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      Therapeutics and Clinical Risk Management (submit here)

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      Intravenous lipid emulsion for treatment of local anesthetic toxicity

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          Abstract

          Clinical question

          Is intravenous lipid emulsion a safe and effective therapy for the reversal and treatment of local anesthetic toxicity?

          Results

          Systematic reviews, human case reports, and experimental animal studies have demonstrated the efficacy of intravenous lipid emulsion therapy in successfully reversing cardiac arrhythmias, cardiac arrest, and cardiac collapse seen with severe systemic local anesthetic toxicity. There are fewer data to support treatment of neurologic toxicities associated with local anesthetics.

          Implementation

          Intravenous lipid emulsion 20% should be available whenever patients receive large doses of local anesthetics in operating rooms and emergency departments. Various dosing protocols have been published in the medical literature. Although the dosing protocols are based on low-level evidence, a lack of major adverse events makes lipid emulsion an appropriate therapy for treating cardiotoxic symptoms induced by local anesthetics.

          Most cited references4

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          ASRA practice advisory on local anesthetic systemic toxicity.

          The American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity assimilates and summarizes current knowledge regarding the prevention, diagnosis, and treatment of this potentially fatal complication. It offers evidence-based and/or expert opinion-based recommendations for all physicians and advanced practitioners who routinely administer local anesthetics in potentially toxic doses. The advisory does not address issues related to local anesthetic-related neurotoxicity, allergy, or methemoglobinemia. Recommendations are based primarily on animal and human experimental trials, case series, and case reports. When objective evidence is lacking or incomplete, recommendations are supplemented by expert opinion from the Practice Advisory Panel plus input from other experts, medical specialty groups, and open forum. Specific recommendations are offered for the prevention, diagnosis, and treatment of local anesthetic systemic toxicity.
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            Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.

            To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects. Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning. The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.
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              Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect.

              Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose. Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml x kg x min, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min. Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min. Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                5 October 2010
                2010
                2010
                : 6
                : 449-451
                Affiliations
                Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina Campus, Columbia, South Carolina, USA
                Author notes
                Correspondence: April D Miller, South Carolina College of Pharmacy, 715 Sumter Street, Columbia, SC 29208, USA, Tel +1 803 777 2265, Fax +1 803 777 1943, Email millerad@ 123456sccp.sc.edu
                Article
                tcrm-6-449
                10.2147/TCRM.S11861
                2952483
                20957136
                7369f3a1-0416-4031-8f7a-dfbe5bac17f7
                © 2010 Kosh et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 14 July 2010
                Categories
                Evidence 2 Practice

                Medicine
                intravenous lipid emulsion,local anesthetics
                Medicine
                intravenous lipid emulsion, local anesthetics

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