Anaesthesia

Define anaesthesia

Dose-dependent state produced by drugs that renders the patient insensible to pain through CONTROLLED and REVERSIBLE toxicity of the CNS or nociceptor blockage → CNS depression → Less interpretation of signals

• Function: Humane chemical restraint for radiography, examination, minor procedures, control of seizures, euthanasia, surgery

• vs. euthanasia = Uncontrolled and irreversible CNS toxicity

  • ALL GA agents are excellent euthanasia agents

Compare the safety of pre-medication drugs vs. GA drugs

Pre-med (sedatives/analgesia) = High TI (10 - 50) → Safer

GA = Low TI

• Injectable TI < 10 (except ketamine > 10)

• Inhalant TI < 2 - 4

3 Properties required for GA (anaesthetic triad)

1. Narcosis = Amnesia and unconsciousness

2. Analgesia

3. Muscle relaxation (except ketamine)

Phases vs. stages of anaesthesia

Phases of anaesthesia = Process of anaesthetising a patient

• Pre-anaesthetic → Recovery

Stages of anaesthesia = Progressive changes that occur during administration of GA agent which indicate anaesthetic depth

• Stage I (excitation) → Stage Iv (bulbar paralysis)

5 Phases of anaesthesia

• Definition

• Duration

• Procedures performed

1. Pre-Anaesthetic = Preparation of patient AND equipment

   • Duration: 6 - 24hr pre-induction

   • Procedures:

     1. Fasting

     2. Pre-anaesthetic assessment (history and PE)

     3. Pre-anaesthetic drugs

     4. Stabilisation and support

     5. Formulate anaesthetic plan/protocol

     6. Equipment and drug preparation (eg. equipment tray, monitoring equipment and anaesthetic circuit checks)

2. Pre-Medication = Provide sedatives and analgesia BEFORE induction

   • Duration: 30 - 60 minutes pre-induction

   • Procedures:

     1. Place IV catheter

     2. Consider clipping if patient is unstable (otherwise after induction)

3. Induction = Administer GA drugs to produce unconsciousness

   • Duration: 5 - 15 minutes

   • Procedures: High risk phase due to rapid loss of consciousness → Anaesthetic ABCs

4. Maintenance = Administer drugs to maintain anaesthesia and support the patient

   • Duration: Depends on procedure

   • Procedures: Use of dangerous drugs → Monitoring q5 minutes and interventions when necessary

5. Recovery = Cessation of drugs and ET extubation

   • Duration: Depends on drugs used and length of procedure (takes 24 - 48hr to return to normal function)

   • Procedures: High risk phase → Monitor q15 minutes

Hypnotic vs. dissociative GA agents

Hypnotic agents → CNS depression through agonism of GABA-A = Main inhibitory neurotransmitter in the CNS → Increased influx of Cl- into neuron → Inhibition of pain pathways and action potentials

• Every GA agent except ketamine (eg. propofol, alfaxalone, thiopentone, etomidate)

Dissociative agents → CNS excitation through interaction with NMDA receptors = Main excitatory neurotransmitter in the CNS (to the point where normal consciousness and reflex messages cannot be processed)

• eg. Ketamine and tiletamine

List the 3 main consequences/considerations/complications of GA

3 Hypo’s:

1. Hypotension (MAP = CO x SVR)

2. Hypoventilation (minute ventilation = RR x TV which is determined by PaCO2)

3. Hypothermia

Describe the TWO phases of the cardiac cycle (+ normal ratio)

1. Systolic = Ventricular contraction

2. Diastole = Relaxation of ventricles (heart refills with blood)

   • Myocardial perfusion via coronary artery circulation

   • Atrial systole at the END of diastole (empties remaining blood from A → V)

Diastole:Systole = 3:1 → Required for adequate myocardial perfusion

What is the most important determinant of tissue perfusion? (+ normal and equation)

MAP = DAP + 1/3(SAP - DAP)

• MAP = 93 - 95mmHg

  • Closer to DAP as it lasts longer except with tachycardia → 1/3 → ½ in equation as diastole : systole = 1:1

• SAP/DAP = 120/80mmHg

Why is a giraffe/elephant’s normal MAP much higher?

Relates to the position of the head above the heart → Higher MAP required for cerebral perfusion

• MAP decreases as brain is lowered closer to the heart (eg. drinking water)

What is an acceptable MAP/SAP under GA? What are 3 organ effects when MAP drops below the level?

Acceptable MAP under GA > 60 - 70mmHg (SAP > 90mmHg) otherwise:

1. AKI (kidneys have high perfusion requirement and little regenerative capacity)

2. Muscle myopathy (horses) → Maintain MAP > 85mmHg

3. Liver/skin → NO effect (high regenerative capacity and can cope with reduced blood flow)

5 Main effects of anaesthesia on CVS

1. Negative chronotropy = Decrease HR

   • Does NOT impact CO due to compensatory increase in SC = more time for ventricular filling

2. Negative inotropy = Decrease contractility via myocardial depression (decreased SV)

3. Peripheral vasodilation (reduced SVR → reduced MAP = CO x SVR)

   • Hypotension during GA due to vasodilation NOT CO

4. Arrhythmia

5. Impaired homeostatic reflexes (eg. baroreceptors)

What is “dead space”? What are 3 different types?

Dead Space: "Proportion of tidal volume that is NOT available for gas exchange (ventilation but no perfusion)

Types:

1. Anatomical dead space = Fixed part of the airway that does NOT participate in gas exchange (aka. conducting zone)

   • Respiratory zone = Airway structures that participates in gas exchange (alveoli)

   • Conducting zone = Airway structures that do NOT participate in gas exchange → Conduit for air to travel to the respiratory zone

2. Alveolar dead space = Poorly perfused alveoli which cannot participate in gas exchange

3. Equipment dead space = Added dead space from anaesthesia equipment (eg. ET tubes and poorly functional breathing circuits)

Dead space : Alveoli ratio = 1:2

Describe the mechanism of breathing

1. Contraction of respiratory muscles expand thoracic cavity and abdominal organs moved caudally

   • Diaphragm

   • Intercostals

   • 2˚ respiratory muscles of head and neck when other muscles fatigue or during respiratory failure

1. Lungs are fixed to the chest wall through surface tension of fluid in the pleural space

2. Negative pressure in airway = Air moves into alveoli

   • Negative pressure → Structures up stream of thorax are prone to collapse (airway obstruction prevented by cartilage/bone in nares, larynx, trachea and bronchi)

3. Pulmonary pump = Negative pressure causes distension of compliant blood vessels to assist blood movement → Increase venous return and CO

4. Passive expiration = Chest wall and lung return to normal position by elastic recoil of the lungs

   • NOT horses (passive phase → active phase with contraction of abdominal wall muscles)

Breathing vs. ventilation

Breathing = Physical movement chest wall and diaphragm

Ventilation = Gas exchange at the level of the alveoli defined level of CO2 in arterial blood (high PaCO2 = hypoventilation)

• Patient can be breathing but NOT ventilating

• Minute volume = RR x TV

• #1 driver of ventilation = PaCO2 (+ pH and PaO2) → Detected by peripheral chemoreceptors and baroreceptors

Main effects of anaesthesia on respiratory system

1. Muscle relaxation of URT → Respiratory obstruction (esp. brachycephalics)

2. Nasal oedema and haemorrhage

3. Medullary respiratory centre depression → Reduced sensitivity to hypercapnia → hypoventilation

   • Higher PaCO2 required to stimulate normal ventilation

4. Impaired thoracic wall movement due to muscle relaxation and recumbency → Lungs squashed by organs or when dependent

5. V:Q mismatch due to:

   1. GA depression of CVS → Hypotension and reduced CO → Reduced Q

   2. Under-perfusion of upper lungs (above heart and blood pools with gravity) and under-ventilation of dependent lungs (atelectasis)

   3. Inhibition of the hypoxic pulmonary vasoconstrictive reflex

Hypoventilation (PaCO2 = and when treatment is required)

PaCO2 > 45mmHg

• PaCO2 of 55 - 60mmHg = minimal consequences on pH due to carbonic acid formation (PaCO2 > 60mmHg required treatment)

PaO2 vs. SaO2 vs. FiO2

PaO2 = Arterial partial pressure of O2 (amount of O2 in arteries)

SaO2 = Arterial saturation of Hb (amount of O2 attached to Hb)

• PaO2 and SaO2 does NOT have a linear relationship (oxydissociation curve) → Good SaO2 with room air

FiO2 = Fractional inspired O2

• PaO2 proportional to FiO2 (PaO2 = 5 x FiO2)

3 Advantages and disadvantage of fasting during the pre-anaesthetic period

Advantages: Empty stomach →

1. Reduced risk of vomiting or gastroesophageal reflux (GOR)

   • GA patients have obtunded protective reflexes (gag reflex of larynx to seal off airway)

2. Reduced weight of GI → Less pressure on thorax while in dorsal recumbency → Reduced risk of respiratory embarrassment and hypoventilation

   • Respiratory embarrassment = Impaired breathing caused by a distended stomach against the diaphragm

3. More accurate assessment of small mammal weight → Appropriate dosing of drugs

Disadvantage: Prolonged fasting → Increased HCl in GI contents → Increased morbidity

Incidence and 3 potential outcomes of gastroesophageal reflux during GA

Incidence: 30 - 40%

Outcomes:

1. Regurgitation → Stomach contents seen coming out of mouth or nose

   • Treatment: Flush oesophagus immediately → Effective in reducing morbidity

2. Oesophagitis (fast onset of clinical signs) → Oesophageal stricture (slow onset of clinical signs)

3. Aspiration pneumonia → Tracheitis, stricture ± death by asphyxiation

3 Risk factors for GOR (+ examples)

1. Physiological

   • GI disease (history of nausea and vomiting)

   • Brachycephalics

   • Pregnant animals

2. Procedural

   • Fasting >6 - 12hr → More HCl → More lethal if GOR occurs

   • GI surgery

   • IVDD disease

   • Laryngeal paralysis → Aspiration pneumonia

   • Intracranial surgery

3. Pharmacological

   • Peri-op NSAIDs

   • Atropine

   • Morphine

   • Propofol

Fasting Duration for dogs and cats (water + food + why?)

• Food = 12hr (ideally 4 - 6hr with ½ MER as wet food → faster passage through GIT but not convenient for owner)

• Water = Free access until pre-medication (passes straight through GIT)

5 Indications for pre-anaesthetic drugs (+ examples)

1. Reduce risk of regurgitation (eg. brachycephalics → omeprazole and maropitant)

2. Stabilise patient with pre-existing disease

3. Analgesia for pre-existing pain (eg. methadone, ketamine, gabapentin for chronic pain)

4. Existing medications that should/should NOT be stopped

   • Do NOT stop exogenous steroids

   • Stop NSAIDs 24hr prior

5. Aggressive/anxious dog → Gabapentin, trazadone, melatonin

Aim and diagnostics for a pre-anaesthetic work-up

Aim: Determine patient’s ability to withstand stress of GA and surgery = Anaesthetic risk assessment (ASA grades)

Work-Up: Minimum (healthy patient)

1. History (complications and drugs used in previous GA events)

2. PE: TPR, MM, CRT, BWT, lung and heart auscultation

3. PCV/TPP →

   1. Hydration status

   2. Baseline if haemorrhage occurs

   3. Crude estimate of protein-binding effects of drugs

   4. Distribution of water if fluid given

4. ± More extensive work-up for compromised patients = Young, old and sick

6 ASA Grades

• Definition

• Examples

• Prognosis

ASA Grade	Definition	Examples	Prognosis
I	Healthy patient with no underlying disease	Elective desexing, hip radiographs, cruciate repair	Excellent
II	Mild systemic disturbance with no clinical signs and patient is well-compensated	Neonates, geriatric, simple fracture, brachycephalic, heart murmur ONLY (well-compensated	Good
III	Moderate to severe systemic disturbance with mild clinical signs	Anaemia, fever, obesity, moderate renal/lung/heart disease, dehydration	Fair
IV	Severe systemic disturbance and disease which is a constant threat to life	GDV, diaphragmatic hernia, uraemia, toxaemia, shock, severe anaemia/dehydration	Poor
V	Moribund patient not expected to survive >24hr	Profound shock, severe trauma, MOD	Grave
E	Emergency	Foreign body obstruction, spinal surgery	Variable

Pre-anaesthetic ABCs

• Equipment

• Function

• Checks

A = Airway

• Equipment:

  1. Laryngoscope

  2. ET tubes

  3. Cuff inflator syringe

  4. ET tube tie

  5. Gauze swab to hold tongue

  6. ± Lignocaine (cat)

• Function: Secure airway

• Checks:

  1. Attach blade of laryngoscope to check light is working

  2. Inflate cuffs for leaks

  3. Ensure ET tube tie is long enough

B = Breathing

• Equipment:

  1. Anaesthetic machine

  2. Breathing circuit

• Function: Assess if patient is breathing

• Checks:

  1. Machine check

  2. Breathing system check

C = Circulation

• Equipment:

  1. IV catheters

  2. Injection ports or T-port

  3. Saline flush

  4. Tape

  5. Alcohol prep for catheter

• Function: Secure IV access to induction drugs, emergency drugs and IVFT

• Checks: Prime sets with saline

D = Depth and Drugs

• Equipment: Drugs = Syringes, needle, drugs drawn up and labelled

• Checks: Check drug calculations and correct volumes drawn up

E = Eye lube and equipment

• Equipment:

  1. Lacrilube

  2. Pulse oximeter

  3. ECG

  4. Doppler/oscillometric cuff

  5. Thermometer

• Function: Protect eyes from drying out

F = Fluids

• Equipment:

  1. Fluid bag

  2. Giving set

• Function: Provide fluid for CVS support during GA-associated fluid loss

• Checks: Primed line and correct fluid rates calculated

3 Factors influencing anaesthetic protocols (+ examples)

1. Patient factors

   1. Signalment (species, breed, age)

      • Paediatric and geriatric dose rates are LOW

      • Juvenile (8 - 14 weeks) dose rates are HIGH

   2. Temperament (wild patients may require 10 - 100x more sedation)

   3. Size and conformation

      • Larger patients → Lower dose rates

   4. BCS

   5. Findings from history, PE and ancillary tests

   6. Concurrent diseases (ASA grades)

   7. Current medications (eg. amount of premed)

2. Type of procedure

   1. Location on body

   2. Estimated duration of procedure

   3. Body position

   4. Anticipated fluid loss

   5. Anticipated pain (reduce relative dose of sedatives)

3. Availability of equipment and facilities

   1. Abilities of vet/clinic (referral?)

   2. Equipment and drug availability

   3. Surgery or in-field?

How to determine what dose rate to select?

Depends on route of administration and desired effect

Opioids

• MoA

• Metabolism

• 3 Effects

• 6 Example drugs

MoA: Modulation of pain via descending inhibitory pathways

• Mu- or kappa-agonists which bind specific G-coupled opioid receptors within the brain and spinal cord → Mimic effect of endogenous opioids (eg. endorphines, enkephalins, dynorphines)

Metabolism: Liver (except remifentanil)

Effects:

1. Analgesia

2. Sedation (dogs) → Enhance sedative effects of other CNS depressants → Reduce dose rate of induction/maintenance agents

   • Less sedation in cats (euphoric ONLY)

3. Tolerance = Up-regulation of NMDA receptors (responsible for wind-up and central sensitisation) which bind glutamate (excitatory neurotransmitter)

Examples:

1. Morphine

2. Methadone

3. Buprenorphine

4. Butorphanol

5. Fentanyl

6. Remifentanil

Morphine

• MoA

• 2 Unique advantages

• 2 Unique disadvantages

• Routes of administration

• Duration of action

MoA: Full mu-agonist

Advantages:

1. Cheap (gold standard against which all other opioids are judged)

2. Reliable, dose-dependent and effective analgesia for visceral AND MSK pain

Disadvantages:

1. IV → Drug-induced histamine release → Hypotension

   • Avoid in MCT surgery

2. Induces emesis and contraindicated for

   1. Oesophageal FBO → Gastric rupture

   2. Cannot open mouth (eg. lock jaw)

   3. Difficulty protecting airways (eg. brachycephalics)

   4. Head trauma → Increased ICP → Cerebellar herniation

   5. Wobbler’s → Damage to cervical spine

Routes: IM, SC ± SLOW IV (care with IV histamine release)

• ALSO epidural/intra-articular → 12 - 24hr duration of action (water-soluble and will stay in epidural space for long time)

Duration: 4 - 6hr IM

Methadone

• MoA

• 4 Unique advantages

• 2 Unique disadvantages

• Routes of administration

• Duration of action

MoA: Full mu-agonist

Advantages:

1. Reliable, dose-dependent and effective analgesia for visceral AND MSK pain

2. NMDA receptor antagonist → Good for chronic pain and prevents tolerance to other opioids

   • Prevent neuronal plasticity associated with chronic glutamate receptor stimulation

3. No histamine release after IV administration → Excellent for rapid onset

4. Lipid-soluble = Rapid onset of action and anti-emetic (crosses BBB)

Disadvantages:

1. Less sedation than morphine (likely SAME sedation, but onset of action later than morphine and hence does NOT coincide with alpha-2-agonist onset of action)

2. $$$

Routes: IV, IM, SC

Duration: 4 - 6hr

Buprenorphine

• MoA

• 2 Unique advantages

• 4 Unique disadvantages

• Routes of administration

• Onset

• Duration of action

MoA: Partial mu-agonist

Advantages:

1. Long duration of action for analgesia

2. Fewer opioid-associated side effects (less respiratory depression, sedation and GI stasis)

Disadvantages:

1. Slow onset of action

2. Less effective analgesia as partial mu-agonist (ceiling effect → increased dose will no longer increase effect)

3. High affinity for mu-opioid receptors → Blocks effects of full mu-opioids

4. Limited reversal with naloxone (may require repeated administration at higher dose rates)

Routes: IV, IM, SC, buccal (cat)

Onset: 30 - 45 minutes

Duration: 6 - 8hr

Butorphanol

• MoA

• 3 Unique advantages

• 4 Unique disadvantages

• Routes of administration

• Duration of action

MoA: Kappa-agonist and mu-antagonist

Advantages:

1. NOT a mu-agonist → No panting and ideal for thoracic radiography

2. Good sedation

3. Antitussive

Disadvantages:

1. Less effective analgesia as fewer kappa receptors (ceiling effect → increased dose will no longer increase effect)

   • Moderate analgesia for visceral pain but NOT orthopaedic pain

2. Kappa-agonists → Dysphoria = Increased movement and excitement in horses and cats

3. Marked bradycardia in SOME dogs

4. Short duration of action

5. Antagonism of mu-opioid receptors → Blocks effects of full mu-opioids

6. $$$

Routes: IV, IM, SC

Duration: 2 - 4hr

Fentanyl vs. remifentanil

• Duration of action

• Inducation

Fentanyl

Duration: 15 minutes

Indication: Polytrauma (bolus → CRI)

Remifentanil

Duration: 3 minutes (metabolised in blood NOT liver)

Indication: Liver disease (only opioid NOT metabolised by liver)

• Avoid bolus → Bradycardia (use as CRI ONLY)

4 CNS effects of opioids

1. Hypothalamus → Opioids lower temperature equilibrium point in the thermoregulatory centre

   • Dogs pant due to activation of heat exchange mechanisms → Hypothermia

   • Avoid for thoracic radiographs (use butorphanol)

2. 4th ventricle → Opioids cross the BBB into the emetic centre → Anti-emetic

3. CRTZ → Morphine cannot cross the BBB as it is water-soluble, so it binds the CRTZ to induce emesis

   • Morphine gradually cross the BBB due to the concentration gradient to bind the vomiting centre and become an anti-emetic (further doses of morphine have an anti-emetic effect)

4. Sedation = Morphine » Methadone

   • More profound sedation with low TP (methadone is highly protein-bound)

Respiratory effects of opioids

Dose-dependent respiratory depression

• Decreased sensitivity of PaCO2 chemoreceptors → Decreased TV and RR

CVS effects of opioids

MINIMAL CVS depression with little change in MAP or cardiac contractility (safe for compromised patient) BUT induces dose-dependent bradycardia

1. Opioids stimulate the vagus nerve which provides parasympathetic innervation to the SA and AV node of the heart

2. → Bradycardia

3. BUT increased ventricular filling time → Higher SV which restores CO

5 Visceral effects of opioid

Opioid receptors located on OUTSIDE of CNS (GIT, biliary tract and urinary tract) → SPHINCTER CONSTRICTORS (except oesophageal sphincter)

1. Dog = Miosis (cat = mydriasis → overdose)

2. Defaecation (anal sphincter)

3. Slow GI motility (pyloric sphincter → reduced gastric emptying and increased GI tone)

4. Urinary retention (bladder sphincter)

5. Increased biliary duct tension (sphincter of Oddi) → Pain with gallstones

7 Reasons to sedate a patient (+ other reasons to premed)

Sedate:

1. Reduce stress from excessive physical restraint and painful manipulations

2. Prevents injury to staff

3. Neuroleptic analgesia = Sedative + analgesia (opioid) → Marked synergism with enhanced sedation and analgesia than what can be achieved by either drug alone → Reduced dose rates used

   • More premed agents (higher TI) → Lower dose of induction/maintenance agents required (low TI)

Pre-Med:

4. Smooth induction and recovery periods → Rapid progression through stage I and II of anaesthesia

5. Pre-emptive analgesia PRIOR to nociception → Less painful recoveries with lower doses of post-op analgesic agents

6. Minimise adverse drug/physiological effects of other agents in the procedure

7. Provision of target analgesia (chronic vs. acute pain)

Tranquillisation vs. sedation vs. anxiolytic

Tranquillisation = Patient easier to handle and less stressed BUT not overtly sedated

Sedation = Calm patient but may be stressed internally if the sedative is not an axiolytic

Anxiolytic = Remove anxiety and appear like they are going to sleep

List 3 classes of sedatives (+ example drugs)

1. Benzodiazepine

   1. Midazolam

   2. Diazepam

2. Phenothiazine (acepromazine)

3. Alpha-2-adrenergic receptor agonists

   1. Xylazine

   2. Medetomidine

   3. Dexmedetomidine

MoA of of benzodiazepine

1. Bind specific receptor sits on the subunit of GABA-A receptor = Gamma-amino-butyric acid

2. Activation of GABA-A receptor

3. Enhanced opening of Cl- channels by GABA inhibitory neurotransmitter

4. Increased influx of Cl- → Hyperpolarisation and resistance to neuronal excitation

5 CNS effects of benzodiazepines

1. Sedative (ANXIOLYTIC) = NOT useful for normal patients due to anxiolysis → Unmasks defensive and aggressive behaviour → Bizarre behaviour and paradoxical excitement in dogs/cats/horses

   • Good sedation in ruminants, camelids, pigs, birds, primates but NOT licensed

2. Excellent anticonvulsant (decreases ICP and anti-epileptic)

   • Seizures in patients with hepatic encephalopathy

3. Excellent muscle relaxant

4. No analgesia

5. Appetite stimulant

2 CVS effects of benzodiazepines

1. Minimal (very high TI → Safe for ASA grade 3 - 5)

   • Good for the very young, very old or very sick

2. Diazepam fast IV → Stimulates histamine release and vasodilation due to propylene glycol

Respiratory effects of benzodiazepines

Minimal (very high TI → Safe for ASA grade 3 - 5)

• Good for the very young, very old or very sick

Visceral effects of benzodiazepines (liver and kidneys)

1. Diazepam → Hepatic necrosis in cats with pre-existing liver disease (metabolised in liver to active metabolites → Take time to dissipate from body)

2. Minimal renal effects

Benzodiazepine: Diazepam vs. midazolam

• Solubility

• Routes of administration

Diazepam

Solubility: Insoluble in water → Dissolved with propylene glycol solvent

Routes: IV, PO, transmucosal (eg. per rectum)

• NOT IM/SC → Pain on injection and unreliable absorption due to propylene glycol

  • Not used as a premed

• Slow IV to avoid haemolysis and histamine release

Midazolam

Solubility: Water-soluble → Shorter-acting and more potent than diazepam

Routes: IV, IM, SC, intra-nasal, PO

Routes of phenothiazine (acepromazine) administration

Transmucosal, IM, IV, SC, PO, transmucosal

• Acepromazine high doses when PO (1 - 2mg/kg → extensive 1st pass metabolism)

7 CNS effects of phenothiazine (acepromazine) + MoA

“Anti-drug” = Histamine-, muscarinic-, serotonin-, dopamine-, alpha-1- antagonist (blocker)

1. Tranquillisation ONLY = Dopamine (D1 and 2) receptor blockade

   • Sedation when combined with opioids = Neuroleptanalgesia

2. NOT a good muscle relaxant (cannot give with ketamine)

3. Antiemetic = Dopamine (D1 and 2) receptor blockade

4. Antihistamine = H1 receptor blockade

   • Can use with MCT

5. Increase ICP ± increased risk of seizures (once considered to lower the seizure threshold) = Alpha-1-antagonist

6. No analgesia

7. Excessive acepromazine → Extra-pyramidal signs = Muscle tremours and spasticity

3 CVS effects of phenothiazine (acepromazine)

1. Antiarrhythmic = Alpha-1-adrenergic receptor ANTAGONIST in heart

2. Vasodilation = Alpha-1-adrenergic receptor ANTAGONIST peripherally → Reflex tachycardia

   • Causes hypothermia

3. Temporary reduction in HCT by 2 - 5% (spleen recruits RBCs) and decreased platelet aggregation

• Avoid with anaemic patients and coagulopathies

Respiratory effects of phenothiazine (acepromazine)

NONE! Excellent for brachycephalic patients that cannot protect their airway (less muscle relaxation)

4 Visceral effects of phenothiazine (acepromazine) (liver + kidneys)

1. Metabolised in liver but NO REVERSAL available → Effects prolonged in patients with liver disease

2. Mild effects on kidneys through vasodilation → hypotension

3. Avoid in breeding stallions → Risk of priapism

4. Splenic enlargement (avoid with laparoscopy)

6 Example alpha-2-agonists (ranked by potency)

Least Potent:

1. Xylazine (LA and SA)

2. Detomidine (LA)

3. Medetomidine

   • Medetomidine = Racemic mixture of levomedetomidine and dexmedetomidine (optical enantiomers)

4. Dexmedetomidine = Active ingredient ONLY ($$$)

Most Potent:

ALSO:

5. Romifidine

6. Clonidine

• Used in humans as a nasal decongestant (produces vasoconstriction of the nasal mucosal blood vessels which reduces mucus production)

Routes of alpha-2-agonists

1. SC, IM, IV

2. Epidural (vasoconstriction → prolong action of local anaesthetics)

3. Transmucosal gel (domosedan and sileo)

5 CNS effects of alpha-2-agonists

1. Sedation (can be profound) → Still can be roused

2. Excellent anticonvulsant (decreases ICP and anti-epileptic)

   • Same side effect as Cushing’s reflex = Hypertension and reflex bradycardia → Avoid for patients with high ICP

3. Excellent muscle relaxation

4. Excellent visceral analgesia (wanes prior to sedation → care with rousability due to pain)

5. Smooth muscle spasm in blood vessels, GIT and uterus

CVS effects of alpha-2-agonists

Prominent BRADYCARDIA at label doses (use lower dose rates than what is suggested on the bottle) ± 2nd degree AV blocks

Biphasic BP

1. Post-Synaptic Effect = Drug stimulates PERIPHERAL alpha-2-receptors in blood vessel walls causing intense vasoconstriction (pale MM) → Reflex bradycardia (increased BP and decreased HR)

   • Treatment: Reversal if severe bradycardia

2. Pre-Synaptic Effect = Drug stimulates CENTRAL alpha-2-receptors (crosses the BBB) → Inhibit negative feedback and release of NA from presynaptic neurons → Increased PNS with bradycardia ± vasodilation (decreased BP, CO and HR)

   • Xylazine causes hypotension (vs. other A2A → normotensive)

   • Treatment: Atropine or glycopyrrolate

2 Respiratory effects of alpha-2-agonists

1. Minimal effects

2. Xylazine → Respiratory distress, pulmonary oedema and hypoxaemia in ruminants (esp. goats and sheep)

   • MoA: Ruminants have unique pulmonary intravascular macrophages with alpha-receptors on their surface to bind xylazine → Stimulates macrophages to release cytokines which causes thickening on alveolar walls → Decreased gas exchange

   • Still used in ruminants due to effective sedation AND analgesia (fewer opioid receptors) and only A2A licensed (otherwise 91d WHP)

6 Visceral effects of alpha-2-agonists

1. Emesis in cats

2. Decreased GI motility

3. Re-narcotisation in some species = Cannot process drug, but can process reversal

4. Decreases GFR and increases urine production (inhibit ADH)

   • Dexmedetomidine is nephroprotective

5. Xylazine → Penile prolapse in bulls and abortion in pregnant mares/cows

6. Decrease pancreatic release of insulin → Hyperglycaemia

Contraindications of:

1. Benzodiazepines

2. Phenothiazines (acepromazine)

3. Alpha-2-agonists

Benzodiazepine:

1. Normal patients (young, old and healthy)

2. Cats with liver disease → Hepatic necrosis

Phenothiazines (Acepromazine):

1. Hypovolaemia or dehydration → Vasodilation (cannot divert blood to vital areas)

2. Liver disease (no reversal available)

3. Young, old and sick

4. mdr-1 mutants

Alpha-2-Agonists:

1. Cardiac disease

2. Nausea and emesis contraindicated in cats

Onset (IM) and duration of:

1. Benzodiazepines

2. Phenothiazines (acepromazine)

3. Alpha-2-agonists

4. Opioids

Benzodiazepine:

• Onset = 10 minutes

• Duration = 1hr (2 - 6hr)

Phenothiazines (acepromazine):

• Onset = 30 - 45 minutes

• Duration = 4 - 6hr (calm on recovery)

Alpha-2-Agonists:

• Onset = 10 minutes

• Duration = 1hr (higher dose → higher duration)

  • Xylazine = 30 minutes

  • Dexmedetomidine SLIGHTLY faster elimination (levomedetomidine increases the half-life of dexmedetomidine by inhibiting its metabolism)

Opioids:

• Onset = 10 minutes (20 minutes for buprenorphine)

Reversals for:

1. Benzodiazepines

2. Phenothiazines (acepromazine)

3. Alpha-2-agonists

4. Opioids

1. Benzodiazepine → Flumazenil IV

2. Phenothiazines → NONE!

3. Alpha-2-agonists → Atipamezole IM

   • Same volume as sedative for dogs and ½ for cats

4. Opioids → Naloxone (can mini reverse patient is recovery is slow post-op; avoid full reversal of analgesia)

   • Onset: Fast

   • Duration: 30 minutes

List 4 types of premeds used (functions)

1. Sedatives

   1. Benzodiazepine (midazolam ONLY)

   2. Acepromazine

   3. Alpha-2-agonists

2. Analgesia

   1. Methadone/morphine

   2. Butorphanol

   3. Buprenorphine

3. Drugs that offset physiological/pharmacological consequences of GA/surgery

   1. Omeprazole

   2. Atropine

   3. Maropitant

   4. Antihistamines

4. Dissociatives

   1. Ketamine

   2. Tiletamine

Describe the use and MoA of premed drugs that offset physiological/pharmacological consequences of GA/surgery:

1. Anticholinergics = Atropine and glycopyrrolate

2. Antihistamines = Mepyramine

3. Antiemetic = Maropitant

4. Gastric pH modifier = Omeprazole

Anticholinergics = Atropine and glycopyrrolate

• MoA: Competitive antagonist of the muscarinic acetylcholine receptors (M1 - 5) → Parasympatholytic (blocks vagal tone)

  • Heart = SA and AV node → Increase HR

  • GI = Slow GIT of LA (eg. colic horses)

  • Eye = Mydriasis

  • Lung = Bronchodilation and reduced respiratory/salivary secretions (eg. cats in laryngospasm)

• Avoid in stallions → Paraphimosis

• Avoid atropine in rabbits (atropinase) → Glycopyrrolate instead (fewer side effects and longer duration of action)

• Indications:

  1. Reduce ketamine-induced ptyalism (excessive salivation) and risk of laryngospasm in cats (UNCOMMON)

  2. Offset pharmacological effects of opioid → Bradycardia

  3. Reduce vasovagal/oculocardial reflex during ophthalmic surgery → Vagus nerve induces bradycardia

Antihistamines = Mepyramine → History of hypersensitivity reactions or MCT

Antiemetic = Maropitant → GI disease, unfasted patient, aspiration risk (eg. brachycephalics), hernia repair, prolonged GA

Gastric pH modifier = Omeprazole → Brachycephalics

Order of loss during GA (10):

1. Pain and memory

2. Consciousness

3. Motor coordination

4. Response to external stimuli

5. Muscle tone

6. Protective reflexes (eg. gag)

7. Autonomic functions (SNS and PNS control)

8. Normal control of cardiovascular and respiratory systems

9. Control of ventilation ending in respiratory arrest

10. Control of cardiovascular function resulting in cardiac arrest

It IS possible to anaesthetised but conscious (stage I = amnesia and analgesia BUT conscious)

List the 4 stages and 4 planes of anaesthetic depth

Stage I = Voluntary excitation

Stage II = Involuntary excitation

Stage III = Surgical anaesthesia

• Plane 1 = Light

• Plane 2 = Medium

• Plane 3 = Deep

• Plane 4 = Very deep

Stage IV = Bulbar paralysis

Transition between stages is NOT obvious and there are species differences, anaesthetic agent differences and individual differences

4 Vital functions used to assess anaesthetic depth (+ examples and what stages they are absent)

1. Autonomic reflexes

   1. Salivation

   2. Lacrimation

2. Protective reflexes

   1. Gag reflex

   2. Cough reflex

   3. Sneeze reflex

   4. Corneal reflex - Sluggish stage III, plane 3 (absent by plane 4)

      • Indicates deeper plane than palpebral reflex

      • Do NOT routinely use as monitoring tool → Corneal damage

   5. Palpebral reflex - Absent in stage III, plane 2

      • Lateral palpebral disappears FIRST

      • Good way to assess induction is progressing → intubation imminent when lateral palpebral is lost

      • MAY remain with ketamine → Incorrect assessment of anaesthetic depth

   6. PLR - Absent stage III plane 3

      • Assess when pupils are dilated and central → Differentiate between stage II (present) and stage II, plane 3/4 (absent)

3. Ocular muscle tone (position and pupil size)

   • DOG

     • Stage I/II = C ± dilated (depends on lighting and premed)

     

     • Stage III, plane 1 = CV (rolling from C → VM) + dilated → constricting

       • Identical to stage III, plane 3 → PLR to assess

     

     • Stage III, plane 2 = VM + constricted (cannot see pupil)

     

     • Stage III, plane 3 = Stage III, plane 1 = CV (rolling VM → C) + constricted → dilating

       

     • Stage III, plane 4 and stage IV = Central and dilated

     

   • CAT:

     • Induction: Central and dilated due to

       1. Stress of environment (catecholamine release)

       2. Premeds do NOT produce profound sedation as in dogs

       3. Mu-opioids produce mydriasis in cats

       4. Atropine once used in cats to reduce ptyalism

     • Ideal: CV

     • Too deep: VM or central and constricted

   

   • Sheep:

     • Induction: Pupils dilate and move ventrally (cannot intubate until eyes are ventral)

     • Ideal: No palpebral, eye central and constricted (rolled V → C)

   

   • Horse:

     • Stage III: Central and dilated for ALL planes

       • Light surgical = Strong palpebral and slow nystagmus

       • Moderate surgical = Central, dilated with sluggish PLR

       • Deep surgical = Absent PLR

4. Skeletal muscle tone (jaw and chest)

   • Ruminants + horses + specific species of dogs and cats have strong intrinsic jaw tone

• Menace response NOT used to assess anaesthetic depth (response to external stimulus disappears very quickly after induction = step 4)

• NOT pedal withdrawal reflex (disappears immediately after induction)

Pupil size with dogs vs. cats on opioids

Dogs = Constriction (miosis)

Cats = Dilation (mydriasis)

Stage I (voluntary excitement)

• Start

• End

• Characteristics

• Cardiopulmonary

• Eye position

• Pupil size

• Palpebral present?

Start: Induction

End: Loss of consciousness

Characteristics: Analgesia + consciousness, disorientation

• ± Salivation, struggling, urination, defaecation

Cardiopulmonary: Increased HR and RR (OR breath-holding)

Eye position: Central

Pupil size: Normal (cats = dilated)

Palpebral present: YES

Rapid with injectables = Stage I may not be noticed (slow with inhalants)

Stage II (involuntary excitement)

• Start

• End

• Characteristics

• Cardiopulmonary

• Eye position

• Pupil size

• Palpebral present?

Start: Loss of consciousness

End: Loss of struggling

Characteristics: Loss of normal voluntary control and often overly responsive to pain

• Exaggerated reflexes

• Struggling

• Laryngeal protective reflexes present

• Chewing, vomiting, swallowing

• Nystagmus in horses

Cardiopulmonary: Irregular breathing (breath-holding)

Eye position: Central

Pupil size: Dilating (sympathetic nervous system stimulated)

Palpebral present: YES

Responsible for dysphoria on recovery (disturbing and dangerous period as cannot be calmed by voices)

Stage III (surgical anaesthesia)

• Start

• End

• Ideal plane

Start: Struggling stops

End: Plane 4 = Respiratory distress

Ideal: Stage III, plane 2

What is the BEST way to determine an appropriate surgical plane?

Response to surgical stimulation should be present (cardiopulmonary system is still reactive = increased HR, MAP and ventilation with surgical stimulation)

• Disappears at plane 3

Stage III, PLANE 1 (light plane)

• Procedures

• Cardiopulmonary

• Eye position

• Pupil size

• Palpebral

• Corneal

• PLR

• Lacrimation

• Pharyngeal and laryngeal reflexes

• Muscle tone

• MM and CRT

Procedures: Minor procedures or imaging

Cardiopulmonary: Decreased TV and RR, normal/rapid HR and strong pulse

Eye position: Rolling (C → V)

Pupil size: Dilating → Constricting

Palpebral: YES

Corneal: YES

PLR: YES

Lacrimation: YES

Pharyngeal and laryngeal reflexes: YES (difficult to intubate)

Muscle tone: Strong (mouth difficult to open)

MM and CRT: Pink and rapid

Stage III, PLANE 2 (medium plane)

• Procedures

• Cardiopulmonary

• Eye position

• Pupil size

• Palpebral

• Corneal

• PLR

• Lacrimation

• Pharyngeal and laryngeal reflexes

• Muscle tone

• MM and CRT

Procedures: Surgical procedures

Cardiopulmonary: Decreased TV and RR, normal/lower HR and strong pulse

Eye position: VM (CV cat and C sheep)

Pupil size: Constricting

Palpebral: NO

Corneal: YES

PLR: YES

Lacrimation: YES

Pharyngeal and laryngeal reflexes: NO (except cat pharyngeal reflexes)

Muscle tone: Reduced (mouth easier to open)

MM and CRT: Pink and normal CRT

Stage III, PLANE 3 (deep plane)

• Procedures

• Cardiopulmonary

• Eye position

• Pupil size

• Palpebral

• Corneal

• PLR

• Lacrimation

• Pharyngeal and laryngeal reflexes

• Muscle tone

Procedures: Deeper than necessary

Cardiopulmonary: Decreased TV, RR, MAP, HR

• Vitals do NOT increase in response to surgical stimulation

Eye position: Rolling (V → C)

Pupil size: Constricting → Dilating

Palpebral: NO

Corneal: Sluggish

PLR: Sluggish

Lacrimation: No (dry eyes)

Pharyngeal and laryngeal reflexes: NO

Muscle tone: Marked relaxation

Stage III, PLANE 3 (deep plane)

• Procedures

• Start

• End

• Cardiopulmonary

• Eye position

• Pupil size

• Eye reflexes

• Lacrimation

• MM and CRT

Procedures: NEVER

Start: Paralysis of intercostal and abdominal muscles which control ventilation

End: Respiratory arrest

Cardiopulmonary: Markedly reduced MAP, weak pulse and heart sounds

Eye position: Central

Pupil size: Dilated

Eye reflexes: NONE

Lacrimation: NONE (dull and dry)

MM and CRT: Pale, blue/grey with slow CRT

• Parasympathetic nervous system tone > sympathetic

• Patient at risk of irreversible tissue damage due to poor perfusion and hypoxia

4 Treatments when anaesthetic plane is too deep

1. Immediately turn off anaesthetic agent

2. Patient ventilated with 100% O2

3. CVS supported with IV fluids

4. ± Emergency drugs

Stage IV (bulbar paralysis)

• Start

• End

• Cardiopulmonary

Difference between stage IV and stage III, plane 4 is that the heart no longer beats in stage IV

Start: Respiratory arrest

End: Cardiac arrest

Cardiopulmonary: No pulse, heart cannot be auscultated, jerky/irregular respiration (agonal gasping and tracheal tug)

• Modern inhalants have reasonable safety margin between respiratory arrest and cardiac arrest (care with critical patients or those not closely monitored)

Steps of induction ABCs

1. Airway = ET intubation

2. Breathing = Inflate cuff and check patient is breathing

3. Circulation = Pulse, heart beat auscultation

4. Depth = Assess eyes and jaw tone to determine depth

5. Equipment and eye lube = Pulse oximeter, NIBP, capnograph, ECG

6. Fluid

List 4 injectable induction agents (+ routes of administration)

1. Ketamine IV

   • IM and SC for cats

2. Alfaxalone IV

   • IM and SC for cats (eg. aggressive cats where ketamine is contraindicated) → Slightly faster uptake than metabolism

     • Duration: 5 - 10 minutes (must watch patient sedate)

   • IV ONLY for dogs → Uptake is slower than metabolism

3. Propofol IV ONLY → Any drug absorbed via IM/SC is immediately metabolised

4. Thiopentone IV ONLY

Onset and duration of action of:

• Propofol

• Thiopentone

• Ketamine

Propofol:

• Onset = 15 - 20s

• Duration = 5 - 7 minutes

Thiopentone:

• Onset = 15 - 20s

• Duration = 10 - 20 minutes

Ketamine:

• Onset = 20 - 30s (5 - 10 minutes IM)

• Duration = 10 - 15 minutes

9 Properties of the ideal anaesthetic agent

1. Rapid onset (seconds) → Rapid transition through excitatory stages

2. Predictable duration

3. Non-irritant if perivascular

4. Non-painful on injection

5. Non-accumulative (metabolised rapidly)

6. Non-allergenic

7. Produces physiological stability (no change in cardiopulmonary function)

8. Cheap

9. Bacteriostatic

How to administer induction agents in small animals (vs. horses)

Small Animals: Dosed to Effect

1. Average dose drawn up

2. Give ½ dose SLOWLY (except thiopentone)

   • Begin with 1mg/kg for propofol

3. Wait for effect of stage III, plane 1/2

4. Give ½ of remainder

5. Wait for effect

6. Administer remainder if required and appropriate stage of GA has not been reached

7. Draw up and administer more if required

Horse: Give ALL as excitement phase in horses is too dangerous

Alfaxalone solubility (+ 4 formulations)

Solubility: Insoluble in water

• Contains cyclodextrin excipients with NO cremaphor (or alphadalone)

Formulations:

1. Preservatives 10mg/mL

2. Without preservatives (fridge) 10mg/mL

3. Alfaxan forte 40mg/mL (licensed for IM in cats to reduce volume required)

4. Historic Drug: Saffan (Althesin) = Steroidal GA agent (alfaxalone + alphadalone) in cremaphor EL

   • +ve: Once #1 GA agent in cats as alphadalone → Excellent analgesia

   • -ve: Castor oil diluent (cremaphor) → Marked histamine release in dogs

3 CNS effects of alfaxalone

1. Hyperaesthetic recoveries → Dysphoric (leave alone during recovery vs. propofol patients SHOULD be woken up)

2. Analgesia through CNS depression ONLY

3. Decreases ICP and anti-epileptic

2 CVS effects of alfaxalone

1. Minimal CVS depression (HR and BP maintained well)

2. Vasodilation with reflex tachycardia during induction with compromised patients (ASA IV/V)

2 Respiratory effects of alfaxalone

1. Minimal respiratory depression (minimal effect on the hypoxic pulmonary vasoconstrictive reflex)

2. Apnoea if given fast IV

Visceral effects of alfaxalone (liver + kidney)

1. Rapid metabolism by liver ± lungs → Multiple top-ups (TIVA) without prolonged recovery

2. Minimal effects on kidneys

Contraindications of alfaxalone

Large patients → $$$

Propofol solubility and 2 formulations

Solubility: Insoluble in water

Formulations: 10mg/mL

1. Intralipid suspension/excipient containing egg phosphatide, glycerol and soyabean oil (excellent bacterial growth medium)

   • Important to discard unused propofol and keep multiuse vials free of contamination to avoid inoculating patients with bacteria

   • Bacterial growth after 6hr of opening

   • Minimise pain on IV injection

2. Aquafol = Clear and water-soluble containing benzo-alcohol

   • -ve: Vehicle effect = Sudden unexplained deaths after administration due to excipient → Histamine release in dogs due to allergic reaction

   • Propylphenol and neutral pH → Not irritating if given perivascularly by accident

4 CNS effects of propofol

1. Myoclonus (muscle twitching) common → Mistaken for seizures or light plane of anaesthesia

2. Excellent anticonvulsant (decreases ICP and anti-epileptic)

3. Excellent muscle relaxant

4. Analgesia through CNS depression ONLY

2 CVS effects of propofol

1. Excellent antiarrhythmic (sympatholytic)

2. Dose-dependent CVS depression (decreased HR, SV, BP)

3 Respiratory effects of propofol

1. Minimal pulmonary depression (little effect on HPVR)

2. Apnoea at induction common

3. Cats accumulate propofol in lungs after consecutive doses

5 Visceral effects of propofol (liver + kidney)

1. Extra-hepatic metabolism = Metabolised by multiple sites as clearance of propofol exceeds hepatic blood flow → Ideal for liver disease

   • Liver 80% and lungs 20%

2. Non-cumulative when used as TIVA (except cats when TIVA > 30 minutes due to deficiency in glucaronidase enzyme)

3. Phenolic compound → Heinz body anaemia in cats when dosed with propofol on consecutive days due to RBC oxidative damage (~1 week)

4. White form stimulates pancreatitis

5. Minimal effects on kidneys (cardiac-induced damage)

Other advantage of propofol

Cheap

Contraindications of propofol

1. Pancreatitis

2. Sepsis

Chemical properties of thiopentone

Chemical: Barbiturate

• Powder to reconstitute with sterile water → Lasts several days in fridge

• pH = 11 → Irritating if given perivascularly (thrombophlebitis)

  • Treatment: Dilute 0.9% NaCl and lignocaine = Acid to neutralise alkaline solution

  • MUST be given IV due to high pH

4 CNS effects of thiopentone

1. Excellent anticonvulsant (barbiturate)

2. Excellent muscle relaxant

3. Rough recovery → Interpreted as seizures

4. Analgesia through CNS depression ONLY

3 CVS effects of thiopentone

1. Minimal CVS depression (HR and BP well-maintained)

2. Vasodilation and reflex tachycardia common on induction in sick patients

3. Arrhythmogenic in 25% of patients (not observed as ECG not present during induction)

Respiratory effects of thiopentone

Apnoea common on induction

5 Visceral effects of thiopentone (liver + kidney)

1. Ultra-short duration of action = Drug hits brain and is rapidly redistributed to lean tissue → fat

2. Highly protein-bound → Greater effect in patients with hypoalbuminaemia

3. Lower pH (acidosis) → More unionised drug free to cross the BBB → Greater effect

4. Very slow hepatic metabolism → Avoid in liver disease and TIVA due to cumulative effect

5. Minimal effect on kidneys