Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration

Abstract

Background: Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local anesthetics and various other drugs. The dosing regimen for the clinical toxicology indications differs significantly from those used for parenteral nutrition. The evidence on the efficacy of ILE to reverse acute toxicity of diverse substances consists mainly of case reports and animal experiments. Adverse events to ILE are important to consider when clinicians need to make a risk/benefit analysis for this therapy. Methods: Multiple publication databases were searched to identify reports of adverse effects associated with acute ILE administration for either treatment of acute poisoning or parenteral nutrition. Articles were selected based on pre-defined criteria to reflect acute use of ILE. Experimental studies and reports of adverse effects as a complication of long-term therapy exceeding 14 days were excluded. Results: The search identified 789 full-text articles, of which 114 met the study criteria. 27 were animal studies, and 87 were human studies. The adverse effects associated with acute ILE administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection. Conclusion: The emerging use of ILE administration in clinical toxicology warrants careful attention to its potential adverse effects. The dosing regimen and context of administration leading to the adverse events documented in this review are not generalizable to all clinical toxicology scenarios. Adverse effects seem to be proportional to the rate of infusion as well as total dose received. Further safety studies in humans and reporting of adverse events associated with ILE administration at the doses advocated in current clinical toxicology literature are needed.

Keywords:

• Gut and hepatotoxicity
• liver
• metabolic

Acknowledgements

Ahmed Al-Sakha, Saad Al-Juma, Daniel Morris, Tudor Botnaru, Aftab Azad, Anne-Ericka Vermette-Marcotte, and the other members of the Lipid Emulsion Workgroup retrieved the full text of the articles used in this review. Sarah Shiffert and Ellen Pak from AACT arranged meetings and conference calls. The manuscript was copyedited by Linda J. Kesselring, MS, ELS, the technical editor/writer in the Department of Emergency Medicine at the University of Maryland School of Medicine.

Disclosure statement

Drs Lavergne and Turgeon are recipients of salary support awards from the Fonds de la Recherche du Québec – Santé (FRQS). All members completed a conflict of interest form for AACT and received no honoraria. Webcast conference and rooms for meeting were provided by AACT. No member has a financial or an academic conflict of interest that prevented his/her neutral assessment of the articles reviewed in this study (i.e., no committee member’s livelihood or academic career depends on grant funding the study of lipid emulsion in poisoning).