Abstract

Background Metformin associated lactic acidosis (MALA) is a serious adverse event with a high mortality rate of 30–50%. Early recognition of MALA and timely starting treatment may reduce its morbidity and mortality. Objective The aim of this study was to explore clinical parameters to identify patients with MALA in patients with suspected sepsis induced lactic acidosis in the emergency department ED. Setting A retrospective single centre study was conducted at the Deventer Teaching Hospital in the Netherlands. Method Patients with lactate concentration > 4.0 mmol/l admitted at the ED between 2010 and 2017 with suspected sepsis or confirmed MALA and referred to the Intensive Care Unit were included. Baseline characteristics (pH, lactate, creatinine and CRP) of MALA patients were compared with patients with suspected sepsis induced lactic acidosis. Creatinine and lactate concentration were selected as potential relevant parameters. Main outcome measure Sensitivity and specificity of the highest tertiles of the creatinine and the lactate concentrations separately, in combination, and both combined with metformin use, were calculated. Results Thirteen MALA and 90 suspected sepsis induced lactic acidosis patients were included. Lactate (14.7 vs 5.9 mmol/l, p < 0.01) and creatinine concentration (642 vs 174 μmol/l, p < 0.01) were significantly higher in the MALA group and arterial pH (7.04 vs 7.38, p < 0.01) and CRP (90 vs 185 mg/l, p < 0.01) were significantly lower. The combined parameters lactate ≥ 8.4 mmol/l, creatinine ≥ 256 μmol/l had a sensitivity of 85% and a specificity of 95% for identifying MALA in suspected sepsis induced lactic acidosis patients in the ED. When combined with metformin use the specificity increased to 99%. Conclusion When managing lactic acidosis in the ED the diagnosis MALA should be considered in patients with a creatinine concentration ≥ 256 μmol/l and lactate concentration ≥ 8.4 mmol/l.

Highlights

  • Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because it decreases cardiovascular morbidity and mortality [1, 2]

  • The treatment modality extracorporeal treatment (ECTR) was more frequently used and mortality was higher in the Metformin associated lactic acidosis (MALA) group. 26% of the suspected sepsis induced lactic acidosis patients used metformin but did not comply with the definition of MALA

  • The results show that the combined parameters lactate ≥ 8.4 mmol/l and creatinine ≥ 256 μmol/l have a sensitivity and specificity of 85% and 95% respectively for identifying MALA in suspected sepsis induced lactic acidosis in the ED

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Summary

Introduction

Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because it decreases cardiovascular morbidity and mortality [1, 2]. The reported incidence of MALA varies from 0 to 138 per 100.000 patient years but this may be increasing the coming years due to the increase in the number of type 2 diabetes mellitus patients and the use of metformin [3,4,5]. Several studies suggest that starting timely treatment of MALA might reduce MALA-related morbidity and mortality [5, 10,11,12,13,14,15]. Recognition of MALA and timely starting treatment may reduce its morbidity and mortality

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