From Shelf to Cyanosis: A Rare Case of Sulfhemoglobinemia Triggered by Over-the-Counter Drugs

Sulfur atoms can irreversibly bind to and oxidize the heme molecule in hemoglobin, impairing its ability to transport oxygen. A common cause of sulfhemoglobinemia is the misuse of sulfur-containing medications, particularly over-the-counter options like phenazopyridine. Due to the irreversible nature of this binding, management is supportive, as no antidote is currently available. We present a 74-year-old female with dyspnea on exertion after being evaluated at a clinic for chronic obstructive pulmonary disease (COPD). The patient had a history of chronic respiratory failure requiring 2 liters of nasal cannula (NC) oxygen. Her oxygen saturation (SpO2) was found to be persistently below 88% despite increasing her oxygen flow. She presented to the emergency department, where she underwent evaluation for acute on chronic respiratory failure. A CT angiogram of the chest revealed no pulmonary embolism and no significant changes in her underlying lung disease. The patient was not in distress, had clear lung auscultation bilaterally, but exhibited cyanosis of her digits. Her pulse oximetry consistently showed SpO2 levels of 88% despite increasing oxygen levels, and an SpO2 of 85% while ambulating on 6 liters of oxygen. An arterial blood gas analysis revealed a partial pressure of oxygen of 157 mmHg, raising suspicion for dyshemoglobinemia. Appropriate laboratory tests for carboxyhemoglobin and methemoglobin were ordered; however, the lab was unable to process these tests due to elevated sulfhemoglobin levels. Further investigation revealed that the patient had been taking high doses of phenazopyridine for cystitis. Sulfhemoglobinemia, although rare, is a known complication associated with phenazopyridine. A confirmatory lab test showed normal carboxyhemoglobin and methemoglobin levels, but sulfhemoglobin was elevated at 3.6% (reference range: 0.0-0.4%). The patient was closely monitored and supportively treated with oxygen supplementation. After several days of inpatient care, her oxygen requirements returned to baseline, and she was discharged. Sulfhemoglobinemia arises from the irreversible binding of sulfur atoms to the heme molecule, rendering it incapable of carrying oxygen, causing a right ward shift of the oxygen dissociation curve. It should be suspected in cases of refractory cyanosis and hypoxia. This irreversible binding means that no antidote is available. Numerous prescription and over-the-counter medications, if not taken as directed, can lead to sulfhemoglobinemia. Recognizing dyshemoglobinemia is essential, while the treatment for sulfhemoglobinemia is largely supportive, exchange transfusions may be considered in rare cases. This case highlights the importance of comprehensive history-taking and medication reconciliation in identifying factors that may contribute to the patient's clinical presentation.