Preanaesthetic assesment pre med iv and inhalant anaesthetic

Confidential Enquiry into Perioperative Small Animal Fatalities (CEPSAF) risks for healthy dog cat and rabbit

Dog 1 in 1849 (0,05%)

Cat 1 in 895 (0,11%)

Rabbit 1 in 137 (073%)

Equine fatalities within 7 days of anaesthesia (CEPEF)

1,9% (when emergency exploratory laparotomy exclusief 0,9%)

What increases the risk of anaesthetic related death

-fluid therapy in cats

-inhalation induction of anaesthesia

-controlled ventilation

-endotracheal intubatuin in cats

-increases duration of procedures

What decreases risk of anaesthetic related death

-monitoring cardiovascular function via pulse rate, heart rate and blood pressure

-use a pulse oximeter

-recording cardiac rhythm (ECG)

-pre med with medetomidine/acepromazine (compared to no pre med)

-IV catheter for easy admin of medications

Breed dispositions which may influence anaesthesia

Persian cat: polycystic kidney disease

Giant breed dog: dilated cardiac myopathy (DCM), atrial fibrillation

Bulldog: brachychephalic airway syndrome

Sighthounds: altered metabolism of barbiturates

Why is age of the animal significant for anaesthesia

Neonatal and young animals have poorly developed renal/hepatic function, an immature cardiovasculair system, are prone to hypothermia and hypoglycaemia and drug distribution and drug effects may vary.

Geriatric animals may have reduced cardiorespiratory reserve and increased risk of concurrent disease

What is baseline data for an anaesthetic record

Pulse rate/quality, mucous membrane color, respiratory rate, presence of ocular/nasal discharge, temperature

What is a geriatric animal

Animal with >80% of anticipated lifespan

When would you withhold water from an animal coming for anesthesia

Prior to endoscopy of the gastrointestinal tract

What is the fasting time for a healthy dog or cat

4-6 hours for adults

1-2 hours in paediatric patients less than eight weeks of age or those less than 2kg in body weight

Why not fast longer (than 4-6hrs)

May be associated withan increased risk of regurgitation

What is the anesthetic triad

Narcosis, muscle relaxation and analgesia

(To achieve this you need multiple agents to create a balanced anaesthesia)

Pharmacokinetics

What the body does to the drug

What are the stages of pharmacokinetics

What is bioavailability

It refers to the fraction of a dose that reaches the systemic circulation after administration compared to the same dose given by the intravenous route

What is bioavailability influenced by

Proporties of the drug itself

Formulation

Route of administration

Interactions with other drugs

Individual patient variation

Patient's disease state

Factors that determine drug distribution

Protein binding

Tissue binding

Organ blood flow

Membrane permeability

Drug solubility

What is the main plasma protein that binds drugs

Albumin

True or false: the more bound drugs there are in the blood the greater is the drug effect

False: it is the free or unbound fraction of drug that is available to interact with the drug target

What can hypoalbuminaemia cause

A relative overdose because it increases the free fraction of drug (because it has nothing to bind with) (this can happen with drugs that are highly protein bound)

How do drugs get metabolised and eliminated from the body

Most drugs are lipophilic and highly plasma protein boundnso are not easily filtered by the kidney. Most lipid soluble drugs are metabolised in the liver before renal excrection. Gastrointestinal tract, lungs, kidney, skin and plasma have some metabolic activity.

What are the 2 phases of liver metabolism of drugs

Phase 1 reactions convert the drug to a more polar metabolite

Phase 2 reactions involve conjugation with substrates and consumption of energy (conjugation may involve glucuronidation (not cats) acetylation (not dogs) methylation or conjugation with sulphate or glycine groups)

Pharmacodynamics

Describes the effects the drug has in the animal/body.

Drug site of action > pharmacological effect > clinical response > therapeutic index OR toxicity

Affinity and potency

Describes how well or avidly a drug binds to its receptor

Relates to the dose of drug required to produces a response

Intrinsic activity or efficacy describes..

The magnitude of effect once the drug is bound

A full agonist can..

Generate a maximal response after binding to its receptor

A partial agonist does..

Not produce a maximal effect, even when the dose is increased

An antagonist has..

Affinity for the receptor but does not produce an effect once bound. However it can block the effect of an agonist (atipamezole which antagonises the effects of the $\alpha-2$ adrenoreceptor agonist (dex)medetomidine)

What are targets for drugs to act on

Receptors

Enzymes

Transporters which carry molecules across a membrane

Ion channels

Nucleic acid (RNA)

Miscellaneous targets

Therapeutic index - LD50/ED50, explain

Crude measure of drug safety: maximum non toxic dose to minimum effective dose.

LD50 - The dose that causes death in 50% of the tested group (lethal dose)

ED50 - The dose that gives the desired healing effect in 50% of the tested population. (Effective dose)

Aims of pre medication

• To calm the animal through anxiolysis

• Allowed safer patient handling

• Provide perioperative analgesia

• Contributie to balanced anaesthesia and reduce the doses of subsequently administered drugs

• Smooth the recovery period

Synergistic effect

Occurs when the interaction of 2 or more drugs cause the total effect of the drugs to be greater then the sum of the individual effects of each drug on their own

Why need a quiet area and calm manners when given pre med

Stress results in high levels of circulating catecholamines which interfere with the sedative effect of the drugs given

What are the rules for drug selection, a sequence of 4:

1. A veterinary licensed product with a marketing authorisation for thatbindication in the species concerned

2. A veterinary medicine authorised foe use in another species or by a different route in the same species (so called off label)

3. A medicine authorised in that country for human use

4. A medicine to be made up on a one off basis by a veterinary surgeon of a properly authorised person

How dose an overweight animal

Dose for their ideal lean weight

Acepromazine, keyboard features, dose range, onset of action etc

• Phenothiazine class of drugs, acts on dopamine receptor antagonist

• Mild to moderate long lasting sedation, typically around 6hrs (duration dose dependant)

• Increasing dose administered does not necessarily increase degree of sedation due to plateau effect at doses above 0,05mg/kg (or total dose of +/- 1mg)

• Autorisation dog/cat in dose range of 0,03-0,125mg/kg IV, IM or SC

• Onset approx. 15min IV or 30min IM

• Metabolised by liver, cannot be antagonised

• Has antihistamine effects

• Alpha1 adrenoreceptor antagonist so gives antiarrhytmic effect and vasodilation

• Has antiemetic effects

• MAC sparing effect when used as pre med

When not to use acepromazine

Shocked animals - due to vasodilation a decrease in blood pressure is often seen

Use with care with cardiovascular disease

Can also reduce packed cell volume (PCV)(=hematocrit) by up to 20% due to splenic sequestration of red blood cells

Why be carefull with acepromazine and brachycephalic breeds

Consider giving low doses: these dogs have high resting vagal tone which can result in syncope and acepromazine is long acting. Can prolong the recovery period. These dogs need a rapid recovery with minimal drug hangover

α2 adrenoreceptor agonist, key features etc

• Xylazine, (dex)medetomidine

• Have some affinity for the α1 adrenoreceptor

• Autorisation dog/cat

• Profound sedation and recumbency

• High levels of adrenaline can compete for the adrenoreceptors

• Onset of 5min IV, 15-20min IM

• Can be given as continous rate infusion

• Well absorbed across mucous membranes

• Metabolised by liver and reduce hepatic blood flow

• Atipamezole is the antagonist (reversal)

• Significant cardiovascular effect: initial vasoconstriction (peripheral vasoconstriction reduces heat loss), reflex bradycardia (blood pressure remming normal or high) and reduces cardic output

• First or second degree AV block may be seen on ECG trace

• Good muscle relaxatio (often given with ketamine to counteract muscle rigidity)

• Vomiting may occur when given IM or SC

• Xylazine sometimes used to induce emesis in cats

• Analgesic effects last shorter than the sedative effects but are MAC sparing (up to m 70%)

• Some animals benefit from adminstration of a small dose (1-2 μg/kg IV) of (dex)medeto to smooth recovery period

What does α2 adrenoreceptor agonists reduce

• Gastrointestinal motility

• Antidiuretic hormone (ADH) and renin (which increases urine production)

• Reduction in insulin secretion resulting in hyperglycaemia

Options for bradycardia after adminstering an α2 adrenoreceptor agonist

• Admin of ketamine; low dose may increase heart rate although responses are unpredictable and there is a delay ofeffect up to 5min

• Partial dose of Atipamezole; antagonises (dex)medeto and increases heart rate, although plane of anaesthesia can lighten

• Antimuscarinic is not recommended; can increase heart rate but risk exacerbating hypertension and increasing myocardial workload

Ketamine

• Phencyclidine derivative

• NMDA antagonist

• Can produce dissociative anaesthesia

• Always administered with other drugs since muscle rigidity and excitement is seen when used alone

• Schedule 2 controller drug

• IM, IV, as continous rate infusion and well absorbed across mucous membranes

• Metabolised by liver and excreted by kidney

• Has active metabolite (norketamine)

• May therefor accumulate in animals with renal dysfunction

• Onset of action and duration depend on combination and dose used but typically onset is 3-10min, duration approx 30-45min

• Maintains cardiovascular function

• Ketamine itself produces myocardial depression but also results in catecholamine release which overall produces positive chronotropic effects

• Stick animals may not have this catecholamine respons

• Do not use with HCM cats > inadequate myocardial perfusion due to positive chronotropic effects

• May increase intraocular pressure and intracranial pressure

• Has antihyperalgesic effects

• Better somatic analgesia than visceral analgesia

• Many reflexes that are normally abolished during anaesthesia are maintained; eye may remain central with brisk palpebral reflex, pharyngeal and laryngeal reflexes, muscle tone remains or increases.

• Plasma protein binding approx. 50%

• Possible neuroprotective effects

• Often used in horses IV

Somatic and visceral pain

Somatic pain results from an injury to the body such as skin, muscle bonen and tends to be localised.

Visceral pain refers to pain from the internal organisatie which is usually dull and diffuse

Benzodiazepines

• Midazolam, diazepam

• GABA agonist (y-aminobutyric acid)

• May produce sedation in young or sick animal especially when given with an opioid, but can produce excitement in healthy animals

• UK authorisation diazepam dog/cat, midazolam horses

• Metabolised in liver

• Midazolam water soluble, IM or IV

• Does not produce active metabolites

• Diazepam solubilised in propylene glycol, painfull on injection, poorly absorbed IM injections, can produce thrombophlebitis if given IV, has active metabolites (nordiazepam, temazepam, oxazepam)

• In cats, diazepam can result in idiosyncratic hepatic necrose

• Both often combined withban opioid

• Dose range 0,2-0,3 mg/kg

• Minimal effect on cardiorespiratory system

• Good muscle relaxation and anticonvulsant activity

• Can be antagonised with flumazenil (UK not licensed)

Tiletamine and zolazepam

• Zoletil and Telazol

• Tiletamine = phencyclidine derivative (like ketamine)

• Zolazepam = benzodiazepine

• Similar effect as an keta/benzo combi

• In dogs, zolazepam is metabolised faster than tiletamine which can lead to rough recovery

• Accumulation if repeated doses are given

Neuroleptanalgesia for rodents, guinea pigs and rabbits

Fentanyl/fluanisone

What is the kitten quad protocol

Medetomidine, ketamine, midazolam and buprenorphine

Neurotransmitters and receptors

Acetylcholine (ACh)

• Found in the brain, spinal cord and peripheral nerves as well as some other cells

• Acts on muscarinic and nicotine receptors

• All motor nerve fibers exciting the CNS release ACh which acts on nicotinic receptors

• All postganglionic parasympathetic fibres release ACh which acts on muscsrinic receptor

Neurotransmitters and receptors

Noradrenaline (norepinephrine)

• Found in many tissues of the body including the brain and sympathetic ganglia

• Acts on α and β adrenoceptors

Neurotranmitters and receptors

Glutamate

• The principle excitatory neurotransmitter in the vertebrate ventral nervous system

• Acts on AMPA, NMDA, metabotropic glutamate and kainite receptors

• Ketamine is an N-methyl-D-aspartate (NMDA) antagonist and antagonises the excitatory neurotransmitter glutamate at NMDA receptorsin the CNS. It also has complex actions at opiod receptors

• Tiletamine is propably also an NMDA antagonist

Neurotransmitters and receptors

γ-aminobutyric acid (GABA)

• The principle inhibitory neurotransmitter in the adult CNS

• Acts on the GABA receptor to decrease excitability of neurones

• Barbiturates, propofol, alfaxalone and etomidate are agonists at the gamma aminozuren butyric acid (GABA) receptor in the CNS

• When these drugs bind to the GABA receptor they increase the frequency or duration of the GABA dependent chloride channel opening > the increase in chloride conductance causes hyperpolarisation and neuronal inhibition

• Zolazepam (benzo) is a GABA agonist

Neurotransmitters and receptors

Histamine

• Widely distributed afferent (=goes to the CNS) neurotransmitter which is involved in the sense of itching and pain

Neurotransmitters and receptors

Dopamine

• Precursor of noradrenaline

• Involved in control of movement and behaviour

Neurotranmitters and receptors

Serotonine (5HT)

• Acts on 5HT receptors to regulate sensory pathways and control mood

Neurotranmitters and receptors

Serotonine (5HT)

• Acts on 5HT receptors to regulate sensory pathways and control mood

Neurotranmitters and receptors

Serotonine (5HT)

• Acts on 5HT receptors to regulate sensory pathways and control mood

Propofol, key features

• 2 versions: 1 without bacteriostat, discard after 24hrs. 1 with benzyl alcohol preservative, can be used for up to 28days. This one should not be administered by infusion particularly in cats (hHeinz bodies)

• Phenol

• GABA agonist

• May be mistaken for penicillin, label syringe!

• Rapid onset of action

• IV

• Rapidly metabolised in liver and eliminated; cats lack glucuronidation pathway in live so metabolism in cats is slower than dogs

• Possible extra hepatic metabolism; drug clearance is faster than hepatic blood flow

• Noncumulative in dogs (not cats), used for TIVA in dogs

• Postinduction apnoea common

• Hypotension, myocardial depression and peripheral vasodilation

• No analgesia

• Fair muscle relaxation although occasionally muscle twitching and muscle rigidity seen

• Consecutive day use should be avoided in cats: oxidative damage to red blood cells (Heinz body formation) seen after 3days, cats became generally unwell after 5-7days of consecutive dag administration

• Non irritant if injected perivascularly

• All formulations may produce an aversive response (attempted limb withdrawal)

• Highly plasma protein bound 96-98%

Alfaxalone, key features

• Not soluble in water, cyclodextrin used to make water soluble. Cyclodextrin donut shaped and alfaxalone molecule sits in middle which is hydrophobic, exterior is water soluble.

• Steroïd anaesthetic

• High therapeutic index

• Non irritant

• IV and rapid onset

• Authorisation for IM use in Australië not Europe

• Injection volume can be large for IM

• Rapid hepatic metabolism and elimination

• Non cumulative

• Respiratory depression and post inductuon apnoea if given rapidly

• Preserves baroreceptor tone; HR increases in response to reduces BP

• No analgesic effects

• Not very high plasma protein bound ~20%

Less commonly used injectable amaesthetic agent

Thiopental, key features

• Acquiring can be difficult

• Barbiturate anaesthetic, is reconstituted from powder to form a 2,5 or 5% solution

• Is very alkaline, can result in perivascular tissue necrosis if accidently injected outside of vein

• Admin IV only

• Rapid onset with predictable effect, especiallly in horses

• Slow recovery from anaesthesia due to redistribution of drug

• Metabolism in liver

• Prolonged recovery in Sighthounds due to lower capacity for metabolism of llthis drug in these species

• Highly plasma protein bound +/ - 80%

• Moderate Cardiopulmonary depression with ventricilar bigeminy seen in 40% of dogs

• Repeated doping significantly prolonges anaesthetic recovery, not suitable for TIVA

Etomidate

• Minimal effects on cardiovascular system

• Produces adrenal supression which has been associated with an increased deathrate in people when used by infusion in ICU settings

• Induction can be smooth in well sedated animals

• Animals that received low doses of pre med induction is unpleasant with vomiting retching, myoclonus and significant pain on injection

• Does not have a marketing authorisation for animals in Europe

Chloral hydrate

• Now obsolete

• Administered orally

Why is it important to give injectable anaesthetics slowly and to effect

They need to reach the brain. In animals with low cardiac output (either due to effects of drugs such as dexemedeto or pathological reasons) the onset of action of an anaesthetic agent is slower.

If an animal is hypoproteinaemic there is greater portion of free unbound drug and you can get a relative overdose

Co induction of anaesthesia

Where more than 1 drug is administered to induces anaesthesia. Most commonly a benzo, keta, or short acting opiod alongside either propofol or alfaxalone.

May be performed after standard pre med (acepromazine or (dex)medeto plus an opioid)

When you give a benzodiazepine to a conscious animal, what can it do

Induce excitement. To avoid this give a small dose of the IV induction agent first, then the benzo, then the rest of the IV agent titrated slowly to effect

What does TIVA stand for

Total intravenous anaesthesia

Name 3 drugs you can use for a CRI / TIVA

Propofol and ketamine have a context sensitive half time that does not increase significantly as the duration of infusion increases (whereas it does for thiopental).

Alfaxalone can also be used for TIVA

what is MAC

Minmum alveolar concentration - the alveolar (end tidal) concentration of inhalant anaesthetic required to prevent purposeful movement in response to a supramaximal noxious stimulus in 50% of subjects.

MAC is decreased by: (needing less of it)

• Sedatives: acepromazine, medetomidine ( up to 70%)

• Analgesics: opiods

• Coadministered anaesthetic agents: midazolam

• Hypothermia: decreased metabolic rate

• Geriatric and neonatal animals less than 2weeks of age: decreased metabolic rate, organ function reduced

• Conditions such as hypothyroidism: decreased metabolic rate

MAC is increased by:

• Young animals: increased metabolic rate

• Hyperthermia: increased metabolic rate

• Concurrent administration of catecholamines and sympathomimetics: ephedrine

• Conditions such as hyperthyroidism: increased metabolic rate

Partial pressure of a gas:

The pressure that the individual gas exerts in a mixture of gases. Thisnpressure of the agent in the brain determines its effects.

The higher the inspired setting on the vaporiser the higher the partial presure of the agent is in the lungs and thus faster onset of anaesthesia

Blood gas partition coefficient

• Also known as the blood gas solubility coefficient

• Describes the solubility of gas in the blood

• Agents with a low blood gas solubility exert a high partial pressure and a rapid induction and recovery from anaesthesia will occur

• The more soluble the inhalant is in blood; the more inhalant is required to increase its partial pressure in the alveoli

• Distribution of the anaesthetic depends on perfusion and the solubility of the agent in different tissues

Meyer-Overton Hypothesis

Theory being the molecules of the inhalational anaesthetics discover in the lipid bilayer of cell membranes within the brain and when this happens in sufficient amounts it induces a state of unconsciousness and anaesthesia.

It is possible that the actual mechanism of action is a combi of this and the following; binding to proteins on ion channels and inhibiting synaptic transmission. And direct effects on specific receptors such as GABA, NMDA etc

Elimination of inhalants are primarly via the lungs but there is a small amount of hepatic metabolism;

Halothane 20%

Sevoflurane 2-5%

Isoflurane 0,2%

Nitrous oxide is negligible

Alveolar ventilation

Increased alveolar ventilation increases the alveolar partial pressure of the inhalant, increasing the rate of update of the inhalant and the speed of induction of anaesthesia. How quickly the pulmonary circulation removes the anaesthetic gas from the alveoli is determined by how soluble the gas is in blood and the alveolar blood flow

What does low cardiac output mean for the speed of onset with an inhalant anaesthetic

It increases the speed of onset > the uptake of anaesthetic agent from the alveoli to the pulmonary circulation is low, so the partial pressure of the agent in the alveoli rises rapidly. Since this reflects the partial pressure of the anaesthetic in the brIn, the onset of anaesthesia is rapid

Which inhalant has the lowest blood gas solubility? What is the MAC for dogs and cats with Isoflurane?

Licencing for inhalant anaesthetics

Isoflurane: dogs and cats, some variations

Sevoflurane: dogs and cats

Desflurane: no veterinary product licenses

Halothane: no longer commercially available

Nitrous oxide

Ether, methoxyflurane, cyclopropane: historical use

Properties of ideal inhalant anaesthetic

• Non irritant to mucous membranes

• Minimal effects on cardiovascular and respiratory function

• Low blood gas solubility: rapid uptake and elimination

• Minimal metabolism

• Non-toxic

• Non-flammable and chemically stable

• Easily vaporised

• Good analgesia and muscle relaxation

• Minimal environmental effects

Side effects of Isoflurane (halogenated ethyl methyl ether without a preservative)

Dose dependant

• Varying degrees of hypotension due to myocardial depression (contractility) and peripheral vasodilation

• Hypoventilation due to respiratory depression may be seen in small animals and be profound in horses

• Bronchodilation

• Irritant to mucous membranes and is not recommended as induction inhalant

Side effects of sevoflurane (polyfluorinated isopropyl methyl ether)

Dose dependant

• Varying degrees of hypotension due to myocardial depression (contractility) and peripheral vasodilation

• May have less effects on cerebral blood flow than other inhalants and is sometimes referred to as being neuroprotective

• It reacts with soda lime to produce the haloalkene Compound A. This is nephrotoxic in rats though clinically does not appear to be a concern in domestic species

• A minimal flow of 500-1000ml/min is recommended if using a circle system to limit accumulation

• Not irritant to mucous membranes

Desflurane