How lipid rescue therapy works: it’s more than just a sink

This study, from Guy Weinberg’s lab at the University of Illinois, used a rat model of bupivacaine toxicity, along with and computational analysis, to investigate the mechanisms by which lipid rescue therapy (LRT) might act in treating overdose from local anesthetics and other cardiotoxic drugs. This is a very complex paper, and I have to admit that I found reading through the experimental protocol rough going. However, the authors findings are important and convincing. The results suggest that — as the title of the paper indicates — there are several modalities that provide benefit: LRT accelerated removal of drug from cardiac tissue within the first several minutes of administration. Once the concentration of drug in cardiac tissue was reduced below a certain threshold, lipid emulsion provided a direct inotropic effect. LRT slowed redistribution of drug from the vascular space into tissues. In summary, LRT works through both a partitioning phenomenon and cardiotonic activity. The implications for this model on use of LRT — especially at what stage of toxicity it should be administered for optimal effect — remain to be seen. Related posts: Intravenous lipid emulsion in oral overdoses: what is the optimal dosing? Excellent review of lipid rescue therapy TPR Podcast #7: Interview with Guy Weinberg about lipid rescue therapy Acute respiratory distress syndrome following intralipid emulsion therapy  Complications associated with lipid emulsion therapy Lipid resc...
Source: The Poison Review - Category: Toxicology Authors: Tags: Medical antidote bupivacaine intralipid lipid emulsion lipid rescue therapy local anesthetic triglyceride Source Type: news