Local anaesthetic toxicity

Risk assessment

• Mostly iatrogenic mistake from inadvertent IV dosing instead of dosing error
• Onset is rapid
• Maximal doses are below but toxicity can occur with direct IV or IA injection
  • Bupivacaine 1-2.5mg/kg (esp. cardiotoxic)
  • Lignocaine 4-5mg//kg
  • Prilocaine 5-7mg/kg
  • Ropivacaine 2.5-3mg/kg
  • Higher if adrenaline
• Methaemoglobinaemia is not dose-related but is more likely with benzocaine, lignocaine or prilocaine

Children

• <6mg/kg ingested doses are safe (e.g. xylocaine viscous)
• Children more likely than adults to develop methaemoglobinaemia (including after topical administration)

Toxic mechanism

• Reversible sodium channel blockade to inhibit sodium influx required to initiate and propagate action potentials
• Methaemoglobinaemia more likely for benzocaine, prilocaine or lignocaine
• Occurs by oxidation of ferrous (Fe2+) of normal Hb to ferric (Fe3+)

toxicokinetics

• Systemic toxicity corresponds to peak concentrations in blood as influenced by:
  • Total dose
  • Route of administration
  • Rate of administration
  • Presence of tourniquets
  • Local blood flow
• Toxicity is rare following ingestions due to high first-pass metabolism
• Hepatically metabolised with short half-lives <2 hours (longer for bupivacaine)

Clinical features

• Earliest signs – Tinnitus, dizziness, anxiety, confusion and perioral numbness
• More severe
  • CNS – Seizures, coma
  • CVS – Bradycardia, hypotension, dysrhythmias, cardiovascular collapse and asystole
  • Respiratory – Respiratory depression, apnoea
• CNS normally manifests before CVS excessive massive IV overdose where cardiac arrest can be almost instant
• Bupivacaine binds to myocardial tissue and is particularly cardiotoxic
• Methaemoglobinaemia manifests as blue discolouration of mucous membranes but may progress to cellular hypoxia, CNS dysfunction, CVS dysfunction and death if methaemoglobin levels rise >70%

Management

• Ix – EUC, ABG, methaemoglobin, serial ECG (sodium-channel blockade)
• Management
  • ABC
  • Immediate I&V if cardiotoxicity evident
  • Ventricular dysrhythmias – Sodium bicarb 100mmol (2mmol/kg) q1-2min until perfusing rhythm
  • Seizures – Benzos
  • Hypotension – Fluids +- inotropes
• Antidotes
  • Sodium bicarb for dysrhythmias
  • IV lipid emulsion for severe cardiovascular toxicity or cardiac arrest refractory to above
  • Methylene blue for methaemoglobinaemia and is administered to all symptomatic patients

intralipid

• MOA: 
  • Intravascular lipid phase extracts agent from tissue binding sites
  • Increase myocardial ATP synthesis due to reversible of inhibition of fatty acid delivery to mitochondria
  • Restoration of myocyte function through activation of Ca and K channels + increase in intracellular calcium
• 1-1.5mL/kg 20% IVLE IV over 1 min q3-5min up to 3 times
• THEN
• 0.25mL/kg/min until stable (increase to 0.5mL/kg/min if required)
• Total dose above 8mL/kg is unlikely to be of benefit
• Can cease once haemodynamically stable but can re-start if hypotension recurs

intralipid

• Adverse reactions
  • Immediate: allergy or anaphylaxis (egg, soya, peanut)
  • Pulmonary HTN, ALI, haematuria, hypertriglyceridaemia, pancreatitis
• Handy tips
  • For 70kg male, 100mL bolus then 400mL over 20 minutes. If no response, bolus twice more and increase infusion rate to 400mL over 10 minutes

Methylene blue

• Indicated for symptomatic drug-induced methaemoglobinaemia (signs of hypoxaemia with chest pain, dyspnoea or confusion)
• Consider even if asymptomatic and metHb level >20%
• 
  Also used as adjunct in anaphylactic and toxic shock states refractory to vasopressors
• CI: 
  • G6PD deficiency: Lack of NADPH means methylene blue ineffective and haemolysis may result
  • Need to dose reduce in renal impairment
  • Nitrite-induced methaemoglobinaemia following treatment of cyanide toxicity
• MOA
  • Increases natural rate of reduction of MetHb to haemoglobin
  • Reduced to leucomethylene blue by MetHb reductase in presence of NADPH. Leucomethylene blue then reduces MetHb to Hb
  • Inhibits nitric oxide synthase and guanylate cyclase and scavenges endothelial NO
  • Has vasoconstrictive and positive inotropic effects in shock states

Methylene blue

• Administration
  • 1-2mg/kg IV over 5 minutes
  • MetHb measured hourly until consistently falling
  • Can do repeat bolus at 30-60 min if no response
  • Q8hr dosing for dapsone poisoning
  • Single dose in shock states as adjunct
• Side effects
  • Local pain and irritation
  • Non-specific headache, dizziness, nausea, vomiting, SOB
  • Blue staining of mucous membranes and urine
  • Can paradoxically cause methaemoglobinaemia in doses >7mg/kg due to direct oxidative effect on Hb

Methylene blue

• Handy tips
  • If pre-existing anaemia or CAD, may benefit at MetHb levels of only 10%
  • Pulse oximetry will be unreliable

Handy tips

• Any neurological symptoms during or shortly after LA administration prompts close observation in resus

Last Updated on October 14, 2020 by Andrew Crofton