Hyperlactataemia and clinical severity of acute metformin overdose

Background: Although metformin-associated lactic acidosis is well described, there is less information on metformin overdose and whether it is of similar severity. Aims: This study aims to describe the clinical features, laboratory investigations and outcome of acute metformin overdoses. Methods: Retrospective case series of acute metformin overdoses (>3 g) admitted to a toxicology unit over 20 years. Cases were identified from a prospective database and data extracted included demographics, dose, coingestants, clinical effects, investigations, treatment and outcomes. Results: There were 36 acute metformin overdose cases. Median age 41 years old (15–68 years old); 25 were female. Median ingested dose was 10 g (interquartile range (IQR): 5–16.1 g; range: 3.5–50 g), with coingestants taken in 34 presentations. Gastrointestinal symptoms were present in 12/36, tachycardia in 10, bradycardia in three, hypotension in four and hypoglycaemia in eight. Hypotension and bradycardia were consistent with coingestants taken. Blood pH and lactate levels were available in 25/36. Median lowest pH was 7.35 (IQR: 7.28–7.38) and acidosis (pH < 7.35) occurred in 11/25. Median peak lactate was 3.9 mmol/L (IQR: 2.6–5.2 mmol/L). There was a statistical association between dose and lactate (r = 0.51; P = 0.01) and dose and pH (r = −0.70; P = 0.0001). Hyperlactataemia (lactate >2 mmol/L) without acidosis occurred in 10/25, and hyperlactataemia with acidosis in 11/25; five had lactic acidosis. The median time to peak lactate in 10 presentations with peak lactate >2 was 6 h (2–19 h). There were six intensive care unit admissions, one for lactic acidosis, and five related to coingestants. There were no deaths. Conclusion: Metformin overdose is characterised by hyperlactataemia and minor gastrointestinal effects, with a few large ingestions progressing to lactic acidosis. Coingestants are common and may dominate toxicity