Article Text

Download PDFPDF

The Mechanisms Underlying Lipid Resuscitation Therapy
  1. Michael R. Fettiplace, MD, PhD* and
  2. Guy Weinberg, MD,
  1. *Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA
  2. Department of Anesthesiology, University of Illinois Hospital and Health Sciences System
  3. Research and Development Service, Jesse Brown Veterans Affairs Medical Center, Chicago, IL
  1. Address correspondence to: Michael R. Fettiplace, MD, PhD, Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, GRB 444U Boston, MA 02114 (e-mail: fettiplace{at}


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.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • G.W. is an officer, director, shareholder and paid consultant of ResQ Pharma, Inc. He also created and maintains, an educational web site.

    The authors otherwise declare no potential conflicts of interest.

    G.W. is supported by a Veterans Affairs Merit Grant.

    The following article discusses an off-label use of lipid emulsion (eg, Intralipid) for treatment of local anesthetic systemic toxicity.