A Rare Case of Hypoxia and Cyanosis Secondary to Multifactorial Medication-Induced Sulfhemoglobinemia

BACKGROUND Fatigue and dyspnea, especially with hypoxia, are common in acute care and can indicate various conditions. Sulfhemoglobinemia is a rare but important consideration when a large saturation gap is present, as most blood gas analyzers do not detect it. Medication exposure, particularly to phenazopyridine and other oxidant drugs, is a leading cause. Early recognition of this diagnosis is crucial, as recurrence is likely with re-exposure to the precipitating agent. CASE REPORT A 37-year-old woman presented with acute dyspnea, lethargy, and hypoxia after exposure to severe oxidizing agents, including first-time use of trimethoprim-sulfamethoxazole and phenazopyridine, as well as lidocaine during a recent dental procedure (not her first exposure). Shortly thereafter, she developed tachycardia, tachypnea, and hypoxia, with concurrent hemolytic anemia. Despite oxygen therapy, she had a persistent elevated saturation gap. Arterial blood gas confirmed dyshemoglobinemia, and further testing identified sulfhemoglobinemia (1.3%). She was treated with blood transfusion and discontinuation of oxidizing agents to prevent further hypoxia. CONCLUSIONS Sulfhemoglobinemia is a rare and often missed diagnosis, as most blood gases analyzers do not measure sulfhemoglobin. Despite this, this diagnosis requires great clinical suspicion, as patients are at high risk for repeated exposure to offending agents and recurrence of life-threatening hypoxia.