The Usefulness of Measuring the Anion Gap in Diagnosing Metformin-associated Lactic Acidosis

A Case Series

Jesus Ruiz-Ramos; Laura Lozano-Polo; Ana Juanes-Borrego; Iván Agra-Montava; Mireia Puig-Campmany; María Antonia Mangues-Bafalluy


J Med Case Reports. 2021;15(17) 

In This Article

Case Presentation

Cases involving six Caucasian patients with suspected MALA who visited the emergency department between September 2019 and December 2019 were analysed. The main characteristics of these patients are presented in Table 1. The mean age was 75.5 (standard deviation = 6.3) years. All the patients exhibited respiratory symptoms at admission; further, based on a blood gas analysis performed at emergency department admission, almost all of them presented with a pH value < 7.35 and lactate level > 2 mmol/L while only one patient had a lactate level of > 5 mmol/L, which is one of the established criteria for an MALA diagnosis.[7] Lactate level was analysed by the "GEM premier 3500 in Instrumentation Laboratory" automated blood gas analysis system blood gas analyser (ABL90, Radiometer, Bronshoj, Denmark). Alternative causes of metabolic acidosis such concomitant drugs or toxics substances were excluded, based on medical history review and patients or relatives interview. Four patients presented with chronic kidney disease as a comorbidity. However, the estimated glomerular filtration rate (calculated by the modification of diet in renal disease (MDRD) formula[6]) was less than 30 mL/min at admission in all cases. All the patients had metformin plasma concentrations above the upper limit of the therapeutic range (> 2.5 mg/L).[7] The highest metformin concentrations were not found in patients with the highest lactate values.

Only two of the included patients met the haemodialysis criteria established by the extracorporeal treatments in poisoning (EXTRIP) recommendations[8] (lactate > 20 mmol/L, pH ≤ 7.0, or failure of standard treatment, including bicarbonate); further, only one of them received haemodialysis, and therefore, the therapeutic effort upon admission was limited to the other patient. Two patients died during hospitalisation, and these patients had the highest metformin plasma concentrations (> 30 mg/L). The anion gap values (calculated as [Na+] + [K+] − [Cl] − [HCO3 ]) ranged from 12.3 to 39.3, with only two patients exhibiting values greater than 14.