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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 < 0.0001) and increased systolic blood pressure (p = 0.012) from immediately prior to ILE administration to 30 min after use. One serious and two minor adverse effects of ILE use were recorded in 48 reported cases (one case of bronchospastic reaction, one case of hyperamylasemia and one case of interference with laboratory testing). In this series of cases reported to the registry, improvements were seen for GCS in patients with central nervous system toxicity and in systolic blood pressure in shocked patients over a short time frame after the injection of ILE. Few adverse effects were recorded. Clinical trials and the reporting of drug concentrations after ILE use are necessary to further elucidate the role of ILE in clinical toxicology.

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:BackgroundLocal anaesthetic systemic toxicity (LAST) is a rare but life-threatening complication that can occur after local anaesthetic administration. Various clinical guidelines recommend an intravenous lipid emulsion as a treatment for local anaesthetic-induced cardiac arrest. However, its therapeutic application in pregnant patients has not yet been established. This scoping review aims to systematically identify and map the evidence on the efficacy and safety of intravenous lipid emulsion for treating LAST during pregnancy.MethodWe searched electronic databases (Medline, Embase and Cochrane Central Register Controlled Trials) and a clinical registry (lipidrescue.org) from inception to Sep 30, 2022. No restriction was placed on the year of publication or the language. We included any study design containing primary data on obstetric patients with signs and symptoms of LAST.ResultsAfter eliminating duplicates, we screened 8,370 titles and abstracts, retrieving 41 full-text articles. We identified 22 women who developed LAST during pregnancy and childbirth, all presented as case reports or series. The most frequent causes of LAST were drug overdose and intravascular migration of the epidural catheter followed by wrong-route drug errors (i.e. intravenous anaesthetic administration). Of the 15 women who received lipid emulsions, all survived and none sustained lasting neurological or cardiovascular damage related to LAST. No adverse events or side effects following intravenous lipid emulsion administration were reported in mothers or neonates. Five of the seven women who did not receive lipid emulsions survived; however, the other two died.ConclusionStudies on the efficacy and safety of lipids in pregnancy are scarce. Further studies with appropriate comparison groups are needed to provide more robust evidence. It will also be necessary to accumulate data-including adverse events-to enable clinicians to conduct risk-benefit analyses of lipids and to facilitate evidence-based decision-making for clinical practice.

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:BackgroundIntravenous lipid emulsions are an essential component of nutritional support for very preterm infants. Many neonatal intensive care units have transitioned from traditional soybean oil-only to fish oil-containing multicomponent lipid emulsions, but the neurodevelopmental implications have not been well-explored. The primary aim of this study was to assess extrauterine third trimester brain growth in very preterm infants supported with soybean oil-only compared to fish-oil containing multicomponent lipid emulsions; white matter development and neurobehavioral regulation at term were also investigated.MethodsHuman milk-fed very preterm infants (born less than or equal to 32 weeks' gestation) receiving either soybean oil-only (before 2019) or multicomponent (after 2019) lipid emulsions underwent quantitative brain MRI (volumetric growth and white matter development) and neurodevelopmental assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at term-equivalent age. Analyses were adjusted for age at birth and term assessments, as well as clinically significant covariates.Results92 infants (61 soybean, 31 multicomponent) were included (mean [SD] birth gestational age: 27.3 [2.3] weeks). Soybean oil-only infants demonstrated smaller brainstem volumes (β [95% CI] = -0.5 [-0.8,-0.1], p = .007); additionally less mature white matter development (mean diffusivity [MD, mm2/second x10- 3] and fractional anisotropy [FA]) in the corpus callosum (MD genu: β = 0.10 [0.01, 0.20], p = .04; splenium: β = 0.14 [0.04, 0.24], p = .006), posterior limbs of internal capsule (MD right (R): β = 0.05 [0.02, 0.08], p = .004, left (L): β = 0.04 [0.01, 0.08], p = .01; FA R: β = -0.03 [-0.06, -0.00], p = .03), and brainstem (FA R: β = 0.07 [0.04, 0.10], p < .001, L: β = 0.05 [0.02, 0.09], p = .002); and lower quality of movement (β = -0.54 [-0.97, -0.11], p = .02) and higher state-related stress (β = 1.41 [0.14, 2.83], p = .04).ConclusionsVery preterm infants supported with a fish-oil containing multicomponent compared to soybean oil-only lipid emulsion demonstrated improved regional brain growth, as well as evidence of enhanced white matter microstructural organization and neurobehavioral regulation, at term corrected age.Trial registrationClinical trial number: Not applicable.

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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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