Introduction
Lidocaine is a widely used amide-type local anesthetic and class IB antiarrhythmic agent first synthesized in 1943. It represents one of the most commonly administered local anesthetics in clinical practice due to its rapid onset, intermediate duration of action, and favorable safety profile when used appropriately. Lidocaine is available in various formulations including injectable solutions, topical preparations, transdermal patches, and mucosal formulations, making it versatile for numerous medical applications.
Mechanism of Action
Lidocaine exerts its pharmacological effects by blocking voltage-gated sodium channels in neuronal membranes. By binding to specific receptors within these channels, lidocaine stabilizes neuronal membranes and inhibits the ionic fluxes required for the initiation and conduction of nerve impulses. This reversible blockade prevents depolarization and subsequent action potential propagation, resulting in localized anesthesia.
As an antiarrhythmic agent, lidocaine decreases automaticity in the Purkinje fibers and suppresses ventricular arrhythmias by increasing the electrical stimulation threshold of the ventricle during diastole.
Indications
FDA-Approved Indications:- Local anesthesia by infiltration, nerve block, epidural, spinal, and topical routes
- Ventricular arrhythmias (particularly during acute myocardial infarction)
- Topical anesthesia for mucous membranes and skin
- Management of neuropathic pain conditions (various formulations)
- Postherpetic neuralgia
- Chronic pain syndromes
- Diagnostic and therapeutic nerve blocks
- Migraine prophylaxis (intranasal formulation)
Dosage and Administration
Local Anesthesia:- Infiltration: 0.5-1% solution, maximum 4.5 mg/kg (not to exceed 300 mg)
- Epidural: 1-2% solution, 100-300 mg single dose
- Peripheral nerve block: 1-1.5% solution, 50-300 mg
- Spinal: 1.5-5% solution, 50-100 mg
- IV loading: 1-1.5 mg/kg bolus (may repeat after 5-10 minutes to maximum 3 mg/kg)
- Maintenance infusion: 1-4 mg/min (30-50 mcg/kg/min)
- Hepatic impairment: Reduce dose by 50%
- Renal impairment: No significant adjustment needed
- Elderly: Reduce dose due to decreased clearance
- Pediatrics: 0.5-1.0 mg/kg for arrhythmias; lower local anesthetic doses
Pharmacokinetics
Absorption: Well-absorbed from mucous membranes and damaged skin; poorly absorbed through intact skin. Systemic absorption varies by route of administration. Distribution: Rapid distribution with volume of distribution approximately 1-2 L/kg. Crosses placenta and blood-brain barrier. Protein binding: 60-80% (primarily to alpha-1 acid glycoprotein). Metabolism: Extensive hepatic metabolism via cytochrome P450 3A4 and 1A2 to active metabolites (monoethylglycinexylidide and glycinexylidide). Elimination: Half-life: 1.5-2 hours. Excreted renally (90% as metabolites, 10% unchanged).Contraindications
- Hypersensitivity to amide-type local anesthetics
- Adams-Stokes syndrome
- Wolff-Parkinson-White syndrome
- Severe heart block (second or third degree) without pacemaker
- Severe hepatic impairment
- Sepsis or infection at injection site (relative)
Warnings and Precautions
Boxed Warning: Cardiac arrest and death have occurred with inappropriate IV administration of local anesthetics. Additional Warnings:- Risk of methemoglobinemia (especially with high doses or predisposed patients)
- Neurological toxicity: tinnitus, metallic taste, seizures
- Cardiovascular toxicity: hypotension, bradycardia, cardiac arrest
- Use caution in patients with cardiac conduction abnormalities
- Monitor for allergic reactions, though rare with amide anesthetics
- Use smallest effective dose to minimize systemic absorption
Drug Interactions
Significant Interactions:- Beta-blockers: May reduce lidocaine metabolism
- Cimetidine: Increases lidocaine levels (inhibits metabolism)
- CYP3A4 inhibitors (ketoconazole, erythromycin): Increase lidocaine concentrations
- Antiarrhythmics: Additive cardiac effects
- Succinylcholine: Prolonged neuromuscular blockade
- MAO inhibitors: Potential hypertensive crisis
Adverse Effects
Common (≥1%):- Application site reactions (erythema, edema)
- Dizziness, drowsiness
- Nausea, vomiting
- Paresthesia
- Hypotension
- Seizures
- Cardiac arrest
- Respiratory depression
- Methemoglobinemia
- Allergic reactions (rare)
- Heart block
- Bradycardia
Monitoring Parameters
- Cardiovascular status (ECG, blood pressure, heart rate)
- Respiratory function
- Neurological status (especially with high doses)
- Signs of local anesthetic toxicity
- Methemoglobinemia symptoms (cyanosis unresponsive to oxygen)
- Injection site for infection or tissue damage
- Plasma levels when used for arrhythmias (therapeutic range: 1.5-5 mcg/mL)
Patient Education
- Report any signs of allergic reaction (rash, itching, swelling)
- Avoid eating or drinking when numb to prevent aspiration
- Do not chew numb areas to prevent self-injury
- Be cautious with heat application to anesthetized areas
- Understand expected duration of numbness
- Report chest pain, dizziness, or palpitations immediately
- Follow specific instructions for transdermal patch removal and disposal
- Do not drive or operate machinery until sensation returns
References
1. Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 6th ed. McGraw-Hill Education; 2018. 2. Lexicomp Online. Lidocaine monograph. Wolters Kluwer Clinical Drug Information; 2023. 3. FDA prescribing information: Xylocaine (lidocaine) injection. 4. Neal JM, Bernards CM, Hadzic A, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35(2):152-161. 5. El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018;11:35-44. 6. Hogan QH. Local anesthetic toxicity: an update. Reg Anesth Pain Med. 2020;45(1):74-76.