ILE

Which administered antidote causes this appearance in a blood sample?

a) Hydroxocobalamin

b) Intravenous Lipid Emulsion (ILE)

c) Methylene blue

d) N-acetylcysteine

Answer: 

b) Intravenous Lipid Emulsion (ILE)

Discussion:

Intravenous lipid emulsion (ILE) will give the blood sample a lipemic appearance as shown. Initially used as a nutritional supplement, ILE has been studied and used as a rescue therapy for local anesthetic toxicity [1,2]. The mechanism of action is not fully understood, but the most common theory is the “lipid sink;” distributing the drugs away from the heart and brain and serving as a direct fuel source for cardiac muscle [2].  Lipid emulsion has since been utilized in overdose cases involving several lipophilic cardiovascular and neurotoxic medications with varying results [3-6]. There are several formulations of lipid emulsions commercially available, with the most commonly reported being 20% Intralipid®, a sterile fat emulsion consisting of 20% soybean oil [7].

When would you use ILE for poisoning?

  • The best evidence for the use of lipid emulsion is in severe local anesthetic systemic toxicity (LAST), predominantly with long acting anesthetics such as bupivacaine [3-6].
  • LAST is characterized by seizures, CNS depression, cardiac conduction defects, arrhythmias, and cardiac arrest.
  • Use of ILE in Non-LAST poisonings show inconsistent results [6,8].
  • ILE can be considered with serious hemodynamic/CNS instability from non-LAST toxins with high lipid solubility such as tricyclic antidepressants, verapamil, propranolol, cocaine, buproprion, and others [6].

How do you administer ILE? [8] 

  • Using the 20% Intralipid® solution, a 1.5 mL/kg initial bolus is given over 2-3 minutes.
  • The bolus may be repeated for persistent cardiovascular collapse.
  • Maintenance rate is 0.25 mL/kg/min for 3-5 minutes with reassessment.
  • If benefit, consider continuing rate at 0.025 mL/kg/min to limit cumulative dosing.
  • If re-emergence of instability consider repeat bolus or increasing infusion rate up to a maximum of 0.5 mL/kg/min.
  • Although there is no known maximal dose, 10mL/kg has been suggested.

What are complications of ILE? [9, 10]

  • Due to lipemia, interference with laboratory assays such as bilirubin, glucose, potassium
  • Acute pancreatitis
  • Adult respiratory distress syndrome
  • Possible interference with dialysis and ECMO
  • Complications are worsened by prolonged or rapid infusion
  • Unclear what the effects may be on other resuscitative medications

Bedside Pearls:

  • Lipid emulsion is the antidote for severe CNS or cardiac effects after local anesthetic toxicity.
  • It can be considered for life threatening toxicity of lipophilic cardiovascular and neurotoxic medications.
  • Lipid emulsion interferes with some common labs and can cause multiple medical complications, particularly if rapidly infused or with prolonged infusions.

This post was peer reviewed on behalf of ACMT by Bryan Judge, Louise Kao, and Diane Calello.

References

  1. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ.Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998 Apr;88(4):1071-5. PMID: 9579517
  2. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003 May-Jun;28(3):198-202. PMID: 12772136
  3. Weinberg GL. Lipid emulsion infusion: resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012 Jul;117(1):180-7.  PMID: 22627464; PMID: 4609208
  4. Shi K, Xia Y, Wang Q, Wu Y, Dong X, Chen C, Tang W, Zhang Y, Luo M, Wang X, Papadimos TJ, Xu X. The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats. Anesth Analg. 2013 Apr;116(4):804-9.  PMID: 23460566
  5. Fettiplace MR, McCabe DJ. Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis. Clin Toxicol (Phila). 2017 Aug;55(7):617-623. doi: 10.1080/15563650.2017.1288911. Epub 2017 Feb 17. Review. PMID: 28346007
  6. Gosselin S, Hoegberg LC, Hoffman RS, Graudins A, Stork CM, Thomas SH, Stellpflug SJ, Hayes BD, Levine M, Morris M, Nesbitt-Miller A, Turgeon AF, Bailey B, Calello DP, Chuang R, Bania TC, Mégarbane B, Bhalla A, Lavergne V. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning(). Clin Toxicol (Phila). 2016 Dec;54(10):899-923. doi:10.1080/15563650.2016.1214275. Epub 2016 Sep 8. Review. PMID: 27608281
  7. Food and Drug Administration. Intralipid® 20% https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017643s072,018449s039lbl.pdf. Date Accessed: 06/21/2019.
  8. American College of Medical Toxicology. ACMT Position Statement: Guidance for the Use of Intravenous Lipid Emulsion. J Med Toxicol. 2017 Mar;13(1):124-125. doi: 10.1007/s13181-016-0550-z. Epub 2016 Apr 27. Erratum in: J Med Toxicol. 2016 Dec;12 (4):416. PMID: 27121236.  PMID: 5330953
  9. Grunbaum AM, Gilfix BM, Hoffman RS, Lavergne V, Morris M, Miller-Nesbitt A, Gosselin S. Review of the effect of intravenous lipid emulsion on laboratory analyses. Clin Toxicol (Phila). 2016;54(2):92-102. doi:10.3109/15563650.2015.1115515. Epub 2015 Dec 1. Review. PMID: 26623668
  10. Hayes BD, Gosselin S, Calello DP, Nacca N, Rollins CJ, Abourbih D, Morris M, Nesbitt-Miller A, Morais JA, Lavergne V; Lipid Emulsion Workgroup. Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol (Phila). 2016 Jun;54(5):365-404.  PMID: 27035513
Austin Costa, MD

Austin Costa, MD

Emergency Medicine Resident
Carolinas Medical Center
Charlotte, NC
Austin Costa, MD

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Kathryn T. Kopec, DO

Kathryn T. Kopec, DO

Associate Professor of Emergency Medicine
Medical Toxicologist
Carolinas Medical Center
Kathryn T. Kopec, DO

@KopecToxEM

Emergency Medicine Physician & Medical Toxicologist