RARE DISEASE
Acquired methemoglobinemia
Acquired methemoglobinemia
Acquired methemoglobinemia
Synonyms: Drug-induced methemoglobinemia
Synonyms: Drug-induced methemoglobinemia
Synonyms: Drug-induced methemoglobinemia
Drug discovery
0
drugs
With orphan designations
Overview
Acquired methemoglobinemia results from exposure to oxidizing agents (e.g., benzocaine, dapsone, nitrates) that convert hemoglobin to methemoglobin, impairing oxygen delivery. Presentation ranges from asymptomatic cyanosis to life-threatening hypoxia, depending on methemoglobin levels (≥30% causes dyspnea, neurologic symptoms; >60% risks mortality). Diagnosis hinges on clinical suspicion, blood gas analysis, and co-oximetry. Immediate treatment involves methylene blue (1–2 mg/kg IV), though it is contraindicated in G6PD deficiency. Supportive care and toxin removal are critical [1][2][8][12].
Population
Infants: Higher susceptibility due to underdeveloped cytochrome b5 reductase activity, particularly with nitrate-contaminated water or foods [1][4][19].
Adults: Associated with procedural topical anesthetics (e.g., TEE, bronchoscopy), dapsone therapy, or recreational nitrite use [2][3][15].
At-risk groups: G6PD deficiency, anemia, or cardiopulmonary comorbidities exacerbate severity [6][8][16].
Burden
Incidence: Rare (0.035% in procedural settings) but potentially fatal; ~3.5 cases per 10,000 exposures [2][12].
Morbidity: Untreated cases risk seizures, coma, or death; delayed diagnosis common due to nonspecific symptoms [4][12][16].
Economic impact: ICU admissions, prolonged hospital stays, and costly therapies (e.g., exchange transfusion) [13][16].
Therapies
First-line: Methylene blue (1–2 mg/kg IV), repeated if needed; avoid in G6PD deficiency [8][9][12].
Alternatives: Ascorbic acid, hyperbaric oxygen, or RBC transfusion in refractory cases [1][13][16].
Supportive: Discontinue causative agents, administer oxygen, and monitor for rebound methemoglobinemia [6][9].
Categories: rare hematological diseases, rare transplant-related disorders
Research Papers
451 drug discovery papers about Acquired methemoglobinemia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
451 drug discovery papers about Acquired methemoglobinemia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-10 | Case Report: Methemoglobinemia associated with compound aminopyrine-phenacetin tablets supported by toxicological evidence
Background Methemoglobinemia (MetHb) is characterized by the oxidation of ferrous iron (Fe2+) in hemoglobin to the ferric state (Fe3+), resulting in impaired oxygen-carrying capacity and subsequent tissue hypoxia. Acquired methemoglobinemia is most commonly induced by drugs or chemical agents; however, it remains relatively rare in clinical practice and is frequently misdiagnosed. Case presentation We report a case of drug-induced methemoglobinemia associated with compound aminopyrine-phenacetin tablets (Qutong tablets). An 80-year-old woman with chronic lower limb pain had intermittently used this analgesic prior to admission. She presented with unexplained hypoxemia that was refractory to oxygen therapy. Arterial blood gas analysis revealed a markedly elevated PaO2 (271 mmHg) despite persistently low pulse oximetry saturation, indicating a significant oxygen saturation gap. The MetHb level was 22.4%. Toxicological testing detected plasma aminopyrine and phenacetin concentrations above the laboratory reference limits, documenting relevant drug exposure and supporting the clinical attribution in the context of the medication history, saturation gap, elevated MetHb level, and treatment response. Following discontinuation of the suspected agent and administration of methylene blue combined with vitamin C, MetHb levels rapidly normalized and hypoxemia significantly improved. Conclusion This case highlights that chronic, irregular exposure to oxidant drugs may be associated with clinically significant methemoglobinemia even in the absence of a clear acute overdose. Clinicians should maintain a high index of suspicion in patients with hypoxemia unresponsive to oxygen therapy and evidence of an oxygen saturation gap. Careful medication history, co-oximetry, and toxicological testing may help document exposure and support diagnostic attribution in clinically compatible cases. Keywords: methemoglobinemia; phenacetin; aminopyrine; methylene blue; drug toxicity; toxicological evidence.
2026-05-22 | Management of nitrobenzene poisoning in a resource-constrained setting: A case report
INTRODUCTION Nitrobenzene poisoning is an uncommon but potentially fatal cause of acquired methemoglobinemia, particularly in agricultural regions. We report an 18-year-old male presenting with acute hypoxia, cyanosis, and refractory low oxygen saturation following unknown pesticide ingestion. Despite limited diagnostic resources, characteristic clinical features, chocolate-colored blood, and a marked saturation gap supported the diagnosis of methemoglobinemia. Prompt empirical treatment with oxygen, methylene blue, and ascorbic acid resulted in rapid recovery. This case highlights the importance of clinical recognition and early intervention in suspected nitrobenzene poisoning, especially in resource-limited settings.
2026-05-19 | Sodium chlorite-induced pediatric methemoglobinemia requiring methylene blue drip: a case report
Acquired methemoglobinemia is a rare and potentially lethal complication of several oxidizing agents, with ingestions reported in patients of various demographics. Here, we present a 30-month-old patient with sodium chlorite-induced methemoglobinemia that was refractory to initial intermittent infusions of methylene blue and ultimately required continuous infusion of the antidote. The hospital course was complicated by hemolytic anemia requiring blood transfusion, with eventual improvement in laboratory testing and clinical presentation.
2026-05-01 | C43-33 Blue But Not Breathless: Phenazopyridine-induced Methemoglobinemia
Abstract Introduction Methemoglobinemia is a rare hematologic disorder caused by oxidation of hemoglobin’s iron from the ferrous (Fe²+) to the ferric (Fe³+) state, impairing oxygen delivery and leading to tissue hypoxia. It can be congenital or acquired following exposure to oxidizing agents such as nitrates, local anesthetics, and certain medications. Phenazopyridine, a commonly used urinary tract analgesic, is an uncommon cause, with fewer than ten cases reported in the past 35 years and an estimated incidence of less than 1%. Although rare, methemoglobinemia can be life-threatening, emphasizing the importance of early recognition and prompt management. Case Presentation A 28-year-old female with a history of recurrent urinary tract infections and mood disorders presented with fatigue, dyspnea, and cyanosis of the lips and nails for one day. Home pulse oximetry revealed SpO2 of 86-88%. She had recently started antibiotics for a urinary tract infection and self-administered over-the-counter phenazopyridine (AZO) for symptom relief, ingesting 24 tablets (99.5 mg each) within a single day. In the emergency department, her vital signs were blood pressure 140/72 mmHg, pulse 95-97/min, respiratory rate 18/min, and SpO2 86% on room air. Despite supplemental oxygen, saturation remained at 86-88%. Imaging was negative for pulmonary embolism or other pulmonary pathology. Arterial blood gas on a non-rebreather mask showed a PaO2 of 250 mmHg, SpO2 86% and methemoglobin level of 12%. Given her symptomatic presentation, she was treated with 2 g of intravenous ascorbic acid. Methylene blue was deferred due to mild symptoms, unknown G6PD status, and potential interaction with buspirone and desvenlafaxine, which could precipitate serotonin syndrome. Six hours post-treatment, methemoglobin levels decreased to 4.2%, and oxygen saturation improved to 94-96% with ambulation. She was counseled to avoid further phenazopyridine use and discharged in stable condition. Discussion Methemoglobinemia should be suspected in patients with cyanosis and low oxygen saturation unresponsive to supplemental oxygen, particularly when a marked gap exists between SpO2 and PaO2. Phenazopyridine-induced cases often result from high-dose or prolonged use beyond two days. Clinical severity correlates with methemoglobin levels—cyanosis typically appears at > 10%, neurologic and cardiovascular symptoms occur at > 30%, and levels >50% may cause seizures, arrhythmias, or coma. Management includes discontinuation of the offending agent, oxygen therapy, and either ascorbic acid for mild or G6PD-deficient cases, or methylene blue for severe presentations. This abstract is funded by: none
2026-05-01 | C53-37 Benzocaine-induced Methemoglobinemia in High-risk Hospitalized Patients: Rethinking Anesthetic Choice Toward Safer Alternatives
Abstract Methemoglobinemia is a rare but potentially life-threatening disorder characterized by the oxidation of hemoglobin iron from the ferrous (Fe²+) to the ferric (Fe³+) state, resulting in impaired oxygen delivery to tissues and functional anemia. Benzocaine, a commonly used topical anesthetic, is a well-established cause of acquired methemoglobinemia, particularly in procedures involving mucous membranes such as nasogastric tube placement, bronchoscopy, and endoscopy. Although the overall prevalence is low (0.035%), the risk is markedly increased in hospitalized patients and with benzocaine-based anesthetics, with 97% of cases occurring in the inpatient setting and benzocaine being the most frequently implicated agent (Chowdhary et al., 2013). Given the availability of safer alternatives, this report aims to highlight the ongoing risk of benzocaine in high-risk patients and to advocate for institutional protocols that prioritize safer anesthetic options. A 70-year-old woman with atrial fibrillation, chronic obstructive pulmonary disease (COPD), and heart failure with preserved ejection fraction (HFpEF) was admitted for elective colostomy. On postoperative day 5, she received benzocaine-containing spray for nasogastric tube placement and continued self-administration for discomfort. By postoperative day 7, she developed acute cyanosis, chocolate-brown blood, and a saturation gap (pulse oximetry 87-90% on 15 L oxygen, normal arterial pO2). Methemoglobin level was 35.7%. She was transferred to the ICU and treated with intravenous methylene blue, resulting in rapid improvement. Topical anesthetics are frequently used in procedures like nasogastric tube placement, bronchoscopy, and endoscopy. Recent evidence calls for a reassessment of anesthetic choice in hospitalized patients with cardiopulmonary issues. Although methemoglobinemia is rare, the risk increases significantly in inpatients, especially with benzocaine, which produces more methemoglobin than alternatives like lidocaine. Even a single application can cause severe, life-threatening toxicity. Despite warnings and guidelines urging caution or avoidance in high-risk groups, benzocaine remains widely used without proper risk stratification. Safer options, including lidocaine and lidocaine-prilocaine mixtures, are equally effective and carry a much lower risk of adverse effects. This case underscores the ongoing gaps in risk assessment and protocol adherence, highlighting an opportunity for institutional change. Prioritizing these safer agents in high-risk populations can prevent avoidable morbidity and mortality associated with benzocaine-induced methemoglobinemia, aligning practice with current safety data. Reference: 1. Risk of Topical Anesthetic-Induced Methemoglobinemia: A 10-Year Retrospective Case-Control Study. Chowdhary S, Bukoye B, Bhansali AM, et al. JAMA Internal Medicine. 2013;173(9):771-6. doi:10.1001/jamainternmed.2013.75. This abstract is funded by: HCA Healthcare
cell therapies
2026-03-17 | A rare cause of acquired methemoglobinemia
Methemoglobinemia is a life-threatening clinical condition with a favorable outcome when diagnosed and treated promptly. It should be suspected in patients with oxygen saturation of around 85% that does not improve despite supplemental oxygen therapy. We report the case of a 48-year-old male with acquired methemoglobinemia due to the consumption of complementary alternative medicine (Ayurvedic medication for chronic kidney disease), who had a good outcome on treatment with Methylene blue. In refractory cases not responding to methylene blue, exchange transfusion is an effective alternative treatment.
2025-11-07 | Aniline-induced refractory methemoglobinemia in polytrauma: successful management with erythrocytapheresis.
Methemoglobinemia is a life-threatening condition characterized by the inability of hemoglobin to transport oxygen efficiently. This case report describes acquired methemoglobinemia caused by exposure to aniline dye, which was successfully treated with erythrocytapheresis following the insufficient effect of methylene blue. A 39-year-old male suffered multiple injuries, including burns and fractures, after falling into a barrel containing aniline. On site, emergency medical services (EMS) intubated the patient, performed chest decompression for pneumothorax, and decontaminated him before transferring him to a trauma centre. In the emergency unit, imaging revealed multiple rib, scapula, and pelvic fractures, retroperitoneal bleeding, and 15% total body surface area (TBS) burns. He was hemodynamically unstable, with metabolic acidosis, an oxygen saturation gap, and an initial methemoglobin level (MetHb) of 19%. Despite methylene blue treatment, the MetHb levels rose to undetectable levels (> 20%), and severe hemodynamic instability, refractory hypoxia, and metabolic derangement required the use of erythrocytapheresis. Aniline exposure leads to the oxidation of ferrous iron (Fe2 +) in hemoglobin to ferric iron (Fe3 +), resulting in methemoglobinemia and impaired oxygen delivery. While methylene blue remains the first-line treatment, erythrocytapheresis proved effective in restoring tissue oxygenation in refractory methemoglobinemia complicated by hemorrhagic and traumatic shock.
2024-10-19 | Critically Ill Patient with Acquired Refractory Methemoglobinemia Successfully Treated with Therapeutic Erythrocytapheresis: A Case Report
REPORTalkalosis, pO 2 -369 mm Hg, and methemoglobin was 15%.The oxygen saturation gap, that is, the difference between oxygen saturation in arterial blood gas sample (SaO 2 ) and SpO 2, was greater than 5%.His blood was chocolate brown in color.The patient had methemoglobinemia, probably due to poisoning.In the meantime, the patient had seizures and was intubated.Around 60 mg (1 mg/kg) of intravenous (IV) methylene blue was administered over 3 hours, and the patient was shifted to the ICU.The patient was continued on mechanical ventilator support.SpO 2 remained 85% on 100% FiO 2 .The patient was drowsy without any sedation.Hemodynamics were stable.G6PD levels and other lab investigations were normal.The ABG taken on the next day at 7:30 am showed 3.9% methemoglobin.As cyanosis persisted, a second dose of 60 mg IV methylene blue was given.Despite two doses of methylene blue, SpO 2 remained 85% on 100% FiO 2 .The 1,
2024-08-28 | Rasburicase-induced hemolytic anemia and methemoglobinemia: a systematic review of current reports.
Since the FDA's approval of rasburicase use for treatment of tumor lysis syndrome (TLS), multiple cases of rasburicase-induced methemoglobinemia and hemolytic anemia have been reported among patients with G6PD deficiency. This study aims to provide a systematic review of cases reporting such adverse reactions to rasburicase. A literature review of published cases in PubMed, Embase, Cochrane, and Web of Science was conducted. Descriptive studies reporting cases of rasburicase-induced methemoglobinemia and/or hemolytic anemia in English were analyzed and summarized in this study. Forty-three cases, including a case from our institution, were included in this study. Most cases (60.5%) received rasburicase for TLS treatment. Almost all patients (93.8%) were tested for G6PD after rasburicase administration. The median time to symptom onset was 24 h. The median methemoglobin level was 10%, peaking after a median of 24 h. The median hemoglobin nadir was 6.1 g/dL, and most patients (n = 32) required blood transfusion. Out of 39 cases with reported outcomes, 35 patients (89.7%) recovered, while four patients (three females and one male) died. The median time to recovery was 4.5 days while the median time to death was 8 days. Screening for G6PD deficiency among high-risk patients is important but not practical in acutely severe settings. When prior screening for G6PD deficiency is not feasible, close monitoring for methemoglobinemia and hemolytic anemia is recommended. Exchange transfusion is increasingly reported as a potentially successful therapeutic modality. Ascorbic acid may provide limited benefits. Methylene blue should be avoided as it may exacerbate hemolysis among these patients.
2024-01-26 | Eating vegetables is not always a good advice. A case report and literature review of acquired methemoglobinemia
Methemoglobinemia (MET) is a life-threatening condition resulting from the development of methemoglobin (MetHb), which binds oxygen irreversibly, causing refractory hypoxia and so-called “functional anemia”. MET can be caused by hereditary or acquired processes. Acquired forms are the most common. Symptoms correlate with the MetHb level and range from cyanosis and dyspnea to dysrhythmias, metabolic acidosis, coma, and cardiac arrest. MetHb levels above 70% are fatal. Methylene blue (MB) is the specific antidote. In all cases, supportive treatment, including intravenous hydration, glucose correction, and oxygen supplementation, must be started immediately. Exchange transfusion has been used successfully to treat MET and may be appropriate in patients for whom MB is ineffective. We report the case of a 54-year-old woman who presented to our emergency department for the acute and sudden development of chest pain, shortness of breath, and severe cyanosis after drinking a significant amount of boiled courgette water. Arterial blood gas analysis revealed a MetHb level of 26%. She was treated immediately with MB, oxygen supplementation, and hydration with normalization of her MetHb in 12 hours. Our recommendation is to always investigate MET in patients with unexplained cyanosis and refractory hypoxia.
small molecules
2026-08-10 | Case Report: Methemoglobinemia associated with compound aminopyrine-phenacetin tablets supported by toxicological evidence
Background Methemoglobinemia (MetHb) is characterized by the oxidation of ferrous iron (Fe2+) in hemoglobin to the ferric state (Fe3+), resulting in impaired oxygen-carrying capacity and subsequent tissue hypoxia. Acquired methemoglobinemia is most commonly induced by drugs or chemical agents; however, it remains relatively rare in clinical practice and is frequently misdiagnosed. Case presentation We report a case of drug-induced methemoglobinemia associated with compound aminopyrine-phenacetin tablets (Qutong tablets). An 80-year-old woman with chronic lower limb pain had intermittently used this analgesic prior to admission. She presented with unexplained hypoxemia that was refractory to oxygen therapy. Arterial blood gas analysis revealed a markedly elevated PaO2 (271 mmHg) despite persistently low pulse oximetry saturation, indicating a significant oxygen saturation gap. The MetHb level was 22.4%. Toxicological testing detected plasma aminopyrine and phenacetin concentrations above the laboratory reference limits, documenting relevant drug exposure and supporting the clinical attribution in the context of the medication history, saturation gap, elevated MetHb level, and treatment response. Following discontinuation of the suspected agent and administration of methylene blue combined with vitamin C, MetHb levels rapidly normalized and hypoxemia significantly improved. Conclusion This case highlights that chronic, irregular exposure to oxidant drugs may be associated with clinically significant methemoglobinemia even in the absence of a clear acute overdose. Clinicians should maintain a high index of suspicion in patients with hypoxemia unresponsive to oxygen therapy and evidence of an oxygen saturation gap. Careful medication history, co-oximetry, and toxicological testing may help document exposure and support diagnostic attribution in clinically compatible cases. Keywords: methemoglobinemia; phenacetin; aminopyrine; methylene blue; drug toxicity; toxicological evidence.
2026-05-22 | Management of nitrobenzene poisoning in a resource-constrained setting: A case report
INTRODUCTION Nitrobenzene poisoning is an uncommon but potentially fatal cause of acquired methemoglobinemia, particularly in agricultural regions. We report an 18-year-old male presenting with acute hypoxia, cyanosis, and refractory low oxygen saturation following unknown pesticide ingestion. Despite limited diagnostic resources, characteristic clinical features, chocolate-colored blood, and a marked saturation gap supported the diagnosis of methemoglobinemia. Prompt empirical treatment with oxygen, methylene blue, and ascorbic acid resulted in rapid recovery. This case highlights the importance of clinical recognition and early intervention in suspected nitrobenzene poisoning, especially in resource-limited settings.
2026-05-19 | Sodium chlorite-induced pediatric methemoglobinemia requiring methylene blue drip: a case report
Acquired methemoglobinemia is a rare and potentially lethal complication of several oxidizing agents, with ingestions reported in patients of various demographics. Here, we present a 30-month-old patient with sodium chlorite-induced methemoglobinemia that was refractory to initial intermittent infusions of methylene blue and ultimately required continuous infusion of the antidote. The hospital course was complicated by hemolytic anemia requiring blood transfusion, with eventual improvement in laboratory testing and clinical presentation.
2026-05-01 | C43-33 Blue But Not Breathless: Phenazopyridine-induced Methemoglobinemia
Abstract Introduction Methemoglobinemia is a rare hematologic disorder caused by oxidation of hemoglobin’s iron from the ferrous (Fe²+) to the ferric (Fe³+) state, impairing oxygen delivery and leading to tissue hypoxia. It can be congenital or acquired following exposure to oxidizing agents such as nitrates, local anesthetics, and certain medications. Phenazopyridine, a commonly used urinary tract analgesic, is an uncommon cause, with fewer than ten cases reported in the past 35 years and an estimated incidence of less than 1%. Although rare, methemoglobinemia can be life-threatening, emphasizing the importance of early recognition and prompt management. Case Presentation A 28-year-old female with a history of recurrent urinary tract infections and mood disorders presented with fatigue, dyspnea, and cyanosis of the lips and nails for one day. Home pulse oximetry revealed SpO2 of 86-88%. She had recently started antibiotics for a urinary tract infection and self-administered over-the-counter phenazopyridine (AZO) for symptom relief, ingesting 24 tablets (99.5 mg each) within a single day. In the emergency department, her vital signs were blood pressure 140/72 mmHg, pulse 95-97/min, respiratory rate 18/min, and SpO2 86% on room air. Despite supplemental oxygen, saturation remained at 86-88%. Imaging was negative for pulmonary embolism or other pulmonary pathology. Arterial blood gas on a non-rebreather mask showed a PaO2 of 250 mmHg, SpO2 86% and methemoglobin level of 12%. Given her symptomatic presentation, she was treated with 2 g of intravenous ascorbic acid. Methylene blue was deferred due to mild symptoms, unknown G6PD status, and potential interaction with buspirone and desvenlafaxine, which could precipitate serotonin syndrome. Six hours post-treatment, methemoglobin levels decreased to 4.2%, and oxygen saturation improved to 94-96% with ambulation. She was counseled to avoid further phenazopyridine use and discharged in stable condition. Discussion Methemoglobinemia should be suspected in patients with cyanosis and low oxygen saturation unresponsive to supplemental oxygen, particularly when a marked gap exists between SpO2 and PaO2. Phenazopyridine-induced cases often result from high-dose or prolonged use beyond two days. Clinical severity correlates with methemoglobin levels—cyanosis typically appears at > 10%, neurologic and cardiovascular symptoms occur at > 30%, and levels >50% may cause seizures, arrhythmias, or coma. Management includes discontinuation of the offending agent, oxygen therapy, and either ascorbic acid for mild or G6PD-deficient cases, or methylene blue for severe presentations. This abstract is funded by: none
2026-05-01 | C53-37 Benzocaine-induced Methemoglobinemia in High-risk Hospitalized Patients: Rethinking Anesthetic Choice Toward Safer Alternatives
Abstract Methemoglobinemia is a rare but potentially life-threatening disorder characterized by the oxidation of hemoglobin iron from the ferrous (Fe²+) to the ferric (Fe³+) state, resulting in impaired oxygen delivery to tissues and functional anemia. Benzocaine, a commonly used topical anesthetic, is a well-established cause of acquired methemoglobinemia, particularly in procedures involving mucous membranes such as nasogastric tube placement, bronchoscopy, and endoscopy. Although the overall prevalence is low (0.035%), the risk is markedly increased in hospitalized patients and with benzocaine-based anesthetics, with 97% of cases occurring in the inpatient setting and benzocaine being the most frequently implicated agent (Chowdhary et al., 2013). Given the availability of safer alternatives, this report aims to highlight the ongoing risk of benzocaine in high-risk patients and to advocate for institutional protocols that prioritize safer anesthetic options. A 70-year-old woman with atrial fibrillation, chronic obstructive pulmonary disease (COPD), and heart failure with preserved ejection fraction (HFpEF) was admitted for elective colostomy. On postoperative day 5, she received benzocaine-containing spray for nasogastric tube placement and continued self-administration for discomfort. By postoperative day 7, she developed acute cyanosis, chocolate-brown blood, and a saturation gap (pulse oximetry 87-90% on 15 L oxygen, normal arterial pO2). Methemoglobin level was 35.7%. She was transferred to the ICU and treated with intravenous methylene blue, resulting in rapid improvement. Topical anesthetics are frequently used in procedures like nasogastric tube placement, bronchoscopy, and endoscopy. Recent evidence calls for a reassessment of anesthetic choice in hospitalized patients with cardiopulmonary issues. Although methemoglobinemia is rare, the risk increases significantly in inpatients, especially with benzocaine, which produces more methemoglobin than alternatives like lidocaine. Even a single application can cause severe, life-threatening toxicity. Despite warnings and guidelines urging caution or avoidance in high-risk groups, benzocaine remains widely used without proper risk stratification. Safer options, including lidocaine and lidocaine-prilocaine mixtures, are equally effective and carry a much lower risk of adverse effects. This case underscores the ongoing gaps in risk assessment and protocol adherence, highlighting an opportunity for institutional change. Prioritizing these safer agents in high-risk populations can prevent avoidable morbidity and mortality associated with benzocaine-induced methemoglobinemia, aligning practice with current safety data. Reference: 1. Risk of Topical Anesthetic-Induced Methemoglobinemia: A 10-Year Retrospective Case-Control Study. Chowdhary S, Bukoye B, Bhansali AM, et al. JAMA Internal Medicine. 2013;173(9):771-6. doi:10.1001/jamainternmed.2013.75. This abstract is funded by: HCA Healthcare
cell therapies
2026-03-17 | A rare cause of acquired methemoglobinemia
Methemoglobinemia is a life-threatening clinical condition with a favorable outcome when diagnosed and treated promptly. It should be suspected in patients with oxygen saturation of around 85% that does not improve despite supplemental oxygen therapy. We report the case of a 48-year-old male with acquired methemoglobinemia due to the consumption of complementary alternative medicine (Ayurvedic medication for chronic kidney disease), who had a good outcome on treatment with Methylene blue. In refractory cases not responding to methylene blue, exchange transfusion is an effective alternative treatment.
2025-11-07 | Aniline-induced refractory methemoglobinemia in polytrauma: successful management with erythrocytapheresis.
Methemoglobinemia is a life-threatening condition characterized by the inability of hemoglobin to transport oxygen efficiently. This case report describes acquired methemoglobinemia caused by exposure to aniline dye, which was successfully treated with erythrocytapheresis following the insufficient effect of methylene blue. A 39-year-old male suffered multiple injuries, including burns and fractures, after falling into a barrel containing aniline. On site, emergency medical services (EMS) intubated the patient, performed chest decompression for pneumothorax, and decontaminated him before transferring him to a trauma centre. In the emergency unit, imaging revealed multiple rib, scapula, and pelvic fractures, retroperitoneal bleeding, and 15% total body surface area (TBS) burns. He was hemodynamically unstable, with metabolic acidosis, an oxygen saturation gap, and an initial methemoglobin level (MetHb) of 19%. Despite methylene blue treatment, the MetHb levels rose to undetectable levels (> 20%), and severe hemodynamic instability, refractory hypoxia, and metabolic derangement required the use of erythrocytapheresis. Aniline exposure leads to the oxidation of ferrous iron (Fe2 +) in hemoglobin to ferric iron (Fe3 +), resulting in methemoglobinemia and impaired oxygen delivery. While methylene blue remains the first-line treatment, erythrocytapheresis proved effective in restoring tissue oxygenation in refractory methemoglobinemia complicated by hemorrhagic and traumatic shock.
2024-10-19 | Critically Ill Patient with Acquired Refractory Methemoglobinemia Successfully Treated with Therapeutic Erythrocytapheresis: A Case Report
REPORTalkalosis, pO 2 -369 mm Hg, and methemoglobin was 15%.The oxygen saturation gap, that is, the difference between oxygen saturation in arterial blood gas sample (SaO 2 ) and SpO 2, was greater than 5%.His blood was chocolate brown in color.The patient had methemoglobinemia, probably due to poisoning.In the meantime, the patient had seizures and was intubated.Around 60 mg (1 mg/kg) of intravenous (IV) methylene blue was administered over 3 hours, and the patient was shifted to the ICU.The patient was continued on mechanical ventilator support.SpO 2 remained 85% on 100% FiO 2 .The patient was drowsy without any sedation.Hemodynamics were stable.G6PD levels and other lab investigations were normal.The ABG taken on the next day at 7:30 am showed 3.9% methemoglobin.As cyanosis persisted, a second dose of 60 mg IV methylene blue was given.Despite two doses of methylene blue, SpO 2 remained 85% on 100% FiO 2 .The 1,
2024-08-28 | Rasburicase-induced hemolytic anemia and methemoglobinemia: a systematic review of current reports.
Since the FDA's approval of rasburicase use for treatment of tumor lysis syndrome (TLS), multiple cases of rasburicase-induced methemoglobinemia and hemolytic anemia have been reported among patients with G6PD deficiency. This study aims to provide a systematic review of cases reporting such adverse reactions to rasburicase. A literature review of published cases in PubMed, Embase, Cochrane, and Web of Science was conducted. Descriptive studies reporting cases of rasburicase-induced methemoglobinemia and/or hemolytic anemia in English were analyzed and summarized in this study. Forty-three cases, including a case from our institution, were included in this study. Most cases (60.5%) received rasburicase for TLS treatment. Almost all patients (93.8%) were tested for G6PD after rasburicase administration. The median time to symptom onset was 24 h. The median methemoglobin level was 10%, peaking after a median of 24 h. The median hemoglobin nadir was 6.1 g/dL, and most patients (n = 32) required blood transfusion. Out of 39 cases with reported outcomes, 35 patients (89.7%) recovered, while four patients (three females and one male) died. The median time to recovery was 4.5 days while the median time to death was 8 days. Screening for G6PD deficiency among high-risk patients is important but not practical in acutely severe settings. When prior screening for G6PD deficiency is not feasible, close monitoring for methemoglobinemia and hemolytic anemia is recommended. Exchange transfusion is increasingly reported as a potentially successful therapeutic modality. Ascorbic acid may provide limited benefits. Methylene blue should be avoided as it may exacerbate hemolysis among these patients.
2024-01-26 | Eating vegetables is not always a good advice. A case report and literature review of acquired methemoglobinemia
Methemoglobinemia (MET) is a life-threatening condition resulting from the development of methemoglobin (MetHb), which binds oxygen irreversibly, causing refractory hypoxia and so-called “functional anemia”. MET can be caused by hereditary or acquired processes. Acquired forms are the most common. Symptoms correlate with the MetHb level and range from cyanosis and dyspnea to dysrhythmias, metabolic acidosis, coma, and cardiac arrest. MetHb levels above 70% are fatal. Methylene blue (MB) is the specific antidote. In all cases, supportive treatment, including intravenous hydration, glucose correction, and oxygen supplementation, must be started immediately. Exchange transfusion has been used successfully to treat MET and may be appropriate in patients for whom MB is ineffective. We report the case of a 54-year-old woman who presented to our emergency department for the acute and sudden development of chest pain, shortness of breath, and severe cyanosis after drinking a significant amount of boiled courgette water. Arterial blood gas analysis revealed a MetHb level of 26%. She was treated immediately with MB, oxygen supplementation, and hydration with normalization of her MetHb in 12 hours. Our recommendation is to always investigate MET in patients with unexplained cyanosis and refractory hypoxia.
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