'Massive' metformin overdose.

Abstract

Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old woman presented 5h after multidrug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH7.0, lactate 17mmoll-1 ) and shock. Despite 3h of CVVHDF, her acidosis worsened (pH6.83, lactate 24mmoll-1 ). Intermittent haemodialysis (IHD) improved acidosis (pH7.13, lactate 26mmoll-1 ) but again worsened (pH6.91, lactate 30mmoll-1 ) with CVVHDF recommencement. IHD (12h), CVVHDF (26h) and vasopressor support for 7days resulted in survival. Measured metformin concentrations were extremely high with a peak of 292μgml-1 at 8h 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 8.2lh-1 and a half-life of approximately 30h. During IHD, the apparent oral clearance increased to 22.2lh-1 with an approximate half-life of 10h. 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.