Case Presentation: A 36 year old male with history of schizophrenia, alcohol dependence and remote drug abuse presented to the emergency department with 3 weeks of dry cough without dyspnea, post-prandial nausea, intermittent lightheadedness, dark urine, jaundice and progressive fatigue. He had no recent travel or sick contacts, medications included chronic monthly injections of paliperidone palmitate and naltrexone as well as daily aripiprazole. He had not used alcohol for 3 weeks and denied illicit drug use. He lived with his father who had been traveling lately. Vital signs were normal except for standard pulse oximetry of 82% on ambient air which increased to 90% on 6 liters per minute (lpm). Exam was only notable for being in no apparent distress with jaundice and decreased bibasilar breath sounds. Lab work was significant for a hemoglobin of 10.9 g/dL (5 months prior was 16.7), total bilirubin of 3.7 mg/dL (previously normal), direct bilirubin 0.4 mg/dL, LDH 422 U/L, undetectable haptoglobin and elevated corrected reticulocyte count of 7%. CT thorax with contrast showed moderate airways disease and trace bibasilar pleural effusions with no pulmonary embolism. He was admitted for hemolytic anemia and acute hypoxic respiratory failure. Subsequent workup included either normal or negative: direct antiglobulin test, INR, fibrinogen, respiratory PCR and urine drug screen. Peripheral smear showed 2+ schistocytes though no other evidence of thrombotic microangiopathy.An arterial blood gas while on 6 lpm showed pH 7.44, PaCO2 37 mmHg with elevated PaO2 of 159 mmHg with measured oxyhemoglobin of only 90%. Methemoglobin was only slightly elevated at 2.2% (normal <1%) and carboxyhemoglobin was normal at 0.8%. The discrepancy between the elevated PaO2 and low measured oxyhemoglobin was consistent with a right shift of the oxyhemoglobin dissociation curve concerning for the presence of an additional dyshemoglobin. The next hospital day, patient’s father discovered empty bottles of “Rush” (isobutyl nitrite) in their home trash can. Patient admitted “huffing” this substance for the past month while his father traveled. The diagnosis of isobutyl nitrite toxicity was made with presumed sulfhemoglobinemia causing the discrepancy PaO2 and measured oxyhemoglobin. This was subsequently confirmed with an elevated sulfhemoglobin level of 5% (normal <2%).

Discussion: Isobutyl nitrite, marketed as “Rush,” is one member of the alkyl nitrites which comprise the recreational inhalant drug class “poppers.” Sold in adult shops as cleaners or room deodorizers, its vasodilatory properties have used to produce euphoria and/or act as a sexual enhancer. Reported adverse effects of the nitrite inhalants include headache, nausea, hypotension, tachycardia, lightheadedness and tracheobronchitis. Our patient’s jaundice precluded the ability to detect the typical cyanosis of sulfhemoglobinemia. The interrelated hemolytic anemia, methemoglobinemia and sulfhemoglobinemia stem from isobutyl nitrite’s oxidative stress on various portions of hemoglobin causing either hemolysis or impaired oxygen transport. Unlike methemoglobinemia, sulfhemoglobinemia is not reversible and therefore methylene blue is ineffective. Levels of sulfhemoglobin decrease only with erythrocyte turnover. Treatment is focused on supportive care and blood transfusions as needed for severe hemolytic anemia.

Conclusions: Identification of discrepancy between PaO2 and oxyhemoglobin on ABG can sharply narrow a differential and shorten time to diagnosis.