Abstract Introduction Sulfhemoglobinemia is an uncommon but potentially life-threatening cause of refractory hypoxemia, often overlooked due to its nonspecific presentation and interference with laboratory assays. Phenazopyridine, a urinary analgesic, has been implicated in case reports. We present a case of sulfhemoglobinemia complicated by pneumonia, rhinovirus infection, and severe aortic stenosis. Case Presentation A 71-year-old woman with coronary artery disease, atrial fibrillation on apixaban, hypertension, insulin-dependent diabetes mellitus, and HFpEF presented with acute dyspnea, dizziness, and oxygen saturation in the 80s despite non-rebreather. In the ED, she required High-Flow Nasal Cannula at 90% FiO2/60 L. She also reported cough, diarrhea, and urinary burning. Labs revealed glucose 432 mg/dL, anion gap 16 with normal pH, hemoglobin 9.1 g/dL, magnesium 1.0 mg/dL, BNP 5978, and troponin 35→108 ng/L. Notably, multiple blood and urine specimens were unreportable—particularly methemoglobin and carboxyhemoglobin—due to assay interference from sulfhemoglobin. CTA chest showed right lower lobe infiltrate. Echocardiography revealed EF 49% (down from 59%), severe aortic stenosis (AVA 0.67 cm², DI 0.21, mean gradient 38 mmHg), and diffuse wall motion abnormalities. Respiratory panel was positive for rhinovirus. Review of medications revealed phenazopyridine use. With unreportable labs and persistent hypoxemia, sulfhemoglobinemia was suspected. Management included discontinuation of phenazopyridine, supplemental oxygen, antibiotics for pneumonia/UTI, electrolyte repletion, and red-cell transfusion for anemia. Transfusion was chosen because sulfhemoglobin is irreversible for the 120-day lifespan of the erythrocyte, and replacing affected cells improves oxygen-carrying capacity. Clinical status improved, and she was discharged home after 1 week. Discussion Phenazopyridine-induced sulfhemoglobinemia has been reported with similar findings of refractory hypoxemia, SpO2-PaO2 discordance, and dark-colored blood. Unlike methemoglobinemia, sulfhemoglobin is irreversible and unresponsive to methylene blue, making withdrawal of the offending agent and supportive care the mainstay of treatment. This case was diagnostically challenging due to overlapping pneumonia, rhinovirus infection, type II myocardial injury, and severe aortic stenosis. Severe aortic stenosis has also been associated with shear-induced hemolysis, potentially contributing to anemia. The coexistence of multiple cardiopulmonary stressors highlights the importance of considering dyshemoglobinemias when laboratory assays are uninterpretable and hypoxemia persists despite escalating FiO2. Conclusion This case underscores sulfhemoglobinemia as a critical differential in unexplained hypoxemia, particularly in phenazopyridine users. Recognition of lab interference was essential, as it explained the inability to measure methemoglobin/carboxyhemoglobin and prevented inappropriate methylene blue administration. Red-cell transfusion provided functional replacement of irreversibly impaired erythrocytes, facilitating recovery. Clinicians should suspect sulfhemoglobinemia when dark blood, refractory hypoxemia, and assay interference occur together. This abstract is funded by: None
Guliani et al. (Fri,) studied this question.
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