Abstract Introduction A discrepancy between pulse oximetry and arterial oxygen saturation, known as the saturation gap, warrants further evaluation. Sulfhemoglobinemia is a rare dyshemoglobinemia that arises when a sulfur atom incorporates within the hemoglobin molecule. This results in irreversible oxidation of ferrous iron (Fe2+) to the ferric state (Fe3+), thus impairing oxygen delivery. Case Presentation A 47-year-old man with a history of asthma and chronic dysuria presented to the emergency department from a routine clinic visit due to hypoxemia on pulse oximetry. The patient appeared comfortable without respiratory distress in the emergency department, though hypoxemia persisted (SpO2 84-88%) despite escalating oxygen support. CT pulmonary angiogram, arterial blood gas (ABG), and lactate were all normal, prompting further evaluation with venous co-oximetry panel. The patient was admitted to the intensive care unit on high-flow nasal cannula. On admission, an echocardiogram with bubble study was obtained which was unremarkable. ABG on high-flow showed a PaO2 of 393 mmHg and a calculated SaO2 of 99%. Upon further review, the patient reported taking phenazopyridine 200 milligrams three times daily for over four months. Overuse of phenazopyridine can be associated with rare dyshemoglobinemias. A subsequent ABG on ambient air showed a PaO2 of 91mmHg while peripheral oxygenation via pulse oximeter continued to read between 80-89%. A repeat co-oximetry panel was sent and revealed normal methemoglobin levels. The summation of the arterial oxyhemoglobin, methemoglobin, and carboxyhemoglobin levels totaled ∼90%. Given suspicion for sulfhemoglobinemia, confirmatory labs were ordered and the patient was discharged with discontinuation of phenazopyridine. One week later, sulfhemoglobin levels returned at 4.1% (reference range: 0-0.4%). Discussion Phenazopyridine is an over-the-counter medication used to treat dysuria. However, its overuse can be associated with rare complications, including methemoglobinemia and sulfhemoglobinemia. As sulfhemoglobin is not measured on standard co-oximetry testing, further investigation should be considered when there is a saturation gap with normal methemoglobin levels, particularly when the total hemoglobin levels on arterial co-oximetry are 95% (normal deoxyhemoglobin levels range between 0% and 5%). Patients with sulfhemoglobinemia present with a saturation gap and may exhibit cyanosis. The incorporation of sulfur within the hemoglobin molecule triggers a conformational change that reduces the carrying capacity of oxygen and causes a rightward shift of the oxyhemoglobin dissociation curve (i.e. increased oxygen unloading in peripheral tissues). Irreversible oxidation of the iron atom renders reducing agents such as methylene blue ineffective. Treatment is supportive and in severe cases exchange transfusion may be required. This abstract is funded by: None
Kim et al. (Fri,) studied this question.