Uncoupling Agents as a Contributor to Refractory Metabolic Acidosis in a Burn Victim: A Case Report

Introduction: Uncoupling agents impair mitochondrial oxidative phosphorylation, which disrupts adenosine triphosphate production and causes high anion gap metabolic acidosis. These agents, linked to environmental toxins or pharmacologic exposures, present diagnostic and therapeutic challenges due to rapid clinical deterioration. Early identification is crucial for intervention. Clinical Findings: A 64-year-old male with type II diabetes mellitus sustained burns covering 14% total body surface area during a shed fire with suspected pesticides and rodenticide exposure. He had hypotension with severe metabolic acidosis (lactate 20 mmol/L, pH 7.0, bicarbonate [HCO3] 11 mmol/L) and an anion gap of 35 mEq/L. He was admitted to the surgical intensive care unit. Clinical Course: His initial treatment included burn debridement, intravenous hydroxocobalamin for potential cyanide toxicity, and bolus sodium bicarbonate therapy followed by a continuous infusion of bicarbonate. Despite continuous renal replacement therapy (CRRT), worsening hyperkalemia (6.2 mEq/L) and hemodynamic instability required escalation of a higher dose of norepinephrine and vasopressin. On day 2, his lactate was 20 mmol/L and HCO3 was 10 mmol/L, and intravenous angiotensin II and epinephrine were started. An abdominal computed tomography scan showed ascites without bowel ischemia. On day 3, his lactate increased to 27 mmol/L and HCO3 decreased to 9 mmol/L, and he was given methylene blue for vasoplegia. An exploratory laparotomy identified colonic necrosis, requiring total abdominal colectomy. Despite maximal CRRT ultrafiltration, the patient died on hospital day 4. Conclusions: Uncoupling agent exposure can cause refractory high anion gap metabolic acidosis. Early CRRT and bicarbonate therapy may offer transient benefit, but toxicologic testing for definitive diagnosis was not obtained per family wishes.