Lidocaine

Why this drug is interesting

Lidocaine is probably the drug an emergency physician administers most frequently and thinks about least. It is drawn up for wound infiltration dozens of times a shift, usually without a weight-based calculation, and the maximum safe dose is one of the more commonly misquoted numbers in the department.

It also has a second, largely forgotten life as a class Ib antiarrhythmic — the alternative to amiodarone in shock-refractory ventricular fibrillation, still named in the Resuscitation Council guidelines. Both roles depend on the same action: blockade of voltage-gated sodium channels. So does the toxicity.

Pharmacology

Mechanism

Lidocaine blocks voltage-gated sodium channels from the intracellular side, preventing the influx of sodium that generates the action potential upstroke.

In peripheral nerve this abolishes impulse conduction — smaller, myelinated and more rapidly firing fibres first, which is why pain and temperature are lost before touch, pressure and motor function. In myocardium it acts as a class Ib agent with rapid association-dissociation kinetics, showing marked use dependence: it binds preferentially to depolarised and ischaemic tissue, which is precisely where ventricular arrhythmias arise, while leaving normal myocardium largely unaffected.

Kinetics

Onset, infiltration

Rapid — within 1–2 minutes

Duration, plain

Roughly 30–120 minutes depending on site and vascularity

Duration, with adrenaline

Prolonged, by local vasoconstriction reducing systemic absorption

Half-life

1.5–2 hours

Metabolism

Hepatic, with significant first-pass extraction — hence no useful oral route

Active metabolites

MEGX and GX, which contribute to toxicity in prolonged infusion

Hepatic clearance is flow-dependent, so anything reducing hepatic blood flow — heart failure, shock, beta-blockade — reduces clearance and raises the risk of accumulation during infusion.

Local anaesthetic dosing

Practical points

• Aspirate before injecting, and inject slowly in incremental doses — inadvertent intravascular injection is the classic route to systemic toxicity
• Buffering with sodium bicarbonate and warming the solution both reduce injection pain; so does injecting through the wound edge rather than through intact skin
• The old teaching to avoid adrenaline in fingers, toes, nose, ears and penis is no longer supported for commercially prepared lidocaine-with-adrenaline in digits; follow current local guidance rather than the aphorism
• Topical and infiltrated doses accumulate. Count what has already been given — including by another clinician earlier in the attendance

Local anaesthetic systemic toxicity

LAST results from excessive plasma concentration, whether from absolute overdose, rapid absorption from a vascular site, or inadvertent intravascular injection.

Recognition

The classical progression runs from CNS excitation to CNS depression to cardiovascular collapse, though it does not always proceed in order and cardiovascular collapse can be the presenting feature.

• Early: perioral tingling and numbness, metallic taste, tinnitus, light-headedness, visual disturbance, agitation, confusion
• Progressing: muscle twitching, tremor, seizures
• Late: coma, respiratory arrest
• Cardiovascular: bradycardia, conduction block, broad QRS, ventricular arrhythmia, asystole, refractory cardiac arrest

Afterwards: arrange safe transfer, exclude pancreatitis with regular review and daily amylase or lipase, and report the case on your local critical incident system and to the relevant national system. Know where your nearest bag of lipid emulsion is kept — the withdrawn AAGBI poster had a blank line for exactly that, because the delay in practice is almost always in finding it.

Lidocaine as an antiarrhythmic

Cardiac arrest — RCUK position

The Resuscitation Council UK guidelines direct amiodarone after 3 shocks in shock-refractory VF or pulseless VT.³ Lidocaine appears as a conditional alternative:

• Lidocaine 100 mg IV may be used if amiodarone is not available, or where a local decision has been made to use lidocaine instead. RCUK gives a flat 100 mg; the 1 mg/kg figure often quoted alongside it is not the guideline's wording and diverges at extremes of weight
• An additional bolus of 50 mg may be given after five defibrillation attempts
• Do not give lidocaine if amiodarone has already been given

Does it work?

ALPS randomised amiodarone, lidocaine and placebo in out-of-hospital shock-refractory VF/pVT and found no statistically significant difference in survival to hospital discharge between the three arms, though both drugs improved survival to admission and there were signals of benefit in bystander-witnessed arrests.⁴ Lidocaine is therefore not an inferior fallback so much as a comparable one — which is a more honest framing than its second-line position implies.

Other antiarrhythmic considerations

Lidocaine's use dependence makes it act preferentially on ischaemic myocardium, which is a theoretical advantage in ischaemia-driven ventricular arrhythmia. Historic routine prophylactic use post-MI was abandoned after it was shown to increase mortality — the same lesson as Flecainide and CAST, from a different direction.

Contraindications, cautions and interactions

Avoid or use with caution

• Known hypersensitivity to amide local anaesthetics — genuine allergy is rare; most reported reactions are to preservatives or are vasovagal
• Severe sino-atrial, atrioventricular or intraventricular conduction block — for antiarrhythmic use, without pacing
• Severe hepatic impairment or low cardiac output states — reduced clearance; reduce infusion doses
• Porphyria
• Myasthenia gravis — caution
• Injection into infected tissue — both less effective and risks spreading infection

Interactions

• Beta-blockers and cimetidine reduce hepatic clearance and raise plasma levels
• Other antiarrhythmics — additive cardiac depression and conduction effects
• Other local anaesthetics — toxicity is additive; count all agents given, including topical preparations

Adverse effects

At therapeutic local doses, adverse effects are largely limited to injection-site discomfort and transient stinging. Systemic effects are essentially the LAST spectrum described above, appearing progressively as plasma concentration rises. Methaemoglobinaemia is described, more commonly with prilocaine and benzocaine than with lidocaine.

Critical appraisal

1. The maximum-dose figures are less precise than their confident quotation suggests, and UK sources do not agree. The SmPC gives 4.5 mg/kg or 200 mg; standard UK teaching uses the more conservative 3 mg/kg. Both derive from limited and dated pharmacokinetic work, and true toxic thresholds vary with site of injection, vascularity, patient physiology and rate of administration. They are sensible working ceilings, not sharp cliffs — which argues for calculating them, and for respecting the absolute cap that the per-kilogram rule quietly overtakes above about 67 kg.
2. Lipid emulsion's evidence base is largely animal work, case reports and registry data, not randomised trials — for the obvious reason that LAST is rare and sudden. The recommendation is nonetheless entirely appropriate: the intervention is cheap, quick, and the alternative is a refractory arrest.
3. Lidocaine's demotion in cardiac arrest was never strongly evidence-based, and ALPS arguably rehabilitated it. Its second-line status reflects guideline history and drug availability as much as demonstrated inferiority.
4. The digital adrenaline myth persists well past the evidence that overturned it, and continues to cost patients longer procedures with poorer haemostasis.
5. The real safety gap is systems, not knowledge. Departments that calculate maximum doses routinely, store lipid emulsion somewhere everyone can name, and rehearse LAST will handle it. Individual recall of a bolus dose under pressure is a weak substitute for any of that.

References

1. 1
   Lidocaine Hydrochloride Injection BP 1% w/v — Summary of Product Characteristics. electronic Medicines Compendium. Source of the 4.5 mg/kg or 200 mg single-dose cap. For the with-adrenaline 500 mg cap see Lidocaine 1% with adrenaline 1:200,000. Verified 21 Aug 2026. Always check the preparation stocked locally.
2. 2
   Lidocaine hydrochloride — dosing, maximum doses and safety monograph. BNF, NICE. bnf.nice.org.uk
3. 3
   Resuscitation Council UK. Adult advanced life support guidelines and algorithm, 2025. resus.org.uk — mirrored at lifesupport.resusdoc.uk. Amiodarone after 3 shocks; lidocaine 100 mg (1 mg/kg) as an alternative if amiodarone is unavailable or by local decision, with a further 50 mg after five defibrillation attempts; do not give lidocaine if amiodarone has been given.
4. 4
   Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest (ALPS). N Engl J Med 2016;374(18):1711–22.
5. 5
   Association of Anaesthetists. Quick Reference Handbook, 3-10 Local anaesthetic toxicity, version 2, June 2023. anaesthetists.org/qrh. Source of the lipid emulsion regimen quoted above; verified 23 Aug 2026. The AAGBI 2010 safety guideline has been withdrawn — see the archived guideline page. The current QRH 3-10 v2 algorithm is mirrored at lifesupport.resusdoc.uk under CC BY-NC-SA 4.0.
6. 6
   Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine local anesthetic systemic toxicity checklist: 2020 version. Reg Anesth Pain Med 2021;46(1):81–82.