Successful treatment of metformin-associated lactic acidosis in a hemodialysis patient

Abstract

The number of diabetic patients is increasing in Japan. Metformin is an antidiabetic agent, which suppresses gluconeogenesis. Unlike other antidiabetic agents, metformin reduces insulin resistance and is not strongly associated with hypoglycemia or weight gain. Furthermore, clinical studies have demonstrated that it is effective against cardiovascular disease. Given its effects and affordability, metformin is a commonly used oral hypoglycemic drug. However, its use is associated with lactic acidosis in extremely rare cases. While lactic acidosis is rare in metformin-treated patients, it requires immediate attention since it can be lethal. We report a case of severe lactic acidosis (pH: 7.0; lactate: >20 mmol/L, potassium [K]: 6.1 mEq/L, creatinine: 2.4 mg/dL, estimated glomerular filtration rate: 23.8 mL/min/1.7 m²) in a 53-year-old male diabetic patient who was taking metformin. On admission, his white blood cell count, C-reactive protein level, and procalcitonin level were elevated, and he was diagnosed with metformin-associated lactic acidosis (MALA) caused by an infection. Since his symptoms did not improve despite supportive care, he was switched to 2-hour hemodialysis using a blood pump (200 mL/min), dialysate pump (500 mL/min), and an APS18MD membrane (polysulfone; Asahikasei Kuraray Medical, Tokyo). After the hemodialysis, his condition improved markedly (pH: 7.4; lactate: 5.2 mmol/L, K: 4.7 mEq/L). Supportive care and extracorporeal circulation are the only treatment options for MALA. Extracorporeal circulation effectively removes metformin from the body. Furthermore, it rapidly controls acidosis, hyperlactatemia, and electrolyte imbalances and compensates for impaired kidney function. Patients with lactate levels of >20 mmol/L and pH values of <7.0 are indicated for extracorporeal circulation, until they achieve a lactate level of <3.0 mmol/L and a pH value of >7.35. In Japan, where dialysis is commonly employed, extracorporeal circulation is a highly safe treatment. Since MALA is a life-threatening disease, extracorporeal circulation should be used to treat high-risk patients with the condition whenever possible.