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Master Thesis

Intoxication à la metformine en réanimation : étude clinique, pronostique et pharmacocinétique

Abstract : Rationale: metformin is the most prescribed anti-diabetic drug in the world. Its main complication called metformin associated lactic acidosis (MALA) is rare, but potentially fatal. The most common cause is the incidental metformin overdose, often triggered by acute renal failure or sepsis. Self-poisoning seems to have a better prognosis. We aimed to compare the self-poisonings and incidental overdoses and assess the prognostic factors of mortality. We also wished to investigate the relationships between plasma metformin and blood lactate levels as well as describe the pharmacokinetics of metformin when possible. Methods: we conducted a single-center retrospective observational study including all successive patients admitted in the Department of Medical and Toxicological Critical Care in Lariboisière Hospital between 2007 and 2016 for metformin poisoning defined by plasma metformin concentration > 2 mg/L and analyzed all the registry of data from the Phamaco-toxicology Laboratory in Cochin Hospital. Results: eighty-seven patients were included. Chronically metformin-overdosed patients differed from self-metformin-poisoned patients mainly by their co-morbidities and their presentation severity like the SOFA score on admission (p<0.0001). Based on a univariate analysis, risk factors of death were plasma lactate concentration >10 mmoL/L (OR=8.80), blood metforminc >10mg/L (OR=10.40) and prothrombin ratio <50% (OR=12.9). A pharmacokinetic model was obtained based on the data of 2 incidentally metformin-poisoned patients. The lactate/metformin relationship fitted an Emax sigmoid model. Conclusion: metformin intoxication is severe and responsible for significant complications. Our study confirms the likely different mechanism of toxicity between self-poisonings and incidental overdoses. Measurement of intra-erythrocyte metformin concentration may be helpful to better understand the mechanisms of metformin-related toxicity and predict metformin-poisoned patient’s prognosis.
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Master Thesis
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Nicolas Peron. Intoxication à la metformine en réanimation : étude clinique, pronostique et pharmacocinétique . Médecine humaine et pathologie. 2016. ⟨dumas-01630565⟩



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