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The use of intravenous fat emulsion (IFE) as an antidote is most extensively studied for the treatment of local anesthetic systemic toxicity. However, new applications that are being investigated and reported include the treatment of overdose from lipophilic xenobiotics such as calcium channel blockers, cyclic antidepressants, and β-adrenergic antagonists, among others.


IFE has been used as a source of parenteral nutrition for over 40 years and is also used as a diluent for intravenous drug delivery of highly lipophilic xenobiotics such as amphotericin and propofol. Recently, liposomal suspensions containing local anesthetics such as bupivacaine have been formulated that slowly release xenobiotics to increase the duration of anesthetic effect.

Although rare, bupivacaine toxicity is usually refractory to standard cardiac resuscitative measures (Chap. 67). In the setting of cardiovascular collapse, fatalities are frequent. Previously, cardiopulmonary bypass was the only effective treatment for these patients, as most cases were unresponsive to less invasive therapy. IFE was first evaluated in several animal models and was successful for the treatment of bupivacaine toxicity. Because of the success in animal models and the ineffectiveness of other therapies, IFE was attempted in humans and multiple case reports document apparent benefit. Subsequently, IFE was recommended by several anesthesia specialty societies for the treatment of local anesthetic toxicity. The initial proposed mechanism of action of IFE is the binding of local anesthetic in the serum lipid phase and decreasing the amount of xenobiotic at the site of toxicity. Subsequently, IFE was evaluated in several animal models of toxicity from lipid soluble xenobiotics. Based on these studies, IFE was used in several case reports of poisoning.



IFE is composed of two types of lipids: triglycerides and phospholipids. Triglycerides are hydrophobic molecules that are formed when three fatty acids are linked to one glycerol. The fatty acid chain lengths vary, producing different triglycerides. The primary triglycerides in IFE are linoleic, linolenic, oleic, palmitic, and stearic acids; their concentrations vary slightly in the different commercially available fat emulsions. These long-chain triglycerides (12 or more carbons) are extracted from safflower oil and/or soybean oil, depending on the brand of the emulsion.79 Newer fat emulsions contain long-chain triglycerides in addition to medium-chain triglycerides (6–12 carbons) derived from coconut, olive, and fish oils, but they are currently not available in the United States.54,84

Phospholipids contain two fatty acids bound to glycerol and a phosphoric acid moiety that is located at the third hydroxyl group (Fig. A20–1). Phospholipids are amphipathic; that is, the nonpolar fatty acids are hydrophobic while the polar phosphate head is hydrophilic. This imparts important pharmacological properties to this carrier molecule, allowing it to solubilize nonpolar xenobiotics in aqueous serum. IFE phospholipids are extracted from egg yolks.


Biologic membranes are comprised of ...

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