Local Anaesthesia 2

• Absorption of LA:

  • All LA eventually ends up in blood stream to be metabolised
  • Rate of entering blood stream depends upon:
  • The drug
  • Dose - volume and concentration
  • Route/site of administration
  • Presence of vasoconstrictor
• Rate of entering blood stream depends upon:

  • The drug
  • Vasodilatory ability; if it's high then it'll enter the blood stream quicker
  • Protein binding capacity; if it's protein-bound then it will take longer to enter the blood stream
• Rate of entering blood stream depends upon:

  • Dose - volume and concentration
  • Higher volume or concentration will take longer to enter the blood stream
• Rate of entering blood stream depends upon:

  • Route/site of administration
  • PDL and intraosseous injections are equivalent to IV administration - therefore enter the blood stream v quickly
  • Vascularity of the tissue
  • Areas of high vascularity (eg where there's an infection) will have LA enter the blood stream quicker
• Rate of entering blood stream depends upon:

  • Presence of vasoconstrictor
  • If vasoconstrictor is present, it'll enter the bloodstream more slowly
• Distribution of LA:

  • Once in circulation LA is partially bound to plasma proteins and red blood cells
  • Unbound portion free to enter any organ
  • Not inhibited by barriers to diffusion, therefore will cross blood-brain barrier and placenta
  • Highly perfused organs will receive higher levels of LA
  • Brain, liver, kidneys
• Metabolism of LA depends on the LA classification.
• Metabolism of esters:

  • Metabolised rapidly in the blood by pseudocholinesterase enzymes
  • Also undergo some hydrolysis in the liver
  • Metabolites are non-active
  • So when it's broken down, the remnants of the drug will no longer have any pharmacological effect
  • Major metabolite is para-aminobenzoic acid (PABA) - most ester allergies are in response to this
  • 1 in 2800 lack pseudocholinesterase, so will be unable to metabolise ester anaesthetics - these patients will have sux apnoea and risk of ester overdose

  
• Metabolism of amides:

  • Amides are used more commonly in dentistry now rather than esters
  • More complex than esters, therefore longer half life
  • Primary state for most is the liver - metabolism process involves: dealkylation, hydrolysis, further dealkylation, and conjugation
  • Metabolites are active - therefore can possess LA and sedative properties
  • Prilocaine partly metabolised in lung (as well as in liver)
  • Articaine also undergoes hydrolysis in plasma by pseudocholinesterase (like in the metabolism of esters)

  
• Excreation:

  • Via kidney
  • <3% excreted unchanged in urine
• Metabolism of adrenaline:

  • Appears in systemic circulation rapidly - peak plasma levels couple of mins after intra-oral injection
  • Adrenaline undergoes methylation by COMT enzyme
  • Transported to liver for deamination
  • Conjugated with sulphate
  • Excreted in urine
  • 1% excreted unchanged in urine

  
• Unwanted effects of LA:

  • LA is not specific to peripheral sensory nerves - will effect any excitable tissue they come into contact with
  • Therefore can effect CNS and CVS
  • Toxicity:
  • Inability to metabolise - medical history
  • Too large a dose
  • Intravascular injection - aspirate
• LA toxicity:

  • If you delivered a cartridge of lidocaine intravascularly...
  • Entire 2.2ml cartridge contains 44mg of lidocaine
  • Average, healthy adult has 3.5 litres of plasma in their body
  • Therefore there would be 12.6mg of lidocaine per litre of blood in their circulation
  • 64% of the lidocaine will be protein bound though, but that still leaves 4.5mg of active lidocaine per litre of plasma in the systemic circulation
  • The central nervous system toxicity of lidocaine in a fit and healthy adult is 5mg/L, so this would be just under the toxic dose

  
• LA toxicity:

  • If you delivered a cartridge of lidocaine intravascularly to a child pt...
  • Entire cartridge still has 44mg of lidocaine
  • That means there would be 29mg of lidocaine per litre of plasma
  • 64% of the lidocaine will still be protein bound, but that means that there will still be 10mg of active lidocaine per litre of plasma in the child's systemic circulation
  • And with the central nervous system toxicity of lidocaine being 5mg/L, that would be double the toxic dose
  • Therefore very important to ASPIRATE!

  
• Toxicity:

  • 2.2ml cartridges only in UK; helps to easily calculate maximum dose
  • 44mg lidocaine/cartridge
  • Maximum dose = 4.4mg/kg
  • Therefore 1/10th  cartridge/kg
  • Or 1 cartridge per 10kg
  • Ceiling dose 500mg, approximately 11 cartridges
  • Should never give more than this, regardless of what patient weighs
• Adult vs child:

  • Adult - 70kg
  • 7 cartridges
  • 5 year old child - 20kg
  • 2 cartridges!
• Liver disease:

  • Important to enquire about in medical history because...
  • Liver is the major site of metabolism of LA, and produces plasma cholinesterase enzyme (required for ester and articaine metabolism)
  • Impaired liver function -> relative LA overdose
  • These patients will have an LA overdose at a lower dose than you'd expect
  • Liver disease:
  • Dose reduction - don't give these patients as much as you typically would
  • Severe disease - consult with physician before giving them any LA
  • Elderly:
  • Liver function decreases with age
  • Over 65 - care with dose
• What happens if you give too much LA: no anaesthesia -> local anaesthesia -> early toxicity -> general anaesthesia -> death

  
• CNS toxicity:

  • At low dose - excitatory:
  • This happens because LA blocks inhibitory activity in CNS, therefore will get excitatory response instead
  • Eg involuntary muscle activity
  • At high dose - inhibitory:
  • Because CNS becomes overwhelmed with LA, so both inhibitory and excitatory activity is blocked
  • Depressant effect, which leads to unconsciousness, which leads to respiratory arrest
• CVS toxicity:

  • Direct action on CVS
• CVS toxicity:

  • Direct action on CVS
  • Indirect action via disinhibition of autonomic nerves
  • Depressant action on heart
  • Toxicity results in reduced cardiac output and circulatory collapse
• LA toxicity - initially:

  • CNS effects - dizziness, sedation, anxiety
  • CVS effects - increased heart rate and blood pressure
• LA toxicity - then:

  • CNS effects - confusion, slow speech, drowsiness, shivering
  • CVS effects - cardiac instability
• LA toxicity - finally (at v high doses - basically toxic):

  • CNS effects - seizure, coma
  • CVS effects - cardiac arrest
• Toxicity risk reduced by:

  • Limiting dose
  • Avoiding intravascular injection - ASPIRATE!
  • Injecting slowly - gives time to monitor patient/look for early signs of toxicity

  
• Treatment of LA overdose:

  • Stop procedure
  • Get help (call ambulance), remember ABCDE (always prioritise one before moving on to the next)
  • Airway
• Treatment of LA overdose:

  • Stop procedure
  • Get help (call ambulance), remember ABCDE (always prioritise one before moving on to the next)
  • Airway
  • Breathing
  • Circulation
  • Disability
  • Exposure
  • Lie pt flat
  • Maintain airway (with a head tilt, chin lift)
  • Administer high-flow oxygen
  • Basic life support
  • IV anticonvulsants, IV lipid emulsion and IV fluids would ultimately be given to the patient, but not by the dentist
• Adrenaline:

  • Toxicity - rare
  • Idiosyncratic reactions are more common
  • Pts are slightly more susceptible to the effects of adrenaline and may report feeling palpitations in response to the small amount of adrenaline in LA cartridge
  • Drug interactions
• Signs of adrenaline overdose:

  • Fear
  • Anxiety
  • Restlessness
  • Headache
  • Trembling
  • Sweating
  • Weakness
  • Dizziness
  • Pallor
  • Respiratory difficulties
  • Palpitations
• Treatment of adrenaline overdose:

  • Stop procedure
  • Get help, remember ABCDE
  • Place in semi-supine or erect position - minimise increase in cerebral blood pressure
  • Reassure pt
  • Administer oxygen if not hyperventilating
  • Unlikely to see an adrenaline overdose because amount in dental LA cartridges is so low
• Drug interactions with adrenaline - CNS drugs:

  • Tricyclic antidepressants
  • Decrease re-uptake of adrenaline into nerve cells
  • Pressor effects of adrenaline are therefore doubled
  • So limits dose of LA with adrenaline in anyone taking tricyclic antidepressants (eg 2-3 cartridges)
  • Monoamine oxidase inhibitors
  • Monoamine oxidase enzyme present in later stage in breakdown of adrenaline
  • Therefore of little concern in terms of dangerous drug interactions with adrenaline
  • Entacapone/tolcapone
  • Anti-parkinsonians
  • COMT antagonists
  • No evidence of clinical interaction but limit dose

  
• Drug interactions with adrenaline - cardiac drugs:

  • Beta blockers
  • Beta-adrenergic effects blocked by beta-blockers
  • Therefore if you give them adrenaline, they'll have unopposed alpha-adrenergic effects
  • This leads to an increase in systolic blood pressure
  • Puts pt at risk of cardiovascular accident (CVA) - i.e. a stroke
  • Limit dose to 2-3 cartridges of LA containing adrenaline
• Drug interactions with adrenaline - cardiac drugs:

  • Diuretics
  • Adrenaline decreases plasma potassium
  • Therefore this can be exaggerated in patients taking non-potassium-sparing diuretics
  • Leads to hypokalaemia (low plasma potassium level)
  • Limit dose to 2-3 cartridges of LA containing adrenaline
• Drug interactions with adrenaline - drugs of abuse:

  • Amphetamines, cannabis, cocaine
  • All of these can increase adrenaline toxicity
  • Avoid using LA containing adrenaline for 24 hours, if possible, if patient had taken any of these drugs
  • Otherwise limit dose to 2-3 cartridges
• Oxytocic action felypressin:

  • To induce labour need 0.025 units of oxytocin activity
  • A dental cartridge contains 0.00021 units of oxytocin activity
  • Therefore would need >100 cartridges to induce labour in pregnant patient, and if they'd been given that many then they would already be dead
• Allergic reactions:

  • V rare - especially because amides used over esters now
  • Idiosyncratic responses more common - report palpitations as a result of having LA - not true allergy though
  • If concerned - allergy testing
• In conclusion, when used correctly, at the right dose, LA is safe. Always remember to aspirate. And medical histories are important!