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Enthusiasm for regional anesthesia has been driven by multimodal benefits to patient outcomes. Despite widespread awareness and improved techniques (including the increasing use of ultrasound guidance for block placement), intravascular sequestration and the attendant risk of local anesthetic systemic toxicity (LAST) remains. Intravenous lipid emulsion (ILE) for the treatment of LAST has been endorsed by anesthetic regulatory societies on the basis of animal study and human case report data. The accumulated mass of reporting now permits objective interrogation of published literature.Although incompletely elucidated the mechanism of action for ILE in LAST seemingly involves beneficial effects on initial drug distribution (i.e., pharmacokinetic effects) and positive cardiotonic and vasoactive effects (i.e., pharmacokinetic effects) acting in concert. Recent systematic review by collaborating international toxicologic societies have provided reserved endorsement for ILE in bupivacaine-induced toxicity, weak support for ILE use in toxicity from other local anesthetics, and largely neutral recommendation for all other drug poisonings. Work since publication of these recommendations has concluded that there is a positive effect on survival for ILE when animal models of LAST are meta-analyzed and evidence of a positive pharmacokinetic effect for lipid in human models of LAST.Lipid emulsion remains first-line therapy (in conjunction with standard resuscitative measures) in LAST. Increasing conjecture as to the clinical efficacy of ILE in LAST, however, calls for high-quality human data to refine clinical recommendations.