Management of Metformin-Associated Lactic Acidosis by Continuous Renal Replacement Therapy

Abstract

BackgroundMetformin-associated lactic acidosis (MALA) is a severe metabolic failure with high related mortality. Although its use is controversial, intermittent hemodialysis is reported to be the most frequently used treatment in conjunction with nonspecific supportive measures. Our aim was to report the evolution and outcome of cases managed by continuous renal replacement therapy (CRRT).Methodology and Principal FindingsOver a 3-year period, we retrospectively identified patients admitted to the intensive care unit for severe lactic acidosis caused by metformin. We included patients in our study who were treated with CRRT because of shock. We describe their clinical and biological features at admission and during renal support, as well as their evolution. We enrolled six patients with severe lactic acidosis; the mean pH and mean lactate was 6.92±0.20 and 14.4±5.1 mmol/l, respectively. Patients had high illness severity scores, including the Simplified Acute Physiology Score II (SAPS II) (average score 63±12 points). Early CRRT comprised either venovenous hemofiltration (n = 3) or hemodiafiltration (n = 3) with a mean effluent flow rate of 34±6 ml/kg/h. Metabolic acidosis control and metformin elimination was rapid and there was no rebound. Outcome was favorable in all cases.Conclusions and SignificanceStandard use of CRRT efficiently treated MALA in association with symptomatic organ supportive therapies.

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

“…However, the survival rate of these old patients, with a mean age of 71.6, reached to about 80%, a value better than those previously estimated [11,14,21,22]. …”

“…Interestingly, the ICU survival rate of 117 RRT-MALA patients was 78.6%, the highest reported in wide clinical records of MALA [11,14,21,22,33]. With more recent data, Doenyas-Barak found an overall survival rate of 43.2% in 44 admitted ICU patients with severe shock.…”

“…As a matter of fact, data regarding the effective incidence of RRT and survival in the setting of MALA patients are limited, mostly relying on a single center, small observational studies, or other extrapolated data [11,14,21,22]. To our knowledge, data collected from the nephrologist network GRANO constitute the largest detailed epidemiologic study on RRT-MALA patients, as it covers all ICU needs of RRT in such a large population [18].…”

“…The amount removed, proportional to the exchanged fluid, could be consistent with high-volume dialysis. Second, even if metformin can be easily removed by convection and/or diffusion, its volume of distribution within a 2-compartment model implied that a continuous (or prolonged) treatment was more effective for its extracorporeal clearance [12,13,14]. Third, an initial correction of acidosis needed a large infusion of bicarbonates.…”

“…As reported for phenformin-induced lactic acidosis more than 15 years ago [12], apart from drug removal, continuous renal replacement therapy (RRT) can support impaired kidney function. RRT corrects significant electrolyte disturbances and severe metabolic acidosis [13,14,15]. It allows removal of fluid and sodium overload due to a large amount of bicarbonate needed to correct acidemia [15,16,17].…”