Uncommon, but not unseen: a potential cause of methemoglobinemia

SESSION TITLE: Respiratory Care Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm INTRODUCTION: Methemoglobin (MetHgb) is a form of hemoglobin that has been oxidized, changing its heme iron configuration from the ferrous (Fe2+) to the ferric (Fe3+) state. Unlike normal hemoglobin, methemoglobin does not bind oxygen and as a result cannot deliver oxygen to the tissues. MetHgb can be congenital or acquired. The latter includes medications such as Dapsone, topical anesthetics, and nitrites. Here we present a case of a woman with acute respiratory failure due to MetHgb secondary to phenazopyridine (AZO) overdose. CASE PRESENTATION: A 27 year old female presented to the emergency room with two week gradual decline in urine output associated with flank pain and urinary frequency. For the previous six days, she reported taking 10 non prescription AZO daily. No dyspnea, lightheadedness, or nausea and denied fatigue, headache, or vomiting. Pulse oximetry obtained with home device indicated values 72-29%. Her past medical history includes Hodgkin lymphoma, prolactinoma, recurrent cystitis, and COVID-19 infection. Her vital signs were: temperature 99.2F, respirations 18 per minute, heart rate 82 beats per minute, and blood pressure 125/84 mm Hg. On room air oxygen saturation was 89%. Physical exam noted scleral icterus. There was absence of decreased mentation, no evidence of increased respiratory effort or cyanosis, and normal reflexes. An arterial blood gas (ABG) indicated: pH 7.33, PCO2 37, PO2 234, bicarbonate 20, and oxygen saturation 97% drawn with inspired oxygen fraction= 0.44. Labs demonstrated bilirubin 0.8mg/dl, hemoglobin 8.7g/dL, creatinine 2.98mg/dl, and methemoglobin of 2.8%. MetHgb level of 2.8% obtained several hours after presentation. No values obtained prior to this read. She was treated with oral Vitamin C. Repeat co oximetry three days later showed methemoglobin at 0.4%. At discharge, she was on room air and given antibiotics for cystitis. DISCUSSION: AZO is a medication used for urinary tract symptom relief. It does have potential direct toxicity to renal tubules(1). It can cause "orange urine," yellow hue to skin, gastrointestinal symptoms (GI), MetHgb, acute renal failure, and hemolytic anemia (2). MetHgb is heme in ferric state which irreversibly binds oxygen and does not deliver oxygen to tissues. Auto oxidation maintains a low level of MetHgb circulating (less than 1%) (3) . Treatment decisions are based on blood levels, severity of clinical symptoms, and reducing the heme. Treatment options include Methylene Blue (only if patient is not Glucose 6 phosphate dehydrogenase deficient) and Vitamin C. In our case, delays in testing likely lead to already declined levels of MetHgb. A clue to diagnosis was suggested by the relatively low saturation of 97% with a PaO2 of >200 and the markedly reduced oximetry values patient obtained at home despite no apparent pulmonary condition. Our patient had nonspecific symptoms that may have been related but did not manifest serious sequalae; management with oral Vitamin C was successful. CONCLUSIONS: Physicians and patients should be mindful that AZO has potentially dangerous side effects. Even though drug induced MetHgb is more common than hereditary, both remain rare (4). Nevertheless, given the potential adverse consequences, it is important that all physicians are aware of the disorder. REFERENCE #1: 1 Tomlinson B, Cohen SL, Smith MR, Fisher C. Nephrotoxicity of phenazopyridine. Hum Toxicol. 1983 Jul;2(3):539-43. doi: 10.1177/096032718300200311. PMID: 6885099. REFERENCE #2: 2 Jaya Prakash NA, Elbokyl M, McQuillan R (2017) Phenazopyridine abuse presenting with acute kidney injury, hemolytic anaemia and jaundice. Arch Clin Nephrol 3(1): 029-031. DOI: 10.17352/acn.000023 REFERENCE #3: 3 Smith RP, Olson MV. Drug-induced methemoglobinemia. Semin Hematol. 1973 Jul;10(3):253-68. PMID: 4577648.4. Iolascon A, Bianchi P, Andolfo I, Russo R, Barcellini W, Fermo E, Toldi G, Ghirardello S, Rees D, Van Wijk R, Kattamis A, Gallagher PG, Roy N, Taher A, Mohty R, Kulozik A, De Franceschi L, Gambale A, De Montalembert M, Forni GL, Harteveld CL, Prchal J; SWG of red cell and iron of EHA and EuroBloodNet. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol. 2021 Dec 1;96(12):1666-1678. doi: 10.1002/ajh.26340. Epub 2021 Sep 23. PMID: 34467556; PMCID: PMC9291883. DISCLOSURES: No relevant relationships by N. Stacy Amadife No relevant relationships by Didar Ul Alam No relevant relationships by Peter Whitesell