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

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...

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Autores principales: Jaffal, Karim, Chevillard, Lucie, Mégarbane, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224337/
https://www.ncbi.nlm.nih.gov/pubmed/37242638
http://dx.doi.org/10.3390/pharmaceutics15051396
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author Jaffal, Karim
Chevillard, Lucie
Mégarbane, Bruno
author_facet Jaffal, Karim
Chevillard, Lucie
Mégarbane, Bruno
author_sort Jaffal, Karim
collection PubMed
description 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.
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spelling pubmed-102243372023-05-28 Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies Jaffal, Karim Chevillard, Lucie Mégarbane, Bruno Pharmaceutics Review 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. MDPI 2023-05-03 /pmc/articles/PMC10224337/ /pubmed/37242638 http://dx.doi.org/10.3390/pharmaceutics15051396 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Jaffal, Karim
Chevillard, Lucie
Mégarbane, Bruno
Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title_full Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title_fullStr Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title_full_unstemmed Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title_short Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies
title_sort lipid emulsion to treat acute poisonings: mechanisms of action, indications, and controversies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224337/
https://www.ncbi.nlm.nih.gov/pubmed/37242638
http://dx.doi.org/10.3390/pharmaceutics15051396
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