Bupivacaine is more cardiotoxic than lidocaine at equivalent doses. Which cellular mechanism explains bupivacaine's disproportionate cardiac toxicity?

• A Bupivacaine blocks potassium channels in myocardium more selectively than lidocaine
• B Bupivacaine irreversibly denatures cardiac sodium channels by covalent binding
• C Bupivacaine has higher plasma protein binding that releases massive free drug during acidosis
• D Bupivacaine binds sodium channels with slow kinetics ('fast in, slow out'), leading to channel accumulation during tachycardia and persistent conduction block ✓

Explanation

Bupivacaine exhibits 'fast in, slow out' sodium channel kinetics — it dissociates from the channel very slowly between action potentials. At normal heart rates there is partial recovery, but during tachycardia (or in accidental intravascular injection) channels accumulate in the blocked state with each depolarization, causing progressive and refractory conduction failure and ventricular fibrillation. Lidocaine has 'fast in, fast out' kinetics, allowing complete channel recovery between beats. This is also why 20% lipid emulsion (Intralipid) is the rescue treatment — it sequesters bupivacaine from cardiac tissues ('lipid sink').

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.