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LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

ABSTRACT: The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought were details of the individual patients' presenting condition, indications for ILE use, ILE administration regimen, potential complications, and of clinical outcome. Forty-eight uses of ILE were reported from 61 participating centers. Ten cases of local anesthetic systemic toxicity were reported; all (10/10) survived. Thirty-eight cases of intoxication by other agents were reported [30 decreased conscious state, 8 cardiovascular collapse (3 deaths)]. There was an elevation in GCS (p?

SUBMITTER: Cave G

PROVIDER: S-EPMC4057551 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

Cave Grant G Harvey Martyn M Willers Johann J Uncles David D Meek Tim T Picard John J Weinberg Guy G

Journal of medical toxicology : official journal of the American College of Medical Toxicology 20140601 2

The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought w ...[more]

PMID: 24414252

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Project description:Local anesthetics can cause severe toxicity when absorbed systemically. Rapid intravenous administration of lipid emulsion (LE) is the standard of care for severe local anesthetic systemic toxicity which can cause cardiovascular and central nervous system (CNS) injury. The biological mechanism by which LE alleviates CNS toxicity remains unknown and understudied. Previous research has suggested that local anesthetics cause an imbalance of excitatory and inhibitory transmission in the brain. Therefore, this study aimed to observe the effect of LE on glutamate- and GABA-induced currents in CA1 pyramidal neurons after bupivacaine-induced CNS toxicity. We further characterized post-synaptic modifications in these cells to try to elucidate the mechanism by which LE mediates bupivacaine-induced CNS toxicity. Sprague-Dawley rats received intravenous bupivacaine (1 mg kg-1 min-1 ) in either normal saline or LE (or LE without bupivacaine) for 5 min. An acute brain slice preparation and a combination of whole-cell patch clamp techniques and whole-cell recordings were used to characterize action potential properties, miniature excitatory, and inhibitory post-synaptic currents, and post-synaptic modifications of excitatory and inhibitory transmission in CA1 hippocampal pyramidal neurons. The expression level of GABAA receptors were assessed with western blotting, whereas H&E and TUNEL staining were used to assess cytoarchitecture and apoptosis levels respectively. Bupivacaine treatment significantly increased the number of observed action potentials, whereas significantly decreasing rheobase, the first interspike interval (ISI), and hyperpolarization-activated cation currents (Ih) in CA1 pyramidal neurons. LE treatment significantly reduced the frequency of miniature inhibitory post-synaptic currents and enhanced GABA-induced paired pulse ratio with 50 ms interval stimulation in bupivacaine-treated rats. Regulation of GABAA levels is a promising mechanism by which LE may ameliorate CNS toxicity after systemic absorption of bupivacaine.

Project description:The southwest coast of Florida experiences annual red tides, a type of harmful algal bloom that results from high concentrations of Karenia brevis. These dinoflagellates release lipophilic neurotoxins, known as brevetoxins, that bind to sodium channels and inhibit their inactivation, resulting in a variety of symptoms that can lead to mass sea turtle strandings. Traditional therapies for brevetoxicosis include standard and supportive care (SSC) and/or dehydration therapy; however, these treatments are slow-acting and often ineffective. Because red tide events occur annually in Florida, our objective was to test intravenous lipid emulsion (ILE) as a rapid treatment for brevetoxicosis in sea turtles and examine potential impacts on toxin clearance rates, symptom reduction, rehabilitation time, and survival rates. Sea turtles exhibiting neurological symptoms related to brevetoxicosis were brought to rehabilitation from 2018-2019. Upon admission, blood samples were collected, followed by immediate administration of 25 mg ILE/kg body mass (Intralipid® 20%) at 1 mL/min using infusion pumps. Blood samples were collected at numerous intervals post-ILE delivery and analyzed for brevetoxins using enzyme-linked immunosorbent assays. In total, nine (four subadults, one adult female, four adult males) loggerheads (Caretta caretta), five (four juvenile, one adult female) Kemp's ridleys (Lepidochelys kempii), and four juvenile green turtles (Chelonia mydas) were included in this study. We found that plasma brevetoxins declined faster compared to turtles that received only SSC. Additionally, survival rate of these patients was 94% (17/18), which is significantly higher than previous studies that used SSC and/or dehydration therapy (47%; 46/99). Nearly all symptoms were eliminated within 24-48 h, whereas using SSC, symptom elimination could take up to seven days or more. The dosage given here (25 mg/kg) was sufficient for turtles in this study, but the use of a higher dosage (50-100 mg/kg) for those animals experiencing severe symptoms may be considered. These types of fast-acting treatment plans are necessary for rehabilitation facilities that are already resource-limited. Intravenous lipid emulsion therapy has the potential to reduce rehabilitation time, save resources, and increase survival of sea turtles and other marine animals experiencing brevetoxicosis.

Dataset Information

LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

Publications

LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

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