Local Anesthetics and Systemic Toxicity

Local anesthetics enter the axon mainly in their uncharged form and bind the intracellular side of voltage-gated sodium channels in their charged form. Binding favors open and inactivated channels, producing frequency- or use-dependent block.

Small myelinated fibers are generally blocked before large motor fibers, although concentration, nerve anatomy, firing frequency, and technique all influence the observed sequence. Sympathetic function is often lost before pain, touch, and motor function.

A pKa closer to physiologic pH increases the fraction of uncharged drug and usually speeds onset. Tissue acidosis reduces the uncharged fraction and can make an infected area difficult to anesthetize.

• Lipid solubility generally correlates with potency.
• Protein binding generally correlates with duration.
• Local blood flow and intrinsic vasoactivity influence systemic absorption and duration.
• Epinephrine can reduce systemic uptake and prolong selected blocks, but it is not appropriate in every site or patient.

Lidocaine is an amide local anesthetic with relatively rapid onset and intermediate duration. It is also a class Ib antiarrhythmic, although regional-anesthesia dosing and antiarrhythmic dosing are distinct clinical uses.

Bupivacaine is highly potent, protein bound, and long acting. It has a narrower cardiovascular safety margin than lidocaine and can produce refractory ventricular arrhythmias and myocardial depression after intravascular exposure.

EMLA is a eutectic topical mixture of lidocaine and prilocaine. Prilocaine can contribute to methemoglobinemia, particularly with excessive exposure or susceptible patients.

Local anesthetic systemic toxicity, or LAST, may begin with circumoral numbness, metallic taste, tinnitus, agitation, or seizures, but cardiovascular collapse can occur without a clear neurologic prodrome. Bupivacaine is especially associated with severe cardiotoxicity.

Management starts with stopping injection, calling for help, oxygenation and ventilation, seizure control, and modified resuscitation. Intravenous lipid emulsion is a key therapy for serious LAST. Prevention includes incremental injection, repeated aspiration, dose calculation, monitoring, and ultrasound guidance when appropriate.

Primary teaching source: Akram Amer, Pharmacology of Anesthesia Drugs, pages 30-34.

Bupivacaine warnings were checked against current prescribing information, and LAST management concepts were aligned with contemporary resuscitation guidance.

This material is educational and remains a draft until reviewed by a qualified clinician. Local protocols and current product information take precedence for patient care.