“Massive” metformin overdose

Abstract

Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old female presented 5h post multi-drug 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) and shock. Despite 3 hours of CVVHDF, her acidosis worsened (pH 6.83, lactate 24 mmol/L). Intermittent haemodialysis(IHD) improved acidosis (pH 7.13, lactate 26 mmol/l), but again worsened (pH 6.91, lactate 30 mmol/L) 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 μg/ml at 8 h post-ingestion. IHD, but not CVVHDF in this case was associated with improvement in metabolic acidosis and hyperlactatemia. Pharmacokinetic analysis of metformin concentrations found a reduced apparent oral clearance (CL/F) of 8.2 L/h and a half-life of approximately 30 h. During IHD, the CL/F increased to 22.2 L/h with an approximate half-life of 10 h. The impact of prolonged oral absorption from a pharmacobezoar and re-distribution of metformin from peripheral sites (including erythrocytes) on the pharmacokinetic profile cannot be determined from the data available.

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