Ron Mandsager, DVM, DACVA
4/3/03

Local Anesthetics

Advantages of local anesthesia

• Minimal equipment needed
• Minimal systemic effects

Disadvantages of local anesthesia

• Requires cooperative patient &/or significant restraint
• May require sedation, w/ resultant systemic effects

Classification of Nerve Fibers

• A (myelinated)
  • - motor
  • - touch and pressure
  • - muscle spindle
  • - pain
• B (myelinated; autonomic – preganglionic sympathetic)
• C (non-myelinated; pain & temperature)

Rate of Transmission dependent on:

• Diameter of axon
• Presence or absence of myelin sheath
• Order of Blockade and Recovery
• Sensation lost in the following order:
  • Pain
  • Cold
  • Warmth
  • Touch
  • Joint
  • Pressure

Mechanism of action

• Local anesthetics prevent the rapid influx of sodium ions into nerve axons, thus preventing the production of an action potential – the site of action is the sodium channels in the nerve membrane

Pharmacokinetics

Absorbtion

• faster the absorbtion rate, the shorter the duration of action, and the greater the potential for systemic toxicity. Epinephrine may be added to provide local vasoconstriction and reduce the rate of absorbtion, thus prolonging the duration of action. Local anesthetics are effective when applied to mucous membranes or to the cornea, but are ineffective when applied to intact skin. EMLA cream is an exception to the rule – it is a eutectic mixture of prilocaine & lidocaine that is effective when applied topically to intact skin.
• Distribution of local anesthetics at injection sites depends primarily upon the volume injected.  Hyaluronidase may be added to enhance spread of local anesthetic through tissues.

Metabolism

• occurs primarily in the liver & lungs, with excretion of metabolites via bile & urine.

Toxicity

• Toxic effects of systemic overdose usually produce either CNS effects (seizures) or cardiovascular effects (arrhythmias/cardiovascular collapse)
• Usually treatable if noted in time; seizures are treated w/ benzodiazepines, thiobarbiturates, or propofol. Cardiovascular collapse is treated symptomatically (fluid expansion, adrenergic agonists, cardioversion, oxygen, sodium bicarbonate)

Local anesthetics available

• Classification by drug type
  • Esters
    • Cocaine
    • Procaine
    • Chlorprocaine
    • Tetracaine
  • Amides
    • Lidocaine
    • Mepivicaine
    • Dibucaine
    • Bupivicaine
    • Ropivicaine
    • Etidocaine
• Classification by duration of action
  • Short acting
    • Procaine: 60-90 minutes, slow onset
    • Chloroprocaine: 30-60 minutes, fast onset
  • Intermediate acting
    • Mepivicaine: 120-240 minutes, fast onset
    • Prilocaine: 120-240 minutes, fast onset
    • Lidocaine: 90-200 minutes, fast onset
  • Long acting
    • Tetricaine: 180-600 minutes, slow onset
    • Bupivicaine: 180-600 minutes, intermediate onset
    • Etidocaine: 180-600 minutes, fast onset
• Types of local anesthesia
  • Surface/topical – apply local anesthetic directly to surfaces of tissues; only effective in areas covered by mucous membrane or on cornea
  • Infiltration – apply local anesthetic diffusely in the area of the surgical incision; potentially can interfere w/ wound healing, potential for overdose
  • Regional – perineural application of local anesthetic; desensitizes area supplied by the specific nerve(s)that is/are being blocked
  • Intraarticular – apply local anesthetic into a joint cavity; desensitizes the joint
  • Intravenous regional (Beer Block) – deposit local anesthetic in a vein distal to a tourniquet, desensitizes area distal to the tourniquet

Neuromuscular Blocking Agents or Relaxants

General considerations

• produce skeletal muscle relaxation
• only used in conjunction with other anesthetic agents
• NO ANALGESIA OR HYPNOTIC EFFECTS
• complete respiratory muscular paralysis is likely with peripheral neuromuscular blocking agents:  you must be prepared to provide respiratory support!
• effects potentiated by most anesthetic agents

Normal neuromuscular transmission

Anatomy of the motor end-plate

• resting state:  random release of acetylcholine "packets" -> produce "mini-endplate potentials" (MEPP's)
• neuronal action potential depolarizes nerve terminal of motor neuron, releasing many acetylcholine "packets" (Ca⁺ dependent process)
• acetylcholine interacts with nicotinic type IV cholinergic receptors on muscle endplates; if sufficient number of receptors are stimulated, endplate potential (EPP) develops and muscular contraction occurs

Mechanism of action

• central
  • depress neuromuscular transmission through spinal polysynaptic pathways (internuncial neurons) that maintain normal skeletal muscle tone
• peripheral - presynaptic
  • inhibit acetylcholine synthesis (e.g. hemicholinium -> block choline uptake)
  • inhibit acetylcholine release (e.g. Ca⁺ deficiency, procaine, tetracyclines, aminoglycoside antibiotics, botulinum toxin)
• peripheral - postsynaptic
  • depolarizing:  persistent depolarization of motor endplate by an agonist with a longer duration of action than acetylcholine (e.g. succinylcholine)
  • nondepolarizing:  competitive blockade of acetylcholine receptors; prevents depolarization of motor endplate (e.g. pancuronium, atracurium, vecuronium)

Classification of agents

• central acting
• guaifenesin
• benzodiazepines
• peripheral neuromuscular blocking agents:
  • Depolarizing:
    • succinylcholine
  • Nondepolarizing
    • d-Tubocurarine Cl
    • gallamine
    • pancuronium
    • vecuronium
    • atracurium

Depolarizing vs. Nondepolarizing agents

• depolarizing agents produce transient muscle fasiculations, followed by relaxation; paralysis is terminated by metabolism of the agent by pseudocholinesterase
• nondepolarizing agents do not cause fasiculations, effects can be reversed by anticholinesterase agents

Specific agents

• Guaifenesin  (Glyceryl Guaiacolate Ether, GGE, Gecolate^®, Guailaxin^®)
  • used primarily in equine and food animal anesthesia
  • used as an adjunct to induction and/or anesthetic maintenance
  • prepared as a 5 to 10% solution
  • solutions >15% cause hemolysis
  • irritating:  perivascular slough can occur if accidentally injected perivascularly
  • minimal (if any!) cardiopulmonary effects
  • very large doses may cause apnea (rare)
  • will accumulate if administered for prolonged period (hours); results in greatly prolonged recoveries
• Succinylcholine
  • currently, rarely used in veterinary anesthesia
  • provides short (2-5 min.) of blockade in most species
  • lasts 15-20 min. in dogs
  • cardiac arrhythmias may be seen (brady- or tachyarrhythmias)
  • histamine release possible
  • contraindications:  liver disease, anemia, cachexia, ­ K⁺, organophosphates, penetrating eye injuries, burns, severe muscle trauma, tetanus, muscle denervation, spinal cord section, brain damage & stroke
  • In patients w/ burns, severe muscle trauma, tetanus, muscle denervation, spinal cord section, brain damage & stroke, there are increased #s of acetylcholine receptors w/in muscle tissue - this provides increased numbers of ion channels, allowing for greater release of K+ w/ administration of succinylcholine - risk hyperkalemia
  • Historically has been used alone for castration of horses - no longer considered an acceptable means of restraint
• d-Tubocurarine
  • 1^st non-depolarizing neuromuscular blocker used
  • rarely used in veterinary anesthesia
  • ganglionic blockade @ high doses ® hypotension
  • histamine release
  • long acting (30 - 90+ min)
  • hepatic metabolism and renal excretion used for elimination
• Gallamine
  • another old neuromuscular blocker
  • rarely used in veterinary anesthesia
  • tachycardia, hypertension can be seen
  • no histamine release
  • long acting (30 - 90+ min)
  • 100% renal excretion: DO NOT use in renal disease!
• Pancuronium (Pavulon^®)
  • minimal cardiovascular effects - although potentially can stimulate release of norepinephrine, resulting in increased heart rate & blood pressure
  • no histamine release
  • moderate duration (15-45 min)
  • primarily eliminated through the bile
  • relatively inexpensive
• Vecuronium (Norcuron^®)
  • minimal cardiovascular effects
  • no histamine release
  • short to moderate duration (15-30 minutes)
  • hepatic and renal excretion
  • packaged as a powder, limited shelf life when reconstituted
  • expensive
• Atracurium (Tracrium^®)
  • minimal cardiovascular effects
  • slight histamine release @ very high doses
  • short to moderate duration (15-30 min)
  • recovery from block due to metabolism by nonspecific plasma esterases and "Hoffman degradation" (falls apart at body temp. and pH!)
  • RENAL AND HEPATIC DISEASE DO NOT AFFECT DURATION OF BLOCK!
  • noncumulative
  • must keep refrigerated
  • expensive (but better than vecuronium)
  • currently, my neuromuscular blocking agent of choice!
• Pipecuronium
  • long acting analog of pancuronium
  • primarily renally excreted
• Doxacurium
  • long acting
  • elimated unchanged in urine & bile in cats
• Mivacurium
  • short duration of action due to rapid hydrolysis by psuedocholinesterase
• Rocuronium
  • rapid onset, short duration of action

Reversal of neuromuscular blockade

• reverse nondepolarizing neuromuscular blockers with anticholinesterase drugs (physostigmine, pyridostigmine, neostigmine, edrophonium)
• these agents increase the amount of acetylcholine available (by slowing degradation of acetylcholine) to compete with the neuromuscular blocker at the motor endplate
• do not use with depolarizing neruomuscular blockers; will exacerbate blockade!
• anticholinesterase drugs produce both muscarinic and nicotinic cholinergic effects: prevent the muscarinic effects (bradycardia, salivation, defecation, etc…) with an anticholinergic drug

Drug interactions

• blockade potentiated by aminoglycoside antibiotics, tetracyclines
• hypothermia potentiates blockade
• respiratory acidosis (hypoventilation) potentiates blockade
• increased K⁺, Ca⁺ potentiates blockade

Monitoring Neuromuscular Blockade

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© 1996-2003, Oklahoma State University College of Veterinary Medicine, all rights reserved Last modified October 19, 2007 by Ron Mandsager, DVM, DACVA Questions? Comments? Contact me at aerrane@okstate.edu

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