Veterinary Anesthesia: Drugs and Pre-meds

Practice Quiz & Key Drugs

• Acepromazine is a tranquilizer without a reversal agent and causes enlargement of the spleen
• Midazolam has the benefit of being water soluble and can be administered via IM
• Methadone has effects as an NMDA antagonist
• Atropine is an anticholinergic that should be used quickly in emergencies
• Atipamezole (antisedan) is a reversal agent for dexmedetomidine
• Xylazine is a shorter acting alpha 2 agonist most often used for equine practice
• Butorphanol is a kappa agonist and mu antagonist
  • This blocks the mu receptor from opioid drugs, preventing them from binding
• Acepromazine causes vasodilation and potential hypotension through alpha 1 antagonism
• Benzodiazepines will likely cause pain relief rather than reliable sedation in dogs/cats
• Simbadol is an FDA-approved drug for cats containing butorphanol
  • It is administered SQ every 24 hours

Pre-meds & Neuroleptanalgesia

• Pre-meds offer synergistic effects, resulting in enhanced outcomes using less drugs
• Neuroleptanalgesia combines a sedative and analgesic drug together
  • Examples are acepromazine with Fentanyl or dexmedetomidine/butorphanol/ketamine, also known as "kitty magic"
• FARAD is a resource for meat and milk withdrawal times in food animals

Considerations with Drugs

• Greyhounds metabolize propofol differently, which prolongs recovery time
• With cats and propofol, hyperthermia may be a side effect when combined with hydromorphone
• Ketamine is normally paired with a benzodiazepine such as diazepam or midazolam
• Be cautious using Etomidate in patients with Addison's or those highly stressed

Inhalants vs Intravenous Anesthesia

• Inhalants (ISO vs SEVO) utilize oxygen containers, CO2 absorption canisters, and ETT tubes
  • ISO is less reactive, more potent, has a lower MAC, and causes respiratory depression and hypotension
  • SEVO offers lower blood-gas parturition, good muscle relaxation, but can trigger malignant hyperthermia
  • SEVO mask induction has less odor, but can degrade by CO2 absorbents to produce compound A
  • Inhalants decrease cerebral metabolic rate, decrease BP and ventilation due to increased CO2
• TIVA is total intravenous anesthesia, which is limited to one hour due to prolonged recovery times
  • Supplemental O2 is still needed for TIVA
  • An example is the "triple drip" of ketamine, xylazine, and guaitenesin for equine castration
  • IV automatic flow meters, catheters, fluids, and syringes are used in TIVA
• PIVA is partial intravenous anesthesia such as MLK with reduced ISO for canine TPLO

Determining Anesthesia Methods

• Properties to determine method of administration include boiling point and liquid density
• Vapor pressure is the measure of the ability to evaporate
  • Increased temperature means more molecules become liquid/gas = higher vapor pressure
• Vaporizers control the amount of anesthetic delivered by pass and vaporizing chamber
• Properties determining kinetics in a patient involve gas solubility
  • Low blood/gas partition reaches the brain more quickly, like with SEVO
  • High blood/gas partition means it has longer reach to the brain and has an increased induction period
  • High oil/gas partition crosses the BBB more easily and has increased potency, which is preferred with MAC sparing
  • Low oil/gas partition requires higher concentration to reach the brain

Alveolar Anesthetic

• Change in alveolar anesthetic tension depend on increased alveolar delivery and decreased alveolar removal
• Increased alveolar delivery is increased by:
  • Increased inspiration
  • Increased concentration vapor
  • Increased vapor dial
  • Increased O2 flow rate
  • Decreased gas volume of P breathing circuit reduces dead spaces
• Increased Alveolar ventilation
  • Includes increased minute ventilation and decreased dead space ventilation
• Decreased alveolar removal keeps a patient asleep and depends on:
  • Decreased blood solubility (SEVO)
  • Decreased CO2
  • Decreased alveolar-venous anesthetic gradient

Other Anesthetic Implications

• Anesthesia can cause prolonged recovery
  • Higher anesthesia in alveoli as compared to blood
• Do NOT administer Guaifenesin outside of the vein due to its potential to cause tissue necrosis
• Inhalant anesthetics are metabolized in the body in the following percentages:
  • HALO = 20-46%
  • SEVO = 2-5%
  • ISO = 0.2%
  • The rest gets eliminated through the lungs

MAC & Considerations

• MAC(minimum alveolar concentration) is the concentration of inhaled anesthetic at 1 atm that results in immobility in 50% of patients exposed to supramaximal noxious stimulus
• MAC is inverse with potency
  • HALO with increased potency = decreased MAC so need LESS drug to anesthetize
• Do not include pre-meds in calculation
• ED95 = 1.2 - 1.4 (95% patients anesthetized)
• Surgical anesthesia = 1.5 MAC (multiply times inhalant)
  • Preferred ISO: 1.3
  • SEVO: 2.3
• Factors that increase MAC:
  • Hyperthermia
  • Increased CNS stimulation
  • Increased metabolic rate/stress (Cushings, hyperthyroidism)
• Factors that Decrease MAC:
  • Hypothermia
  • Drugs that cause CNS depression
  • Geriatric patients
  • Pregnancy
  • Hyponatremia
  • Disease
  • BP < 50 mmHg

Loading Doses & Gene Mutation

• Loading doses increase the amount of circulating drug to reach a therapeutic window
  • Not necessary to give continuous doses
• MDR1/ABCB1 gene mutation affects herding-breed dogs
  • It affects the gene coding for P-glycoprotein, which influences the BBB
  • Defect allows drugs such as Butorphanol and Acepromazine to penetrate the BBB, prolonging recovery
  • Adjustment involves decreasing the normal dose by 25-50%

Balanced Anesthesia, Analgesia & Fluid Management

• Balanced anesthesia: simultaneous drug/technique to produce stable anesthetic plane
• Multimodal analgesia: Uses more than 2 drugs/techniques to manage pain.
  • Examples include morphine/lidocaine/ketamine/MLK and dexmedetomidine/MLK/DMLK
• • NEVER administer glucocorticoids at the same time as NSAIDS
• Lidocaine can treat ileus, impactions, inflammation, laminitis, and post-opt pain in horses when carefully managed for 1-3 days to prevent overdose
• Alpha 2 induced bradycardia results from increased systematic vascular resistance with decreased sympathetic tone
  • Examples include Xylazine, detomidine, and dexmedetomidine

Species & Water Considerations

• Kangaroo rats don’t drink water because they consume increased foods that have it
• Fluid overload easily occurs in cats
• Fluid therapy began to combat the cholera epidemic
• The spleen in horses autoinjects 2-3 liters of blood into the vascular system, where half of the water is contained
  • Because of this horses can last longer without water (8-9 days)
• Fluid overload = >10% increase in BW
• 95% plasma (w/o RBCs) = H2O
• Organ results with fluid overload include pulmonary, gut, cerebral, and myocardial edemas with hepatic congestion, increased renal venous pressure, and impaired lymphatic drainage

Fluid Flux & Edema Control

• Blood volume is = 8% of BW
• Transvascular fluid flux depends on:
  • Capillary colloid osmotic pressure (albumin protein pulling water)
  • Capillary hydrostatic pressure
• The endothelial glycocalyx is a "gatekeeper" that prevents fluid leakage, maintains fluid balance, prevents edema, and maintains vascular permeability
• The interstitium is a series of fluid-filled spaces made of flexible connective tissue ("slinky") that "stretches” when fluid is added and condenses when fluid is reduced
  • Normal is -2 to -3 mmHg
  • Inflammation with excess causes -10 to -20 mmHg which is indicative of regulatory mechanism issue
• IV fluids reduce hypotension while excess fluids cause slow exchange associated with distribution and elimination
  • This can cause "over-stretching” of interstitium

Fluid Goals

• The goal of fluids is to:
  • Prevent/treat dehydration when > 5% BW

    • 5-6% BW shows clinical signs of hyperkalemia and acidosis

  • Prevent/treat hypovolemia when > 15-20%
  • Maintain hydration at 30-60 ml/kg/day
  • Treat hypotension when < 60 mmHg
  • Support acid-base balance
  • Replace electrolytes
  • Provide calories, 50-100 cal/kg/day
  • Provide ** access to vein **
• Be cautious when using excess fluid to treat patients who are dehydrated --Treat them, but slowly, over 16-36 hours = NaCl, colloids

Canine Anesthesia Problems

Majority issues in dogs with anesthesia are:

• Arousal and break through PAIN (15%)
• Hypoventilation (14%)
• Hypotension (10-15%)
  • A measure of “Quality of Anesthetic Care”
  • Results from disturbed homeostatic reflexes, hypothermia, hypercarbia, acidemia, hyperkalemia, arrhythmia, and sepsis
• Arrhythmia
• Temperature Mechanism that anesthesia uses to create hypotension is:
• Increased circulating volume from arteries to veins (relative hypovolemia) due to maldistribution of fluids as result of vasodilation of veins
• Veins typically carry 70% blood volume, while arteries usually carry 10% Compensation to hypotension:
• Body decreases arterial pressure; this removes baroreceptor reflex and reduces cardiac stimulation/vasoconstriction
• Body alters blood gases which removes chemoreceptor reflexes Eventually there is loss of lymphatic return
• Give K+ within fluids in acute situations
• Treatment should be administered at the “golden hour"
  • ex) splenic entrapment treated with alpha 1 agonist
• 45 mmHg indicates the circulatory system begins removing organ functions, beginning with the kidneys then the gut

Hypovolemia Types

• Can progress to where the animal can no longer compensate

• 10-15% blood volume lost = animal not able to compensate

• 15 -30% Lost is the danger zone which progresses to, Class II blood loss, Hypovolemia, Hypotension
• Urine output decreases to < 1.0 ml/hr.

Fluid management during anesthesia Colloid osmotic pressure: soluble molecules (ex- plasma proteins) exert osmotic pressure

Fluid Characterizations and Distribution

• TONICITY: ability of water to move in or out of a cell with osmosis
• Colloid- Colliod osmotic pressure: albumin exerts pressure that is higher than 30-40kDa.
  • Stays in the bloodstream longer than other fluids because they are too big to leave. Therefore, they block the other molecules from leaving, too. Avoids inadequete or excess fluids.
  • Not often given to humans, because of allergic reaction
  • WATER is better than colliods, but it must have something that has water, to not harm the animal. DRUG: Substance has a phisological affect, and is produced in the body
• • ex. FLUIDS as change electrolytes, osmolarity, tonicity, viscosity, and acid-base balance. CRYSTALOID, salt (etc.) solutions which contain small molecules, but may also contain glucose or lactate in water. - saline, invented by Hamburger. A high amounts of NaCl can make the animal acidosic. -balanced solution electrolytes, most plasma is that! -plasma is a blood donor that contains electrolytes and buffers
• -colliods are a bio-theraphy Hydroxyethyl starch and polyethylene, are not the most given today
• normal animal plasma= 300m0/L the distribution of liquid

Bolus Management

• Groups that react first to bolus increasing cardiac output
  • Vessel poor group
  • Fat Group Rate/timing of fluid therapy
• Rate determines shock or overdose
• Volume: increased volume is given more than a longer period because of time 40-60ml is norm. 80-90ml increase death of heart attacks

Spacing & Overload

Third Spacing= FLUIDS ARE NOT HELPING THE ANIMAL fluids building in parts that are not in the bodies Compartment, so they are not being nourished.

• Perfusion is an indicator of hypovolemia, NOT THE FLUID AMOUNTS
• Maintaining Certain pressure does not prevent fluids
• Measure BP in the arteries!
• Overal Guiding therapy leads to over-feeding with water

Pulses & Vasoplegia

• Overall, the importance lies in the administration is not used to moniter fluid balance
• Best WAY to excess fluid is to SPO2, increases pulses.

Pain Sensations

• Most Common is ICE , to slow the pain and sensations reaching to brain, to perceive pain for different things.
• PAIN: potential damage for the sensations.
• Sensations of physiology detects pain
• -trandcution caried by the sords transmission: through the chords of the spine
• nociecption nervous system and encodes Stimuli
• the cell can process psychological pain but it is damaging.

Receptors & Pain Channels

• Receptors within all organisms , like inner organs detect changes through
• Activate G-protein-coupled receptors or channel
• Protective warnign system is pain pesist, silent receptors of be would expeessed. ex) Allodynia, periphery sensation or cetral sentations through the wounds and becoming painful alpha dentinal fibers make the neurons and are important for keeping the body alive through the nerve c-fibers cause a dull pain
• sentization mediations

Pain Plasticity

• The changes and amplifies, in a way
• Central sntation has a assciations with chrnoic paims
• infection inflmation is casued though
• SILENT pain receptor: only actiavte if signifcant damage
• Limbic system :behavior and best indicator
• Hippocampus : memory
• Amygalda : for and behavior
• septal are : emotions

Hypothalmus: hemo-stasis

• locus coeruleus: large parts of pain are not reaching the brain -activated during stress

Pain & Sensitization

• Pathologic pain caues - amplifies and amplifes the painful stimulus that is created throufgp chrinic pain- fibromyalgia.
• Central entiatzion increase spinal cord and the activiation of NMDA receptor

Glial Pain

• glial cells : increases exicablty of nerve system. contributes too euro-imflimation

Hypersensitivity Types

• Difference between result of Peripheral vs. central Sensitization
• Peripheral - allodyna non pain-sensitive
• central-hyperalgesia has a high sensitivity to pain
• Increased stress increased pain as increases central stimulation and

Disinhibition

• IN inhibition through: Chronic pain, or when GABA and glycine are not there.

Comatting Desention

• GABA: binds to receptors and reduces pain

Nociception Modulation

• nocieption modulates: glutamate : inhibits pain signals.
• SNRI- sertonitin: reduces the pain of muscle system due to the inhibitor.

Collateral Sprouting: leads to chronic pain adaptive immunity: sends signals that are hyperalgesia

Surgery Pain

• malpractice- doe snot promote healing and repair
• Normally not trating acute pain due to waiting for long
• traniste to persist pain

Worst Visceral Pain

• Affects symmetric NS and decreases appetite Pain: test assess VISUAL, behavior. Numerical 100 is worrst
• Grimace gaining populatitly
• Multimodel analgesic: use method to control the pain
• multimodal analgesic: synergism
• analgesic effects with effects overalls!
• Alpha 2 is not important because it increases the seizures
• Normally combine+ + alpha 2 agonist Gallium is a treatment of ep4 receptors

Review of key drugs used in veterinary anesthesia, including acepromazine, midazolam, methadone, and atropine. Focus on mechanisms of action, reversal agents, and clinical considerations. Also, covers pre-medications and neuroleptanalgesia.