Download intravenous fat emulsion: an emerging antidote for acute local

World Journal of Engineering
To identify the relevant literature,
both authors searched multiple computerized
databases, including PubMed as well as the
website (www.lipidrescue.org), a non-forprofit, open-access, educational website that
compiles voluntarily reports by physicians
of acute local anesthetic-induced systemic
toxicity treated with intravenous fat
emulsion. The following keywords were
used: local anesthetic, toxicity, intravenous
fat emulsion, lipid emulsion, lipid rescue,
Intralipid® and resuscitation.
All relevant articles and abstracts of
major conferences in clinical toxicology,
emergency medicine and anesthesiology
were then retrieved and reviewed, including
references, by both authors. Pertinent
demographic and clinical information was
extracted in each case. The primary outcome
measure was mortality after intravenous
administration of fat emulsion during
cardiopulmonary resuscitation from local
anesthetic-induced cardiac arrest.
Intravenous Fat Nanoemulsion: a Novel
Antidote for Local Anesthetic-Induced
Systemic Toxicity in Humans
Guy Weinberg1,3 and Israel Rubinstein2,3
Departments of Anesthesiology1
and Medicine2
University of Illinois at Chicago and Jesse
Brown VA Medical Center3
Chicago, Illinois 60612
U.S.A
Introduction
Administration of local anesthetics,
such as during nerve block and
bronchoscopy, is associated infrequently
with acute systemic toxicity that, in some
patients, progresses to refractory
cardiovascular collapse and death.
Unfortunately, no antidote(s) is
presently available to reverse acute local
anesthetic-induced cardiovascular collapse.
Hence, this life-threatening condition still
represents an unmet medical need.
To this end, intravenous fat
nanoemulsion, such as Intralipid® 20%
(hydrodynamic diameter, ~300-400 nm)
which is approved for use in patients
requiring parenteral nutrition, has recently
been shown to reverse acute local
anesthetic-induced cardiovascular collapse
in both animals and humans (Figure 1).
Currently, the use of intravenous fat
nanoemulsion as antidote in patients with
local anesthetic-induced cardiac arrest is
endorsed by several professional
anesthesiology societies worldwide as well
as by the American Heart Association.
Accordingly, the purpose of this
study was to review the literature on the
salutary effects of Intravenous fat
nanoemulsion in patients with local
anesthetic induced cardiac arrest.
Results
The first case report of successful
treatment of acute local anesthetic-induced
cardiovascular collapse with intravenous fat
nanoemulsion (Intralipid® 20%) in humans
was reported in 2006. Similar favorable
outcome has since been reported in 58
additional patients.
Incidence among males and females
was similar. Age ranged from 3 days to 92
years and weight from 3.2 to 85 kg. All
patients made complete uneventful recovery
with no serious adverse events reported.
Discussion
In this review, we sought to
summarize published human experience
with intravenous fat nanoemulsion as
antidote for local anesthetic-induced cardiac
arrest that does not respond to conventional
measures. Although the number of reported
cases is limited, the results of this review
Methods
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World Journal of Engineering
indicate that this novel treatment modality
which is used off-label could save lives.
The mechanism(s) underlying the
salutary effects of intravenous fat
nanoemulsion (Intralipid® 20%) in local
anesthetic-induced cardiac arrest in humans
is uncertain.
Given its rapid onset of action,
usually within one minute, it is postulated
that intravenous fat nanoemulsion creates an
intravascular fat compartment (‘lipid sink’)
into which lipophilic (hydrophobic) local
anesthetics, such as bupivacaine, may
preferentially partition from the heart.
Migration of local anesthetic molecules
creates a rapid shift of the drug away from
its binding sites in the heart into the
circulating fat nanoemulsion thereby
reversing cardiac arrest. Local anestheticloaded fat nanoemulsion is then cleared
from the circulation by the liver and
metabolized to inactive drug metabolites.
The salutary effects of intra-venous
fat nanoemulsion may also be attributed, in
part, to beneficial energetic-metabolic
effects of fatty acids in the heart that restore
oxygen-energy coupling in cardiomyocyte
mitochondria.
Figure 1. The salutary effects of intravenous fat
nanoemlusion (L; Intralipid® 20%) on
bupivacaine (B)-induced cardiovascular collapse
in rat. C, chest compressions (Weinberg G,
Ripper R, Hoffman W. Reg Anesth Pain Med
2003;28:198-202).
References
1. Jamaty C, Bailey B, Larocque A,
Notebaert E, Sanogo K, Chauny JM. Lipid
emulsions in the treatment of acute
poisoning: a systematic review of human
and animal studies. Clin Toxicol (Phila).
2010;48:1-27.
2. Bern S, Akpa BS, Kuo I, Weinberg G.
Lipid Resuscitation: a life-saving antidote
for local anesthetic toxicity.
Curr Pharm Biotechnol 2011;12:313-319.
3. Cave G, Harvey M, Graudins A. Review
article: Intravenous lipid emulsion as
antidote: A summary of published human
experience. Emerg Med Australas
2011;23:123-41.
Conclusion
Intravenous fat nanoemulsion
(Intralipid® 20%) is emerging as a novel
antidote for local anesthetic-induced cardiac
arrest in humans. Whether this approach
could also be applied to other
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