Toxicology Rounds: LET Recommendations Fall Short

Gussow, Leon MD

doi: 10.1097/01.EEM.0000515675.99305.17
Toxicology Rounds

Dr. Gussow is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Read his blog at www.thepoisonreview.com, follow him on Twitter @poisonreview, and read his past columns at http://bit.ly/EMN-ToxRounds.

Article Outline

An enormous amount of work and an elaborate methodological framework went into creating the recommendations for intravenous lipid emulsion therapy in poisoning, and it's disappointing to say that the results are, well, disappointing.

The American Academy of Clinical Toxicology tasked a Lipid Emulsion Therapy (LET) workgroup several years ago with establishing practice recommendations to assist clinicians in deciding when and how to use lipid emulsion in treating poisoned patients.

The project was massive, producing six papers totaling 139 pages that cover specific topics such as adverse events and laboratory interference caused by lipid emulsion. A total of 25 authors reviewed hundreds of animal studies and case reports, employing obscure research techniques such as the two-round modified Delphi technique and the RAND/UCLA Appropriateness Method. The group published its results in a summary article, “Evidence-based Recommendations on the Use of Intravenous Lipid Emulsion Therapy in Poisoning.” (Clin Toxicol 2016;54:899.)

The authors support using LET in cardiac arrest or life-threatening toxicity for exposure to the local anesthetic bupivacaine, an indication already considered routine practice among anesthesiologists and procedural pain specialists. The workgroup issued “neutral” recommendations regarding LET in all other cardiac arrest scenarios and most situations involving life-threatening toxicity, reflecting the workgroup's self-described “caution to make recommendations for or against a therapy where so little moderate or high-quality human data exist.”

This caution is well taken, as is the observation that good data relating to the questions asked by the workgroup are sparse. We must ask, however, what is the point of doing a systematic review given the lack of data? Issuing neutral recommendations all around is certainly honest, but it's not useful.

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LET Takeaways

These papers do represent a helpful compendium of the published LET literature through 2015. If one were to read all six articles, a drudgery I don't recommend, it is possible to come away with some valuable lessons.

LET can interfere with various laboratory tests: The effect of LET on critical laboratory values, which are dependent on the dose and the measuring technology, is somewhat unpredictable. Previous case reports found spuriously low hepatic transaminase levels after LET was administered; others have documented misleadingly high amylase results. Ultracentrifugation can sometimes but not always enable the laboratory to determine basic critical values. The key points for the clinician are to draw blood samples before administering LET, be skeptical of unusual lab results obtained after giving LET, and communicate with your laboratory about potential interference and possible corrective measures.

Limit administered volume of lipid emulsion: The incidence of most adverse effects associated with the infusion of lipid emulsion is directly related to the dose and rate of administration. The workgroup suggests using the lowest possible dose to treat poisonings. Of course, no one really knows what the lowest possible dose or maximum safe dose really is in each case. The workgroup suggests following established guidelines for lipid emulsion related to parenteral nutrition. The maximum daily dose in adults receiving intravenous lipids for nutritional support is 12.5 mL/kg (20%), according to the U.S. Food and Drug Administration. A poisoning treatment protocol recently proposed by Guy Weinberg, MD, and his group at the University of Illinois-Chicago would keep the total dose below this limit. All dose calculations should be made on lean (ideal) body weight. (See table.)

Consider interactions between LET and other medications: Some members of the workgroup expressed concern that lipid emulsion might interfere with critical care drugs such as epinephrine. I am not aware of evidence supporting this, but at least one in vitro study indicated that mixing LET with some resuscitation drugs could disrupt the stability of the lipid emulsion, resulting in the formation of large fat droplets. (SOJ Pharm PharmSci 2014;1[1]:3.) It might be best to administer other medications in a line separate from that delivering LET.

Do not use LET when it is unnecessary or there are better options: Besides acute local anesthetic toxicity, the workgroup generally suggests not using LET as first-line therapy over general supportive care or specific treatment. This is an unremarkable recommendation because no toxicologist, poison center, or protocol would suggest otherwise. This still-unresolved question concerns when to pull the trigger on LET in individual cases.

The available literature on LET comprises animal studies, case reports, and small case series — low quality data — and the workgroup is somewhat disingenuous in calling its recommendations “evidence-based” though they admit evidence reviewed was “very low quality.” It seems this project was somewhat misguided from the beginning, though it is valuable to have an up-to-date list of LET citations.

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Suggested Dosing for Lipid Emulsion (20%) Therapy

* Bolus 1.5 mL/kg (lean body mass)

* Infusion 0.25 mL/kg/min over three minutes

* Infusion 0.025 mL/kg/min as needed for up to 6.5 hours

Source: Ann Emerg Med 2015;66(2):185.

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