C49-03 Mitochondrial Mayhem: When Metformin Turns Deadly

Abstract Metformin-induced lactic acidosis (MILA) is a rare but life-threatening complication of metformin use, resulting from impaired mitochondrial oxidative phosphorylation and lactate accumulation. We present an interesting case of severe acidemia due to MILA precipitated by post-obstructive acute kidney injury. A 65-year-old man with type 2 diabetes, hypertension and prostate cancer presented to an outside hospital with six hours of worsening nausea, vomiting, and abdominal pain. He had undergone a transrectal prostate biopsy five days earlier and had not voided since. On arrival, he was lethargic, hypoglycemic (glucose 54 mg/dL) and hypothermic (91 °F). Labs revealed profound anion gap metabolic acidosis (anion gap 39), BUN 113 mg/dL and Creatinine 9 mg/dL. CT abdomen demonstrated bilateral perinephric stranding without obstruction. Despite fluid resuscitation and bicarbonate infusion, he developed refractory shock requiring initiation of norepinephrine and vasopressin followed by intubation prior to transfer. On arrival, he remained acidemic on high-dose vasopressors. Venous blood gas demonstrated pH 6.92, pCO2 24 mmHg and pO2 101 mmHg, consistent with severe metabolic acidosis and paradoxically elevated venous oxygen - suggestive of impaired cellular oxygen utilization. MILA was suspected, metformin levels were sent, and continuous renal replacement therapy (CRRT) was initiated but rapidly clotted due to access issues. To expedite drug clearance and severe acidemia, a short session of intermittent hemodialysis was performed, which necessitated escalation of vasopressor support. CRRT resumed afterwards for ongoing clearance. Methylene blue was administered for refractory vasoplegia to bypass Complex I inhibition and scavenge nitric oxide. Over 24 hours, there was a decrease in vasopressor requirements with improved urine output, acidosis, and lactate (2.9 mmol/L). He was extubated the following day and eventually discharged home six days later. Lactic acidosis in patients on metformin exists along a continuum - Metformin Induced (MILA), Metformin-Associated (MALA) and Metformin-Unrelated (MULA). The primary toxic effect of metformin is inhibition of mitochondrial Complex I in the electron transport chain, effectively halting mitochondrial ATP production. This blockade causes NADH accumulation, Krebs cycle inhibition, and diversion of pyruvate to lactate, leading to profound metabolic acidosis. This case illustrates the diagnostic and therapeutic challenges of MILA within the broader MILA-MALA-MULA spectrum. The elevated venous pO2 in this patient reflects dysoxia which is characteristic of MILA. Methylene blue may provide transient hemodynamic benefit by bypassing Complex I and mitigating vasoplegia. The use of bicarbonate remains controversial. Awareness of the pathophysiology of metformin toxicity and metabolic spectrum can guide timely intervention and improve outcomes. This abstract is funded by: None