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Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (I(Na)) in stable cell lines expressing human cardiac sodium channels. Linolenic (polyunsaturated) and stearic (saturated) fatty acids were selected for study as they are components of commonly used lipid infusions. Bupivacaine-induced significant tonic and use dependent I(Na) block, as expected. Linolenic and stearic fatty acids directly modulated I(Na), inducing primarily tonic block. Greater block was seen with linolenic acid as compared with stearic acid. Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine-induced I(Na) block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels.

A 43-year-old woman with a medical history significant only for hepatitis B carrier status presented to an emergency department with generalized weakness, dizziness, nausea, and diarrhea 36 h after eating an estimated 170 g of sautéed Lepiota subincarnata J.E. Lange (basionym Lepiota josserandii). Laboratory evaluation revealed profound metabolic acidosis with mild transaminitis, mild coagulopathy, and renal insufficiency. Marked biochemical evidence of pancreatitis was present prior to significant hepatotoxicity. The patient ultimately required liver transplantation on hospital day 7 and was discharged home on hospital day 12.