The Pre-brief:
A 33-year-old female presents to the emergency department (ED) in cardiac arrest from an outpatient cosmetic procedure. EMS states that the patient received an unknown amount of a local anesthetic prior to the cardiac arrest. The ED physician suspects that the cardiac arrest may be due to local anesthetic systemic toxicity (LAST) and immediately requests for intravenous lipid emulsion (ILE) therapy.
Introduction
ILE is commonly used as a source of calories and essential fatty acids for patients requiring parenteral nutrition and, in recent years, has gained steam for the management of LAST and various other life-threatening overdoses due to lipophilic (fat-soluble) medications. Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia and occurs in approximately 1 out of every 1000 peripheral nerve blocks. Toxicity may occur after an overdose, an intravascular injection, or inadvertent systemic absorption of a local anesthetic.
ILE therapy has also been used in life-threatening overdose from lipophilic medications, including but not limited to, calcium channel blockers, beta-blockers, and cyclic antidepressants.
What is Intralipid?
Intralipid®, or intravenous fat emulsion, is the most commonly reported ILE used for drug toxicity and is composed of two types of lipids: triglycerides and phospholipids. The 20% IV fat emulsion is made up of 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water for injection. The primary triglycerides include linoleic, linolenic, oleic, palmitic, and stearic acids.
Mechanism of Action of ILE Therapy
The mechanism of action of ILE in toxicology is not clearly understood, but one of the most prevalent theories is that it acts as a “lipid sink.” According to this theory, ILE reduces the volume of distribution of the toxic agent by pulling lipid soluble drugs out of the periphery and into the intravascular compartment, effectively removing them from their site of action, reversing toxicity. Other proposed mechanisms include modulation of intracellular metabolism and activation of ion channels. Theoretically, by providing excess fatty acids, ILE overcomes blocked or inhibited enzymes by mass activation, facilitating myocardial free fatty acid utilization. In addition to the aforementioned mechanisms, it was hypothesized that ILE activates either or both calcium and sodium channels. For LAST specifically, other mechanisms include active shuttling of local anesthetics away from the heart and brain, cardiotonic effects, and postconditioning cardioprotective effects. Although there are various theorized mechanisms of action for ILE, the “lipid sink” seems the most compelling as it has demonstrated beneficial effects, most frequently in lipid soluble drug overdose, independent of the mechanism of toxicity.
When to use?
ILE therapy should be considered when there is high suspicion of LAST and hemodynamic instability, such as hypotension and/or bradycardia. If a patient decompensates while receiving regional anesthesia, ILE therapy may be considered along with standard BLS/ACLS protocols. ILE has been successfully used to treat LAST associated with various regional anesthetic techniques and multiple local anesthetics.
The Lipid Emulsion Workgroup (a collaboration of representatives from all of the major toxicology organizations) published recommendations for the use of ILE in cardiac arrest due to various medications. Based on the current data available from animal models and clinical case reports, they recommend ILE in cardiac arrest from bupivacaine toxicity and suggest its use if other therapies fail in life-threatening toxicity from other local anesthetics. In patients with hemodynamic instability and bupropion, or amitriptyline overdose, ILE may be considered after other conventional treatments have failed. For lipid soluble beta-blockers, they provide a neutral recommendation for cardiac arrest and life-threatening toxicity and for calcium channel blockers they provide a neutral recommendation for cardiac arrest and suggest not using it as first-line therapy in life-threatening toxicity.
However, it is reasonable to consider ILE in severe toxicity caused by a lipid soluble medication despite maximal treatment with standard resuscitative efforts, even if the current evidence for this treatment is low grade.
Potential complications associated with ILE include acute kidney injury, cardiac arrest, ventilation perfusion mismatch, ARDS, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection. Patient’s laboratory results may also be affected.
How do I use ILE?
A summary from the Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on LAST on the use of ILE therapy is as follows:
The American College of Medical Toxicology (ACMT) published guidance on the use of ILE for cardiotoxic, lipophilic drug overdoses. There are no validated, evidence-based dosing regimens. The guideline for dosing recommended from ACMT is the following:
The ILE infusion should be administered with a 1.2 micron filter. For all overdose cases, contact your poison control center at 1-800-222-1222.
The Debrief:
- ILE is normally thought of in the realm of parenteral nutrition, but has gained interest in the treatment of LAST and in the management of various life-threatening drug overdoses attributed to lipid-soluble medications
- ILE has various proposed mechanisms of action, with the “lipid sink” theory being the most compelling
- ILE should be considered when there is high suspicion for LAST and concomitant hemodynamic instability
- There are various case reports showing the benefit of ILE in life-threatening overdose due to lipid-soluble medications
- Call the poison control center at 1-800-222-1222 when these patients present
References:
- Burch M, McAllister R, Meyer T. Treatment of local-anesthetic toxicity with lipid emulsion therapy. Am J Health-Syst Pharm. 2011; 68: 125 – 129.
- Gosselin S, Bania T. Chapter A23: Lipid Emulsion. Goldfrank’s Toxicologic Emergencies 11th ed.
- Intralipid 20% [package insert]. Manufactured by Fresenius Kabi for Baxter Healthcare Corporation, Deerfield, IL.
- Levine M, et. al. Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol (Phila). 2016;54(3): 194 – 221.
- Gosselin S, et. al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol (Phila). 2016; 54(10): 899 – 923.
- Hayes BD, et. al. Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol (Phila). 2016;54(5): 365 – 404.
- Rothschild L, et. al. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010; 188(51): 1 – 8.
- Neal J, et. al. The third American society of regional anesthesia and pain medicine practice advisory on local anesthetic systemic toxicity: executive summary 2017. Reg Anesth Pain Med. 2018; 43: 113 – 123.
- Lipid Rescue Resuscitation – 20% lipid emulsion for rescue from drug toxicity. http://www.lipidrescue.org. Accessed December 10, 2021.
- ACMT Position Statement: Guidance for the Use of Intravenous Lipid Emulsion. J Med Toxicol. 2017; 13: 124 – 125.
