Veterinary Anaesthesia: Injectable Agents

Injectable Anaesthetic Agents

• Injectable anaesthetic agents are used in veterinary anaesthesia in various ways.
• Pharmacokinetics of these agents are important to understand.
• Factors affecting the speed of anaesthesia induction are discussed.
• Intravenous drug delivery techniques in domestic species are described.
• Contemporary veterinary anaesthesia uses intravenous anaesthetic agents, whose pharmacology is examined.
• Methods of providing muscle relaxation during general anaesthesia are outlined.

Ideal Anaesthetic Agent Characteristics

• There's no perfect anaesthetic agent.
• Desired properties include:
  • Fast onset of action
  • Short duration of action
  • Reversability
  • Good bioavailability by various routes
  • Long shelf life
  • Rapid metabolism
  • Minimal side effects
  • Non-irritating to tissues
  • Inexpensive
  • Muscle relaxation
  • Analgesic properties
  • Minimal environmental pollution
  • Stable in storage and solution
  • Non-cumulative

Injectable Agents

• Propofol:

  • Hypnotic alkyl phenol
  • Lipid water macroemulsion (propofol in soybean oil, glycerol, egg lecithin, sodium hydroxide)
  • Licensed in dogs and cats
  • Concentration: 1% (10mg/ml)
  • Indications: Induction and maintenance of anaesthesia, status epilepticus, fish and reptile anaesthesia
  • Available in preservative-free and preservative-containing formulations (PropoFlo Plus)

• Alfaxalone:

  • Synthetic neuroactive steroid
  • Insoluble in water (Cyclodextrin)
  • Preservatives (last 28 days)
  • Licensed in dogs, cats and rabbits for IV administration
  • Concentration: 10mg/ml
  • Indications: Induction and maintenance of anaesthesia, sedation (not licensed), suitable for immersion anaesthesia in amphibians, reptiles & fish

• Ketamine:

  • Phencyclidine derivative
  • Licensed for dogs, cats, horses, cattle, sheep, goats, pigs, rabbits, and exotics.
  • IV, IM, SC, and transmucosal absorption
  • Aqueous solution: acidic pH: pain on IM injection
  • 10% solution (most commonly used)
  • Indications: induction (+ other agent(s) to provide myorelaxation), analgesia, sedation (aggressive/painful patients)
  • No reversal

• Etomidate:

  • Imidazole derivative
  • Not licensed for animals in the UK
  • Different formulations available
  • Hypnomidate (propylene glycol)
    • Pain on injection
    • Damage to RBCs, tissue irritation/necrosis
  • Etomidate-Lipuro (lipid emulsion)
    • No pain on injection
    • No tissue irritation
  • Indications: Induction (with premedication +/- co-induction), 1-3 mg/kg IV

Total Intravenous Anaesthesia (TIVA)

• Use of injectable agents to both induce and maintain anaesthesia.
• Intermittent boluses or constant rate infusion (CRI)
  • Adjust infusion rate over time to avoid accumulation and prolonged recoveries
• Indications include patient movement, field anaesthesia, disbudding, severe cardiovascular pathologies, raised ICP, bronchoscopy/thoracostomies.

Partial Intravenous Anaesthesia (PIVA)

• Co-administration of injectable and inhalational anaesthetics.
• Ketamine, alpha-2 adrenoceptor agonists, opioids (e.g., fentanyl, remifentanil), and lidocaine
• Decreases inhalational anaesthetic requirements, reducing side effects.
• Provides analgesia and muscle relaxation

Rate of Induction

• Factors affecting induction rate include:
  • Dose
  • Concentration
  • Speed of injection
  • Cardiac output
  • Lipid solubility
  • Degree of protein binding
  • Rate of metabolism and excretion

Induction Agents Pharmacokinetics

• IV administration of a single bolus leads to a high concentration in the blood.
• Rapid redistribution to highly perfused organs (heart, brain, kidneys).
• Redistribution to less perfused tissues (muscles, fat).
• Slow release from fat.
• Hepatic metabolism (+/- extra-hepatic).
• Renal excretion

Propofol Formulations

• Preservative-free formulations encourage bacterial growth, and require discarding at the end of the day.
• Preservative-containing (PropoFlo Plus) formulations last for 28 days, but no CRI should be used.

Propofol in Cats

• Slower hepatic metabolism (glucuronidation enzyme deficiency).
• Felines are prone to oxidative injury from repeated dosages and daily administering.

Alfaxalone Mechanism of Action

• Enhances the inhibitory effect of GABA on the GABAA receptor.
• At high doses, it acts as a GABAA agonist, opening chloride channels.

Alfaxalone Pharmacokinetics

• IV, IM, SC administration (occasional pain).
• Rapid induction (30-60 minutes, IV).
• Dose premedicated animals (1-2 mg/kg to effect).
• IM sedation/anaesthesia (7-10 minutes).
• Alpha 2 agonist, opioids, ACP, midazolam: reduce induction dose
• Induction usually smooth without excitement
• Recovery quality similar to propofol
• Prolonged recoveries if long infusions
• Excitable recovery (paddling, rigidity, vocalization possible, especially if used alone)
• Rapid metabolism (hepatic)

Ketamine Mechanism of Action

• Interacts with multiple receptors.
• Acts as a non-competitive NMDA receptor antagonist, preventing glutamate from binding.
• Affects pain, memory, learning, and neural activity.
• Affects the function of NMDA, non-NMDA glutamate receptors, muscarinic and nicotinic receptors, and monoaminergic and opioid receptors
• Inhibits voltage-dependent, sodium- and calcium-channels

Ketamine Pharmacokinetics

• Can be administered as a bolus or CRI
• Sedation dose: 0.5-3 mg/kg IM
• Induction dose: ~2.5-5 mg/Kg (higher dose for exotics)
• Rapid onset IV (60-90 minutes)
• Pain (CRI 10-20 mcg/kg/min intra-op, 2-5 mcg/kg/min post-op)
• Hepatic metabolism → active metabolite: Norketamine
• Ketamine & Norketamine excreted unchanged (urine) in ; careful if renal dx
• Dog, horse: Norketamine further metabolised (inactive compounds), urinary + biliary excretion

Etomidate

• Imidazole derivative
• Not licensed for animals in the UK
• Different formulations available (Hypnomidate, Etomidate-Lipuro (lipid emulsion))

Etomidate Pharmacokinetics

• Rapid induction and recovery (often poor quality).
• Metabolism (hepatic and plasma esterases).
• Inactive metabolites excreted in urine, bile, and feces
• Mechanisms of action differ at low and higher doses

Co-induction

• Administration of two or more drugs together for induction
• Synergistic effects, potentially decreasing side effects and improving stability.
• Drugs to be used for co-induction, include:
  • Midazolam
  • Ketamine
  • Lidocaine
  • Fentanyl

Muscle Relaxation

• Obtaining additional myorelaxation involves:
  • Central muscle relaxation: Depressing inter-nuncial transmission in the spinal cord and brainstem (e.g., benzodiazepines, Guaifenesin).
  • Peripheral muscle relaxation: Acting at the neuromuscular junction, often via acetylcholine receptors or neuromuscular blocking agents (NMDA). (e.g., depolarizing and non-depolarizing)

This quiz covers injectable anaesthetic agents used in veterinary anaesthesia, focusing on their pharmacokinetics, induction factors, and intravenous delivery techniques. It explores the characteristics of ideal anaesthetic agents and their properties essential for effective use in veterinary medicine.