Chapter 201. Lipid Emulsion (LE)

Pharmacology. Lipid emulsion (LE) therapy is one of the newest antidotes touted for cardiovascular toxicity from fat-soluble drugs. It was first used in resuscitations from local anesthetic toxicity, particularly bupivicaine. Animal studies have demonstrated dramatic effects, including resuscitation from cardiac arrest, severe hypotension, and bradycardia induced by cardiotoxic drugs. Anecdotal human case reports suggest it might be useful, but its efficacy and safety are not established.

1. Multiple mechanisms have been proposed for the efficacy of LE:

   1. LE may sequester lipid-soluble drugs within the intravascular compartment, making less of the drug available for tissue toxicity.

   2. LE may provide extra fatty acids for a heart unable to use its usual energy supply when stressed.

   3. Long-chain fatty acids may activate calcium channels in myocytes, augmenting further release of intracellular calcium and resulting in improved contractility.

   4. Medium- and long-chain fatty acids stimulate a rise of cytosolic calcium in pancreatic cells, causing release of insulin, which in turn may improve cardiac performance in shock.

   5. LE enhances the blood pressure rise in response to alpha-adrenergic vasopressors.

2. The infused fat particles behave like natural chylomicrons. Circulating triglycerides are quickly hydrolyzed by intravascular lipoprotein lipase, releasing free fatty acids. These fatty acids are taken up by Kupfer cells in the liver as well as the reticuloendothelial system. With large infusions, free fatty acids are also taken up by skeletal muscle and subcutaneous tissue. Any free fatty acids that enter tissues can be stored or transported into the mitochondria, where they undergo beta-oxidation.

Indications

1. The initial use of LE for overdose was based on case reports of return of spontaneous circulation in patients with local anesthetic overdoses, including overdoses of bupivacaine and mepivacaine.

2. More recent animal studies suggest efficacy of LE in toxicity from calcium channel blockers, clomipramine, and to some extent beta blockers. Human case reports have demonstrated reversal of cardiovascular toxicity in overdoses of verapamil, bupropion, lamotrigine, and amphetamine.

3. In patients who are hemodynamically unstable from overdoses with fat-soluble drugs, when more conventional interventions have failed, consider LE as adjunctive therapy for refractory hypotension, especially if it is accompanied by bradycardia.

Contraindications

1. Allergy to soy or egg products.

2. Black box warning. Neonates: Deaths have occurred in preterm infants owing to intravenous lipid accumulation in the lungs as a result of impaired clearance and elimination of the drug.

3. Relative contraindications include pulmonary disease, pancreatitis, and fat metabolism disorders.

   1. LE given too quickly in large amounts to patients with lung disease, particularly ARDS, can temporarily impair proper oxygenation.

   2. Pancreatitis has resulted after repeated doses, and LE infusion may exacerbate existing pancreatitis.

   3. The manufacturer states that abnormal fat metabolism, hyperlipidemia, and lipid nephrosis are all contraindications to the administration of LE.

Adverse Effects

1. Fat emboli syndrome. Excessive infusion of lipid emulsion may transiently increase pulmonary vascular resistance and decrease pulmonary gas diffusion, especially in patients with underlying pulmonary disease. However, 10-fold dosing errors, with infusions approaching 10 mL/kg/h for several hours, have not resulted in untoward effects. Animal studies suggest 70 mL/kg infused over 30 minutes as ...