Successful use of ECMO and lipid emulsion for massive bupropion overdose: a case report

AbstractIntroduction Bupropion overdose can produce seizures, arrhythmias, and shock. The toxicokinetics of massive bupropion ingestions are not well characterized.Case report A 22-year-old female ingested an estimated 40.5 g (644 mg/kg) of extended release bupropion. Subsequently she experienced seizures, required intubation, developed torsades des pointes that progressed to cardiac arrest, and required cannulation with venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Intravenous lipid emulsion was administered without adversely affecting the ECMO circuit. The patient was successfully decannulated after 84 h of ECMO support and discharged neurologically intact. Serial bupropion and hydroxybupropion serum concentrations were drawn every 6-12 h starting on hospital day one and continuing for seven days, for a total of 22 serum concentrations each.Discussion The patient’s first bupropion and hydroxybupropion serum concentrations were 4000 ng/mL and 5300 ng/mL, respectively. Clearance of bupropion followed first order kinetics (t ½ = 20.6 h) while hydroxybupropion had zero order kinetics (t ½ = 118.5 h).Conclusion This bupropion overdose was treated with VA-ECMO with 20% lipid emulsion therapy, without complications. In this patient, the toxicokinetics of bupropion were first-order

FAS and NF-kappa B signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient(1,2). This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-kappa B pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-kappa B through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of I kappa B (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-kappa B enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-kappa B inhibitor I kappa B predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-kappa B as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence