REFRACTORY HYPOXEMIA: A CASE OF DAPSONE-INDUCED METHEMOGLOBINEMIA IN A PATIENT WITH COVID-19

Abstract

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2SESSION TYPE: Case Report PostersPRESENTED ON: 10/19/2022 12:45 pm - 01:45 pmINTRODUCTION: Methemoglobinemia is an increase in methemoglobin (mHb) level characterized by functional anemia and tissue hypoxia. It can be caused by congenital enzymes deficiencies, but it is usually acquired. Dapsone, an oxidizing agent, is a medication commonly associated with acquired methemoglobinemia (1). We describe the diagnosis and management of a COVID-19 patient with acquired methemoglobinemia due to Dapsone.CASE PRESENTATION: 84-year-old female with history of MPO-ANCA vasculitis with renal involvement, CKD4 and anemia of chronic disease presented with shortness of breath, lethargy and weakness. Initially, the patient was saturating (SpO2) 80% on room air and was placed on 4L nasal cannula (NC) with improvement to 92%. CT of the chest showed b/l GGOs consistent with atypical pneumonia and patient tested positive for COVID-19. About 4 months prior, she had received 2 doses of Rituximab and on high steroid therapy that was tapered to 5mg of prednisone daily. She has been on Trimethoprim/Sulfamethoxazole for PJP prophylaxis, but due to hyperkalemia the medication was stopped. After confirming no G6PD deficiency, she was started on Dapsone 100mg daily. During hospitalization, she was given dexamethasone 6 mg daily and Dapsone was continued. On hospital stay day 6, a rapid response was called after oxygen dropped to 78% while walking on 6L NC. She was placed on high flow NC 100% and SpO2 went up to 90%. An arterial blood gas (ABG) was then obtained showing pO2 of 334, oxyhemoglobin (oxyHb) of 83 and mHb of 17.4. The SpO2-PaO2 gap and elevated mHb lead to the diagnosis of Dapsone-induced methemoglobinemia. Dapsone was discontinued. Patient received a one-time dose of 1mg/kg IV of methylene blue. One hour later her dyspnea had improved and was on 3L NC. Repeat ABG showed improvement of oxyHb (98) and decreased mHb (2.2).DISCUSSION: Physiologically, mHb is less than 1% of total Hb (1) and occurs when the iron in the porphyrin group of heme is oxidized from ferrous to the ferric form (2). Ferric heme binds oxygen irreversibly causing a left shift of the oxygen-hemoglobin dissociation curve. Clinical presentation tends to correlate with mHb levels, and it varies from being asymptomatic to fatigue, dyspnea, confusion, seizure, cyanosis resistant to oxygen therapy (mHb > 15%) and death. Methylene blue is safe and can be consider when mHb level is greater than 10 to 20% (2). Methylene blue was administer to our patient given the presence of COVID (leaving patient more susceptible to medication-induced methemoglobinemia (3)) and chronic anemia which made her less likely to tolerate state of reduced oxygen delivery.CONCLUSIONS: The diagnosis of methemoglobinemia is a rare cause of hypoxemia that is often overlooked. In patients with risk factors (COVID, medication exposure) a high index of suspicion is needed when interpreting an ABG (SpO2-PaO2 gap) for correct diagnosis and appropriate treatment.Reference #1: Toker, Ibrahim, et al. "Methemoglobinemia Caused by Dapsone Overdose: Which Treatment Is Best?” Turkish Journal of Emergency Medicine, vol. 15, no. 4, Dec. 2015, pp. 182–184, 10.1016/j.tjem.2014.09.002. Accessed 31 Aug. 2020.Reference #2: Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for management. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):1043-7. doi: 10.1053/j.jvca.2013.02.005. Epub 2013 Aug 13. PMID: 23953868.Reference #3: Naymagon, Leonard, et al. "The Emergence of Methemoglobinemia amidst the COVID -19 Pandemic.” American Journal of Hematology, vol. 95, no. 8, 3 June 2020, 10.1002/ajh.25868. Accessed 3 Mar. 2021.DISCLOSURES: No relevant relationships by Mileydis AlonsoNo relevant relationships by Samantha GillenwaterNo relevant relationships by Christine GirardNo relevant relationships by Sikandar KhanNo relevant relationships by Jose RiveraNo relevant relationships by Frederick Ross SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Methemoglobinemia is an increase in methemoglobin (mHb) level characterized by functional anemia and tissue hypoxia. It can be caused by congenital enzymes deficiencies, but it is usually acquired. Dapsone, an oxidizing agent, is a medication commonly associated with acquired methemoglobinemia (1). We describe the diagnosis and management of a COVID-19 patient with acquired methemoglobinemia due to Dapsone. CASE PRESENTATION: 84-year-old female with history of MPO-ANCA vasculitis with renal involvement, CKD4 and anemia of chronic disease presented with shortness of breath, lethargy and weakness. Initially, the patient was saturating (SpO2) 80% on room air and was placed on 4L nasal cannula (NC) with improvement to 92%. CT of the chest showed b/l GGOs consistent with atypical pneumonia and patient tested positive for COVID-19. About 4 months prior, she had received 2 doses of Rituximab and on high steroid therapy that was tapered to 5mg of prednisone daily. She has been on Trimethoprim/Sulfamethoxazole for PJP prophylaxis, but due to hyperkalemia the medication was stopped. After confirming no G6PD deficiency, she was started on Dapsone 100mg daily. During hospitalization, she was given dexamethasone 6 mg daily and Dapsone was continued. On hospital stay day 6, a rapid response was called after oxygen dropped to 78% while walking on 6L NC. She was placed on high flow NC 100% and SpO2 went up to 90%. An arterial blood gas (ABG) was then obtained showing pO2 of 334, oxyhemoglobin (oxyHb) of 83 and mHb of 17.4. The SpO2-PaO2 gap and elevated mHb lead to the diagnosis of Dapsone-induced methemoglobinemia. Dapsone was discontinued. Patient received a one-time dose of 1mg/kg IV of methylene blue. One hour later her dyspnea had improved and was on 3L NC. Repeat ABG showed improvement of oxyHb (98) and decreased mHb (2.2). DISCUSSION: Physiologically, mHb is less than 1% of total Hb (1) and occurs when the iron in the porphyrin group of heme is oxidized from ferrous to the ferric form (2). Ferric heme binds oxygen irreversibly causing a left shift of the oxygen-hemoglobin dissociation curve. Clinical presentation tends to correlate with mHb levels, and it varies from being asymptomatic to fatigue, dyspnea, confusion, seizure, cyanosis resistant to oxygen therapy (mHb > 15%) and death. Methylene blue is safe and can be consider when mHb level is greater than 10 to 20% (2). Methylene blue was administer to our patient given the presence of COVID (leaving patient more susceptible to medication-induced methemoglobinemia (3)) and chronic anemia which made her less likely to tolerate state of reduced oxygen delivery. CONCLUSIONS: The diagnosis of methemoglobinemia is a rare cause of hypoxemia that is often overlooked. In patients with risk factors (COVID, medication exposure) a high index of suspicion is needed when interpreting an ABG (SpO2-PaO2 gap) for correct diagnosis and appropriate treatment. Reference #1: Toker, Ibrahim, et al. "Methemoglobinemia Caused by Dapsone Overdose: Which Treatment Is Best?” Turkish Journal of Emergency Medicine, vol. 15, no. 4, Dec. 2015, pp. 182–184, 10.1016/j.tjem.2014.09.002. Accessed 31 Aug. 2020. Reference #2: Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for management. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):1043-7. doi: 10.1053/j.jvca.2013.02.005. Epub 2013 Aug 13. PMID: 23953868. Reference #3: Naymagon, Leonard, et al. "The Emergence of Methemoglobinemia amidst the COVID -19 Pandemic.” American Journal of Hematology, vol. 95, no. 8, 3 June 2020, 10.1002/ajh.25868. Accessed 3 Mar. 2021. DISCLOSURES: No relevant relationships by Mileydis Alonso No relevant relationships by Samantha Gillenwater No relevant relationships by Christine Girard No relevant relationships by Sikandar Khan No relevant relationships by Jose Rivera No relevant relationships by Frederick Ross