Toxicokinetics of metformin overdose treated with CVVHDF

A 53-year-old man died following a reported ingestion of 80 g of his metformin tablets resulting in severe, refractory shock and metformin-associated lactic acidosis. His peak serum metformin concentration was 53 μg/mL (therapeutic range 1-2 μg/mL), peak lactic acid concentration was 49.7 mmol/L, and arterial pH nadir was 7.06. He died despite vasopressors and renal replacement therapy [RRT; both intermittent hemodialysis (IHD) and continuous venovenous hemodiafiltration (CVVHDF)]. Serial metformin concentrations during CVVHDF suggested a half-life of 33-h. Similar to previous reports of RRT for metformin toxicity, CVVHDF appears to provide first-order elimination of metformin.