Mechanisms underlying lipid emulsion resuscitation for drug toxicity: a narrative review.

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Currently, lipid emulsion (LE) is widely used in the treatment of local anesthetic systemic toxicity (LAST). Additionally, LE has been shown to be effective to ameliorate intractable cardiovascular collapse evoked by toxicity of lipid soluble non-local anesthetic drug. The goal of this review focused on the underlying mechanism of LE treatment in the drug toxicity including LAST, LE treatment, and further research direction. We searched the relevant articles using following keywords: "local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning" and "Intralipid or lipid emulsion". The underlying mechanism associated with LE treatment can be divided into indirect and direct effects. Lipid shuttle (indirect effect) of LE treatment is the commonly accepted mechanism: lipid phase of LE absorbs highly lipid soluble drugs ( bupivacaine) from heart and brain, and then LE containing lipid soluble drugs is delivered to muscle, adipose tissue, and liver for storage and detoxification. The direct effects are as follows: inotropic effects, supply of fatty acid, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3β phosphorylation, and inhibition of nitric oxide. These mechanisms seem to synergistically act to alleviate drug toxicity. The recommended LE dosage for LAST is as follows: bolus administration of 20% LE 1.5 ml/kg over 2 to 3 min followed by 20% LE infusion 0.25 ml/kg/min. LAST most occurs via intravenous administration. However, as drug toxicity caused by non-local anesthetic drugs occurs via oral administration, further study is needed to examine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.