Intravenous lipid emulsion as antidote

Emergency physician intensivist Grant Cave and colleagues review the literature on intravenous lipid emulsion (ILE) therapy for human poisoning in this month’s Emergency Medicine Australasia

Intravenous lipid emulsion (ILE) has been demonstrated to be effective in amelioration of cardiovascular and central nervous system sequelae of local-anaesthetic and non-local-anaesthetic drug toxicity in animal models. Sequestration of lipophilic toxins to an expanded plasma lipid phase is credited as the predominant beneficial mechanism of action of ILE. Systematic review of published human experience is however lacking. We determined to report a comprehensive literature search of all human reports of ILE application in drug poisoning. Forty-two cases of ILE use (19 local-anaesthetic, 23 non-local-anaesthetic) were identified, with anecdotal reports of successful resuscitation from cardiovascular collapse and central nervous system depression associated with ILE administration in lipophilic toxin overdose. Although significant heterogeneity was observed in both agents of intoxication, and reported outcomes; case report data suggest a possible benefit of ILE in potentially life-threatening cardio-toxicity from bupivacaine, mepivacaine, ropivacaine, haloperidol, tricyclic antidepressants, lipophilic beta blockers and calcium channel blockers. Further controlled study and systematic evaluation of human cases is required to define the clinical role of ILE in acute poisonings.

Review article: Intravenous lipid emulsion as antidote: A summary of published human experience.
Emerg Med Australas. 2011 Apr;23(2):123-41
An editorial by Guy Weinberg, the researcher who first demonstrated the effect of ILE on bupivacaine toxicity, has some interesting observations and recommendations:

  • Each of the first six case reports of lipid resuscitation from local anaesthetic systemic toxicity (LAST) were noted to have one or more of either underlying ischaemia, conduction defect or low cardiac output. For patients in these susceptible groups, reduce the dose of local anaesthetics used in nerve blocks
  • There is laboratory evidence that epinephrine (adrenaline) can impair lipid resuscitation. Weinberg believes that epinephrine should be used only in small doses, if at all, in treating LAST
  • In bupivacaine toxicity, use it early rather than later, as outcomes are likely to be better when intervention occurs before tissue perfusion has been compromised and too much pressor therapy has been used

Weinberg informs us that more examples of lipid resuscitation can be found at the educational website: http://www.lipidrescue.org/ and the registry site: http://www.lipidregistry.org/.
Intravenous lipid emulsion: Why wait to save a life?
Emerg Med Australas. 2011 Apr;23(2):113-5
In his editorial Weinberg refers to the review article by Jamaty et al, whose suggested regimen included 20% ILE 1.5mL/kg bolus then 0.25–0.5 mL/kg/min for 30–60 min.

OBJECTIVE: To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients.
METHODS: We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects.
RESULTS: Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning.
CONCLUSION: The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.

Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.
Clin Toxicol (Phila). 2010 Jan;48(1):1-27
The Guidelines from the Association of Anaesthetists of Great Britain and Ireland, also endorsed by the Australian and New Zealand College of Anaesthetists, outline the dose and indications for ILE in LAST. The full guideline can be accessed by clicking the image below:

3 thoughts on “Intravenous lipid emulsion as antidote”

  1. The paper by Cave et al — while valuable as a reasonably complete and up-to-date list of references related to ILE therapy — has many flaws. These include: use of anecdotal case reports, many of which lack laboratory confirmation of toxicity; inability to control for confounding factors such as additional interventions and possible spontaneous recovery; inappropriate tool for measuring therapeutic efficacy; and possible bias in evaluation of cases. I have discussed these limitations on The Poison Review: http://bit.ly/h75C5H

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