Additional dose-response experiments in the same study found that when 20% lipid emulsion was given during resuscitation after the intravenous bupivacaine bolus dose (post-treatment) the LD50 of bupivacaine was increased from 12.5 mg/kg to 18 mg/kg. This observation led to animal studies that ultimately identified the benefit of ILE resuscitation.Įxperiments demonstrated that rats pretreated with lipid became resistant to bupivacaine-induced cardiac effects, as a larger dose of bupivacaine was required to induce asystole. This case led to studies of the potential interaction of bupivacaine and elements of the carnitine cycle that later confirmed bupivacaine potently inhibits the mitochondrial enzyme carnitine-acylcarnitine translocase. described a patient with severe carnitine deficiency who suffered a cardiac arrest from only 22 mg of bupivacaine administered subcutaneously with injection of tumescent solution during a general anesthetic. ILE was initially identified as an antidote for LAST, the most feared complication of regional anesthesia. These events all appeared to resist standard forms of resuscitation. Long acting lipophilic local anesthetics such as bupivacaine and etidocaine were implicated in several fatal cardiac arrests reported in 1979 by Albright. Administration of any formulation of ILE and a range of outcome measures (mortality, hemodynamics, mental status, cardiac function, adverse effects) were considered.Ĭardiotoxicity resulting from bupivacaine and other local anesthetics has been the subject of laboratory investigation for over three decades. Relevant articles were gathered by the authors' independent searches of multiple bibliographic databases. This article focuses on the history of lipid resucitation, its theorized mechanisms of action, and its use in local and non-LA drug overdoses. Recent research has focused on the efficacy of lipid emulsion in resuscitating patients from overdoses of lipophilic, non-LA agents. Lipid therapy has also been utilized in patients suffering from poisonings other than those involving LA toxicities. Subsequent case reports demonstrated rapid reversal of LAST with use of ILE often after standard resuscitative efforts had failed. Follow up studies in dogs confirmed the efficacy of ILE in treating an otherwise fatal overdose of bupivacaine, even after an interval of 20 minutes. reported the effective use of a lipid emulsion infusion in resuscitation of bupivacaine overdose in rats. LAST is generally considered to be resistant to conventional modes of resuscitation. Cardiovascular collapse is the most life-endangering complication of local anesthetic (LA) absorption or intravascular injection during regional anesthesia. Intravenous lipid emulsion (ILE) is a novel method for treating local anesthetic systemic toxicity (LAST) that also shows promise as an effective antidote for other lipophilic drug poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse.
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