Case Presentation: We present the case of a 64-year-old male with a history of pulmonary embolism status post IVC filter, and recent viral constrictive pericarditis with exudative pericardial effusion requiring pericardiocentesis and bilateral pleural effusions requiring chest tubes, who was admitted for dyspnea, cyanosis, and confusion. Vitals were blood pressure 78/51, heart rate 60, respiratory rate 36, and oxygen saturation 88% on 2 liters nasal cannula, for which he was immediately given fluids and placed on a non-rebreather mask. Hemoglobin was stable at 12.8. Given his recent hospitalization one month prior for constrictive pericarditis and pleural effusions requiring drains, diagnostic work up focused on potential recurrence of structural pathophysiologies. EKG showed normal sinus rhythm. An echocardiogram showed trace pericardial effusion without tamponade. CTA chest was negative for pulmonary embolism and showed interval resolution of the prior pulmonary effusions. His O2 saturation remained at 88-90% despite administration of 60 liters at 100% fiO2 on high-flow nasal cannula. An ABG demonstrated pH 7.43, pCO2 44, pAO2 482, methemoglobin 20.9. Upon review of his medication list, it was noted that Dapsone was initiated 3 weeks prior for PJP prophylaxis while on high dose prednisone for treatment of constrictive pericarditis. In the ICU, he was treated with Methylene Blue and Vitamin C infusions, with a rapid decrease of methemoglobin level to 8.3. His Dapsone was switched to Atovaquone for PJP prophylaxis. He was weaned off all oxygen, and discharged home.

Discussion: Methemoglobinemia is a rare but life-threatening condition where early recognition and treatment are critical. Based on the American Association of Poison Control data reports of methylene blue requests, there are an average of 100 cases of methemoglobinemia annually in the US. This case demonstrates a classic presentation of methemoglobinemia with cyanosis and hypoxia “stuck” at 88-90% by pulse oximetry despite maximal oxygen delivery. This is due to the functional anemia caused by the oxidized ferric heme causing an inability of the methemoglobin units to bind oxygen, as well as a left-shift in the hemoglobin dissociation curve from the normal hemoglobin units binding oxygen tighter. Genetic mutations can contribute to hereditary causes, however the most common triggers are from acquired causes, such as Dapsone, topical anesthetics, antimalarial agents, Rasburicase (when G6PD deficiency is present), and nitrates. The offending agent should be immediately stopped, and Methylene Blue is the first-line treatment as long as the patient does not have a G6PD deficiency. Additionally, serotonergic medications should be held (as they were with this patient) until treatment is completed. Vitamin C infusions are also effective, however the time to onset is longer.

Conclusions: In the work-up of hypoxia, clinicians should recognize the classic symptoms of methemoglobinemia, and avoid anchoring bias towards the most common etiologies of respiratory failure. This patient had multiple predisposing risk factors for intrathoracic pathology, however other intrinsic causes should be considered. When oxygen levels on peripheral pulse oximetry are not improving congruently with increasing oxygen delivery, an ABG should be completed to consider other causes. Once methemoglobinemia is identified, rapid treatment is essential. Once methemoglobin levels approach 70%, fatality is imminent.