after thiopental? options for short term injectable ... · pdf file36th world small animal...

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Proceedings of the 36th World Small Animal Veterinary Congress

WSAVA

Oct 14 - 17 2011 Jeju Korea

Next Congress

Reprinted in IVIS with the permission of WSAVA httpwwwivisorg

592011 WSAVAmiddotFASAVA World Congress Proceedings

14(Fri) ~ 17(Mon) October 2011

ICC Jeju Korea

2011 WSAVAFASAVA World Congress

wwwwsava2011org

AFTER THIOPENTALOPTIONS FOR SHORT TERM INJECTAbLE ANAESTHESIA

KW Clarke MA VetMb DVetMed DVA Dip ECVA MRCA FRCVS

Hon Prof of Veterinary Anaesthesia Royal Veterinary College

Hatfield Hertfordshire AL9 7TA UK

IntroductionThiopental and other barbiturates have been the mainstay for induction of anaesthesia since the 1940s

Over the past 30 years they have been replaced gradually mainly by propofol and ketamine and now can be

difficult to obtain This presentation will consider what is currently and easily available for induction of

anaesthesia the advantages and disadvantages for use in both dogs and cats in the practice situation and will

concentrate then on what is (relatively) new or controversial

This presentation will consider

(a) Some general principles of use of injectable anaesthetic agents in small animals

(b) Brief revision of most relevant clinical pharmacology in particular re unwanted side effects

(c) Whatrsquos new or controversial

(d) In the verbal presentation some suggested protocols for induction of or very short-term anaesthesia

General Principles1 A cat is not a small dog The catrsquos lack of glucuronyl transferes enzymes mean that metabolism of some

drugs (in particular propofol) is delayed and that some of the solvents or preservatives may be cumulative

andor toxic

2 Once a drug is injected it can only be removed by metabolism- this may vary with species or breed and

may be influenced by disease states

3 The dose of anaesthetic required will vary with the premedication used (combinations may have

synergistic effects) and with the clinical state of the patient

4 Some agents used in anaesthetic combinations (alpha 2 adrenoceptor agonists benzodiazepines opioids)

CAN be antagonised-it is important to match duration of antagonist and agonist

5 Route of administration - Intravenous (IV) best as easiest to judge depth BUT not all agents work in a

circulation time (thiopental does so but pentobarbitone not) so effect is delayed IV administration is

AP-C21

Reprinted in IVIS with the permission of WSAVA Close this window to return to IVIS

36th World Small Animal Veterinary Congress 2011 - Jeju Korea

60 2011 WSAVAmiddotFASAVA World Congress Proceedings

usually best given slowly Intramuscular (IM) or similar is always second best - depth of anaesthesia

achieved is much less controllable and depend is on speed of uptake 6 ALL anaesthetics are respiratory

depressant even if the animal breaths fast so using injectable agents still needs OXYGEN a clear

AIRWAY the ability to VENTILATE if necessary and excellent MONITORING

Anaesthetic agentscombinations A (very) brief resume of the major clinically important pharmacology [1]

Thiopental Barbiturate presented as solid to dissolve in water Irritant extravascularly IV route only Rapid

onset of anaesthesia (one circulation time) initital recovery by re-distribution slow metabolism and cumulative

Poor analgesia Very respiratory depressant Vasodilates Increases heart rate

Propofol Presentation usually in lipid but see below Non-irritant but sometimes pain on injection IV route

only Rapid onset anaesthesia non-cumulative and recovery fast-and complete except in cats [2 Poor

analgesia Very respiratory depressant Cardiovascular effects as thiopental but less tachycardia

Ketamine Presentation in solution with preservatives Many routes of administration Non-irritant but pain on

IM injection Onset of anaesthesia after IV injection not immediate Excellent analgesia Respiratory depressant

but animal may breath rapidly and shallowly Technically myocardial depression but sympathetic stimulation

result in CV system being well maintained Hallucinogenic and muscle rigidity so usually used in combination

with alpha 2 agonists or benzodiazepines

Etomidate Rapidly acting IV induction agent with rapid recovery from induction dose Pain on injection

Venous phlebitis Poor analgesia Myoclonic activity Minimal cardiovascular effects (so popular for the

compromised dog) See below for concern re cortisol suppression

Alphaxalone - see detail below

Benzodiazepineopioids may also be used to induce anaesthesia [3] Neither of these agents work in a circulation

time

Whatrsquos new or currently controversial(a) Propofol in catsThe major route (there are others) of metabolism of propofol is through glucuronidation of the parent drug

followed by glucuro‐conjugation of hydroxylated metabolite via cytochrome P450 to produce other conjugates Cats lack the enzymes necessary for this and also are slow to metabolise the lipids in the

carrier As a result propofol is not as short acting in the cat as in the dog Its safe use as an induction agent

and use for short duration infusion appears satisfactory but there is continual controversy as to whether it is

suitable for longer infusions or for use several days in succession (when under experimental conditions

toxicity has occurred [2])

(b) Propofol formulationsThe original lecithin based formulation of propofol had to be used within a very short time of opening-

making it expensive Since becoming lsquoout of patent a number of new versions have included preservatives

of varying efficacy These versions state on their marketing authorisation the time after opening the vial

when the product is considered safe The most recent on the veterinary market includes benzyl alcholol




AFTER THIOPENTAL OPTIONS FOR SHORT TERM INJECTAbLE ANAESTHESIA

and in the USA has authorisation to be open for 28 days (some other countries give a shorter time) There

are some questions as to the toxicity of the Benzyl alcohol particularly in cats but again this is only likely

to be a problem with prolonged infusions

An emulsion formulation of propofol that does not include oils and again has a long lsquoshelf lifersquo after

opening has been available but in the UK has been (possibly temporarily) withdrawn for commercial

reasons

Etomidate Etomidate has not been used as a CRI in intensive care for many years since it was realised that the

adrenocortical suppression in such patients increased the overall death rate most usually from infections In the

last few years there has been considerable controversy over whether the short-term (a few hours) adrenocortical

suppression it induces means that it should not be used for IV induction of anaesthesia in particular in patients

with sepsis There is no evidence as to whether this is a potential problem in veterinary anaesthesia

Alfaxalone (3-alpha-hydroxy-5-alpha-pregnane-1120-dione) solubalized in 2 alpha-hydroxypropyl beta

cyclodextrin (HPBCD) Licenced product - Alfaxanreg

Steroid anaesthesia is not new- over the last 50 years a number of agents have been used - the problem has been

solubility Alphaxalone alphadalone combination solublised in cremaphor was used in humans and in cats

(Saffanreg) - but the cremaphor caused histamine release

Facts about Alfaxalone as Alfaxanreg

(a) Originally licenced in Australia and used there now for some years Now licenced in many countries for

cats and dogs Licensed dose rates without sedative premedication are 3mg kg-1 dogs and 5 mg kg-1 cats

Administer IV over 60 seconds Recommended to premedicate healthy animals

(b) Effective anaesthesia on IV use in (close to) a circulation time Induction quality usually good but

improved by sedation Advise from practice use is to ensure anaesthesia is adequate before endotracheal

intubation otherwise if the animal is stimulated it wakes up

(c) Non irritant IV or if accidental extra-vascular It could be given IM but volume too large for use

without deep sedation

(d) Short half-life non-cumulative Metabolised by the liver

(e) Very good safety margin especially if ventilate (massive overdose may causes apnoea)

(f) No evidence of histamine release

(g) Can be used together (not in same syringe) with most commonly used sedatives analgesics or

subsequent inhalation agents

(h) Cardiovascular effects - minimal at clinical or even heavy clinical doses [345]- after this (supra-

clinical doses for licensing procedures) dose dependant fall in blood pressure and systemic vascular

resistance

(i) Transient apnoea if injected fast - more prolonged at massive overdose

(j) Can get some disturbed recoveries These are much less likely to happen if extubation is whilst

anaesthesia is still deep and the animal allowed to recover somewhere quiet




References1 Hall LW Clarke KW and Trim CM 2001 Chapter 5 In Veterinary Anaesthesia WB Saunders London Pgs

113-131

2 Andress JL Day TK Day D 1995 The effects of consecutive day propofol anesthesia on feline red blood

cells Vet Surg 24 277-82

3Psatha E Alibhai HI Jimenez-Lozano A et al2011 Clinical efficacy and cardiorespiratory effects of

alfaxalone or diazepamfentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk Vet

Anaesth Analg 38 24-36

4Muir W Lerche P Wiese A et al 2008 Cardiorespiratory and anesthetic effects of clinical and supraclinical

doses of alphaxalone in dogs Vet Anaesth Analg 35 1-12

5 Muir W Lerche P Wiese A et al 2009 Cardiorespiratory and anesthetic effects of clinical and supraclinical

doses of alphaxalone in cats Vet Anaesth Analg 36 42-54




14(Fri) ~ 17(Mon) October 2011

ICC Jeju Korea

2011 WSAVAFASAVA World Congress

wwwwsava2011org

AFTER THIOPENTALOPTIONS FOR SHORT TERM INJECTAbLE ANAESTHESIA

KW Clarke MA VetMb DVetMed DVA Dip ECVA MRCA FRCVS

Hon Prof of Veterinary Anaesthesia Royal Veterinary College

Hatfield Hertfordshire AL9 7TA UK

IntroductionThiopental and other barbiturates have been the mainstay for induction of anaesthesia since the 1940s

Over the past 30 years they have been replaced gradually mainly by propofol and ketamine and now can be

difficult to obtain This presentation will consider what is currently and easily available for induction of

anaesthesia the advantages and disadvantages for use in both dogs and cats in the practice situation and will

concentrate then on what is (relatively) new or controversial

This presentation will consider

(a) Some general principles of use of injectable anaesthetic agents in small animals

(b) Brief revision of most relevant clinical pharmacology in particular re unwanted side effects

(c) Whatrsquos new or controversial

(d) In the verbal presentation some suggested protocols for induction of or very short-term anaesthesia

General Principles1 A cat is not a small dog The catrsquos lack of glucuronyl transferes enzymes mean that metabolism of some

drugs (in particular propofol) is delayed and that some of the solvents or preservatives may be cumulative

andor toxic

2 Once a drug is injected it can only be removed by metabolism- this may vary with species or breed and

may be influenced by disease states

3 The dose of anaesthetic required will vary with the premedication used (combinations may have

synergistic effects) and with the clinical state of the patient

4 Some agents used in anaesthetic combinations (alpha 2 adrenoceptor agonists benzodiazepines opioids)

CAN be antagonised-it is important to match duration of antagonist and agonist

5 Route of administration - Intravenous (IV) best as easiest to judge depth BUT not all agents work in a

circulation time (thiopental does so but pentobarbitone not) so effect is delayed IV administration is

AP-C21

























time




















reasons



























resistance








113-131


































time




















reasons



























resistance








113-131



















reasons



























resistance








113-131














113-131












after thiopental? options for short term injectable ... · pdf file36th world small animal...

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