{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:21:27Z","timestamp":1792272087459,"version":"4.4.0"},"reference-count":135,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 \u201clipid sink\u201d 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics15051396","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:33:36Z","timestamp":1683164016000},"page":"1396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies"],"prefix":"10.3390","volume":"15","author":[{"given":"Karim","family":"Jaffal","sequence":"first","affiliation":[{"name":"Department of Medical and Toxicological Critical Care, Federation of Toxicology, Lariboisi\u00e8re Hospital, 75010 Paris, France"},{"name":"INSERM UMRS-1144, Paris-Cit\u00e9 University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-9117","authenticated-orcid":false,"given":"Lucie","family":"Chevillard","sequence":"additional","affiliation":[{"name":"Department of Medical and Toxicological Critical Care, Federation of Toxicology, Lariboisi\u00e8re Hospital, 75010 Paris, France"},{"name":"INSERM UMRS-1144, Paris-Cit\u00e9 University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"M\u00e9garbane","sequence":"additional","affiliation":[{"name":"Department of Medical and Toxicological Critical Care, Federation of Toxicology, Lariboisi\u00e8re Hospital, 75010 Paris, France"},{"name":"INSERM UMRS-1144, Paris-Cit\u00e9 University, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1080\/15563650.2022.2132768","article-title":"2021 Annual report of the National Poison Data System\u00a9 (NPDS) from America\u2019s poison centers: 39th annual report","volume":"60","author":"Gummin","year":"2022","journal-title":"Clin. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3109\/15563650.2015.1121270","article-title":"Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity","volume":"54","author":"Hoegberg","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/j.1553-2712.2009.00499.x","article-title":"Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review","volume":"16","author":"Cave","year":"2009","journal-title":"Acad. Emerg. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s13054-014-0457-5","article-title":"Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients?","volume":"18","author":"Cave","year":"2014","journal-title":"Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3109\/15563650.2015.1126286","article-title":"Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity","volume":"54","author":"Levine","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/ALN.0b013e31825ad8de","article-title":"Lipid Emulsion Infusion","volume":"117","author":"Weinberg","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0140-6736(08)60270-6","article-title":"Multiple-dose activated charcoal in acute self-poisoning: A randomised controlled trial","volume":"371","author":"Eddleston","year":"2008","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3109\/15563650.2013.770154","article-title":"Position paper update: Gastric lavage for gastrointestinal decontamination","volume":"51","author":"Benson","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1097\/CCM.0000000000000274","article-title":"The intoxicated ICU patient","volume":"42","author":"Clark","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_10","first-page":"582","article-title":"Alleviation of barbiturate depression","volume":"41","author":"Russel","year":"1962","journal-title":"Anesth. Analg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/00002480-196504000-00034","article-title":"Dialysis for intoxication with lipid soluble drugs: Enhancement of glutethimide extraction with lipid dialysate","volume":"11","author":"Shinaberger","year":"1965","journal-title":"Trans. Am. Soc. Artif. Intern. Organs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1001\/jama.1968.03140030062018","article-title":"Camphor intoxication treated by lipid dialysis","volume":"203","author":"Ginn","year":"1968","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1001\/jama.1970.03170040056012","article-title":"A clinically efficient and economical lipid dialyzer. Use in treatment of glutethimide intoxication","volume":"211","author":"King","year":"1970","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3109\/15563657008990127","article-title":"Lipid-electrolyte dialysis--experimental and preliminary clinical observations","volume":"3","author":"Whang","year":"1970","journal-title":"Clin. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1365-2125.1974.tb00285.x","article-title":"Dialysis of drugs in vitro","volume":"1","author":"Clarke","year":"1974","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/BF01938365","article-title":"Influence of emulsified fat on chlorpromazine availability in rabbit blood","volume":"30","author":"Krieglstein","year":"1974","journal-title":"Experientia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1097\/00000542-199804000-00028","article-title":"Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats","volume":"88","author":"Weinberg","year":"1998","journal-title":"Anesthesiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/00115550-200305000-00005","article-title":"Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity","volume":"28","author":"Weinberg","year":"2003","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2014.11.018","article-title":"Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion","volume":"198","author":"Fettiplace","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/00000542-200510000-00026","article-title":"Propofol: The challenges of formulation","volume":"103","author":"Baker","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_21","first-page":"5","article-title":"Lipid emulsion therapy: Non-nutritive uses of lipid emulsions in anaesthesia and intensive care","volume":"21","author":"Buys","year":"2015","journal-title":"S. Afr. J. Anaesth. Analg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1177\/0148607106030004351","article-title":"New parenteral lipid emulsions for clinical use","volume":"30","author":"Waitzberg","year":"2006","journal-title":"J. Parenter. Enteral Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1208\/s12249-010-9526-5","article-title":"Injectable lipid emulsions-advancements, opportunities and challenges","volume":"11","author":"Hippalgaonkar","year":"2010","journal-title":"Aaps Pharm. Sci. Tech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.plipres.2004.09.001","article-title":"Oil-in-water lipid emulsions: Implications for parenteral and ocular delivering systems","volume":"43","author":"Tamilvanan","year":"2004","journal-title":"Prog. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.addr.2017.04.003","article-title":"Nanoformulation-based sequential combination cancer therapy","volume":"115","author":"Shim","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nnano.2007.339","article-title":"Injectable nanocarriers for biodetoxification","volume":"2","author":"Leroux","year":"2007","journal-title":"Nat. Nanotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.2217\/nnm.14.168","article-title":"Challenges and opportunities in developing nanoparticles for detoxification","volume":"9","author":"Qu","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00000542-198408000-00003","article-title":"The influence of lactic acid on the serum protein binding of bupivacaine: Species differences","volume":"61","author":"Coyle","year":"1984","journal-title":"Anesthesiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/ALN.0b013e318242a5f1","article-title":"A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion","volume":"116","author":"Ruan","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1365-2710.1993.tb00578.x","article-title":"Physicochemical properties of parenteral fat emulsions containing 20% triglyceride; Intralipid and Ivelip","volume":"18","author":"Washington","year":"1993","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1021\/mp0700209","article-title":"The rule of five revisited: Applying log D in place of log P in drug-likeness filters","volume":"4","author":"Bhal","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jconrel.2022.04.011","article-title":"Prediction of drug capturing by lipid emulsions in vivo for the treatment of a drug overdose","volume":"346","author":"Li","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s13181-013-0375-y","article-title":"LIPAEMIC report: Results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry","volume":"10","author":"Cave","year":"2014","journal-title":"J. Med. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/0885066612445978","article-title":"Intravenous lipid emulsion for the treatment of drug toxicity","volume":"29","author":"Ozcan","year":"2014","journal-title":"J. Intensive Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1093\/bja\/aeu010","article-title":"Lipid rescue: Does the sink hold water? And other controversies","volume":"112","author":"Harvey","year":"2014","journal-title":"Br. J. Anaesth."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1097\/ALN.0b013e318194b252","article-title":"Binding of long-lasting local anesthetics to lipid emulsions","volume":"110","author":"Mazoit","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1007\/s00216-009-3435-z","article-title":"Interaction of a commercial lipid dispersion and local anesthetics in human plasma: Implications for drug trapping by \u201clipid-sinks\u201d","volume":"396","author":"Laine","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1002\/jssc.201101038","article-title":"Comparison of lipid sinks in sequestering common intoxicating drugs","volume":"35","author":"Holopainen","year":"2012","journal-title":"J. Sep. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1213\/ANE.0000000000000011","article-title":"The effect of lipid emulsion on intracellular bupivacaine as a mechanism of lipid resuscitation: An electrophysiological study using voltage-gated proton channels","volume":"117","author":"Hori","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18683","DOI":"10.1038\/s41598-022-21790-4","article-title":"Predicting the efficacy of opioid sequestration by intravenous lipid emulsion using biologically relevant in vitro models of drug distribution","volume":"12","author":"Tikhomirov","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3109\/15563650.2011.617308","article-title":"Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies","volume":"49","author":"French","year":"2011","journal-title":"Clin. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.rapm.2005.02.011","article-title":"Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart","volume":"31","author":"Weinberg","year":"2006","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1097\/CCM.0b013e3181f17d85","article-title":"Partitioning effect in lipid resuscitation: Further evidence for the lipid sink","volume":"38","author":"Weinberg","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.annemergmed.2010.06.001","article-title":"Intravenous lipid emulsion sequesters amiodarone in plasma and eliminates its hypotensive action in pigs","volume":"56","author":"Niiya","year":"2010","journal-title":"Ann. Emerg. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1742-7843.2011.00826.x","article-title":"No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline","volume":"110","author":"Litonius","year":"2012","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1553-2712.2008.00313.x","article-title":"Correlation of plasma and peritoneal diasylate clomipramine concentration with hemodynamic recovery after Intralipid infusion in rabbits","volume":"16","author":"Harvey","year":"2009","journal-title":"Acad. Emerg. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1097\/ALN.0b013e31828ce74d","article-title":"Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic toxicity","volume":"118","author":"Kuo","year":"2013","journal-title":"Anesthesiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3109\/15563650.2013.866242","article-title":"Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink","volume":"52","author":"Harvey","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1865-1380-5-8","article-title":"Case report: Successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome","volume":"5","author":"Harvey","year":"2012","journal-title":"Int. J. Emerg. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3109\/15563650.2011.572556","article-title":"Serum verapamil concentrations before and after Intralipid\u00ae therapy during treatment of an overdose","volume":"49","author":"French","year":"2011","journal-title":"Clin. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1213\/ANE.0b013e318284123e","article-title":"The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats","volume":"116","author":"Shi","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1365-2044.2012.07056.x","article-title":"Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans","volume":"67","author":"Litonius","year":"2012","journal-title":"Anaesthesia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/bcpt.12082","article-title":"Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration-An experimental intoxication study in pigs","volume":"113","author":"Heinonen","year":"2013","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/bcpt.12321","article-title":"Intravenous lipid emulsion given to volunteers does not affect symptoms of lidocaine brain toxicity","volume":"116","author":"Heinonen","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/ALN.0000000000001230","article-title":"Effect of Intralipid\u00ae on the dose of ropivacaine or levobupivacaine tolerated by volunteers: A clinical and pharmacokinetic study","volume":"125","author":"Dureau","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3109\/15563650.2013.778994","article-title":"An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose","volume":"51","author":"Perichon","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/15563650.2013.766748","article-title":"Effect of intravenous lipid emulsion and octreotide on enteric thiopentone absorption; a pilot study","volume":"51","author":"Harvey","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1213\/ane.0b013e3181979e17","article-title":"Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest","volume":"108","author":"Marwick","year":"2009","journal-title":"Anesth. Analg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1097\/CCM.0b013e318287f874","article-title":"Rapid cardiotonic effects of lipid emulsion infusion","volume":"41","author":"Fettiplace","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1213\/01.ane.0000248220.01320.58","article-title":"The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart","volume":"104","author":"Stehr","year":"2007","journal-title":"Anesth. Analg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1197\/j.aem.2007.04.006","article-title":"Hemodynamic effects of intralipid after verapamil intoxication may be due to a direct effect of fatty acids on myocardial calcium channels","volume":"14","author":"Gueret","year":"2007","journal-title":"Acad. Emerg. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1097\/CCM.0b013e3182544f48","article-title":"Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats","volume":"40","author":"Partownavid","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/ALN.0000000000000974","article-title":"Insulin signaling in bupivacaine-induced cardiac toxicity: Sensitization during recovery and potentiation by lipid emulsion","volume":"124","author":"Fettiplace","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0008-6363(00)00151-6","article-title":"Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts","volume":"48","author":"DeWolff","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"367","DOI":"10.7150\/ijbs.8048","article-title":"Systemic blockage of nitric oxide synthase by L-NAME increases left ventricular systolic pressure, which is not augmented further by Intralipid\u00ae","volume":"10","author":"Shin","year":"2014","journal-title":"Int. J. Biol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/00005344-200012000-00001","article-title":"Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery","volume":"36","author":"Osanai","year":"2000","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"R1674","DOI":"10.1152\/ajpregu.2001.280.6.R1674","article-title":"Hemodynamic effects of lipids in humans","volume":"280","author":"Stojiljkovic","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s12012-013-9218-y","article-title":"Effect of two lipid emulsions on reversing high-dose levobupivacaine-induced reduced vasoconstriction in the rat aortas","volume":"13","author":"Ok","year":"2013","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1161\/01.HYP.32.4.693","article-title":"Intralipid enhances alpha1-adrenergic receptor mediated pressor sensitivity","volume":"32","author":"Haastrup","year":"1998","journal-title":"Hypertension"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"729","DOI":"10.3109\/15563650.2011.613399","article-title":"Fatty acids antagonize bupivacaine-induced I(Na) blockade","volume":"49","author":"Mottram","year":"2011","journal-title":"Clin. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1213\/ANE.0b013e3182a1af78","article-title":"The distinct effects of lipid emulsions used for \u201clipid resuscitation\u201d on gating and bupivacaine-induced inhibition of the cardiac sodium channel Nav1.5","volume":"117","author":"Nadrowitz","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1097\/ALN.0b013e3182a66d4d","article-title":"Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle","volume":"120","author":"Wagner","year":"2014","journal-title":"Anesthesiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3109\/15563650.2011.590940","article-title":"Use of intravenous lipid 20% emulsion for the treatment of a voluntary intoxication of flecainide with refractory shock","volume":"49","author":"Moussot","year":"2011","journal-title":"Clin. Toxicol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.annemergmed.2013.11.017","article-title":"Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model","volume":"64","author":"Carreiro","year":"2014","journal-title":"Ann. Emerg. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/ALN.0b013e318223b8b9","article-title":"Phosphorylation of GSK-3\u03b2 mediates intralipid-induced cardioprotection against ischemia\/reperfusion injury","volume":"115","author":"Rahman","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e734","DOI":"10.1097\/CCM.0000000000000656","article-title":"Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: A comparison with therapeutic hypothermia","volume":"42","author":"Li","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/ALN.0b013e3182655e73","article-title":"Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A","volume":"117","author":"Li","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.yjmcc.2016.11.006","article-title":"Intralipid protects the heart in late pregnancy against ischemia\/reperfusion injury via Caveolin2\/STAT3\/GSK-3\u03b2 pathway","volume":"102","author":"Li","year":"2017","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lou, P.-H., Lucchinetti, E., Zhang, L., Affolter, A., Schaub, M.C., Gandhi, M., Hersberger, M., Warren, B.E., Lemieux, H., and Sobhi, H.F. (2014). The mechanism of Intralipid\u00ae-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087205"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1080\/15563650.2017.1288911","article-title":"Lipid emulsion improves survival in animal models of local anesthetic toxicity: A meta-analysis","volume":"55","author":"Fettiplace","year":"2017","journal-title":"Clin. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1080\/15563650.2018.1560461","article-title":"Comparative effectiveness of methylene blue versus intravenous lipid emulsion in a rodent model of amlodipine toxicity","volume":"57","author":"Nafea","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1213\/ANE.0000000000002707","article-title":"Superior efficacy of lipid emulsion infusion over serum alkalinization in reversing amitriptyline-induced cardiotoxicity in guinea pig","volume":"126","author":"Tsujikawa","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15563650.2020.1814316","article-title":"Heterogeneity and bias in animal models of lipid emulsion therapy: A systematic review and meta-analysis","volume":"59","author":"Fettiplace","year":"2021","journal-title":"Clin. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1080\/15563650.2016.1214275","article-title":"Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning","volume":"54","author":"Gosselin","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: An emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3109\/15563650.2015.1052498","article-title":"Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning","volume":"53","author":"Gosselin","year":"2015","journal-title":"Clin. Toxicol."},{"key":"ref_87","first-page":"38","article-title":"Lipid emulsion improves Glasgow coma scale and decreases blood glucose level in the setting of acute non-local anesthetic drug poisoning--a randomized controlled trial","volume":"16","author":"Taftachi","year":"2012","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3109\/15563650.2013.821129","article-title":"Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication","volume":"51","author":"Gil","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1213\/01.ane.0000286176.55971.f0","article-title":"Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child","volume":"106","author":"Ludot","year":"2008","journal-title":"Anesth. Analg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.annemergmed.2015.01.020","article-title":"Confusion about infusion: Rational volume limits for intravenous lipid emulsion during treatment of oral overdoses","volume":"66","author":"Fettiplace","year":"2015","journal-title":"Ann. Emerg. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1345\/aph.1M626","article-title":"State of the art review: Intravenous fat emulsions: Current applications, safety profile, and clinical implications","volume":"44","author":"Mirtallo","year":"2010","journal-title":"Ann. Pharmacother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3109\/15563650.2015.1115515","article-title":"Review of the effect of intravenous lipid emulsion on laboratory analyses","volume":"54","author":"Grunbaum","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bpa.2014.07.002","article-title":"Guiding principles of fluid and volume therapy","volume":"28","author":"Aditianingsih","year":"2014","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/ALN.0b013e3181afde0a","article-title":"Epinephrine impairs lipid resuscitation from bupivacaine overdose: A threshold effect","volume":"111","author":"Hiller","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.annfar.2010.08.003","article-title":"Early administration of lipid rescue after initial signs of local anesthetic-induced systemic toxicity","volume":"29","author":"Benhamou","year":"2010","journal-title":"Ann. Fr. Anesth. Reanim."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3109\/15563650.2016.1151528","article-title":"Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration","volume":"54","author":"Hayes","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1515\/cclm-2018-0430","article-title":"Effects of high-dose, intravenous lipid emulsion on laboratory tests in humans: A randomized, placebo-controlled, double-blind, clinical crossover trial","volume":"56","author":"Petersen","year":"2018","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3109\/15563650.2015.1004582","article-title":"What are the adverse effects associated with the combination use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient?","volume":"53","author":"Lee","year":"2015","journal-title":"Clin. Toxicol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.3109\/15563650.2014.981824","article-title":"Continuous renal replacement therapy circuit failure after antidote administration","volume":"52","author":"Jeong","year":"2008","journal-title":"Clin. Toxicol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/15563650.2017.1341633","article-title":"High-dose intravenous lipid emulsion affecting successful initiation of continuous venovenous hemofiltration and extracorporeal membrane oxygenation","volume":"56","author":"Sin","year":"2018","journal-title":"Clin. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/17512433.2019.1621163","article-title":"Literature review of the evidence regarding intravenous lipid administration in drug-induced cardiotoxicity","volume":"12","author":"Paneta","year":"2019","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/0960327116679715","article-title":"No support for lipid rescue in oral poisoning: A systematic review and analysis of 160 published cases","volume":"36","author":"Forsberg","year":"2017","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Lee, S.H., and Sohn, J.T. The underlying mechanism of lipid emulsion resuscitation for drug toxicity: A narrative review. Korean J. Anesthesiol., 2023. in press.","DOI":"10.4097\/kja.23031"},{"key":"ref_104","first-page":"421","article-title":"Lipid emulsions in the treatment of intoxications by local anesthesics and other drugs. Review of mechanisms of action and recommendations for use","volume":"69","author":"Fernandez","year":"2021","journal-title":"Rev. Esp. Anestesiol. Reanim. (Engl. Ed.)"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/PEC.0000000000002828","article-title":"Lipid emulsion treatment for drug toxicity caused by nonlocal anesthetic drugs in pediatric patients: A narrative review","volume":"39","author":"Lee","year":"2023","journal-title":"Pediatr. Emerg. Care"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.ajem.2018.11.022","article-title":"Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis","volume":"37","author":"Yu","year":"2019","journal-title":"Am. J. Emerg. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1080\/15563650.2021.2013496","article-title":"Lipid emulsion for the treatment of acute organophosphate poisoning: An Open-Label randomized trial","volume":"60","author":"Pannu","year":"2022","journal-title":"Clin. Toxicol."},{"key":"ref_108","first-page":"e20","article-title":"Effects of intravenous lipid emulsion on tramadol-induced seizure; a randomized clinical trial","volume":"9","author":"Kazemifar","year":"2021","journal-title":"Arch. Acad. Emerg. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1177\/0960327120983873","article-title":"Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning","volume":"40","author":"Lgazzar","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1080\/15563650.2020.1746800","article-title":"Antidotal use of lipid emulsion-The pendulum swings","volume":"58","author":"Mullins","year":"2020","journal-title":"Clin. Toxicol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1080\/15563650.2020.1761025","article-title":"Comment on antidotal use of lipid emulsion-The pendulum swings","volume":"58","author":"Hoffman","year":"2020","journal-title":"Clin. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/15563650.2018.1504954","article-title":"Utilization of lipid emulsion therapy in fatal overdose cases: An observational study","volume":"57","author":"Smolinske","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/01480545.2016.1277736","article-title":"A review on nanoparticle-based technologies for biodetoxification","volume":"40","author":"Muhammad","year":"2017","journal-title":"Drug Chem. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"290ps14","DOI":"10.1126\/scitranslmed.3008736","article-title":"Nano-antidotes for drug overdose and poisoning","volume":"7","author":"Forster","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.addr.2015.06.004","article-title":"Parenteral emulsions and liposomes to treat drug overdose","volume":"90","author":"Damitz","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1021\/ja0394479","article-title":"Pluronic microemulsions as nanoreservoirs for extraction of bupivacaine from normal saline","volume":"126","author":"Varshney","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ijpharm.2015.03.057","article-title":"Kinetically stable propofol emulsions with reduced free drug concentration for intravenous delivery","volume":"486","author":"Damitz","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: From concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1126\/science.180.4083.300","article-title":"Intracellular plutonium: Removal by liposome-encapsulated chelating agent","volume":"180","author":"Rahman","year":"1973","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.bbamem.2006.08.005","article-title":"Characterization and in vitro evaluation of spherulites as sequestering vesicles with potential application in drug detoxification","volume":"1758","author":"Dhanikula","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.cardiores.2007.02.017","article-title":"Rescue of amitriptyline-intoxicated hearts with nanosized vesicles","volume":"74","author":"Dhanikula","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1021\/nn101924a","article-title":"Transmembrane pH-gradient liposomes to treat cardiovascular drug intoxication","volume":"4","author":"Bertrand","year":"2010","journal-title":"ACS Nano"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1016\/j.biomaterials.2012.01.042","article-title":"Treatment of calcium channel blocker-induced cardiovascular toxicity with drug scavenging liposomes","volume":"33","author":"Forster","year":"2012","journal-title":"Biomaterials"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"258ra141","DOI":"10.1126\/scitranslmed.3009135","article-title":"Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites","volume":"6","author":"Forster","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jcis.2006.03.065","article-title":"Sequestration of amitriptyline by liposomes","volume":"300","author":"Fallon","year":"2006","journal-title":"J. Colloid Interface Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jcis.2007.11.018","article-title":"Uptake of amitriptyline and nortriptyline with liposomes, proteins, and serum: Implications for drug detoxification","volume":"319","author":"Howell","year":"2008","journal-title":"J. Colloid Interface Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"12056","DOI":"10.1021\/la901644h","article-title":"Interaction of cationic drugs with liposomes","volume":"25","author":"Howell","year":"2008","journal-title":"Langmuir"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.chembiol.2009.08.011","article-title":"Inorganic mercury detection and controlled release of chelating agents from ion-responsive liposomes","volume":"16","author":"Yigit","year":"2009","journal-title":"Chem. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/HP.0b013e3181b9dbbc","article-title":"Aminothiol receptors for decorporation of intravenously administered 60Co in the rat","volume":"98","author":"Levitskaia","year":"2010","journal-title":"Health Phys."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1177\/0748233711416946","article-title":"Nanoencapsulated and microencapsulated enzymes in drug antidotal therapy","volume":"28","author":"Szilasi","year":"2012","journal-title":"Toxicol. Ind. Health"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1111\/acem.12224","article-title":"Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in rabbit clomipramine toxicity","volume":"20","author":"Cave","year":"2013","journal-title":"Acad. Emerg. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jconrel.2014.06.007","article-title":"Lipid nanoparticles: Drug localization is substance-specific and achievable load depends on the size and physical state of the particles","volume":"189","author":"Kupetz","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jconrel.2011.09.098","article-title":"The journey of a drug-carrier in the body: An anatomo-physiological perspective","volume":"161","author":"Bertrand","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ijpharm.2014.06.024","article-title":"A continuous flow method for estimation of drug release rates from emulsion formulations","volume":"472","author":"Salmela","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"72S","DOI":"10.1177\/0148607115595979","article-title":"Past, present, and future of lipid resuscitation therapy","volume":"39","author":"Fettiplace","year":"2015","journal-title":"J. Parenter. Enteral Nutr."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:28:33Z","timestamp":1760124513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":135,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["pharmaceutics15051396"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15051396","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]}}}