Chapter A23: Lipid Emulsion

INTRODUCTION

The use of intravenous lipid emulsion (ILE) as an antidote is best studied for the treatment of local anesthetic systemic toxicity. However, it is also used for the treatment of overdose from other lipophilic xenobiotics such as calcium channel blockers, cyclic antidepressants, insecticides, and β-adrenergic antagonists, among many others.

HISTORY

Lipid emulsion was used as one component of parenteral nutrition for more than 40 years and is also used as a diluent for intravenous (IV) drug delivery of highly lipophilic xenobiotics such as amphotericin and propofol. More recently, liposomal suspensions containing local anesthetics such as bupivacaine were formulated that slowly release xenobiotics to increase their duration of anesthetic effect.

Bupivacaine toxicity is uncommon and sometimes refractory to Advanced Cardiac Life Support measures (Chap. 64). In the setting of local anesthetic–induced cardiovascular collapse, fatalities occur. Previously, cardiopulmonary bypass was essentially the only effective treatment for these patients.⁴ Intravenous lipid emulsion (ILE) was initially evaluated in animal models of bupivacaine toxicity with some reported efficacy. Because of the success in animal models and the limitations of other therapies, ILE was attempted in humans with local anaesthetic toxicity. Multiple reports are published that suggest benefit.^34,41 Intravenous lipid emulsion was subsequently recommended by several anesthesia and medical toxicology specialty societies for the treatment of local anesthetic toxicity, especially bupivacaine.⁵⁶ The most commonly proposed mechanism of action is the entrapment of local anesthetic in the serum lipid phase thus, likely decreasing the amount of xenobiotic at the site of toxicity.

In 2008, the first case of nonlocal anaesthetic toxicity treated with ILE was published. After this report, ILE was evaluated in animal models of toxicity from a multitude of lipid-soluble xenobiotics. Based on these studies, ILE was used in many cases of human and animal clinical poisoning.⁴¹

PHARMACOLOGY

Chemistry and Preparation

Lipid emulsion 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 lipid emulsions are linoleic, linolenic, oleic, palmitic, and stearic acids; their concentrations vary slightly in the different commercially available formulations. These long-chain triglycerides (12 or more carbons) are extracted from safflower oil or soybean oil (or both), depending on the brand.²⁵ Newer lipid emulsions containing long-chain triglycerides in addition to medium-chain triglycerides (6–12 carbons) are derived from coconut, olive, and fish oils, and their availability and cost vary.⁵¹

Phospholipids contain two fatty acids bound to glycerol and a phosphoric acid moiety that is located at the third hydroxyl group. Phospholipids are amphipathic; the nonpolar fatty acids are hydrophobic, and the polar phosphate head is hydrophilic. This imparts important pharmacologic properties to this carrier molecule, ...