Case Presentation: A 71-year-old male presented to the ER with complaints of constipation for one week. He has a past medical history of coronary artery disease status post CABG, congestive heart failure with reduced ejection fraction, Type II diabetes, chronic obstructive pulmonary disease, obstructive sleep apnea, peripheral vascular disease and hyperlipidemia. The patient was recently discharged from hospital after being treated for COVID-19 infection where his hospital course was complicated by acute kidney injury secondary to acute tubular necrosis. While the patient’s overall medical condition improved, his kidney function never recovered. He was subsequently started on intermittent hemodialysis. In the ER, the patient denied abdominal pain, nausea, vomiting, hematemesis or melena. Initial work up showed creatinine 3.52, anion gap 20, lactic acid 14.7, BUN 21 and bicarbonate 23. ABG showed pH 7.37, pCO2 33, pO2 103 and bicarbonate of 19.1. CT abdomen and pelvis without contrast was obtained which showed a large stool burden. The patient’s stool was disimpacted in the ER, and he denied any further symptoms. Due to the significantly elevated lactic acid levels, CT abdomen and pelvis with IV contrast was obtained which did not show any evidence of bowel ischemia. The lactic acid continued to trend up and peaked at 18.6. The patient was noted to be taking metformin despite it being discontinued secondary to his renal failure. Nephrology was consulted for the lactic acidosis, and the patient was started on intermittent hemodialysis with high flux dialyzer followed by direct transition to continuous renal replacement therapy. The patient’s lactic acid trended down with continuous renal replacement therapy. The patient remained asymptomatic throughout his hospitalization and metformin use was felt to be the cause of his lactic acidosis as no other etiology was found. The patient was discharged home with a normal lactic acid level.
Discussion: Metformin associated lactic acidosis (MALA) is life threatening complication of metformin use. The association between metformin and lactic acidosis has been known for decades and occurs via a complex mechanism where metformin increases anaerobic metabolism and lactate levels. While metformin is widely prescribed, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Metformin is renally cleared and has been contraindicated in moderate and severe renal impairment since its FDA approval, and MALA is usually associated with a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion). However, in our patient’s case, there was no inciting event, and the buildup of metformin was likely chronic given the patient’s normal serum pH and lack of symptoms. Mortality is high in patients with MALA with a metanalysis reporting it at 36%. Treatment consists of sodium bicarbonate for severe acidosis and hemodialysis to correct acidosis and remove metformin from the blood.
Conclusions: It is important for hospitalists to be aware of metformin and its association with lactic acidosis so treatment can be started immediately minimizing morbidity and mortality. Furthermore, it is important for the hospitalist to discontinue metformin in patients with renal failure or any condition that decreases renal perfusion.