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J Pediatr Intensive Care 2020; 09(02): 151-152
DOI: 10.1055/s-0040-1702234
Letter to the Editor
Georg Thieme Verlag KG Stuttgart · New York

Treatment of Bupropion Toxicity with Lipid Emulsion

Soo Hee Lee
1   Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si, Republic of Korea
,
Ju-Tae Sohn 
2   Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
3   Institute of Health Sciences, Gyeonsang National University, Jinju-si, Republic of Korea
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Publication History

18 December 2019
18 December 2019

20 January 2020
20 January 2020

Publication Date:
25 February 2020 (online)

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We have read with interest the case report, “Successful Management of Adolescent Bupropion Overdose with Intravenous Lipid Emulsion Therapy,” recently published in the Journal of Pediatric Intensive Care.[1] Lipid emulsion is effective in the treatment of acute toxicity induced by local anesthetics or nonlocal anesthetic drugs, including amitriptyline, bupropion, and verapamil, in pediatric patients.[2] A previous in vitro study reported that the magnitude of the reduction of the serum concentration of bupropion, which is a highly lipid-soluble antidepressant (log [octanol/water partition coefficient]: 3.2), was 46 by 2% lipid emulsion (Intralipid).[3] In addition, the magnitude of the sequestration of drugs with varied lipid solubility by lipid emulsion is dependent mainly on the lipid partition coefficient and partially on the volume of distribution, which appears to account for 88% of variations in the reduction of drug serum concentration by lipid emulsion.[3] As suggested by Bornstein et al, the lipid sink theory, which is considered the mechanism underlying the effect of lipid emulsion as a nonspecific antidote, states that lipid emulsion absorbs highly lipid-soluble drugs, such as bupivacaine (log [octanol/water partition coefficient]: 3.41), from the heart.[1] [4] However, the following comments should be considered to understand this case report well. First, the first administration of lipid emulsion improved the mental status of the patient.[1] On day 3, the second administration of lipid emulsion was performed due to the recurrence of an altered mental status.[1] The elimination half-life of bupropion is 29 ± 9 hours.[5] In addition, the absorption of a toxic dose following oral administration (enteral route) is more prolonged than that following intravenous administration, leading to extended toxicity.[6] In contrast, Intralipid has a very short half-life (13.7 ± 5.2 minutes).[7] Considering previous reports, the lipid phase of lipid emulsion appears to absorb highly lipid-soluble bupropion from the heart and brain for a very short period following lipid emulsion administration.[3] [7] Furthermore, 1% of plasma triglyceride concentration, which provides lipemic plasma without fat overload, is sufficient to exert scavenging and cardiotonic effects on the toxicity induced by an enteral overdose.[6] Thus, the altered mental status on day 3 following a marked improvement after the first administration of lipid emulsion may be ascribed to a greatly reduced concentration of Intralipid.[1] A previous report recommends the following lipid emulsion regimen to treat toxicity induced by enteral overdose: bolus administration of Intralipid 1.5 mL/kg for 1 minute and subsequently 0.25 mL/kg/min for an additional 3 minutes, followed by intravenous infusion of 0.025 mL/kg/min (up to 6.5 hours) to theoretically maintain a 1% plasma triglyceride concentration.[6] This regimen, as an adjuvant, can be used with supportive care in cases of toxicity induced by oral overdose.[6] However, further research in an in vivo model on the optimal dosing regimen of lipid emulsion for the treatment of toxicity following oral overdose of bupropion is needed because the pharmacokinetics of an oral overdose are different from those of intravenous overdose (e.g., local anesthetic systemic toxicity). Second, initially, lipid sink was widely accepted as the underlying mechanism of lipid emulsion treatment.[4] However, a previous study using a physiologically based pharmacokinetic model reported that lipid emulsion decreased only 11 and 18% bupivacaine concentrations in the heart and brain, respectively.[8] The free bupivacaine concentration was not significantly different between the control and lipid emulsion groups in an in vivo study after administration of a nontoxic dose of bupivacaine in humans.[9] Thus, lipid shuttle has recently been widely accepted as the mechanism of lipid emulsion treatment; it states that lipid emulsion absorbs lipid-soluble drugs, such as bupivacaine, from the heart and then the lipid emulsion, containing the sequestered lipid-soluble drug (e.g., bupivacaine), is transported to the liver and muscle for detoxification and storage, leading to enhanced redistribution.[4] We believe that this case report contributes valuable data on the efficacy of lipid emulsion treatment in bupropion toxicity and emphasizes the need for continuous infusion of lipid emulsion following the initial bolus administration in lipid emulsion treatment.