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  1. Pharmacology. Intravenous lipid emulsion (ILE) therapy is one of the newest treatments touted for cardiovascular toxicity from fat-soluble drugs. It was first used in resuscitations from local anesthetic toxicity, particularly bupivacaine. Some animal studies have demonstrated dramatic benefits, including resuscitation from cardiac arrest, severe hypotension, and bradycardia induced by cardiotoxic drugs, but others had variable results. Anecdotal human case reports suggest that ILE might be effective for reversal of cardiovascular or neurological toxicity in some cases of local anesthetic and other poisonings but is less or not effective in others and may be subject to reporting bias in favor of positive results. Effectiveness in controlled studies with animal models has been inconsistent with human case experiences.

    1. The mechanisms for the efficacy of ILE are uncertain and several of the following have been proposed:

      1. The "lipid sink" theory—ILE may sequester lipid-soluble drugs within the intravascular compartment, making less of the drug available for tissue toxicity.

      2. ILE may provide extra fatty acids to cardiac myocyte mitochondria 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. ILE may reverse nitric oxide-induced vasodilation by inhibition of endothelial nitric oxide synthase.

    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.

  2. Indications

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

    2. Human case reports of a variety of other poisonings (tricyclic antidepressants, calcium channel blockers, beta-blockers, GABA agonists, antiarrhythmics, anticonvulsants, pesticides, diphenhydramine, sedative hypnotics, cocaine, and others) have demonstrated mixed results.

    3. In patients who are hemodynamically unstable from overdoses with fat-soluble xenobiotics, when more conventional resuscitative interventions have failed, consider ILE as adjunctive therapy for refractory hypotension. This should be reserved for life-threatening situations and not considered a standard of care.

  3. 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. ILE 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 ILE infusion may exacerbate existing pancreatitis.

      3. The manufacturer states ...

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