Lipid Emulsion Therapy

Intro

Intravenous lipid emulsion (ILE, also known as lipid emulsion therapy, lipid resuscitation therapy, lipid rescue, intravenous fat emulsion and Intralipid®) has been used in the past for caloric supplementation and treatment of essential fatty acid deficiency.  Since 1998, ILE has been considered for resuscitative therapy in drug-induced cardiovascular and neurologic toxicity.  The use of ILE has been best described for cardiovascular collapse and seizures caused by local anesthetic systemic toxicity (LAST) with successful animal trials and human case reports.  Subsequent to these findings, the use of ILE in LAST is recommended by the latest guidelines for the American Heart Association, American Society of Regional Anesthesia and Pain Medicine (ASRA), and the Association of Anaesthetists of Great Britain and Ireland.  ILE has also been used as a resuscitative agent for a number of lipid- and water-soluble xenobiotics that induce cardiac and/or neurologic toxicity including tricyclic antidepressants, non-dihydropyridine calcium channel blockers, bupropion, citalopram, venlafaxine, atypical anti-psychotics, beta-blockers, diphenhydramine, etc.  See table 1 for a complete list of xenobiotics for which ILE has been attempted in case reports and abstracts.

Proposed Mechanisms

The exact mechanism of action has yet to be elucidated.  Two theoretical mechanisms of action have been widely described: partitioning and enhanced metabolism.  The partitioning theory or otherwise termed the “lipid sink” theory postulates that the administration of lipids compartmentalizes the offending xenobiotic into lipid phase and away from the target receptors.  Resuscitation of toxicity mediated by xenobiotics with high lipid solubility (defined as log P, octanol:water partition coefficient, greater than 2) are more likely to be successful although the intervention has worked for water-soluble xenobiotics.  The enhanced metabolism theory argues that the infusion of triglyceride and phospholipids are capable of providing fatty acid energy source to myocytes under toxic conditions.  Myocardium is capable of utilizing fatty acids for energy although in stressed states, cardiac myocytes preferentially utilized carbohydrates, a theory that gives credence to the use of high dose insulin therapy in calcium channel and beta blocker toxicity.

Administration Recommendations

Current recommendation from ARSA for 20% lipid emulsion therapy for LAST:

  1. Bolus 1.5 mL/kg (lean body mass) intravenously over one minute (Note that the dose is in volume, not weight)
    • 100 mL for a 70 kg patient
    • Repeat bolus for persistent cardiovascular collapse
  2. Continuous infusion 0.25 mL/kg/min
    • 18 mL/min for a 70 kg patient
    • Can double the infusion rate for persistent hemodynamic instability
    • Continue infusion for at least 10 minutes after hemodynamic recovery

In the setting of persistent cardiovascular collapse or hemodynamic instability, the upper limits of therapy are also not established.  ARSA recommends the upper limits of 10 mL/kg (700 mL in a 70 kg patient) over the first 30 minutes.

Pitfalls

Elevated serum triglycerides may interfere and prevent routine laboratory analysis including serum electrolytes, hematocrit, liver function tests, and coagulation function.  A false negative aspartate transaminase (AST) resulted in the premature discontinuation of n-acetylcysteine in a co-ingestion of acetaminophen, amitriptyline, and diphenhydramine.  A 13-year-old female developed acute pancreatitis and acute respiratory distress syndrome after receiving the ARSA recommended dose of lipid emulsion therapy for a tricyclic antidepressant overdose.  Serum amylase elevations have also been reported.

Bottom Line

Unfortunately, the lack of high-quality controlled human studies precludes lipid emulsion therapy as a first-line agent for indications other than local anesthetic systemic toxicity.  In the setting of severe hemodynamic compromise caused by a lipid-soluble xenobiotic or drugs with cardiovascular and/or neurologic toxicity, lipid emulsion therapy should be considered early in the resuscitation but is not the standard of care at this time.

Discussion Questions

  • What is the evidence supporting the use of intravenous lipid emulsion (ILE) in this patient?
  • Under what other acute poisonings should emergency department providers consider the use of ILE?
  • How should ILE be administered?
  • What are reported and potential adverse effects of ILE?
  • How does ILE adversely impact laboratory monitoring?
  • What are the considerations for stocking ILE in emergency departments?

Further Reading

  1. Weinberg GL. Lipid emulsion infusion: resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117:180-7.
  2. Neal JM, Mulroy MF, Weinberg GL, American Society of Regional A, Pain M. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Regional Anesthesia and Pain Medicine. 2012;37:16-8.
  3. American College of Medical Toxicology. ACMT position statement: interim guidance for the use of lipid resuscitation therapy. Journal of Medical Toxicology. 2011;7:81-2.
  4. http://www.ncbi.nlm.nih.gov/pubmed/24338451
  5. http://www.ncbi.nlm.nih.gov/pubmed/23518248
  6. http://www.ncbi.nlm.nih.gov/pubmed/23992445
  7. http://www.ncbi.nlm.nih.gov/pubmed/23685061
  8. http://www.ncbi.nlm.nih.gov/pubmed/20923546
  9. http://www.ncbi.nlm.nih.gov/pubmed/20688937
Edited by Alex Koyfman, MD

 

Table 1: Xenobiotic overdose responses to ILE from 2006 to 2013 in case reports and abstracts.

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