A patient with metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy: a case report

Abstract

BackgroundMetformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Recent studies noted a correlation between metformin accumulation and lactic acidosis. Continuous renal replacement therapy for the treatment of metformin-associated lactic acidosis has been documented in some case reports; however, there is currently no specific treatment for metformin-associated lactic acidosis.Case presentationA 70-year-old Japanese woman with type 2 diabetes mellitus presented to an emergency room with metformin-associated lactic acidosis. She was found to be hypotensive and laboratory examinations revealed severe lactic acidosis: pH 6.618, partial pressure of carbon dioxide in arterial blood 17.3 mmHg, bicarbonate 1.7 mmol/L, and lactate 18 mmol/L. Severe acidemia persisted despite supportive care including intravenously administered fluids, sodium bicarbonate, antibiotics, and vasopressors. Continuous renal replacement therapy was initiated in our intensive care unit. After dialysis for 3 days, her lactate level and pH value completely normalized. The concentration of metformin detected was 77.5 mg/L, which is one of the highest in metformin-associated lactic acidosis successfully treated without overdose.ConclusionsThe present case had one of the highest metformin concentrations in metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy, and serum metformin concentrations may be useful for the diagnosis of metformin-associated lactic acidosis. Metformin-associated lactic acidosis is a rare but important etiology of lactic acidosis. Continuous renal replacement therapy is advantageous for the treatment of hemodynamically unstable patients with metformin-associated lactic acidosis.

Metformin intoksikasyonuna sekonder gelişen akut böbrek hasari ve laktik asidoz

“…Metformin ilişkili laktik asidozun mekanizması metforminin dokulardaki mitokondriyal oksidatif fosforilizasyonu inhibe ederek laktatın birikmesine ve klirensinde azalmaya neden olmasıdır [6]. Metformin ilişkili laktik asidoz sıklığı 1-9 vaka/100.000 hasta yılıdır ve mortalite oranı %30-50'dir [10]. Yarı ömrü yaklaşık 4-8 saat olan ve %90'ı renal yolla elimine edilen metforminin sağlıklı böbreklere sahip bireylerde bu komplikasyona sık olarak yol açmadığı da bilinmektedir ki dünya üzerinde yaygın olarak kullanılmaktadır [1].…”

Etiology and Management of Acute Metabolic Acidosis: An Update

“…They concluded that RRT is more effective in aMA control than buffer therapy alone. The feasibility and efficacy of RRT in this situation was also reported by Kinoshita et al [37]. In 2015, the Extracorporeal Treatments in Poisoning Workgroup evaluated 175 articles reporting on RRT in metformin intoxication [38].…”

A Case Report on Metformin-Associated Lactic Acidosis and Transient Blindness

“…Other side effects include chest discomfort, flushing, palpitations, diaphoresis, cyanocobalamin deficiency, hypoglycemia, headache, and rhinitis. Lactic acidosis and blindness are rare, and their incidence is not clear, as they are reported only in some case reports and case series [9]. The most common symptoms of MALA are those related to the gastrointestinal tract (including nausea, vomiting, and diarrhea) followed by an altered mental status, shortness of breath, hypothermia, and hypotension [8].…”

“…Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. MALA is characterized by a blood lactate concentration greater than 5 mmol/L and arterial pH less than 7.35 in association with metformin exposure [9]. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment [12].…”

“…Metformin-associated lactic acidosis (MALA) and transient blindness are rare, life-threatening phenomena, resulting in hemodynamic instability and severe metabolic abnormalities, usually requiring renal replacement therapy (RRT) [1]. As it has a large volume of distribution, the initiation and duration of dialysis depend on clinical and laboratory targets [2] like the normalization of pH and lactate.…”