PC3093: Successful Treatment of Metformin Toxicity Using ECMO and CVVHD Following Massive Intentional Ingestion

Introduction: Metformin is a biguanide medication used in the treatment of diabetes mellitus. Acute overdose of metformin causes lactic acidosis, which is associated with 30% mortality. Here, we present the successful use of central venoarterial extracorporeal membrane oxygenation (VA-ECMO) and continuous venovenous hemodiafiltration (CVVHD) in an adolescent female after intentional ingestion of > 100 g of metformin.

Case Description: A previously healthy adolescent female presented after intentional ingestion of > 100 g of metformin. Though she was initially oriented with no evidence of hemodynamic instability or respiratory compromise, serum lactate was 5 mmol/L (normal 0.7-2.1mmol/L). She was started on dextrose and sodium bicarbonate infusions on route to our center. On arrival, she was hypotensive, hypoxic, hypoglycemic, and had altered mentation leading to intubation. Her initial venous blood gas showed pH 6.96, PCO2 43.5 mmHg, HCO3 10.5 mmol/L, base deficit -21 mmol/L and lactate 13.9 mmol/L. She was initiated on inotropic support with epinephrine prior to transfer to the pediatric intensive care unit. Within 3.5 hours, the serum lactate rose to >20 mmol/L and she was started on high flux hemodialysis then transitioned to CRRT (hemodiafiltration) due to hemodynamic instability, with blood flow rates of 190-350 mL/min. Despite inotropic support with epinephrine at 0.2 mcg/kg/min and norepinephrine at 0.1 mcg/kg/min, she progressed to cardiovascular collapse. Central VA-ECMO was initiated and continued for 4 days with CVVHD provided through the ECMO circuit. Her peak metformin level was 76 mcg/mL (toxic >4 mcg/mL; lethal > 50 mcg/mL2). Peak lactate was 31.9 mmol/L. True peak metformin and lactate levels are believed to be higher as they were obtained after initiating dialysis (see Table 1). She transitioned to hemodialysis on day 9, extubated day 13, and discharged on day 25. At the time of discharge, her neurological and renal function were at her pre-illness baseline.

Discussion: Extracorporeal removal of metformin should be attempted with hemodialysis or CVVHD in cases of acute toxicity associated with severe lactic acidosis (pH < 7.0, lactate > 20 mmol/L). Clearance of metformin can reach 200 mL/minute with hemodialysis compared to 50 mL/minute with CVVHD. Nevertheless, CVVHD should be utilized in cases of hemodynamic collapse. ECMO should be considered in patients who are unresponsive to inotropic infusions, allowing improved cardiorespiratory function while allowing CVVHD to remove circulating metformin and clear lactic acidosis.

Conclusion: This case reports the successful management of a patient with one of the largest intentional metformin ingestions found in literature by utilizing VA-ECMO and CVVHD.