Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning

Abstract

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

Past, Present, and Future of Lipid Resuscitation Therapy

“…All these retrospective analyses have come to the conclusion that the evidence is strongest for the treatment of LAST, but evidence for treating toxicity aside from LAST is less compelling. Recently, a working group was formed by the American Academy of Clinical Toxicologists with the explicit purpose of providing guidelines for the use of LRT in both local anesthetic and overdose from other drugs based on the available evidence 95 . While it is obvious that robust clinical trials are needed for nonlocal anesthetic toxicity (with appropriate dosing and timing), in the interim, lipid will remain as a “Lazarus” measure for many overdoses.…”

“…Finally, we know the lipid is effective when delivered via the intraosseous space, and this may change treatment options in high‐risk or battlefield overdose situations, but further research is needed 180 . As mentioned earlier, a working group has been developed to provide recommendations for use of LRT in both local anesthetic and non–local anesthetic toxicity 95 . Standardization of use is a worthy goal for current usage parameters of LRT as a “Lazarus” measure with bolus + infusion derived from LAST treatment recommendations.…”

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

“…Hence, there are many open questions remaining such as the mechanism of ILE action, the optimal time and dose of ILE administration [9,11,13], and the interaction of ILE with other therapy being administrated. A working group charged with developing evidence-based recommendations on the use of ILE therapy in poisoning has recently been formed [14].…”

The Effect of L-Carnitine and Intralipid Emulsion in Acute Verapamil Cardiotoxicity in Albino Rats

“…Likewise, ILE as an adjunctive antidote used in selected critically ill poisoned patients is well known to ameliorate toxicity of lipid soluble drugs (Gosselin et al, 2015), giving the fact that verapamil is a lipid soluble drug, it is possible that the mechanism for the effect of ILE is sequestration of fat-soluble toxins within an intravascular lipid compartment (Cave and Harvey, 2014). The "lipid sink" theory explains that infusion of a large amount of lipids to the blood can move the lipophilic substances away from the affected tissues and dissolve them in the plasma (Mir and Rasool, 2014).This eventually reduces free drug availability and may also enhance clearance because intralipid chylomicrons deliver compounds to the liver within the lipid phase.…”