Local anaesthetics: toxicity and lipid rescue

8 min read Last updated April 8, 2026

Immediate management (A–E) of suspected LAST

  • Stop LA injection; call for help; summon lipid emulsion + LAST kit
    • Inform theatre/ICU; allocate roles; prepare defibrillator and airway equipment
  • Airway and breathing: 100% oxygen, secure airway early, avoid hypoventilation
    • Ventilate to normocapnia (hypercapnia/acidosis increase LA toxicity)
    • Treat seizures promptly to reduce hypoxia/acidosis (benzodiazepine first line)
  • Circulation: treat hypotension/bradycardia early; start CPR if arrest
    • Use small-dose adrenaline (e.g. 10–100 micrograms boluses) rather than large doses
    • Avoid vasopressin; avoid calcium channel blockers and beta-blockers in refractory instability
  • Give lipid emulsion early if significant neurological symptoms, cardiovascular instability, or arrest
    • Continue standard ALS with modifications; prolonged resuscitation may be required
  • After ROSC/stabilisation: ICU/HDU; monitor for recurrence; document and report
    • Observe for at least 6–12 h if cardiovascular features; shorter (e.g. 2 h) may be acceptable after isolated, rapidly resolving CNS symptoms (local policy)
    • Check ABG, electrolytes, glucose; manage acidosis, hypoxia, hyperkalaemia

Lipid rescue dosing (20% lipid emulsion)

  • Bolus: 1.5 mL/kg IV over ~1 min
    • May repeat bolus (e.g. every 5 min) if persistent cardiovascular collapse (up to 2 further boluses depending on guideline/local protocol)
  • Infusion: 0.25 mL/kg/min (15 mL/kg/hour)
    • If instability persists: increase infusion to 0.5 mL/kg/min
  • Maximum total dose: commonly 10–12 mL/kg over first 30 min (follow local/national guideline)
    • Continue infusion for at least 10 min after haemodynamic stability

Definition and scope

  • LAST = systemic toxicity from local anaesthetic causing CNS and/or cardiovascular disturbance, typically from intravascular injection or excessive absorption
  • Highest-risk agents: potent, lipophilic, highly protein-bound (e.g. bupivacaine, levobupivacaine, ropivacaine) with prominent cardiotoxicity

Pathophysiology (what toxicity does)

  • Primary mechanism: blockade of voltage-gated sodium channels (Nav) in CNS and myocardium; at higher concentrations also affects calcium and potassium channels and mitochondrial function
  • CNS: early inhibitory pathway blockade → excitation (tinnitus, circumoral numbness, agitation, seizures) then CNS depression (coma, respiratory arrest)
  • Cardiac: conduction slowing, PR/QRS prolongation, AV block, ventricular arrhythmias; negative inotropy; bupivacaine binds inactivated Nav with slow dissociation → refractory VF/asystole
  • Acidosis, hypercapnia, hypoxia increase free (active) LA fraction and worsen toxicity

Clinical features and patterns

  • Typical progression: CNS symptoms precede cardiovascular collapse, but cardiovascular toxicity may occur first (especially with potent agents, rapid intravascular injection, GA/sedation masking CNS signs)
  • Early CNS: metallic taste, tinnitus, perioral numbness, dizziness, blurred vision, agitation, tremor
  • Severe CNS: seizures, reduced consciousness, apnoea
  • Cardiovascular: hypertension/tachycardia early (from seizures/catecholamines) then hypotension, bradycardia, conduction block, VT/VF, asystole

Risk factors (patient, technique, drug)

  • Patient: extremes of age, pregnancy, low cardiac output, hepatic dysfunction (amide metabolism), renal failure (protein binding changes), acidosis, hypoxia, hypoalbuminaemia
  • Technique: intravascular injection, high vascularity sites (intercostal > caudal > epidural > brachial plexus > sciatic/femoral > subcutaneous), large volumes, rapid injection
  • Drug: higher dose, higher lipid solubility/potency, lower therapeutic index; bupivacaine more cardiotoxic than lidocaine; ropivacaine/levobupivacaine less cardiotoxic than racemic bupivacaine

Prevention strategies

  • Use the lowest effective dose and concentration; calculate maximum safe dose (mg/kg) and consider additive dosing if mixing agents
  • Incremental injection with frequent aspiration; inject slowly; communicate with awake patient
  • Use ultrasound guidance where appropriate (reduces vascular puncture and total dose requirements but does not eliminate LAST)
  • Consider intravascular marker: adrenaline 1:200,000 (5 micrograms/mL) test dose—look for HR/BP changes (may be unreliable in beta-blockade, labour, GA)
  • Ensure immediate availability of 20% lipid emulsion and a local LAST protocol wherever large-volume LA blocks are performed

Seizure management in LAST

  • First line: benzodiazepine (e.g. midazolam 1–2 mg IV increments; or diazepam 5–10 mg IV)
  • If ongoing: consider small-dose propofol only if haemodynamically stable (propofol can worsen hypotension and has no role in cardiac arrest due to LAST)
  • If refractory or airway compromise: intubate and use a non-depolarising NMBD; maintain normocapnia and oxygenation

Cardiac arrest / peri-arrest modifications

  • Continue high-quality CPR; early lipid; treat reversible causes (hypoxia, acidosis)
  • Adrenaline: use smaller doses than standard ALS (avoid large cumulative doses which may worsen arrhythmias and impair lipid efficacy)
  • Antiarrhythmics: amiodarone preferred if needed; avoid lidocaine and other sodium-channel blockers (may worsen toxicity)
  • If refractory: consider cardiopulmonary bypass/ECMO early where available (bridge while LA redistributes/metabolises)

Lipid emulsion: proposed mechanisms and practicalities

  • Mechanisms: ‘lipid sink/shuttle’ (sequestration and redistribution of lipophilic LA), improved myocardial fatty-acid substrate delivery, direct inotropic effects, modulation of ion channels/mitochondria
  • Most effective for lipophilic agents (e.g. bupivacaine) but recommended for severe toxicity from any LA
  • Complications: fat overload, pancreatitis, hypertriglyceridaemia, interference with lab assays (lipemia), pulmonary complications (rare); weigh against life-saving benefit

Differential diagnosis (peri-block collapse/seizure)

  • Vasovagal episode, high/total spinal, intrathecal opioid, hypoglycaemia, hypoxia, local anaesthetic allergy (rare true IgE), anaphylaxis to other agents (chlorhexidine, antibiotics), LA-induced methemoglobinaemia (prilocaine/benzocaine), pulmonary embolism, arrhythmia unrelated to LA
You are called to recovery: a patient has tinnitus, metallic taste and agitation shortly after an axillary block. What is your immediate management?

Treat as evolving LAST; prevent progression to seizures/cardiovascular collapse.

  • Stop LA injection; call for help; bring LAST kit and 20% lipid emulsion
  • A/B: 100% oxygen, support ventilation, aim normocapnia; prepare for early airway control if deteriorating
  • Treat seizures promptly if they occur: benzodiazepine first line
  • Monitor ECG/NIBP/SpO2; establish IV access; consider early lipid if symptoms are significant or progressing
Describe the pathophysiology of bupivacaine cardiotoxicity and why it can be refractory to standard resuscitation.
  • Potent Nav blockade in myocardium → slowed conduction, widened QRS, re-entry arrhythmias, reduced contractility
  • Bupivacaine has high lipid solubility and strong binding to inactivated sodium channels with slow dissociation (‘slow off-rate’) → persistent channel blockade
  • Acidosis/hypercapnia increase free fraction and worsen binding; hypoxia reduces myocardial reserve
  • Standard ALS drugs (large-dose adrenaline, sodium-channel blockers) may worsen arrhythmias or impair recovery; lipid and prolonged CPR may be required
Outline a prevention strategy for LAST when performing a large-volume peripheral nerve block.
  • Pre-procedure: calculate maximum dose (mg/kg), account for comorbidities (pregnancy, low CO, liver disease), plan lowest effective concentration/volume
  • Technique: ultrasound guidance; incremental injection with frequent aspiration; slow injection; avoid high opening injection pressures; maintain verbal contact if awake
  • Consider adrenaline as intravascular marker (recognise limitations)
  • Environment: monitoring during and after injection; immediate access to lipid emulsion and a LAST algorithm
Give the dosing regimen for 20% lipid emulsion in severe LAST.
  • Bolus 1.5 mL/kg IV over ~1 min
  • Infusion 0.25 mL/kg/min; increase to 0.5 mL/kg/min if ongoing instability
  • Repeat bolus if persistent cardiovascular collapse (per guideline/local protocol)
  • Do not exceed ~10–12 mL/kg in first 30 min (follow local policy); continue infusion for at least 10 min after stability
How does lipid emulsion work in LAST? Give more than one mechanism.
  • ‘Lipid sink’/‘lipid shuttle’: partitions lipophilic LA into an intravascular lipid phase, reducing free plasma concentration and redistributing drug away from heart/brain
  • Metabolic effect: provides fatty acids to myocardium and may improve energy supply during toxicity
  • Direct myocardial effects: possible inotropy and modulation of ion channels/mitochondrial function
A patient develops seizures after an epidural top-up. What drugs do you use, and what do you avoid?
  • Use benzodiazepines first line (e.g. midazolam IV increments); secure airway and ventilate to normocapnia
  • Consider small-dose propofol only if haemodynamically stable; otherwise avoid due to cardiovascular depression
  • If refractory: intubate and paralyse with non-depolarising NMBD; start lipid early if significant toxicity
During a block the patient becomes bradycardic and hypotensive with a widening QRS. How do you distinguish LAST from high spinal, and how does management differ?
  • Clues for LAST: temporal relation to LA injection; CNS prodrome (tinnitus/metallic taste) may precede; arrhythmias/QRS widening prominent
  • Clues for high spinal: rapid onset after neuraxial dosing; high sensory level, upper limb weakness, dyspnoea, hypotension/bradycardia from sympathectomy; usually no QRS widening
  • Management overlap: airway/ventilation, vasopressors, fluids; key difference: in suspected LAST give lipid early and avoid sodium-channel blocking antiarrhythmics
What ALS modifications are recommended in LAST-related cardiac arrest?
  • Early lipid emulsion plus high-quality CPR; anticipate prolonged resuscitation
  • Use small-dose adrenaline; avoid large cumulative doses
  • Avoid vasopressin; avoid lidocaine and other sodium-channel blockers; amiodarone preferred if antiarrhythmic required
  • Consider early ECMO/CPB if refractory and available
List complications or downsides of lipid emulsion therapy relevant to ICU follow-up and investigations.
  • Hypertriglyceridaemia and fat overload; pancreatitis (rare but important)
  • Lipemia can interfere with laboratory assays (electrolytes, LFTs, coagulation, ABG analysers depending on method)
  • Potential pulmonary complications in susceptible patients; monitor oxygenation and consider CXR if clinically indicated
An FRCA written-style question: Explain why acidosis and hypercapnia worsen LAST and how your management addresses this.
  • Acidosis increases the unbound (free) fraction of LA (reduced protein binding) and increases ion trapping in tissues; hypercapnia and hypoxia reduce seizure threshold and myocardial reserve
  • Management: early oxygenation and controlled ventilation to normocapnia; treat seizures to reduce lactate production; support circulation to improve perfusion; consider bicarbonate only for severe metabolic acidosis as part of broader resuscitation
A previous FRCA-style viva: What factors influence systemic absorption of local anaesthetic and therefore toxicity risk?
  • Site vascularity (intercostal > caudal > epidural > brachial plexus > sciatic/femoral > subcutaneous)
  • Total dose, concentration and volume; addition of vasoconstrictor (adrenaline reduces peak plasma levels for many agents)
  • Patient factors: cardiac output, pregnancy, hepatic function, protein binding (albumin, alpha-1 acid glycoprotein), acid–base status
A previous FRCA-style question: Compare lignocaine and bupivacaine toxicity profiles.
  • Lignocaine: CNS toxicity often prominent; cardiotoxicity occurs at higher plasma concentrations; shorter duration and less potent than bupivacaine
  • Bupivacaine: more potent, more lipophilic and more protein-bound; greater cardiotoxicity with severe ventricular arrhythmias and refractory arrest due to slow dissociation from cardiac sodium channels
  • Ropivacaine/levobupivacaine: reduced cardiotoxicity compared with racemic bupivacaine (still can cause LAST)

0 comments