Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy

Abstract

Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=471917.

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

“…The overall mortality of 40% in our study is in line with the mortality reported in previous studies, ranging from 20 to 50% [7,8,[12][13][14][17][18][19][20][21]. Blood pH, lactate, creatinine, and serum metformin concentration in the ECTR group in this study are similar to that reported in the literature [9,13,[20][21][22]. The significantly higher lactate and creatinine concentrations in the ECTR group compared to the non-ECTR group have also been reported in other studies [9,12,19].…”

“…The incidence of MALA varies from 0 to 138 per 100.000 patient years and may increase in the coming years due to the increase in the number of type 2 diabetes mellitus patients and the use of metformin [4,6,8,9]. Several studies suggest that starting timely treatment might reduce MALA-related morbidity and mortality [8][9][10][11][12][13][14]. Extracorporeal treatments (ECTRs) may be necessary to remove metformin, clear lactate, and correct acid-base abnormalities [1,11].…”

Metformin Induced Lactic Acidosis What Is the Effective Treatment?

“…Metformin reduces glucose levels by increasing insulin sensitivity, reducing hepatic glucose release and increasing muscle uptake [1] [2]. It prevents hepatic gluconeogenesis by reducing the lactate reuptake.…”

“…Metformin is one of the first-line treatments for patients with type 2 diabetes mellitus [1]. Metformin reduces the risk of mortality and morbidity in patients with diabetes.…”

“…Phenformin, an earlier biguanide was withdrawn from the market after associations with lactic acidosis. Lactic acidosis is one of rare but life-threatening metformin side effects especially in the presence of acute kidney injury (AKI) [1]. Metformin induced lactic acidosis (MALA) is a serious illness which should identify and treat ur-*First author and author of reference.…”