Combined Metformin Associated Lactic Acidosis and Starvation Ketoacidosis with Very High Osmolal Gap

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Introduction: Metformin is the principal biguanide in clinical use to treat Type 2 Diabetes mellitus. owing to its favorable safety profile. Metformin-Associated Lactic Acidosis (MALA) is rare and primarily seen in patients with renal impairment. Only few cases of coexisting MALA and ketoacidosis have been reported as case reports of MALA usually attribute high anion gap to lactic acidosis and uremia (1). We report a case of combined MALA and ketoacidosis with elevated osmolal gap (OG) in setting of AKI with successful outcome. Case Presentation: 49- year-old male with history of Type 2 Diabetes Miletus was brought to hospital abdominal pain, nausea, poor oral intake and altered mental status. Patient had hypoglycemia the night before which resolved with apple juice. Physical exam was remarkable for tachypnea and tachycardia. Laboratory findings are shown on table 1. Supportive management was started with intravenous fluids, sodium bicarbonate, and mechanical ventilation. MALA was suspected, metformin level was sent along with ethylene glycol, methanol and isopropyl alcohol levels due to very high anion gap and OG. While arrangements were made for hemodialysis, Poison control center was contacted. Fomepizole was recommended. Hemodialysis session lasted only for 90 minutes only due to hypotension. See Table 1 for post-hemodialysis labs. Fomepizole was discontinued as anion gap and OG improved drastically. Patient was extubated next day and serum creatinine improved. Metformin level was 27mcg/m (therapeutic range 1-2mcg/mL). Ethylene Glycol, Methanol and Isopropyl alcohol levels were undetectable. Acetone level was 15mmol/L. Discussion: The mortality rate of MALA is 25.4% and is associated with the severity of acidosis. Non-surviving cases tend to have multiple comorbidities other than renal failure [2], Lactic acidosis or ketoacidosis causes mild increase in OG, while methanol or ethylene glycol ingestion often leads to more profound rise in OG [3]. Metformin-induced inhibition of gluconeogenesis and stimulation of fatty acid oxidation is a likely cofactor for ketogenesis in the absence of other known ketogenic situations [4]. Although there are no randomized trials of renal replacement therapy in MALA, retrospective series and case reports support this approach. Indications for hemodialysis in MALA include lactate 20 mmol/L, pH 7.0, shock, failure of standard supportive measures and decreased level of consciousness [5]. Conclusion: MALA can be deadly if not recognized timely but carries good prognosis if suspected and treated early. Though profound elevation in OG is frequently attributed to toxic alcohol intoxication, combined lactic and ketoacidosis can also be contributory.