Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis

Abstract

Introduction: The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models.

Methods: We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran’s Q for heterogeneity and I² to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger’s test to assess for publication bias in studies.

Results: Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1–0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models.

Discussion: Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

Keywords:

• Intravenous lipid emulsion
• local anesthetics
• meta-analysis
• systematic review
• epinephrine
• toxicity

Acknowledgements

We would like to thank Leon Gussow for providing a third party to mediate discrepancies in data extraction and interpretation. We would like to thank Guy Weinberg, Marina Gitman, Robert Fettiplace, and Chris Wu for helpful discussion and comments regarding the manuscript. We provided Guy Weinberg an early set of figures to present on our behalf at the 36th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 24–27 May, 2016, Madrid, Spain.

Disclosure statement

Neither Mr. Fettiplace or Dr. McCabe receive any grant funding or have any conflicts of interest. Neither Mr. Fettiplace or Dr. McCabe has a financial or academic conflict of interest preventing neutral assessment of the literature (i.e., no committee member’s livelihood or academic career is depending on a grant studying lipid emulsion in poisoning).

Additional information

Funding

Mr. Fettiplace is supported by the University of Illinois College of Medicine (Chicago, IL, USA) and an NIH (Washington DC, USA) T32 Medical Scientist Training Program grant number 3T32GM079086-09S1. Dr. McCabe receives residency training support from Cook County Hospital (Chicago, IL, USA) and Direct Graduate Medical Education payments from The Centers of Medicare & Medicaid (Washington DC, USA).