’s nominated veterinarian.
Guidelines for General Anaesthesia and Analgesia
PUBLICATIONS CONJOINTES IFRH Sélection de 25 articles dans des revues à comité de lecture Publications Communes à au moins deux composantes de l’IFRH (n = 97) 1. Ancel PY, Livinec F, Larroque B, Marret S, Arnaud C, Pierrat V, Dehan M, N’Guyen S, Escande B, Burguet A, Thiriez G, Picaud JC, André M, Bréart G, Kaminski M, and the Epipage study group. Cerebral palsy in very pre
________________________________________________________________ Módulo 9: COMPETENCIA DESLEAL ________________________________________________________________ ¿Qué es la competencia desleal? En términos generales, se entiende por competencia desleal todo acto de competencia que sea contrario a las prácticas honestas en el ámbito industrial y comercial. Definir con precisión lo q