Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies

Abstract

Biodetoxification using intravenous lipid emulsion (ILE) in acute poisoning is of growing interest. As well as for local anesthetics, ILE is currently used to reverse toxicity caused by a broad-spectrum of lipophilic drugs. Both pharmacokinetic and pharmacodynamic mechanisms have been postulated to explain its possible benefits, mainly combining a scavenging effect called “lipid sink” and cardiotonic activity. Additional mechanisms based on ILE-attributed vasoactive and cytoprotective properties are still under investigation. Here, we present a narrative review on lipid resuscitation, focusing on the recent literature with advances in understanding ILE-attributed mechanisms of action and evaluating the evidence supporting ILE administration that enabled the international recommendations. Many practical aspects are still controversial, including the optimal dose, the optimal administration timing, and the optimal duration of infusion for clinical efficacy, as well as the threshold dose for adverse effects. Present evidence supports the use of ILE as first-line therapy to reverse local anesthetic-related systemic toxicity and as adjunct therapy in lipophilic non-local anesthetic drug overdoses refractory to well-established antidotes and supportive care. However, the level of evidence is low to very low, as for most other commonly used antidotes. Our review presents the internationally accepted recommendations according to the clinical poisoning scenario and provides the precautions of use to optimize the expected efficacy of ILE and limit the inconveniences of its futile administration. Based on their absorptive properties, the next generation of scavenging agents is additionally presented. Although emerging research shows great potential, several challenges need to be overcome before parenteral detoxifying agents could be considered as an established treatment for severe poisonings.

Case report: Treatment of cyclobenzaprine ingestion in two dogs with intravenous intralipid therapy

“…ILE is a relatively new and increasingly popular treatment for various toxicoses in veterinary medicine, though treatment guidelines and safety information are lacking. ILE is mostly used in the treatment of toxicity due to fat-soluble substances, and many reports exist of its utility in veterinary patients ( 16 , 18 , 22 – 24 ).…”

“…The logP of cyclobenzaprine has been reported as 4.8 ( 18 ) and 5.2 ( 19 ), making ILE a reasonable treatment option for animals that have ingested fat-soluble substances. ILE is made up of sterile, nanometer-sized droplets of triglyceride oils in water that are stabilized by phospholipid surfactants ( 16 , 22 ). The particle size of the triglyceride droplets ranges between 200 and 600 nm, similar in size to a chylomicron ( 20 ).…”

“…The particle size of the triglyceride droplets ranges between 200 and 600 nm, similar in size to a chylomicron ( 20 ). The osmolality of ILE is 270 mOsm/L, and it has a zeta potential of −45 to −40 mV, making the particle negatively charged ( 22 ).…”

“…The toxin may also bind to the negatively charged exterior of the lipid spherule for further clearance ( 20 ). The lipid shuttle theory promotes the removal of toxin from the peripheral tissue into the lipid emulsion and then shuttles it to the liver for metabolism ( 16 , 22 , 23 ). This theory hypothesizes that the toxin will be cleared faster within the lipid emulsion than it would on its own.…”

Metabolic management of accidental intoxication

“…Intravenous lipid emulsion therapy may be used in patients with local anaesthetist related systemic toxicity, especially by Bupivacaine. Its use in poisoning with other lipophilic drugs like beta blockers, calcium channel blockers, baclofen is less certain [61].…”