Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series

Abstract

BackgroundThe current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT.MethodsWe searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Case-level data including case’s demographics and clinical information related to MALA were abstracted. Multiple logistic regression modeling was used to examine the predictors of mortality.ResultsA total of 253 unique cases were identified with cumulative mortality of 17.2%. Eighty-seven percent of patients had acute kidney injury. Serum lactate level was significantly higher in non-survivors (median 22.5 mmol/L) than in survivors (17.0 mmol/L, p-value <0.01) and so did the median blood metformin concentrations (58.5 vs. 43.9 mg/L, p-value = 0.05). The survival advantage was not significantly different between the modalities of RRT. The adjusted odds ratio of mortality for every one mmol/L increase in serum lactate level was 1.09 (95% CI 1.02–1.17, p-value = 0.01). The dose-response curve indicated a lactate threshold greater than 20 mmol/L was significantly associated with mortality.ConclusionsOur study suggests that predialysis level of serum lactate level is an important marker of mortality in MALA patients requiring RRT with a linear dose-response relationship. To better evaluate the optimal prescription of RRT in MALA, we recommend fostering an international consortium to support prospective research and large-scale standardized case collection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0640-4) contains supplementary material, which is available to authorized users.

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

“…Patients in the ECTR group were sicker than patients in the non-ECTR group considering the degree of lactic acidosis, kidney function, and vasopressor requirement while having a lower but not statistically different, mortality. As hyperlactatemia in general and in MALA patients is associated with increased mortality [8,11,[23][24][25], this at least comparable outcome suggests there might be a benefit for ECTR. This is also suggested by Peters et al [19].…”

“…Calello et al [1] have not formulated a threshold for metformin serum concentration because at the time of formulation of these recommendations, there was much uncertainty regarding the value of metformin concentrations in relation to the prognosis and the limited availability of the metformin assays. Some studies have shown a correlation between metformin concentration and mortality [8,9,20] while others have not [17,21,25,26]. Despite the uncertainty concerning its prognostic value, measuring metformin serum concentrations could be of diagnostic value in MALA and may assist in its management [9,22,26].…”

Schwere Metformin-assoziierte Laktatazidose bei einem 67-jährigen Patienten

“…Die Metformin-assoziierte Laktatazidose (MALA) ist ein schweres Krankheitsbild und wird definiert als eine arterielle Laktatkonzentration von ≥ 5 mmol/l und einem pH ≤ 7,35 in Assoziation mit der Einnahme von Metformin [1]. Pathophysiologisch ist sie bedingt durch einen erhöhten anaeroben Glukoseumsatz, insbesondere im Splanchnikusgebiet, mit inadäquater hepatischer Laktatelimination bei Nieren-/Leberversagen oder übermäßiger Bildung [2,3]. Der exakte zelluläre Mechanismus ist Gegenstand aktueller Forschung, jedoch scheint die Metformin-bedingte Hemmung von Komplex I der mitochondrialen Atmungskette von essenzieller Bedeutung [4].…”

“…Diese Unterscheidung ist jedoch unscharf und wird uneinheitlich angewandt. Die MALA hat eine Inzidenz von 1 bis 9 pro 100 000 Patientenjahren [6] und weist eine Mortalität zwischen 17 und 47 % auf [3,6,7]. Als prognoseverschlechternde Faktoren gelten das Ausmaß der Hyperlaktatämie und der Azidose [6], auch wenn dies nicht uniform akzeptiert ist [2,7].…”

“…Typischerweise präsentiert sich ein MALA-Patient klinisch mit einer gastrointestinalen Symptomatik, Vigilanzminderung, Hypothermie sowie Hypotension und erfüllt die Kriterien eines akuten Nierenversagens [3,6]. Während die Genese der Vigilanzminderung bislang ungeklärt ist, können Hypotension und Hypothermie auf das Vorliegen einer Vasoplegie im Rahmen der Azidose zurückgeführt werden [8].…”