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

Abstract

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.

Letter re: “Local Anesthetic Systemic Toxicity During Transversus Abdominis Plane Block With Liposomal Bupivacaine”

“…The widely accepted underlying mechanism of lipid emulsion treatment for LAST is the lipid shuttle, which is an indirect mechanism. 2 In the shuttle state, the lipid phase of the lipid emulsion absorbs the highly lipid-soluble local anesthetic bupivacaine from the heart and brain. Then, the lipid emulsion containing bupivacaine is transported to the liver, adipose tissue, and muscle for detoxification and storage.…”

“…Then, the lipid emulsion containing bupivacaine is transported to the liver, adipose tissue, and muscle for detoxification and storage. 2 In addition, the direct mechanism of lipid emulsion treatment for LAST is as follows: positive inotropic effect, fatty acid supply, inhibition of mitochondrial dysfunction, attenuation of nitric oxide release, and glycogen synthase kinase-3β phosphorylation. 2 The recommended lipid emulsion dosing regimen for treating LAST involves administering an initial intravenous bolus of 20% lipid emulsion at a rate of 1.5 mL/kg over a period of 2 to 3 minutes, followed by a continuous intravenous infusion of 20% lipid emulsion at a rate of .25 mL/kg/min.…”

“…2 In addition, the direct mechanism of lipid emulsion treatment for LAST is as follows: positive inotropic effect, fatty acid supply, inhibition of mitochondrial dysfunction, attenuation of nitric oxide release, and glycogen synthase kinase-3β phosphorylation. 2 The recommended lipid emulsion dosing regimen for treating LAST involves administering an initial intravenous bolus of 20% lipid emulsion at a rate of 1.5 mL/kg over a period of 2 to 3 minutes, followed by a continuous intravenous infusion of 20% lipid emulsion at a rate of .25 mL/kg/min. 2 Lipid emulsion should be readily available for immediate administration in all locations where local anesthetics are utilized to treat cases of LAST.…”

“…2 The recommended lipid emulsion dosing regimen for treating LAST involves administering an initial intravenous bolus of 20% lipid emulsion at a rate of 1.5 mL/kg over a period of 2 to 3 minutes, followed by a continuous intravenous infusion of 20% lipid emulsion at a rate of .25 mL/kg/min. 2 Lipid emulsion should be readily available for immediate administration in all locations where local anesthetics are utilized to treat cases of LAST. The maximum recommended doses of liposomal and plain bupivacaine with epinephrine are 266 mg (or 3.8 mg/kg) and 3 mg/kg, respectively.…”

“…Lipid emulsion is employed as a therapeutic approach for the management of LAST. 2 I would like to comment on the predisposing factors of LAST and the underlying mechanisms of lipid emulsion resuscitation used to treat LAST. As the 68-year-old patient described in this Brief Report had unintentional 20 pound weight loss over 3 months, they may have had reduced muscle mass and were elderly (>60 years), both of which are risk factor of LAST.…”