The undifferentiated becomes obvious: the perfect timeline [abstract]
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Background: Metformin-associated lactic acidosis (MALA) is well described, usually with chronic use in the setting of renal dysfunction. With less than 10 cases per 100,000 patient-years, the incidence is rare. Methods: Single-patient chart review illustrating the timeline of severe acute MALA from a single ingestion in a metformin-naïve patient. Case: One-hour post-ingestion A 22-year-old female presented within 1 h of an intentional ingestion. Providers were presented with three empty unlabeled prescription bottles. In the first hours, patient was nauseous with normal mental status. Initial labs were unremarkable for metabolic or electrolyte derangements and an EKG had normal intervals. Four hours post-ingestion Patient abruptly developed delirium, mydriasis, anhidrosis, flushing, absent bowel sounds tachycardia, and hypertension. Administration of physostigmine improved delirium. Repeat labs revealed an anion gap metabolic acidosis (AGMA) and she developed a prolonged QTc. Five hours post-ingestion Patient became lethargic and tachypneic with worsening AGMA. Lactate was found to be 18.1 mmol/L and venous pH was 6.9. Sodium bicarbonate was administered. Six hours post-ingestion Patient became hypotensive and unresponsive. Fluid boluses and sodium bicarbonate infusion were initiated. She was intubated with mechanical hyperventilation and vasopressors were started. High-volume urine output was observed. Eight to 10 hours post-ingestion Repeat labs revealed worsening AGMA, increasing lactate, and acute hypoglycemia. Bedside ultrasound revealed grossly normal cardiac inotropy and patient was warm peripherally. Patient had a positive hemodynamic response to calcium gluconate, though EKG had prolongation of QRS and QTc. Thirteen hours post-ingestion Patient developed profound hypothermia and lactate increased to 33 mmol/L. Despite sodium bicarbonate infusion and hyperventilation, there was no improvement of acidosis. Family presented prescription labels for metformin, ibuprofen, and meloxicam. Fifteen hours post-ingestion Hemodialysis was initiated with rapid complete recovery. Discussion: We present an acute undifferentiated ingestion with delayed altered mental status, tachypnea, acidosis, hypotension, hypoglycemia, hypothermia, normal cardiac inotropy, and insidious increase of lactate, requiring hemodialysis due to MALA. No patients in a previous study of 234 patients with MALA (22 deaths) developed this level of serum lactate. This is the first real-time description of a potentially lethal acute metformin overdose with corresponding clinical context.