Key Facts

Local anaesthetics are the foundation of regional anaesthesia and are among the most widely used drugs in medical practice. Understanding their pharmacology is essential for safe administration.

Epidemiology

Local anaesthetic use is ubiquitous across medical specialties. LAST is rare (estimated 1 in 1,000-10,000 peripheral nerve blocks) but potentially fatal. The introduction of Intralipid rescue therapy has significantly reduced mortality from LAST.

Aetiology

LAs work by reversibly blocking voltage-gated sodium channels on the inner surface of the nerve cell membrane. This prevents depolarisation and action potential propagation. The unionised (base) form crosses the nerve membrane; the ionised form then blocks the sodium channel from the intracellular side.

Pathophysiology

Classification:

• Amides (lidocaine, bupivacaine, levobupivacaine, ropivacaine, prilocaine): Contain an amide bond; hepatic metabolism; allergic reactions rare
• Esters (cocaine, procaine, tetracaine, chloroprocaine): Contain an ester bond; hydrolysed by plasma cholinesterases; PABA metabolite can cause allergy

Differential blockade (smallest fibres blocked first):

• Autonomic (B fibres) → Pain/temperature (Aδ, C) → Touch/proprioception (Aβ) → Motor (Aα)

Factors affecting LA action:

• Tissue pH: Infection (acidic pH) reduces LA efficacy — more ionised form, less crosses membrane
• Nerve fibre size: Smaller fibres blocked more readily
• Myelination: Myelinated fibres require block at 3 consecutive nodes of Ranvier

Routes of Administration

• Topical: EMLA cream, lidocaine gel, Ametop (tetracaine)
• Infiltration: Wound infiltration, field block
• Peripheral nerve block: Single injection or catheter
• Neuraxial: Spinal (intrathecal), epidural
• IV regional (Bier's block): Lidocaine 0.5% 3mg/kg for upper limb surgery under tourniquet

Systemic Toxicity (LAST) — Progression

1. Circumoral tingling, metallic taste
2. Light-headedness, tinnitus, visual disturbance
3. Slurred speech, drowsiness
4. Tremor, muscle twitching
5. Seizures (generalised tonic-clonic)
6. Loss of consciousness
7. Cardiovascular collapse (bradycardia → VF → asystole)

Specific Toxicity Syndromes

• Bupivacaine cardiotoxicity: Resistant VF/VT — prolonged CPR needed, Intralipid essential
• Prilocaine: Methaemoglobinaemia at doses >600mg (treat with methylene blue 1-2mg/kg IV)
• Cocaine: Sympathomimetic effects — tachycardia, hypertension, arrhythmias

Red Flags

• Any CNS symptoms during or after LA administration — suspect LAST
• Cardiovascular collapse within minutes of LA injection — LAST or intravascular injection
• Cyanosis unresponsive to O2 after prilocaine — methaemoglobinaemia
• Prolonged numbness >24 hours — possible nerve injury

Bedside

• Clinical observation: Monitor for LAST symptoms during and after injection
• SpO2 monitoring: May show ~85% if methaemoglobinaemia
• ECG: Prolonged QRS, bradycardia in bupivacaine toxicity

Bloods

• ABG with co-oximetry: If methaemoglobinaemia suspected — measures metHb level directly
• Serum tryptase: If allergic reaction suspected (take at 1 hour and 24 hours)

Imaging

• Not typically required acutely

Special Tests

• Allergy testing: Skin prick and intradermal testing — if true LA allergy suspected (extremely rare with amides)
• Plasma cholinesterase levels: If prolonged ester LA effect (suxamethonium sensitivity testing as well)

Non-pharmacological

• Dose calculation: Always calculate maximum safe dose before injection
• Aspiration: Aspirate before injecting to reduce risk of intravascular injection
• Incremental injection: Inject slowly with frequent aspiration
• Monitoring: Standard monitoring during significant LA procedures

Pharmacological

• LAST management: Stop injection → 100% O2 → Intralipid 20% 1.5mL/kg bolus → infusion 15mL/kg/hr → repeat bolus ×2 if needed → ALS (avoid lidocaine, limit adrenaline to 1mcg/kg)
• Seizure management: Midazolam 0.05mg/kg IV or propofol — small doses to avoid CVS depression
• Methaemoglobinaemia: Methylene blue 1-2mg/kg IV over 5 minutes
• Adrenaline: Added at 1:200,000 (5mcg/mL) to reduce absorption; contraindicated in end-artery regions

Surgical/Interventional

• No specific surgical management — ensure Intralipid is immediately available wherever LA is used

Referral Criteria

• Any LAST event — report to AAGBI, local incident reporting
• Suspected LA allergy — immunology/allergy clinic referral
• Persistent nerve deficit after LA procedure — neurology referral

• LAST: Historically 50% mortality from bupivacaine cardiac arrest; now significantly reduced with Intralipid rescue (>75% survival)
• Methaemoglobinaemia: Rapidly reversible with methylene blue; rarely fatal
• Nerve injury from LA: Most are neuropraxia — >95% recover fully within 6 weeks
• Allergy: True allergy to amide LAs is extremely rare (<0.01%); ester allergy more common (PABA cross-reactivity)

Pharmacological Properties of Common LAs

Physicochemical Properties and Clinical Effect