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Local Anaesthetic Toxicity John Kilic 28th October 2005 Mode of action Factors affecting toxicity • • • • • Absorption Distribution Metabolism Protein binding Placental transfer Absorption Sites and rates Fastest • Intercostal space • Epidural space • Brachial plexus • Lower limb blocks Slowest • Local infiltration Distribution Other factors • Metabolism • Amidases in liver • Proportional to hepatic flow • Protein binding • Values don’t correlate with toxicity acurately • Placental transfer • total protein [LA] / same free [LA] • rate hepatic metabolism in foetus • no significant problems with toxicity as long as episode not close prior to delivery Common Las and toxic doses Lignocaine Lignocaine with adrenaline Bupivocaine Ropivocaine Prilocaine Prilocaine with felypressin Cocaine 3 mg/kg 7 mg/kg 2 mg/kg 3 mg/kg 6 mg/kg 8 mg/kg 3 mg/kg Symptoms - CVS rate phase IV depolarisation duration action potential effective refactory period conduction velocity slight in SVR (slight in BP) • Low dose • • • • • • High dose • SVR • myocardial contractility • possible cardiovascular collapse due to these Symptoms - CNS • Low doses Inhibitory pathway • High doses Inhibitory + facilitatory pathways • Intra-arterial • • • • Lightheadedness Dizziness Visual/auditory hallucinations Seizures • Drowsiness • Disorientation • Coma • LA/neurotransmitter/receptor complex formed • Neuromuscular blockade Symptoms - Other • GI • • Metabolic • some anticholinergic activity • some antihistamine activity contraction of intact bowel Risk of anaphylaxis with LAs very rare Treatment • Stop injection/infusion • ABC !! • Treat initial Sx with O2 • Repeated doses midazolam (1-4mg) Treatment (cont) • Modsevere • Drug OD in presence of hypoxia • Prevent convulsions • Maintain oxygenation • GCS/ convulsions • Intubate • Preferentially sux/thiopentone • Ventilate 100% O2 • CV collapse • Commence CPR Methaemoglobin • Hepatic metabolism prilocaine produces otoluidine • o-toluidine oxidises Hb to methaemoglobin • Especially doses >600mg prilocaine • Avoid prilocaine in anaemia/pregnancy • Treatment with 1mg/kg methylene blue Prevention of toxicity AVOID INTRAVASCULAR INJECTION!!!!! • • • • • Repeat careful aspiration Use adrenaline 1:200,000/vasoconstrictor Care with site of injection Care with patient’s general condition Care with dose used Any questions?