SESSION TITLE: Close Critical Care CallsSESSION TYPE: Case ReportsPRESENTED ON: 10/18/2022 11:15 am - 12:15 pmINTRODUCTION: Metformin induced lactic acidosis (MILA) is a unique pathology that requires a high index of suspicion for diagnosis. It is imperative to understand the pathophysiology of metformin metabolism to make the easily missed diagnosis. This case highlights the unique laboratory values integral to distinguishing MILA.CASE PRESENTATION: A 57-year-old female with history of hypertension, hyperlipidemia, type II diabetes presented to the emergency room (ER) for nausea, abdominal pain and confusion for 4 days. Labs were significant for high anion gap greater than detectable on the assay, osmolar gap of 15mEq/L, lactic acid of 19mmol/L, beta-hydroxybutyrate of 42mg/dL, acetone level of 27mg/dL, creatinine of 13mg/dL (baseline: 1mg/dL) and blood glucose of 82mg/dL. ABG showed a pH of 6.62, pO2 of 149 mm Hg, pCO2 of 12 mm Hg and bicarbonate of 1 mmol/L. She was noted to be hypotensive and encephalopathic. She underwent treatment with empiric antibiotics, IVF resuscitation and was started on norepinephrine prior to ICU admission. Initial differential included possible intoxication or euglycemic diabetic ketoacidosis with acute renal failure. On bedside history, her daughter reported that patient was compliant with her home medications including metformin despite her poor oral intake prior to admission. A venous blood gas (VBG) was ordered which showed pO2 of 154mmHg (almost identical to pO2 of 149 mm Hg noted on ABG). Due to her high venous pO2, we had a concern for metformin toxicity. She clinically improved after renal replacement therapy (RRT) and was transferred to the floor two days later. Her metformin level was noted to be 20 times higher than the therapeutic range confirming our suspected diagnosis of MILA.DISCUSSION: MILA is a rare complication of metformin which has mortality up to 45%. Diagnosis is difficult as the concurrent ketoacidosis and associated osmolar gap can be confusing with various intoxications or euglycemic DKA. The pathophysiology involves the accumulation of metformin which inhibits complex I of the electron transport chain. This inhibition prevents utilization of oxygen that is delivered to tissue for aerobic respiration. As a result, there is a profound lactic acidosis usually over 15mmol/L with a VBG showing pO2 similar to ABG as noted in animal studies. The metformin levels must be elevated enough to cause this cascade which can happen in overdose or acute renal failure. Treatment requires RRT and in some cases, extracorporeal membrane oxygenation (ECMO).CONCLUSIONS: MILA is a rare critical illness with high mortality. Diagnosis can be challenging due to broad differentials of anion gap metabolic acidosis (AGMA). This patient had a favorable outcome due to high suspicion and prompt treatment. Metformin levels take time to result and analyzing VBG to determine oxygen consumption can help make the diagnosis.Reference #1: Renda F, Mura P, Finco G, Ferrazin F, Pani L, Landoni G. Metformin-associated Lactic Acidosis Requiring Hospitalization. A National 10 Year Survey and a Systematic Literature Review. European Review for Medical and Pharmacological Sciences. 2013; 17; 45-49Reference #2: Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585. https://doi.org/10.1007/s00125-017-4342-zReference #3: Protti, A., Fortunato, F., Monti, M. et al. Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs. Crit Care 16, R75 (2012). https://doi.org/10.1186/cc11332DISCLOSURES: No relevant relationships by Nitin GuptaNo relevant relationships by Kushagra GuptaNo relevant relationships by Rana Mohamed SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: Metformin induced lactic acidosis (MILA) is a unique pathology that requires a high index of suspicion for diagnosis. It is imperative to understand the pathophysiology of metformin metabolism to make the easily missed diagnosis. This case highlights the unique laboratory values integral to distinguishing MILA. CASE PRESENTATION: A 57-year-old female with history of hypertension, hyperlipidemia, type II diabetes presented to the emergency room (ER) for nausea, abdominal pain and confusion for 4 days. Labs were significant for high anion gap greater than detectable on the assay, osmolar gap of 15mEq/L, lactic acid of 19mmol/L, beta-hydroxybutyrate of 42mg/dL, acetone level of 27mg/dL, creatinine of 13mg/dL (baseline: 1mg/dL) and blood glucose of 82mg/dL. ABG showed a pH of 6.62, pO2 of 149 mm Hg, pCO2 of 12 mm Hg and bicarbonate of 1 mmol/L. She was noted to be hypotensive and encephalopathic. She underwent treatment with empiric antibiotics, IVF resuscitation and was started on norepinephrine prior to ICU admission. Initial differential included possible intoxication or euglycemic diabetic ketoacidosis with acute renal failure. On bedside history, her daughter reported that patient was compliant with her home medications including metformin despite her poor oral intake prior to admission. A venous blood gas (VBG) was ordered which showed pO2 of 154mmHg (almost identical to pO2 of 149 mm Hg noted on ABG). Due to her high venous pO2, we had a concern for metformin toxicity. She clinically improved after renal replacement therapy (RRT) and was transferred to the floor two days later. Her metformin level was noted to be 20 times higher than the therapeutic range confirming our suspected diagnosis of MILA. DISCUSSION: MILA is a rare complication of metformin which has mortality up to 45%. Diagnosis is difficult as the concurrent ketoacidosis and associated osmolar gap can be confusing with various intoxications or euglycemic DKA. The pathophysiology involves the accumulation of metformin which inhibits complex I of the electron transport chain. This inhibition prevents utilization of oxygen that is delivered to tissue for aerobic respiration. As a result, there is a profound lactic acidosis usually over 15mmol/L with a VBG showing pO2 similar to ABG as noted in animal studies. The metformin levels must be elevated enough to cause this cascade which can happen in overdose or acute renal failure. Treatment requires RRT and in some cases, extracorporeal membrane oxygenation (ECMO). CONCLUSIONS: MILA is a rare critical illness with high mortality. Diagnosis can be challenging due to broad differentials of anion gap metabolic acidosis (AGMA). This patient had a favorable outcome due to high suspicion and prompt treatment. Metformin levels take time to result and analyzing VBG to determine oxygen consumption can help make the diagnosis. Reference #1: Renda F, Mura P, Finco G, Ferrazin F, Pani L, Landoni G. Metformin-associated Lactic Acidosis Requiring Hospitalization. A National 10 Year Survey and a Systematic Literature Review. European Review for Medical and Pharmacological Sciences. 2013; 17; 45-49 Reference #2: Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585. https://doi.org/10.1007/s00125-017-4342-z Reference #3: Protti, A., Fortunato, F., Monti, M. et al. Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs. Crit Care 16, R75 (2012). https://doi.org/10.1186/cc11332 DISCLOSURES: No relevant relationships by Nitin Gupta No relevant relationships by Kushagra Gupta No relevant relationships by Rana Mohamed