Question 19

College Answer

Most questions lacked a systematic approach to the question and specific detail. The relationship between systemic toxicity (CNS and CVS) and plasma levels should be described. Many candidates did not clearly state that CNS toxicity occurs at lower plasma levels that CVS toxicity. Factors that affect toxicity (e.g. drug factors, patient factors, interactions) needed to be elaborated with some detail. Patient factors such as age, pregnancy, acidosis, hyperkalaemia, hepatic failure were often omitted. Finally, marks were also awarded for noting methaemoglobinaemia as possible toxicity and the existence of specific therapy (intralipid).

Discussion

• Clinical features of local anaesthetic toxicity:
  • Central nervous system effects:
    • Occur at lower concentration than cardiovascular effects
    • At lower doses:
      • Visual disturbances (resembling nystagmus)
      • Perioral numbness
    • At increasing doses:
      • Slurred speach
      • Incoherent conversation
      • Confusion and decreased level of consciousness
    • With very large doses:
      • Seizures
      • Coma with EEG features of non-convusove status or burst suppression
  • Cardiovascular effects:
    • Require approximately 3 times as much dose as CNS effects
    • Some agents (eg. bupivacaine) are particularly cardiotoxic
    • Lower dose effects are sympathomimetic:
      • Hypertension
      • Vasoconstriction
      • Tachycardia
    • Higher dose effects:
      • Hypotension (systemic vasodilation) 
      • Bradycardia and heart block
      • QRS prolongation, arrhythmias, cardiac arrest
  • Other effects:
    • Methaemoglobinaemia (prilocaine only)
    • Allergy (to ester metabolites or preservative excipents)
    • Myonecrosis from IM injection

• Patient risk factors for local anaesthetic toxicity:
  • Acidosis (decreased protein binding, increased availability of active ionised form of agent)
  • Old age: slower clearance, more cardiofragile
  • Young age: lower α₁-acid glycoprotein level, higher free fraction
  • Pregnant patients: lower α₁-acid glycoprotein level, better perfusion of blocked tissue
  • Hyperkalemia (decreased toxic dose of agent)
• Pharmacological factors which contribute to local anaesthetic toxicity:
  • Dose (obviously)
  • Choice of agent (some drugs, eg. bupivacaine, have a lower CC/CNS ratio)
  • Site of administration (eg. closer to large vessels, hyperaemic site, epidural)
  • Coadministration of vasoconstrictor (slows systemic absorption)
  • Slower dissociation from sodium channels (eg. bupivacaine)
  • Drug interactions:
    • displacement from protein binding (eg. by phenytoin)
    • decreased metabolism (eg. by cimetidine)
• Management of local anaesthetic toxicity:
  • Alkalinise or hyperventilate:
    • Increase protein binding
    • Decrease charged fraction (active and capable of binding sodium channels)
  • Increase the distribution into lipid:
    • Give intralipid emulsion to increase lipid-bound fraction and decrease free fraction

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