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J Pediatr Intensive Care
DOI: 10.1055/s-0044-1786769
Original Article

Extracorporeal Membrane Oxygenation: Rescue Therapy in Pediatric Bupropion Cardiotoxicity

Travis D. Olives 
1   Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, United States
,
Christopher N. Sweat
2   Department of Emergency Medicine, UCSF—Fresno, Fresno, California, United States
,
Lauren Dorsey-Spitz
3   Department of Pediatrics, Children's Hospital Colorado, Colorado Springs, Colorado, United States
,
Farbod Bahadori-Esfahani
4   Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
,
Ann M. Arens
5   Minnesota Poison Control System, Minneapolis, Minnesota, United States
6   Department of Emergency Medicine, Oeschner Medical Center, New Orleans, Louisiana, United States
,
Jon B. Cole
1   Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, United States
5   Minnesota Poison Control System, Minneapolis, Minnesota, United States
,
Arif Somani
7   Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States
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Abstract

Objective Our objective was to describe clinical characteristics and course of pediatric bupropion ingestions requiring extracorporeal membrane oxygenation (ECMO) life support.

Desgin The study included a retrospective cohort of patients ≤18 years of age reported to a regional poison control (PC) system covering three states in the upper Midwest United States. All bupropion exposures ≤18 years of age, coded as receiving ECMO to treat toxicity, were included. Clinical presentation and management including ECMO are presented as descriptive statistics.

Results During the study period, 4,951 bupropion exposures were reported; 1,145 (23.1%) were children. Nine patients were coded as undergoing ECMO; four (44.4%) were ≤18 years of age (median 16, range 14–17). All were treated with venoarterial ECMO. The median time from ingestion to presentation was 2.25 hours (range: 1–3.5). Median first systolic blood pressure and pulse were 100 mm Hg (range: 70–124) and 119.5 (range: 70–175). The median time from ingestion to ECMO was 17.63 hours (range: 7.25–33.75); median number of vasopressors was 2.5 (range: 2–3). All experienced multiple seizures, ventricular dysrhythmias, and hypotension. Three of four sustained cardiac arrest. All but one required transfer to an ECMO-capable facility for definitive care. Three patients survived with full neurologic recovery; one died.

Conclusion Pediatric bupropion cases requiring ECMO were rare in this study. Time to initiation and duration of EMCO suggest that the variable onset of hemodynamic instability may delay ECMO initiation. It is incumbent on PCs and medical toxicologists to educate prescribers and pediatricians about bupropion's potential lethality and to consider early transfer to an ECMO center.

Keywords

ECMO - Poison Control Center - bupropion - overdose


Publication History

Received: 21 November 2023

Accepted: 08 April 2024

Article published online:
17 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Patel AM, Carroll NV, Wheeler DC. et al. Economic burden of pediatric prescription opioid poisonings in the United States. J Manag Care Spec Pharm 2021; 27 (01) 16-26
    PubMedGoogle Scholar
  • 2 Park J, Jeon W, Ko Y, Choi YJ, Yang H, Lee J. Comparison of the clinical characteristics of pediatric poisoning patients who visited emergency department before and during the COVID-19 pandemic. J Korean Med Sci 2022; 37 (47) e337
    CrossrefPubMedGoogle Scholar
  • 3 Bond GR, Woodward RW, Ho M. The growing impact of pediatric pharmaceutical poisoning. J Pediatr 2012; 160 (02) 265-270.e1
    CrossrefPubMedGoogle Scholar
  • 4 Padmanathan P, Bould H, Winstone L, Moran P, Gunnell D. Social media use, economic recession and income inequality in relation to trends in youth suicide in high-income countries: a time trends analysis. J Affect Disord 2020; 275: 58-65
    CrossrefPubMedGoogle Scholar
  • 5 Li Z, Xiao L, Yang L, Li S, Tan L. Characterization of acute poisoning in hospitalized children in Southwest China. Front Pediatr 2021; 9: 727900
    CrossrefPubMedGoogle Scholar
  • 6 Plemmons G, Hall M, Doupnik S. et al. Hospitalization for suicide ideation or attempt: 2008-2015. Pediatrics 2018; 141 (06) e20172426
    CrossrefPubMedGoogle Scholar
  • 7 Gummin DD, Mowry JB, Beuhler MC. et al. 2019 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th annual report. Clin Toxicol (Phila) 2020; 58 (12) 1360-1541
    CrossrefPubMedGoogle Scholar
  • 8 Gummin DD, Mowry JB, Beuhler MC. et al. 2020 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 38th annual report. Clin Toxicol (Phila) 2021; 59 (12) 1282-1501
    CrossrefPubMedGoogle Scholar
  • 9 Hormazábal A N, Yzoard A M, Bustos B R, Müller-Ramírez C. Retrospective study of poisoned patients admitted to a hospital's pediatric intensive care unit in Chile. Arch Argent Pediatr 2022; 120 (04) 257-263
    PubMedGoogle Scholar
  • 10 Cairns R, Karanges EA, Wong A. et al. Trends in self-poisoning and psychotropic drug use in people aged 5-19 years: a population-based retrospective cohort study in Australia. BMJ Open 2019; 9 (02) e026001
    CrossrefPubMedGoogle Scholar
  • 11 Lukmanji A, Pringsheim T, Bulloch AG. et al. Antidepressant prescriptions, including tricyclics, continue to increase in Canadian Children. J Child Adolesc Psychopharmacol 2020; 30 (06) 381-388
    CrossrefPubMedGoogle Scholar
  • 12 Wellbutrin SR. Highlights of Prescribing Information. Glaxo Smith Kline; 2022
    Google Scholar
  • 13 Shiffman S, Johnston JA, Khayrallah M. et al. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology (Berl) 2000; 148 (01) 33-40
    CrossrefPubMedGoogle Scholar
  • 14 Livingstone-Banks J, Norris E, Hartmann-Boyce J, West R, Jarvis M, Hajek P. Relapse prevention interventions for smoking cessation. Cochrane Database Syst Rev 2019; 2 (02) CD003999
    PubMedGoogle Scholar
  • 15 Hsieh MT, Tseng PT, Wu YC. et al. Effects of different pharmacologic smoking cessation treatments on body weight changes and success rates in patients with nicotine dependence: A network meta-analysis. Obes Rev 2019; 20 (06) 895-905
    CrossrefPubMedGoogle Scholar
  • 16 Trivedi MH, Walker R, Ling W. et al. Bupropion and naltrexone in methamphetamine use disorder. N Engl J Med 2021; 384 (02) 140-153
    CrossrefPubMedGoogle Scholar
  • 17 Hankosky ER, Bush HM, Dwoskin LP. et al. Retrospective analysis of health claims to evaluate pharmacotherapies with potential for repurposing: association of bupropion and stimulant use disorder remission. AMIA Annu Symp Proc 2018; 2018: 1292-1299
    PubMedGoogle Scholar
  • 18 Meesters Y, Gordijn MC. Seasonal affective disorder, winter type: current insights and treatment options. Psychol Res Behav Manag 2016; 9: 317-327
    CrossrefPubMedGoogle Scholar
  • 19 Wilens TE, Spencer TJ, Biederman J. et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 2001; 158 (02) 282-288
    CrossrefPubMedGoogle Scholar
  • 20 Agency for Healthcare Research and Quality. Total purchases by prescribed drug, United States, 2000 to 2019. Medical ExpenditurePanel Survey. Medical Expenditure Panel Survey (MEPS) Household Component (HC). Accessed May 2, 2022 at: https://datatools.ahrq.gov/meps-hc
    PubMedGoogle Scholar
  • 21 Overberg A, Morton S, Wagner E, Froberg B. Toxicity of bupropion overdose compared with selective serotonin reuptake inhibitors. Pediatrics 2019; 144 (02) e20183295 DOI: 10.1542/peds.2018-3295.
    CrossrefPubMedGoogle Scholar
  • 22 Offerman S, Levine M, Gosen J, Thomas SH. Pediatric bupropion ingestions in adolescents vs. younger children—a tale of two populations. J Med Toxicol 2020; 16 (01) 6-11
    CrossrefPubMedGoogle Scholar
  • 23 McCabe DJ, Radke JB, Wilson BZ. Disposition, outcomes, and lengths of stay due to bupropion overdose at a tertiary care center with a medical toxicology service. Am J Emerg Med 2022; 54: 269-273
    CrossrefPubMedGoogle Scholar
  • 24 Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D. Emerging drugs of abuse: current perspectives on substituted cathinones. Subst Abuse Rehabil 2014; 5: 37-52
    PubMedGoogle Scholar
  • 25 Preskorn SH, Othmer SC. Evaluation of bupropion hydrochloride: the first of a new class of atypical antidepressants. Pharmacotherapy 1984; 4 (01) 20-34
    CrossrefPubMedGoogle Scholar
  • 26 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 (04) 412-415 , 415.e1
    CrossrefPubMedGoogle Scholar
  • 27 Wills BK, Zell-Kanter M, Aks SE. Bupropion-associated QRS prolongation unresponsive to sodium bicarbonate therapy. Am J Ther 2009; 16 (02) 193-196
    CrossrefPubMedGoogle Scholar
  • 28 Shenoi AN, Gertz SJ, Mikkilineni S, Kalyanaraman M. Refractory hypotension from massive bupropion overdose successfully treated with extracorporeal membrane oxygenation. Pediatr Emerg Care 2011; 27 (01) 43-45
    CrossrefPubMedGoogle Scholar
  • 29 Offerman S, Gosen J, Thomas SH, Padilla-Jones A, Ruha AM, Levine M. Bupropion associated seizures following acute overdose: who develops late seizures. Clin Toxicol (Phila) 2020; 58 (12) 1306-1312
    CrossrefPubMedGoogle Scholar
  • 30 Sidlak AM, Koivisto KO, Marino RT, Abesamis MG. Serotonin toxicity from isolated bupropion overdoses. Clin Toxicol (Phila) 2020; 58 (12) 1347-1349
    CrossrefPubMedGoogle Scholar
  • 31 Upchurch C, Blumenberg A, Brodie D, MacLaren G, Zakhary B, Hendrickson RG. Extracorporeal membrane oxygenation use in poisoning: a narrative review with clinical recommendations. Clin Toxicol (Phila) 2021; 59 (10) 877-887
    CrossrefPubMedGoogle Scholar
  • 32 Cole JB, Olives TD, Ulici A. et al. Extracorporeal membrane oxygenation for poisonings reported to U.S. poison centers from 2000 to 2018: an analysis of the national poison data system. Crit Care Med 2020; 48 (08) 1111-1119
    CrossrefPubMedGoogle Scholar
  • 33 Heise CW, Skolnik AB, Raschke RA, Owen-Reece H, Graeme KA. Two cases of refractory cardiogenic shock secondary to bupropion successfully treated with veno-arterial extracorporeal membrane oxygenation. J Med Toxicol 2016; 12 (03) 301-304
    CrossrefPubMedGoogle Scholar
  • 34 Beuhler MC, Spiller HA, Sasser HC. The outcome of unintentional pediatric bupropion ingestions: a NPDS database review. J Med Toxicol 2010; 6 (01) 4-8
    CrossrefPubMedGoogle Scholar
  • 35 Caillier B, Pilote S, Castonguay A. et al. QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile. Fundam Clin Pharmacol 2012; 26 (05) 599-608
    CrossrefPubMedGoogle Scholar
  • 36 Franco V. Wide complex tachycardia after bupropion overdose. Am J Emerg Med 2015; 33 (10) 1540.e3-1540.e5
    CrossrefPubMedGoogle Scholar
  • 37 Bruccoleri RE, Demeter BL, Chai PR, Burns MM. Massive lamotrigine and bupropion overdose resulting in status epilepticus without cardiovascular collapse. Toxicol Commun 2019; 3 (01) 102-105
    CrossrefPubMedGoogle Scholar
  • 38 Rohr S. Role of gap junctions in the propagation of the cardiac action potential. Cardiovasc Res 2004; 62 (02) 309-322
    CrossrefPubMedGoogle Scholar
  • 39 Beauchamp P, Choby C, Desplantez T. et al. Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ Res 2004; 95 (02) 170-178
    CrossrefPubMedGoogle Scholar
  • 40 Vink MJ, Suadicani SO, Vieira DM. et al. Alterations of intercellular communication in neonatal cardiac myocytes from connexin43 null mice. Cardiovasc Res 2004; 62 (02) 397-406
    CrossrefPubMedGoogle Scholar
  • 41 Petrecca K, Atanasiu R, Grinstein S, Orlowski J, Shrier A. Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium. Am J Physiol 1999; 276 (02) H709-H717
    PubMedGoogle Scholar
  • 42 Weiner L, Mazzeffi MA, Hines EQ, Gordon D, Herr DL, Kim HK. Clinical utility of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) in patients with drug-induced cardiogenic shock: a retrospective study of the Extracorporeal Life Support Organizations' ECMO case registry. Clin Toxicol (Phila) 2020; 58 (07) 705-710
    CrossrefPubMedGoogle Scholar
  • 43 de Lange DW, Sikma MA, Meulenbelt J. Extracorporeal membrane oxygenation in the treatment of poisoned patients. Clin Toxicol (Phila) 2013; 51 (05) 385-393
    CrossrefPubMedGoogle Scholar
  • 44 Belcher RM, Oldham C, Rapier AM, Gutteridge D. Hydroxocobalamin and extracorporeal membrane oxygenation (ECMO) for severe refractory shock in bupropion and citalopram overdose: a case report. Toxicol Commun 2021; 5 (01) 136-139
    CrossrefPubMedGoogle Scholar
  • 45 Engebretsen KM, Harris CR, Wood JE. Cardiotoxicity and late onset seizures with citalopram overdose. J Emerg Med 2003; 25 (02) 163-166
    CrossrefPubMedGoogle Scholar
  • 46 Armitage R. Antidepressants, primary care, and adult mental health services in England during COVID-19. Lancet Psychiatry 2021; 8 (02) e3
    CrossrefPubMedGoogle Scholar
  • 47 Ettman CK, Abdalla SM, Cohen GH, Sampson L, Vivier PM, Galea S. Prevalence of depression symptoms in US adults before and during the COVID-19 pandemic. JAMA Netw Open 2020; 3 (09) e2019686-e2019686
    CrossrefPubMedGoogle Scholar
  • 48 Bachmann CJ, Aagaard L, Burcu M. et al. Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012. Eur Neuropsychopharmacol 2016; 26 (03) 411-419
    CrossrefPubMedGoogle Scholar
  • 49 Kane SP, Phar BCPS. The Top 300 of 2019. Accessed February 7, 2022 at: https://clincalc.com/DrugStats/Top300Drugs.aspx
    PubMedGoogle Scholar
  • 50 Tenenbein M. Do you really need that emergency drug screen?. Clin Toxicol (Phila) 2009; 47 (04) 286-291
    CrossrefPubMedGoogle Scholar
  • 51 Christian MR, Lowry JA, Algren DA, Thornton SL, Deng S, Garg U. Do rapid comprehensive urine drug screens change clinical management in children?. Clin Toxicol (Phila) 2017; 55 (09) 977-980
    CrossrefPubMedGoogle Scholar