Metformin-associated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit

Abstract

BACKGROUND: Metformin, a widely used hypoglycaemic agent in type 2 diabetes mellitus, is uncommonly associated with lactic acidosis, a serious condition with high mortality. OBJECTIVE: To evaluate the incidence of metforminassociated lactic acidosis (MALA) in an Australian intensive care unit, and the clinical profile and outcomes of patients admitted to the ICU with this diagnosis. DESIGN, SETTING AND PARTICIPANTS: We analysed data on patients admitted to a 14-bed tertiary care adult ICU over a 5-year period (January 2003 to December 2007). We did manual searches of ICU discharge summaries, reviewing case notes and cross-referencing with the ICU electronic database to identify and characterise patients with an ICU discharge diagnosis of MALA. MALA was defined as a syndrome of elevated blood lactate level with acidaemia in patients taking metformin (after other causes of lactic acidosis had been excluded). RESULTS: There were 17 patients in our study cohort, with a mean age of 65 (SD, 9.9) years. MALA was diagnosed in 6 per 1000 ICU admissions. All patients with MALA presented with gastrointestinal symptoms of nausea, vomiting and/or diarrhoea, and 11 had clinical signs of dehydration. Patients had evidence of severe acidosis (mean pH 6.92 [SD, 0.26]; anion gap, 34 [SD, 10]); high lactate levels (mean 9.6 [SD, 4.1] mmol/L); and acute renal dysfunction (mean creatinine level 585 [SD, 305] µmol/L). The mean APACHE (Acute Physiology and Chronic Health Evaluation) III score was 106.4 (SD, 42.9). The mean invasive mechanical ventilation time (for 13 patients who required ventilation) was 23.4 (SD, 32.3) hours, and mean ICU length of stay was 62.8 (SD, 53.5) hours. Thirteen patients required dialysis and vasopressor support and two had a negative laparotomy; 5/17 patients (29%) died. APACHE III score, arterial pH on admission and male sex were associated with an increased risk of death in hospital (P < 0.05). CONCLUSION: MALA is a not uncommon cause of ICU admission. Gastrointestinal symptoms predominate in MALA, and the condition is associated with significant morbidity and mortality.