Something Old, Something New, Something Borrowed, Something BLUE: A Novel Treatment of MALA

Introduction: We report a case of metformin associated lactic acidosis (MALA) with profound shock unresponsive to traditional therapy that was managed with a novel combination of methylene blue (MB) and thiamine.


Description: 75-year-old woman with type 2 diabetes presented to the ED with back pain. Laboratory data demonstrated a high-anion gap metabolic acidosis, acute kidney injury (lactate 24 mmol/L, pH 6.8, creatinine 6.2 mg/dL). Initial treatment was focused on sepsis, hemodynamic and respiratory support with levophed and intubation. After review of home medications differential diagnosis was broadened to MALA. Bicarbonate infusion and CRRT were initiated within 2 hours of ICU arrival. She required additional support with vasopressin, epinephrine, and angiotensin II. MB infusion (1mg/kg bolus, followed by infusion of 0.5mg/kg/hr) and parenteral thiamine (200mg q8hrs) were started. Over the next 24 hours, her clinical trajectory noted marked improvement. CRRT was stopped at 48 hours and liberation from mechanical ventilation occurred on day 4. Hospital discharge occurred on day 11. Metformin level resulted at 36 mcg/mL.


Discussion: Recognition of MALA is critical to ensure timely treatment as mortality can range from 10 to 36%. MALA is typically reported with levels of metformin at > 5mcg/mL. Traditional management of severe MALA includes supportive care and renal replacement therapy (ideally initiated within 6 hours of presentation) with or without a bicarbonate infusion. We report the additional therapeutic use of MB and parenteral thiamine. MB’s mechanism of action centres on impeding nitric oxide induced vasodilation. Hypothetically MB improves mitochondrial dysfunction in oxidative stress by serving as an adjunct in the electron transport chain and functioning as a redox mediator. Thiamine deficiency impacts the Krebs cycle. Metformin can induce systemic thiamine deficiency by reducing its reuptake. Parenteral thiamine repletion serves to counterbalance systemic deficiency. Prior literature has described the use of MB and thiamine as individual therapies. We postulate that the synergistic modalities of both helped with recovery of our patient with severe MALA. Future work should look at this combination as a rescue therapy for MALA patients that have failed hemodialysis.