Life-threatening bupropion poisoning successfully treated by intravenous lipid emulsion

Life-threatening bupropion poisoning successfully treated by intravenous lipid emulsion | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 February 2026 V1 Latest version Share on Life-threatening bupropion poisoning successfully treated by intravenous lipid emulsion Authors : Francesca Chiara Della Casa , Vincent Haufroid , Kevin Delongie , Thomas Coppens , Ester Ponzetto , and Nicolas De Schryver 0000-0003-4584-0903 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.177079692.26880898/v1 175 views 48 downloads Contents Abstract Abstract Case presentation Discussion References Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Bupropion is a synthetic cathinone that acts as a norepinephrine and dopamine reuptake inhibitor, and is an atypical antidepressant commonly prescribed for major depressive disorder and smoking cessation. While generally well tolerated at therapeutic doses, bupropion overdose can lead to severe toxicity, primarily characterized by seizures and cardiac arrhythmias. Management of severe intoxications remains mainly supportive, with no specific antidote available. Intravenous lipid emulsion (ILE) therapy has emerged as a potential treatment for poisoning with highly lipophilic drugs. Initially developed for local anesthetic toxicity, ILE is hypothesized to work via multiple mechanisms, including a ”lipid sink” effect and direct stabilization of highly excitable membranes in the brain and heart. However, its precise role in non-anesthetic drug intoxications remains incompletely understood. We report a case of a massive, intentional bupropion overdose (24,000 mg) in a patient with no co-ingestion of other toxic substances aside from alcohol. The patient developed refractory seizures and severe ventricular arrhythmias, which were successfully reversed after ILE administration. Serial blood measurements of bupropion and its metabolites were performed before and after ILE administration, supporting both lipid sequestration of the drug and direct cardioprotective effects. Life-threatening bupropion poisoning successfully treated by intravenous lipid emulsion Francesca Chiara Della Casa 1 MD, Vincent Haufroid² PharmD, PhD, Kevin Delongie 2 , Thomas Coppens³ MD, Ester Ponzetto 1 MD, Nicolas De Schryver 1 MD 1 Intensive Care Unit. Clinique Saint-Pierre. Ottignies, Belgium. 2 Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, Belgium & Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, Belgium 3 Department of Neurology. Clinique Saint-Pierre. Ottignies, Belgium Corresponding author: Nicolas De Schryver Intensive Care Unit.Clinique Saint-Pierre.Avenue Reine Fabiola, 91340 OttigniesBelgiumE-mail: [email protected] : +32 10 43 72 51Fax: +32 10 43 71 23 Word count: 1724 Key Words: Intravenous lipid emulsion, bupropion, poisoning Conflict of interest/financial disclosure: none to declare Ethics approval statement: The authors confirm that the Principal Investigator for this paper is Nicolas De Schryver and that he had direct clinical responsibility for patients. Written informed consent was obtained from the patient for the publication of this case report. Abstract Bupropion is a synthetic cathinone that acts as a norepinephrine and dopamine reuptake inhibitor, and is an atypical antidepressant commonly prescribed for major depressive disorder and smoking cessation. While generally well tolerated at therapeutic doses, bupropion overdose can lead to severe toxicity, primarily characterized by seizures and cardiac arrhythmias. Management of severe intoxications remains mainly supportive, with no specific antidote available. Intravenous lipid emulsion (ILE) therapy has emerged as a potential treatment for poisoning with highly lipophilic drugs. Initially developed for local anesthetic toxicity, ILE is hypothesized to work via multiple mechanisms, including a ”lipid sink” effect and direct stabilization of highly excitable membranes in the brain and heart. However, its precise role in non-anesthetic drug intoxications remains incompletely understood. We report a case of a massive, intentional bupropion overdose (24,000 mg) in a patient with no co-ingestion of other toxic substances aside from alcohol. The patient developed refractory seizures and severe ventricular arrhythmias, which were successfully reversed after ILE administration. Serial blood measurements of bupropion and its metabolites were performed before and after ILE administration, supporting both lipid sequestration of the drug and direct cardioprotective effects. Case presentation A 35-year-old woman with a history of alcohol abuse and depression presented to the emergency department two hours after intentionally ingesting approximately 24,000 mg of extended-release bupropion together with alcohol. On admission, heart rate was 137 bpm, blood pressure was 150/80 mmHg, respiratory rate was 15/min and pulse oxygen saturation was 98% while breathing ambient air. The Glasgow Coma Scale (GCS) score was 12/15 (E4V2M6). Laboratory analysis revealed an ethanol level of 2.41 g/l while the other laboratory investigations were unremarkable. She rapidly deteriorated with the GCS score falling to 6/15 (E4V1M1) and experienced a first generalized tonic-clonic seizure. She was then intubated, and activated charcoal (50 g) was administered via a nasogastric tube. She was transferred to the intensive care unit (ICU) 4 .5 hours after ingestion. Upon ICU admission, she presented with two additional seizures, and was treated with 5 mg diazepam followed by a continuous infusion of 0.05 mg/kg/h and levetiracetam 60 mg/kg. Continuous electroencephalogram (EEG) monitoring was initiated and showed a severe burst-suppression pattern with approximately 90% of the time in suppression. The bursts were highly symmetric. General anesthesia was maintained with a continuous infusion of 3 mg/kg/h of Propofol. The initial electrocardiogram (ECG) revealed sinus tachycardia at 110 bpm, with a slightly prolonged QRS duration (126 ms) and a corrected QT interval (QTc) of 470 msec. A transthoracic echocardiogram showed preserved biventricular systolic function. Blood gas analysis revealed metabolic acidosis with pH of 7.20, pCO 2 of 42mmHg, bicarbonates of 16.3 mmol/L, and lactate of 5.74 mmol/L. She began to exhibit frequent polymorphic premature ventricular contractions (PVCs) that progressed to multiple episodes of incessant sustained and unsustained ventricular tachycardia (Figure 1). Blood pressure progressively decreased and norepinephrine was started and titrated up to 0.15 mcg/kg/min. She was then given two 100-mEq boluses sodium bicarbonate (3.3 mEq/kg), 2g of calcium gluconate and 3g of magnesium sulfate, but the arrhythmic storm persisted and hemodynamic instability worsened. Serum sodium level rose to 151 mmol/l precluding further significant sodium bicarbonate administration. Considering the life-threatening situation, intravenous lipid emulsion (ILE) (Intralipid® 20%) was then administered 8 hours after bupropion ingestion, with a bolus of 1.5 mL/kg, followed by an infusion of 0.25 mL/kg/min during the next three minutes. Two minutes after the start of ILE bolus, ventricular tachycardia completely resolved and did not recur. QRS duration remained increased at 120 msec, and the QTc interval was still prolonged (460 msec) but no further PVCs were observed. Norepinephrine was discontinued during the bolus administration and lactate levels normalized. Simultaneously, the EEG pattern showed a reduction in inter-burst intervals and an increase in burst amplitude, with approximately 50% of the bursts demonstrating epileptic characteristics. Given the excellent immediate response following the bolus and the initial ILE infusion, and considering the long elimination half-life of bupropion, as well as the theoretical maximum recommended cumulative dose of ILE, the infusion was reduced after the initial bolus to 1.5 mL/kg/hour (0.025 mL/kg/min) for the next two hours. It was then gradually tapered to 45 mL/hour (0.0125 mL/kg/min) during the third hour, 22 mL/hour (0.00625 mL/kg/min) during the fourth hour, and 11 mL/hour (0.003125 mL/kg/min) for an additional 10 hours before discontinuation. The total dose administered was 500 ml (8.3 ml/kg) over 14 hours. QRS and QTc intervals gradually shortened and completely normalized within 24 hours after ingestion. The patient was extubated on day 3 and transferred to the ward. She received psychiatric support, denied any genuine suicidal intent and was finally discharged from the hospital on day 6. Blood samples for determination of bupropion and metabolites serum levels were obtained 2 hours before the ILE bolus, immediately before the bolus, 10 minutes after the bolus, then hourly for the first 6 hours, and at hours 12, 15, 17, 19, 20 and 25 after the initial measurement. The evolution of the serum levels of bupropion and its metabolites over time is depicted in figure 2. The initial sampling 90 minutes before ILE administration revealed a very high serum concentration of bupropion (26,952 ng/ml) and hydroxybupropion (3,788 ng/ml). A repeated sample obtained immediately before the ILE bolus showed a two-fold decrease in bupropion concentration, while hydroxybupropion continued to increase slightly. After ILE administration, bupropion serum levels increased whereas its metabolites levels progressively decreased over time. Genetic testing revealed that our patient was a normal metabolizer for CYP2B6, suggesting that bupropion metabolism was not inherently impaired. Discussion Bupropion is a norepinephrine and dopamine reuptake inhibitor used in the treatment of depressive disorders and smoking cessation. Among other antidepressants, it is also a leading cause of intentional poisoning. 1 Bupropion toxicity is characterized by neurological and cardiovascular complications. Common symptoms include sinus tachycardia (83%), hypertension (56%), seizures (37%), gastrointestinal symptoms (37%) and agitation (32%). 2 However most severe intoxications may progress to severe cardiovascular collapse and death primarily related to myocardial sodium channel blockade. The recommended daily dose of bupropion ranges from 150 to 300 mg. The drug is metabolized mainly by the cytochrome P450 2B6 (CYP2B6) into hydroxybupropion, its main active metabolite. Additional metabolism via CYP3A4 and CYP2C19 produces threo- and erythro-dihydrobupropion, which retain 20–50% of the parent drug’s pharmacological activity. Oral administration of 300 mg of extended-release bupropion results in a maximal serum concentration (Cmax) of approximately 160 ng/ml after 5 hours, while metabolites peak between 7 and 8 hours. Therapeutic serum concentrations of hydroxybupropion are 3 to 14 times higher than those of bupropion (600-2000 ng/ml). Elimination occurs mainly via the kidneys, with 87% excreted in urine and about 10% in feces. The elimination half-life is approximately 21 hours for bupropion and hydroxybupropion. Management of bupropion poisoning is mainly supportive and aims to stabilize hemodynamics and control seizures while awaiting endogenous drug elimination. Activated charcoal may reduce absorption if administered within 1-2 hours after ingestion. 3 Sodium bicarbonate is recommended in case of cardiovascular toxicity, as for other forms of intoxications with sodium channel blockers, typically characterized by QRS widening on ECG. 4 In the absence of specific antidote, and when these conservative measures fail to stabilize the hemodynamics, the lipophilic profile of bupropion with its high octanol/water partition coefficient (log P 3.47) makes it a potential candidate for ILE therapy. 5 ILE consists of nanometer-sized triglyceride droplets emulsified in water by phospholipid surfactant. Initially used to treat local anesthetic agents toxicity, increasing evidence supports its potential role in other lipophilic drug poisonings. The most widely accepted mechanism is the “lipid sink” theory whereby lipophilic drugs are sequestered within the intravascular lipid compartment and redistributed to biologically inert tissues. The efficacy of ILE to absorb a toxicant depends on several factors including the octanol/water partition coefficient (LogP), the distribution coefficient (LogD) and drug accommodation capacity. 6 More recently, the lipid sink concept has evolved into the “lipid shuttle” theory whereby ILE transiently binds the drug and facilitates its transport from target organs (brain and heart) to tissues involved in storage, metabolism and elimination of the drug (muscle, adipose tissue, liver and kidneys. This mechanism may explain the transient increase followed by a decrease in plasma concentrations of lipophilic drugs observed after ILE administration in both animal and human studies. 6 Additional mechanisms have also been hypothesized, including enhanced myocardial fatty-acid utilization for ATP synthesis, positive inotropic effects by limiting the toxicant interference with sodium channels and promoting calcium entry trough voltage-dependant calcium channels, activation of protein kinase leading to a cytoprotective signaling cascade, decreased vasodilation trough decreased nitric oxide bioavailability, and increased liver shunting. 6 The benefit of ILE in bupropion remains uncertain. Favourable outcomes reported in some case reports of must be interpreted cautiously because of the potential “publication bias” as positive outcome are more likely to be published than negative ones. 1 Altough animal studies suggest improved outcomes when ILE is included in rescuscitation protocols after bupropion overdose, 7 to date no randomized controlled trial in humans have evaluated its efficacy or safety. In 2016, an expert panel endorsed by several American and European toxicology societies recommended considering ILE as a second-line treatment for life-threatening bupropion toxicity after failure of standard treatments. 8 These recommendations were however based on a very low quality of evidence and no recommendation was made regarding dosing or duration of ILE treatment. Potential complications of ILE including hypertriglyceridemia, pancreatitis, anaphylaxis, and interference with laboratory results should also be know when assessing the risk/benefit balance of its use. ILE may also interfere with other treatments, such as benzodiazepines which could explain the recurrence of seizures after ILE administration in our patient. The multiple serum measurements obtained before, during and after ILE administration in our patient provide a unique opportunity to explore its potential mechanisms of action. Before ILE, a spontaneous decrease of bupropion levels was observed, while metabolites levels continued to rise in parallel with the observed increased toxicity. Immediately after the ILE bolus, a 30% increase in bupropion concentration was observed, a phenomenon commonly reported with other lipophilic drug intoxications and consistent with a redistribution from target organs into the intravascular lipid phase. Hydroxybupropion, which is much less lipophilic remained relatively unaffected, but importantly, did not further increase thereafter, suggesting that ILE administered about 8 hours after ingestion of bupropion may have limited further metabolism of bupropion. The dramatic and immediate hemodynamic improvement that occurred immediately after ILE administration is a finding already described in other case reports. 9,10 The fact that this improvement was observed without any change in the blood levels of hydroxybupropion, which is the main active metabolite of bupropion, supports mechanisms beyond simple metabolite sequestration, including direct cardioprotective effects. Several limitations must be acknowledged when interpreting our results. First, serum drug concentration do not reflect tissue levels at target organs. Second, while in normal blood, the measurement of bupropion and its metabolites reflects the total drug concentration (including both protein-bound and unbound fractions), in ILE-treated serum, it remains unknown whether the measured levels accurately represent the total fraction of the drug. Third, no consensus exists regarding optimal ILE dosing or duration. Given the long elimination half-life of bupropion and the short half-life of ILE (13.7 minutes), a progressive tapering strategy was chosen to prolong therapeutic exposure while avoiding excessive cumulative dose as previously described by others. 11 Conclusions : We presented a case of severe bupropion poisoning with refractory neurological and cardiovascular toxicity. ILE administration was followed by immediate hemodynamic improvement. Serial measurements of bupropion and its metabolites supports both intravascular lipid sequestration theory and additional cardioprotective effects of ILE. Figure 2 : Buproprion and metabolites serum levels over time. The plasma quantification of Bupropion and its three major metabolites was performed by high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) using a Waters Aquity I Class system coupled to a Xevo TQs Triple Quadrupole instrument (Waters). References 1. Chhabra N, Deslauriers C, Wahl M et al. Management of severe bupropion poisoning with intravenous lipid emulsion. Clin Toxicol 2018;56:51-54. Crossref Google Scholar 2. Balit CR, Lynch CN, Isbister GK. Bupropion poisoning: a case series. Med J Aust 2003;178:61-3 Google Scholar 3. Chyka PA, Seger D. Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centers and Clinical Toxicologists. J Toxicol Clin Toxicol 1997;35(7):721-41. Google Scholar 4. Crossref Google Scholar 5. Lavonas EJ, Akpunonu PD, Arens AM et al. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2023;148:e149-184. Google Scholar 6. Delgado JN, Gisvold O, Remers WA et al. Caclulated log P, log D, and pKa. In: Delgado JN, Gisvold O, Remers WA, eds. Gisvold’s Textbook of Organic, Medicinal and Pharmaceutical Chemistry. Philadelphia, PA: Lippincott Williams & Wilkins 1998:948-956. Google Scholar 7. Jaffal K, Chevillard L, Megarbane B. Lipid Emulsion to treat acute poisonnings: mechanisms of action, indications and controversies. Pharmaceutics 2023;15:1396. Google Scholar 8. Fulton LV, Fabich RA, Bhatta J et al. Comparison of resuscitative protocols for bupropion overdose using lipid emulsion in a swine model. Mil Med 2016 ;181(5):482-7 Google Scholar 9. Gosselin S, Hoegberg LCG, Hoffman R et al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol 2016; 54:899-923 Google Scholar 10. Sirianni AJ, Osterhoudt KC, Calello DP et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51:412-5. Crossref Google Scholar 11. Herrmann NW, Kaliesieski MJ, Fung C. Bupropion overdose complicated by cardiogenic shock requiring vasopressor support and lipid emulsion therapy. J Emerg Med 2020;58:e47-e50 Google Scholar 12. Lee SH, Sohn JT. Lipid emulsion treatment of cardiogenic shock induced by toxic dose of bupropion. J Emer Med 2020;59(1):e33 Google Scholar 13. Figure 1 Google Scholar 14. Electrocardiogram recorded after ICU admission showing sustained ventricular tachycardia. Google Scholar Information & Authors Information Version history V1 Version 1 11 February 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Francesca Chiara Della Casa Clinique Saint-Pierre Ottignies View all articles by this author Vincent Haufroid Cliniques universitaires Saint-Luc View all articles by this author Kevin Delongie Cliniques universitaires Saint-Luc View all articles by this author Thomas Coppens Clinique Saint-Pierre Ottignies View all articles by this author Ester Ponzetto Clinique Saint-Pierre Ottignies View all articles by this author Nicolas De Schryver 0000-0003-4584-0903 [email protected] Clinique Saint-Pierre Ottignies View all articles by this author Metrics & Citations Metrics Article Usage 175 views 48 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Francesca Chiara Della Casa, Vincent Haufroid, Kevin Delongie, et al. 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