Injectable Anesthetics: Properties & Effects

• The lecture covers injectable drugs used for induction and their properties.
• The goal is to describe the mechanism of action, effects on the body, onset/duration, species considerations, contraindications, and clinical usage for:
  • Propofol
  • Dissociative anesthetics
  • Alfaxalone
  • Etomidate

Ideal Injectable Drug Characteristics

• Provides reliable sedation, analgesia, and muscle relaxation.
• Causes minimal changes in cardiovascular or respiratory function.
• Requires a small volume for administration.
• Possesses a wide safety index.
• Exhibits rapid onset and short duration of action.
• Is reversible.
• Is non-cumulative, allowing subsequent doses.
• Is readily metabolized and excreted by the body.
• Has a long shelf-life and is stable in heat and light.
• Is inexpensive.
• Is currently available on the market.
• Has low potential for human abuse and is not a controlled substance.

Common Side Effects of Anesthesia

• Decreased myocardial contractility, cardiac output, and tissue perfusion are common side effects.
• Vasodilation leading to relative hypovolemia and hypotension can occur. Hypotension is the most common side effect.
• Decreased minute ventilation may lead to respiratory acidosis (increased PaCO2).
• Decreased urine production and renal concentrating ability can occur.
• Predisposition to hypothermia can occur.
• Autoregulatory compensatory mechanisms are affected.
• General anesthesia usually depresses sympathoadrenal and compensatory reflex responses to hypotension, hypercapnea and hypoxemia.

Propofol

• Chemically distinct from other IV anesthetics, has a rapid awakening and minimal residual effects.
• It is a milky white oil in water emulsion
• Formulation: 1% propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide.
• There is no preservative in propofol, discard open vial within 6 hours.
• Propofol28 has a benzyl alcohol preservative to prevent bacterial/fungal growth for 28 days after opening and is approved for use in dogs only.
• It activates GABAA receptor, increasing chloride ion (Cl-) conduction and blocks sodium channels, leading to hyperpolarization.
• Results in CNS depression and loss of consciousness.
• Rapidly distributes, followed by slower clearance.
• Can be used as a constant rate infusion (CRI) in many species.
• Does not accumulate in most species, leading to good quality rapid recovery.
• Undergoes rapid hepatic metabolism and excretion by the kidneys.
• Cats and Greyhounds: Exception, longer recovery
• Decreases intracranial pressure and cerebral metabolism of oxygen, anticonvulsant effects.
• Reasonable choice in patient with head trauma
• Decreases blood pressure (BP) due to vasodilation.
• Not a good choice for patients not hemodynamically stable
• Causes dose-dependent respiratory depression and transient apnea, often with cyanosis, rapid injection increases likelihood of apnea
• Produces muscle relaxation and transient myoclonus (uncommon).
• Crosses the placenta but is rapidly cleared from the neonate. Acceptable use in dogs for C-sections
• In Greyhounds, the same dose is needed for induction, but recovery time is longer.
• In cats caution with repeated daily use.
• Propofol28 is not recommended by the manufacturer for use in cats; however, studies show that administering to healthy cats does not cause organ damage.
• Rarely used for induction in horses due to excitation and volume/cost, can be bolus intra-op or CRI for smooth recovery
• Does not induce malignant hyperthermia in swine
• Offers smooth rapid induction with good quality recovery in small ruminants and camelids.
• Induction relies on titrating to effect over 60-90 seconds.
• Provides swift induction in 20-30 seconds.
• Be prepared to ventilate the patient.
• Recovery in about 2-12 minutes.
• Provides no analgesia.
• Can cause pain on injection, especially in smaller vessels.
• Lidocaine IV prior, or dilute, or ensure new IVC prior

Dissociative Anesthetics

• Characterized by the dissociation from thalamocortical (consciousness) and limbic systems (emotion and memory), which changes awareness.
• Act mainly via antagonist effects at the NMDA receptor, other MOAs involved as well
• Ketamine and tiletamine are commonly used.
• Telazol: tiletamine + zolazepam
• Available as a powder reconstituted with 5mL of NaCl or sterile water, 50 mg/ml of each
• Water-soluble (IV, IM, SQ, OTM, IN, rectally)
• Rapid onset
  • About 60 sec if IV
  • About 10 min if IM
• Short duration (7 to 23 min)
  • Telazol lasts 35-70 min
• Highly lipophilic (quickly crosses BBB)
• Metabolized by the liver, excreted by kidneys
• Cats form an active metabolite (nor ketamine) and excrete unchanged in urine (avoid if renal issues)
• Telazol metabolism differs between species. -Cats: zolazepam > tiletamine -Dogs: tiletamine > zolazepam
• Cause a cataleptic state (not asleep, but not responding to external stimuli)
• Emergence delirium (ataxia, hyper-reflexive, sensitivity to touch, increased motor activity)
• Direct negative cardiac inotropic effects are overcome by sympathomimetic effects.
• Increase BP, HR, cardiac output, myocardial oxygen requirements, and cardiac work.
• Inhibit NE reuptake (increased plasma catecholamines).
• Avoid in critically ill patients with decreased reserve, see decreased BP.
• Avoid in patients with severe CV disease or tachycardia/arrhythmias.
• Do not cause significant respiratory depression
  • cause "apneustic" respiratory pattern (prolonged inspiration and relatively short expiratory time, with several shallow breaths taken).
  • bronchodilation and decreased airway resistance.
• Pharyngeal and laryngeal reflexes remain, but always want to intubate to protect airway, increased salivation and respiratory tract secretion
• Musculoskeletal: cause muscle rigidity and even spontaneous movements (diminish with use of benzodiazepines).
• IOP can increase (increased tone of extraocular muscles).
• Cross placenta; avoid using in C-section patient
• Combine ketamine with benzo for induction.
• Can also use α2 agonist or opioid
• In cats, can spray into their mouth for IV sedation.
• Dissociatives in tigers caution seizure-like behavior
• Horses need to be adequately sedate before induction
  • Administer ketamine with benzo, α2 agonist, guaifenesin, smooth, but recovery rough
• Ruminants Combine ketamine with a benzo or guaifenesin
  • “ketamine stun” technique sub-anesthetic dose of both to keep animal standing
• Swine does not induce malignant hyperthermia
  • Telozol: Calm, slow recovery, not recommended for pot belly pigs due to prolonged recovery
• Ketamine given w benzos, alpha 2 agonists
• Ketamine given as CRI at sub-anesthetic doses to reduce inhalant requirements
• Ketamine and tiletamine are not reversible, other drugs are not reversed
• Oral, ocular, and swallowing reflexes remain intact; nystagmus is common
• Must provide lubrication so eyes stay open

Alfaxalone

• Newer schedule IV drug
• Older formulations were combined with castor oil, causing histamine release and anaphylactic reaction in dogs.
• The newer formulations are combined with non-cremophor vehicle and no longer causes histamine release, improved water solubility
• Alfaxan can be given IV and IM
• A clear, 1% solution with no antimicrobial preservative
• Alfaxan multidose product has a shelf life of 56 days after vial broached due to preservative (reduces microbial contamination)
• it binds to GABAA increasing Cl- conduction into cell, decreasing cell function
• P450 hepatic metabolism and elimination via kidneys and feces -Decreases CBF, ICP, and CMRO2, head trauma/ intracranial lesions
  • hemodynamic stability in clinically relevant doses, can cause dose-dependent hypotension because of vasodilation -Dose-dependent respiratory depression and/or apnea
• crosses placenta and can cause dose-dependent fetal depression safe choice for C-Sections
• Muscle relaxation
• Used commonly to maintain anesthesia
• acceptable induction agent transient paddling in cats excitment in dogs after use can cause rough recovery

Etomidate

• Available in a clear, 0.2% solution in 35% propylene glycol.
• The pH is 6.9.
• Insoluble in water.
• High osmolality - adverse effects
• Enhances action of GABA (inhibitory neurotransmitter) at the GABAA receptor, which increases Cl- conduction into the cell and leads to hyperpolarization of the postsynaptic neuron, causes CNS depression and hypnosis
• Fast recovery that is safe for patients with renal/hepatic metabolism abnormalities
  • Rapid penetration of the brain for quick induction.
  • Rapid redistribution to inactive tissue for fast recovery after single bolus (5-12 min).
  • Has a large therapeutic index.
  • Undergoes metabolism by the liver and plasma esterases and is excreted in the urine.
• Has cerebroprotective effects, vasoconstriction, and decreases incranial pressure
• minimal to no changes in vitals can handle unstable, even in hypovolemic individuals
• Causes adrenocortical suppression for up to 6 hours in dogs and 5 hours in cats
• Not for the stressed

Inhalants

• Mask or chamber inductions may be needed for exotics, or very aggressive patients
• Caution due to exposure and harming personnel
• Masking down and box inductions not standard in care

Drug Combo

• "opioid induction" (ex. Fentanyl + benzodiazepine)
• Ketamine + propofol ("ketofol")
• Guaifenesin + ketamine ("double drip")
• Guaifenesin + ketamine + xylazine ("triple drip")
• Guaifenesin + thiopental
• Propofol + thiopental
• Ketamine + xylazine (or dexmedetomidine for SA: or detomidine for LA)
• Telazol + ketamine + xylazine or dexmedetomidine (“TKX" or "TKD")
• Ketamine + alfaxalone