American Journal of Emergency Medicine 57 (2022) 195–196

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American Journal of Emergency Medicine

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Lipid emulsion treatment of local anesthetic cardiovascular collapse induced by prilocaine and lidocaine toxicity
systemic toxicity in pediatric patients and were treated with lipid emulsion [1,8,9]. Third, for nutritional
support in pediatric patients, only 20% Intralipid —15 mL/kg/24 h
(3 g/kg/24 h), is recommended by the Food and Drug Administration
[10]. Similar to the adult dosage (<70 kg), the dosing regimen of lipid
To the Editor
emulsion treatment used in this pediatric patient involved 1.5 mL/kg
followed by 0.25 mL/kg/min over 1 h. However, further studies regard-
I read with interest the excellent case report and review entitled
ing the optimal dosing regimen of lipid emulsion treatment of LAST in
“Local anesthetic systemic toxicity in the pediatric patient: A case report
pediatric patients are needed [11]. This case report described that mea-
and review of the literature” recently published in the American Journal
surement of serum lidocaine concentration due to lipemic interference
of Emergency Medicine [1]. Lipid emulsions have been widely used to
induced by lipid emulsion administration cannot be performed. High-
treat local anesthetic systemic toxicity (LAST) [2]. In addition, lipid
speed centrifugation, which clears lipids in the blood, may be helpful
emulsion reportedly alleviates cardiovascular collapse induced by
in determining serum anesthetic concentration after lipid emulsion ad-
toxic doses of non-local anesthetic drugs [3]. I would like to add some
ministration [12]. Fourth, as described by the authors, lower muscle
comments. First, “lipid sink,” which was described as the underlying
mass in children is a risk factor for LAST in pediatric patients [11]. Fur-
mechanism of lipid emulsion treatment for LAST in this case report, is
thermore, as hepatic cytochrome P450 contributes to the metabolism
proposed at an early stage of lipid emulsion treatment for LAST [2].
of amino-amide local anesthetics, immaturity of hepatic cytochrome
However, a study using pharmacologically based pharmacokinetic
P450 observed in neonates and infants increases the accumulation of
models suggested that lipid emulsion produced only an 18% decrease
amino-amide local anesthetic in the plasma and leads to enhanced po-
in bupivacaine concentration in the brain and only an 11% decrease in
tential of LAST [11]. Since alpha-1 acid glycoprotein extensively binds
bupivacaine concentration in the heart, which is not enough to explain
to amino-amide local anesthetics in the plasma, the reduced level of
the lipid sink as an underlying mechanism responsible for lipid emul-
alpha-1 acid glycoprotein observed in infants increases the concentra-
sion resuscitation of LAST [4]. Moreover, a clinical study that employed
tion of free amino-amide local anesthetics, contributing to the enhanced
bupivacaine infusion followed by lipid emulsion or Hartman's solution
potential of LAST [13].
infusion in humans indicated that lipid emulsion decreased the total
plasma concentration of bupivacaine compared with Hartman's solu-
Funding
tion [5]. However, lipid emulsion did not exhibit a significant difference
between total plasma bupivacaine concentration and un-entrapped
This research did not receive any specific grant from funding agen-
(non-lipid bound) plasma bupivacaine concentration [5]. Additionally,
cies in the public, commercial, or not-for-profit sectors.
lipid emulsion reduced the context-sensitive half-life of total plasma
bupivacaine, which may be associated with enhanced bupivacaine tis-
Source(s) of support
sue distribution [5]. Thus, lipid shuttles are widely accepted as the un-
derlying mechanism of lipid emulsion treatment for LAST [6]. Lipid
None.
shuttles have shown that triglycerides in lipid emulsions absorb highly
lipid-soluble local anesthetics (for example: Log [octanol/water parti-
tion coefficient] > 2; Log [octanol/water partition coefficient of Presentations
prilocaine] = 2.11; Log [octanol/water partition coefficient of lido-
caine] = 2.44) from vital organs, including the heart, kidneys, and Not applicable.
brain [6]. Triglyceride, which is a transporting medium containing
lipid-soluble local anesthetics, is transported to the muscle, adipose tis- Declaration of Competing Interest
sue, and liver, leading to enhanced redistribution and detoxification
[6,7]. Furthermore, other suggested underlying mechanisms of lipid The author declares no conflict of interest.
emulsion resuscitation in LAST include inotropic effect, fatty acid sup-
ply, attenuation of mitochondrial dysfunction, inhibition of nitric Acknowledgements
oxide release, reversal of cardiac sodium channel blockade, and glyco-
gen synthase kinase-3β phosphorylation [2]. Second, LAST typically pro- None.
duces central nervous system toxicity followed by cardiovascular
toxicity, which ultimately leads to cardiac arrest [2]. Lipid emulsion References
was reported to be effective in treating seizures and central nervous sys- [1] McMahon K, Paster J, Baker KA. Local anesthetic systemic toxicity in the pediatric pa-
tem symptoms induced by the toxicity of ropivacaine and bupivacaine tient: a case report and review of the literature. Am J Emerg Med. 2021. https://doi.
before this toxicity could progress to cardiovascular collapse [8,9]. Sim- org/10.1016/j.ajem.2021.10.021.
ilar to previous reports, seizures were observed in this patient without [2] Ok SH, Hong JM, Lee SH, Sohn JT. Lipid emulsion for treating local anesthetic sys-
temic toxicity. Int J Med Sci. 2018;15:713–22.

https://doi.org/10.1016/j.ajem.2021.12.057
0735-6757/© 2021 Elsevier Inc. All rights reserved.
J.-T. Sohn
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American Journal of Emergency Medicine 57 (2022) 195–196
[12] Sohn JT. Plasma clearance and lipaemic index of lipid emulsion used for lipid emul-
sion treatment. Ann Clin Biochem. 2021;58:547–8.
[13] Mazoit JX, Denson DD, Samii K. Pharmacokinetics of bupivacaine following caudal
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Ju-Tae Sohn MD
Department of Anesthesiology and Pain Medicine, Gyeongsang National
University College of Medicine, Gyeongsang National University Hospital,
15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do 52727,
Republic of Korea
Institute of Health Sciences, Gyeongsang National University,
Jinju-si 52727, Republic of Korea
Department of Anesthesiology and Pain Medicine, Gyeongsang National
University Hospital, 79 Gangnam-ro, Jinju-si 52727, Republic of Korea.
E-mail address: jtsohn@gnu.ac.kr