Local anaesthetic dosing and toxicity thresholds

Surgical approach (if applicable)

• Not an operation: topic applies to local infiltration, peripheral nerve blocks, neuraxial techniques, and topical LA use across many procedures.

Anaesthetic management (context-dependent)

• Type of anaesthesia: local infiltration / regional anaesthesia (PNB, neuraxial) ± sedation; GA sometimes for major surgery with adjunct regional
• Airway: usually none; if deep sedation/GA then SGA/ETT as appropriate
• Duration: depends on procedure and LA choice (e.g., lidocaine 1–2 h, bupivacaine/ropivacaine 4–12 h; longer with adjuvants/infusions)
• Painfulness: varies; blocks can provide profound analgesia; infiltration often incomplete for deep pain
• Monitoring: standard monitoring for any significant LA dose/major block; consider IV access, resus drugs and lipid immediately available

Core principles of LA dosing (what sets toxicity risk)

• Toxicity relates to peak arterial plasma concentration at target organs (CNS/heart), not just total mg given.
• Determinants of systemic absorption (highest → lowest): intercostal > caudal/epidural > brachial plexus > sciatic/femoral > subcutaneous.
• Dose factors: total mg (concentration × volume), incremental dosing, aspiration, ultrasound guidance, catheter boluses/infusions, multiple blocks in same sitting.
• Patient factors increasing risk: extremes of age, low lean body mass, pregnancy, hepatic impairment (amide metabolism), cardiac failure/low CO, renal failure (active metabolites), acidosis/hypercarbia, hypoalbuminaemia (↓ protein binding), interacting drugs (e.g., CYP inhibitors).
• LA factors: potency/lipid solubility (bupivacaine > ropivacaine > lidocaine), protein binding, pKa (onset), stereoisomerism (levobupivacaine/ropivacaine less cardiotoxic than racemic bupivacaine).
• Adrenaline (epinephrine) reduces systemic absorption and acts as intravascular marker; effect varies by site and LA; does not eliminate risk.

Maximum recommended doses (adult single-shot; typical exam values)

• Principle: use the lowest effective dose; calculate mg = % × 10 × mL (e.g., 0.5% = 5 mg/mL).
• Lidocaine (lignocaine): 3 mg/kg (plain); 7 mg/kg with adrenaline. Practical caps often quoted: 200 mg plain; 500 mg with adrenaline.
  • Concentrations: 1% = 10 mg/mL; 2% = 20 mg/mL.
• Bupivacaine: 2 mg/kg (plain); 3 mg/kg with adrenaline. Practical cap often quoted: 150 mg.
  • 0.25% = 2.5 mg/mL; 0.5% = 5 mg/mL.
• Levobupivacaine: commonly treated similarly to bupivacaine for dosing (e.g., ~2 mg/kg; some references allow slightly higher). Use local policy; do not assume ‘safe’.
• Ropivacaine: 3 mg/kg commonly quoted (some sources 3–4 mg/kg depending on technique). Less cardiotoxic than bupivacaine but still causes LAST.
• Prilocaine: 6 mg/kg plain; 8 mg/kg with adrenaline. Risk: methaemoglobinaemia (especially high dose, infants, topical use).
• Mepivacaine: ~5 mg/kg plain; ~7 mg/kg with adrenaline (less commonly used in UK).
• Articaine (dental): ~7 mg/kg (commonly used with adrenaline).
• Topical/cocaine (ENT): cocaine maximum commonly 1.5 mg/kg (often capped at 100–200 mg depending on institutional policy); significant sympathomimetic toxicity risk.
• Important: maximum dose guidance varies between formularies/manufacturers; in exams, quote a standard set and emphasise individualisation and risk reduction.

Toxicity thresholds (plasma concentrations: typical teaching values)

• CNS toxicity generally occurs at lower plasma levels than cardiovascular collapse (exception: bupivacaine may cause severe cardiotoxicity with minimal preceding CNS signs).
• Lidocaine: early CNS symptoms often around ~5 micrograms/mL; seizures ~10 micrograms/mL; CVS depression/arrhythmias at higher levels.
• Bupivacaine: CNS symptoms may occur around ~2–4 micrograms/mL; serious cardiotoxicity can occur at relatively low levels compared with lidocaine (high affinity/slow dissociation from cardiac Na+ channels).
• Ropivacaine/levobupivacaine: higher threshold for severe cardiotoxicity than racemic bupivacaine, but seizures and CVS toxicity still occur.
• Exam approach: give approximate numbers if asked, but prioritise clinical recognition and management over exact plasma thresholds.

Clinical features of LAST (Local Anaesthetic Systemic Toxicity)

• Timing: usually within minutes of injection (intravascular/intra-arterial), but can be delayed (e.g., continuous infusions, tissue depot, liposomal preparations).
• Early CNS: circumoral numbness, metallic taste, tinnitus, dizziness, blurred vision, agitation, slurred speech.
• CNS progression: tremor → seizures → CNS depression/coma/respiratory arrest.
• Cardiovascular: hypertension/tachycardia early (from CNS excitation/adrenaline), then hypotension, conduction delay (PR/QRS prolongation), bradycardia, ventricular arrhythmias, PEA/asystole.
• Bupivacaine pattern: malignant ventricular arrhythmias and refractory cardiac arrest may occur abruptly.

Prevention and risk reduction (high-yield viva content)

• Before injection: calculate maximum dose (mg/kg) and total planned mg across all sites; consider dose reduction in high-risk patients.
• Technique: ultrasound guidance, incremental injection (e.g., 3–5 mL aliquots), frequent aspiration, slow injection with verbal contact, avoid high-pressure injection.
• Adrenaline test dose/marker (where appropriate): look for HR rise, BP rise, or T-wave changes; less reliable under GA, beta-blockade, pregnancy, elderly.
• Monitoring: standard monitoring during and after injection; observe longer for high-dose blocks/infusions.
• Preparedness: immediate access to airway equipment, benzodiazepines, vasopressors, and 20% lipid emulsion; team brief.

Immediate management of LAST (structured approach)

• Stop LA injection; call for help; start ABC approach.
• Airway/ventilation: 100% oxygen, secure airway early if needed; avoid hypoxia, hypercarbia and acidosis (they worsen toxicity).
• Seizure control: benzodiazepine first line (e.g., midazolam); consider small-dose propofol only if haemodynamically stable; avoid large propofol doses in cardiovascular instability.
• Circulation: treat hypotension/bradycardia with vasopressors/inotropes; use small incremental adrenaline doses (avoid large boluses).
• Lipid emulsion therapy (20%): give early in significant CNS toxicity (seizures) or any cardiovascular features.
• If cardiac arrest: high-quality CPR; follow ALS with LAST modifications (lipid, avoid certain drugs, prolonged resuscitation may be required).

Lipid emulsion (20%) dosing (typical AAGBI/UK practice values to quote)

• Bolus: 1.5 mL/kg of 20% lipid IV over ~1 minute.
• Infusion: 0.25 mL/kg/min (i.e., 15 mL/kg/hour).
• If ongoing instability: repeat bolus (up to two further boluses at 5-minute intervals) and increase infusion to 0.5 mL/kg/min.
• Maximum total dose: commonly 12 mL/kg (20% lipid).
• Continue infusion for at least 10 minutes after achieving stability; monitor for recurrence (lipid redistribution).

Drug considerations in LAST-related cardiac arrest (viva points)

• Adrenaline: use smaller doses than standard ALS (aim to avoid worsening arrhythmias and impairing lipid efficacy).
• Avoid: vasopressin, calcium channel blockers, beta-blockers, and local anaesthetic antiarrhythmics (lidocaine).
• Amiodarone may be used for refractory ventricular arrhythmias if required; defibrillate as per ALS.
• Consider cardiopulmonary bypass/ECMO early if refractory cardiovascular collapse and available.

Special situations

• Pregnancy: increased sensitivity and higher free fraction (↓ alpha-1 acid glycoprotein), epidural venous engorgement (↑ intravascular injection risk) → reduce dose and be vigilant.
• Children: dose strictly by weight; consider lower thresholds in neonates/infants (reduced protein binding and immature metabolism).
• Continuous catheter techniques: cumulative dose and delayed toxicity; document total mg/hour and mg/24 h; ensure monitoring and handover.
• Topical LA (airway/ENT): unpredictable absorption; beware combining multiple preparations (e.g., lidocaine spray + gel + infiltration).
• Methaemoglobinaemia (prilocaine/benzocaine): cyanosis with normal PaO2, low SpO2 not improving with O2; treat with methylene blue if significant/symptomatic (if no contraindication such as G6PD deficiency).