PC3054: A Case of Metformin Overdose: The Utility of Extracorporeal Membrane Oxygenation in Severe Overdose

Introduction: Metformin is an antidiabetic medication (oral biguanide) for patients with Type 2 Diabetes mellitus. Side effects include diarrhea, nausea, and vomiting, and very rarely, lactic acidosis. When taken in extreme amounts, it can cause severe lactic acidosis that requires dialysis to clear.

Case Description: A healthy 18-year-old female, presented with abdominal pain and vomiting after intentionally ingesting 30 g of instant-release metformin and unknown amount of ginseng. Initially, vital signs and mental status were normal and lactate was elevated at 7.5 mmol/L. Four hours later, she became altered. Repeat lactate was 15 mmol/L with a pH of 6.92. She became hypotensive (65/47 mmHg), bradycardic (55 bpm), and minimally responsive. She was intubated and started on norepinephrine. She was treated with sodium bicarbonate and placed on continuous renal replacement therapy (CRRT). To optimize clearance, she was switched to hemodialysis for four hours. To tolerate it, she was given multiple fluid boluses and vasopressors were adjusted. Due to refractory hypotension, she was given methylene blue without improvement. She developed refractory hypoxemia. Echocardiogram showed normal function, and she was placed on veno-venous (VV) ECMO for refractory respiratory failure. Broad-spectrum antibiotics and stress dose steroids were started.
The lactate was above the laboratory’s upper detection limit at time of cannulation with an anion gap of 46 mEq/L. She developed multi-organ failure. The lactate cleared on HD 7. Vasopressors were stopped on HD 10. She was decannulated on HD 5 and extubated on HD 9 with resolution of organ dysfunction and normal neurologic function. Metformin serum concentrations on HD 1 and 3 were 63 and 3.8 mcg/ml, respectively (therapeutic range: 1 to 2 mcg/ml).

Discussion: Lactic acidosis is a rare effect of metformin but can occur with renal insufficiency or large ingestions. In toxic amounts, metformin inhibits the electron transport chain, preventing oxidative phosphorylation leading to metformin-associated lactic acidosis. Our patient had profound vasoplegia despite high dose vasopressors, normal cardiac function, and normalization of pH. Given this, she required significant fluid resuscitation leading to refractory hypoxemia requiring VV ECMO.

Conclusion: We describe a severe case of metformin overdose causing refractory shock despite normalization of pH. ECMO was utilized successfully to allow stabilization of the patient and time for toxin clearance using CRRT.