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Introduction

  1. Pharmacology. Intravenous lipid emulsion (ILE) therapy has been used for the treatment of cardiovascular toxicity from fat-soluble drugs. It was first used in resuscitations from local anesthetic toxicity, in particular bupivacaine. Some animal studies have demonstrated dramatic benefits, including resuscitation from cardiac arrest, severe hypotension, and bradycardia induced by cardiotoxic drugs, while others have 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. However, the human data is mixed, of low quality, and subject to reporting bias in favor of positive results.
    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, bupropion, 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 cardiac arrest or refractory hypotension. This should be reserved for life-threatening situations and is 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.
  4. Adverse effects
    1. Fat emboli syndrome. Excessive infusion of lipid emulsion may transiently increase pulmonary vascular resistance and decrease pulmonary gas diffusion, leading to acute respiratory distress syndrome (ARDS). The risk is increased with rapid administration and larger amounts, especially in patients with underlying pulmonary disease.
    2. There is a potential for pancreatitis or exacerbation of preexisting disease.
    3. Phlebitis, macroscopic hematuria, and occlusion of continuous renal replacement therapy (CRRT) filtration equipment have been noted in case reports.
    4. Use in pregnancy. Owing to lack of data, the FDA has assigned ILE to Pregnancy Category C (Introduction) for all trimesters. However, parenteral lipid products have been used in pregnant women for nutrition without untoward effects.
  5. Drug or laboratory interactions
    1. Mixing of ILE with calcium can cause flocculation, and, therefore, simultaneous administration should be avoided.
    2. Immediately after very high infusions of ILE, tests of hemoglobin, hematocrit, white blood cell count, platelet count, electrolytes, glucose, hepatic transaminases, creatinine, creatine kinase, and coagulation studies are uninterpretable for several hours. There are also problems with co-oximetry for blood gases: oxygen saturation may not be measurable, and methemoglobin may be falsely elevated.
    3. Higher doses of vasopressors (epinephrine or vasopressin) impaired the efficacy of ILE in animal studies. It is unclear whether ILE interferes with the efficacy of other therapies commonly used in overdose.
  6. Dosage and method of administration
    1. Initial bolus. Typical starting dose in adults is 100 mL (or 1.5 mL/kg of lean body mass) of a 20% ILE suspension given over 2-3 minutes. In children, start with 1.5 mL/kg. If there is minimal or no response initially, the bolus can be repeated twice at 5-minute intervals.
    2. Infusion. Continuous infusions can be given after the initial bolus at 0.25-0.5 mL/kg/min for 30-60 minutes. A maximum dose of 10-12 mL/kg over the first 30-60 minutes has been recommended and is the total dose in most case reports with successful results.
    3. Note: The optimal dose and duration of therapy of ILE are uncertain. A patient's condition can deteriorate after initial improvement because the duration of benefit from ILE therapy may be shorter than the effects of the cardiotoxic drug.