'Massive' metformin overdose

Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old woman presented 5 h after multidrug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH 7.0, lactate 17 mmol l(-1)) and shock. Despite 3 h of CVVHDF, her acidosis worsened (pH 6.83, lactate 24 mmol l(-1)). Intermittent haemodialysis (IHD) improved acidosis (pH 7.13, lactate 26 mmol l(-1)) but again worsened (pH 6.91, lactate 30 mmol l(-1)) with CVVHDF recommencement. IHD (12 h), CVVHDF (26 h) and vasopressor support for 7 days resulted in survival. Measured metformin concentrations were extremely high with a peak of 292 mu g ml(-1) at 8 h postingestion. IHD, but not CVVHDF in this case, was associated with improvement in metabolic acidosis and hyperlactataemia. Pharmacokinetic analysis of metformin concentrations found a reduced apparent oral clearance of 8.2 l h(-1) and a half-life of approximately 30 h. During IHD, the apparent oral clearance increased to 22.2 l h(-1) with an approximate half-life of 10 h. The impact of prolonged oral absorption from a pharmacobezoar and redistribution of metformin from peripheral sites (including erythrocytes) on the pharmacokinetic profile cannot be determined from the data available.