Severe Metformin Associated Lactic Acidosis: a Case Series of an Intensive Care Unit

Background: Severe metformin-associated lactic acidosis (MALA) is a rare but potentially fatal side effect of metformin. The clinical presentation is often unspecific, thus hindering early recognition. We aimed to assess the prevalence of MALA in an intensive care unit (ICU) and describe the demographic and clinical characteristics according to patient outcome. Methods: We conducted a 13-year single-center retrospective study, including all patients admitted in ICU with a high anion-gap metabolic acidosis and hyperlactatemia secondary to therapeutic use of metformin, after excluding other medical causes of acidosis. Results: Twenty one patients were admitted in ICU due to severe MALA (less than 1% of all admissions) with an ICU mortality rate of 23.8% (N=5). The baseline clinical characteristics were similar in survivors and nonsurvivors, both with a high prevalence of cardiovascular comorbidities as well as frequent concomitant therapy with angiotensin-converting-enzyme inhibitors and diuretics. All patients were treated with continuous renal replacement therapy (CRRT) and other organ failure support. Normal acid-base balance was achieved in all survivors in the first 24 hours. At baseline, the clinical and laboratory features of nonsurvivors were undistinguishable from survivors. Conclusions: Severe MALA is a rare cause of admission in the ICU. Although early institution of supportive therapy, MALA can progress to severe multiple-organ failure, especially when diagnosis and CRRT are delayed. Clinicians should suspect of MALA in all diabetic patients taking metformin with unexplained high anion-gap metabolic acidosis and hyperlactatemia.