Based on a case of apparent cardiotoxicity from a very low dose of bupivacaine in a patient with carnitine deficiency, Weinberg postulated that this metabolic derangement led to enhanced toxicity due to the accumulation of fatty acids within the cardiac myocyte. He hypothesized that administration of lipid would similarly potentiate bupivacaine cardiotoxicity, but experiments performed to test this hypothesis demonstrated exactly the opposite effect. Accordingly, he began systematic laboratory investigations, which clearly demonstrated the potential efficacy of an intravenous lipid emulsion (ILE) for resuscitation from bupi-vacaine cardiotoxicity. Clinical confirmation came 8 years later with the report of the successful resuscitation of a patient who sustained an anesthetic-induced (bupivacaine plus mepivacaine) cardiac arrest refractory to standard advanced cardiac life sup-port procedures (ACLS). Numerous similar reports of successful resuscitations soon followed, extending this clinical experience to other anesthetics including levobupivacaine and ropivacaine, anesthetic-induced CNS toxicity, as well as toxicity induced by other classes of compounds, eg, bupropion-induced cardiovas-cular collapse and multiform ventricular tachycardia provoked byhaloperidol. Laboratory investigations have likewise provided evidence of efficacy for treatment of diverse toxic challenges (eg, verapamil, clomipramine, and propranolol).
The mechanism by which lipid is effective is incompletely understood, but its predominant effect appears to stem from its ability to extract a lipophilic drug from aqueous plasma and tis-sue targets, a mechanism termed lipid sink. With respect to bupi-vacaine cardiotoxicity, there may be an additive effect of restoring energy to the myocardium by overcoming bupivacaine-induced inhibition of fatty acid transport. Although numerous questions remain, the evolving evidence is sufficient to warrant administra-tion of lipid in cases of systemic anesthetic toxicity. Its use has been promulgated by a task force of the American Society of Regional Anesthesia, and administration of lipid has been incor-porated into the most recent revision of ACLS guidelines for Cardiac Arrest in Special Situations. Importantly, propofol cannot be administered for this purpose, as the relatively enormous vol-ume of this solution required for lipid therapy would deliver lethal quantities of propofol.