The Mechanisms Underlying Lipid Resuscitation Therapy

Abstract

The experimental use of lipid emulsion for local anesthetic toxicity was originally identified in 1998. It was then translated to clinical practice in 2006 and expanded to drugs other than local anesthetics in 2008. Our understanding of lipid resuscitation therapy has progressed considerably since the previous update from the American Society of Regional Anesthesia and Pain Medicine, and the scientific evidence has coalesced around specific discrete mechanisms. Intravenous lipid emulsion therapy provides a multimodal resuscitation benefit that includes both scavenging (eg, the lipid shuttle) and nonscavenging components. The intravascular lipid compartment scavenges drug from organs susceptible to toxicity and accelerates redistribution to organs where drug (eg, bupivacaine) is stored, detoxified, and later excreted. In addition, lipid exerts nonscavenging effects that include postconditioning (via activation of prosurvival kinases) along with cardiotonic and vasoconstrictive benefits. These effects protect tissue from ischemic damage and increase tissue perfusion during recovery from toxicity. Other mechanisms have diminished in favor based on lack of evidence; these include direct effects on channel currents (eg, calcium) and mass-effect overpowering a block in mitochondrial metabolism. In this narrative review, we discuss these proposed mechanisms and address questions left to answer in the field. Further work is needed, but the field has made considerable strides towards understanding the mechanisms.

The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity

“…10 Over this timeframe, a number of potential mechanisms of action were proposed, the most prominent of which involved the hypothesis that lipid emulsion infusion effectively created an intravascular lipophilic "sink" into which lipid soluble local anesthetics such as bupivacaine partitioned and were ultimately removed from the body. 17 Twenty years later, lipid emulsion therapy is believed to involve multiple mechanisms that involve active shuttling of local anesthetic away from the heart and brain, cardiotonic effects that involve the heart and/or vasculature, and postconditioning cardioprotective effects.…”

“…17 Twenty years later, lipid emulsion therapy is believed to involve multiple mechanisms that involve active shuttling of local anesthetic away from the heart and brain, cardiotonic effects that involve the heart and/or vasculature, and postconditioning cardioprotective effects. 10 …”

“…[10][11][12][13] Practitioners are encouraged to read these articles to understand the basis underlying our recommendations.…”

Lipid Emulsion Pretreatment Decreased the Maximum Total and Free Plasma Concentration of Levobupivacaine for Femoral and Sciatic Nerve Block in Below-Knee Fracture Surgery

“…Fettiplace and Weinberg 23 summarized the proposed mechanisms underlying lipid resuscitation including "lipid sink" or partitioning effect, positive inotropy, postconditioning, and the metabolism theory. The "lipid sink" or partitioning effect is that, after intravenous lipid infusion, lipid droplets are thought to exist in a discrete hydrophobic phase, following which the lipophilic drug is entrapped in the lipid fraction.…”

Lipid emulsion treatment of amlodipine toxicity

“…Highly lipid-soluble drugs, like the local anaesthetic bupivacaine, are absorbed into the emulsified lipid from organs such as the heart and brain. 10 Then, the lipid emulsion (termed a theoretical 'lipid shuttle') is transported into the liver and muscles for detoxification and storage, respectively, leading to enhanced redistribution of the lipidsoluble drug. 10 Thus, as amlodipine is highly lipid soluble and has a relatively large volume of distribution (21.4 L/kg), the lipid shuttle may contribute to lipid emulsion resuscitation in amlodipine toxicity.…”