Introduction: Metformin is one of the most prescribed medications in the United States, in 2022, over 86 million prescriptions filled. Although generally well tolerated, metformin carries a rare but serious risk of metformin-associated lactic acidosis. The incidence of MALA is approximately 47 cases per 100,000 patient-years and is associated with a high mortality rate ranging from 30% to 50%. Standard management involves supportive care and extracorporeal removal of metformin via hemodialysis. In cases of refractory vasoplegic shock, adjunctive therapies such as methylene blue have been explored.
Description: A 47-year-old male with diabetes presented with intractable nausea and vomiting for 3 days, which began during a cruise. He was compliant with metformin, tirzepatide, and losartan. On arrival, he was tachypneic, dehydrated, and lethargic. Labs revealed acute renal failure, severe metabolic acidosis pH 6.69, HCO₃ 3, lactate 12.8 mmol/L, and potassium K⁺ 6.7. Clinical deterioration prompted suspicion for metformin-associated lactic acidosis. Lactic acid peaked at 21.4 mmol/L. ICU treatment included IV fluids norepinephrine and vasopressin infusions at escalating doses to treat refractory vasoplegic shock. Methylene blue was administered as continuous infusion. He stabilized soon after allowing for transition to CRRT, and vasopressor weaning.
Discussion: Methylene blue may offer therapeutic benefit in this case through two key mechanisms. By acting as a metabolic rescue agent by accepting electrons from NADH and transferring them to cytochrome c within the mitochondria. Restoring electron flow, potentially restarting the Krebs cycle and correcting the metabolic dysfunction induced by metformin. Second, it exerts vasoconstrictive effects by inhibiting nitric oxide synthase, thereby reducing nitric oxide-mediated vasodilation and improving vascular tone. Early initiation of hemodialysis—ideally within six hours of presentation—has been independently associated with reduced mortality. While this case and others in the literature suggest a role for methylene blue in such scenarios, current evidence is limited to isolated case reports and small series. No large-scale clinical trials have confirmed its efficacy, so its use should be reserved for cases where standard therapies fail.
