{ "schemaVersion": 2, "eyebrow": "Hematology / Toxicology", "title": "Methemoglobinemia", "summary": "Confirm suspected methemoglobinemia with blood-gas co-oximetry when cyanosis or low pulse oximetry is disproportionate to cardiopulmonary findings, immediately remove oxidant exposure, and use symptom-, concentration-, and oxygen-delivery risk–based antidotal treatment while avoiding methylene blue in G6PD deficiency.", "seoDescription": "Physician guide to diagnosing and treating methemoglobinemia with co-oximetry, exposure assessment, treatment thresholds, and G6PD precautions.", "clinicalQuestion": "How should physicians confirm, risk-stratify, treat, and monitor suspected acquired or hereditary methemoglobinemia?", "specialty": "Emergency Medicine, Hematology, Medical Toxicology", "audience": "U.S. physicians and medical trainees", "tags": [ "methemoglobinemia", "co-oximetry", "methylene blue", "G6PD deficiency", "dapsone", "benzocaine", "saturation gap", "cyanosis" ], "keyTakeaways": [ "Order arterial or venous blood-gas co-oximetry—not pulse oximetry alone—to confirm and quantify methemoglobin in unexplained cyanosis or hypoxemia that does not correct as expected with oxygen. [7][12][23]", "Acute onset after an oxidant exposure favors acquired disease; lifelong cyanosis, affected relatives, blue sclera, or consanguinity should trigger evaluation for CYB5R3 deficiency or HbM disease. [18][21][24]", "For acquired methemoglobinemia, treat symptomatic patients at a methemoglobin concentration of 20% and asymptomatic patients at 30%; consider treatment at 10% to 30% when anemia, cardiopulmonary disease, carbon monoxide poisoning, or other impaired oxygen delivery is present. [21]", "Do not administer methylene blue to patients with G6PD deficiency because it may be ineffective and can precipitate severe hemolysis; discontinue it and pursue alternatives if severe hemolysis occurs. [1][16]", "After dapsone or aryl-amine/sulfa exposures, monitor serial methemoglobin by co-oximetry through resolution because levels may rebound after an initial methylene blue response. [1]" ], "sections": [ { "id": "recognize-and-stabilize", "eyebrow": "Immediate assessment", "heading": "When to suspect methemoglobinemia and what to do first", "intro": "Treat clinically important oxygen-delivery failure while confirming the dyshemoglobinemia.", "paragraphs": [ "Suspect methemoglobinemia when cyanosis, dyspnea, neurologic symptoms, tachycardia, or low SpO2 is out of proportion to cardiopulmonary examination findings, particularly when hypoxemia appears refractory to supplemental oxygen. Dark or chocolate-brown blood and a normal PaO2 despite low pulse oximetry strengthen the diagnosis; neither finding replaces co-oximetry. [19][23]", "Immediately stop the suspected oxidant medication or exposure, administer supplemental oxygen, and assess airway, ventilation, hemodynamics, mental status, ECG, hemoglobin concentration, and acid-base status. The clinical danger is functional anemia: ferric hemoglobin cannot bind oxygen, reducing effective oxygen-carrying capacity despite a measured total hemoglobin that may appear acceptable. [7][8][19]", "Escalate urgency when there is altered mental status, hemodynamic instability, significant anemia, cardiac or pulmonary compromise, concomitant carbon monoxide poisoning, or rapidly rising methemoglobin. These conditions reduce oxygen-delivery reserve and justify treatment at lower methemoglobin concentrations than in otherwise healthy patients. [21]" ], "bullets": [ "Ask specifically about dapsone, topical or local anesthetics, nitrates/nitrites, nitroglycerin, nitroprusside, nitric oxide, sulfonamides, nitrofurantoin, rasburicase, primaquine, chloroquine, phenazopyridine, aniline dyes, and oxidant industrial or ingestion exposures. [3][4][19]", "Recognize high-risk hosts: infants younger than 6 months, G6PD deficiency, congenital or idiopathic methemoglobinemia, cardiopulmonary disease, and concurrent oxidant exposure. [3][4]", "After local anesthetic exposure, symptoms can occur immediately or be delayed for several hours; do not dismiss an initially normal examination if cyanosis or abnormal blood color develops after discharge-level observation. [3][4]" ], "subsections": [], "table": { "caption": "Clinical pattern that should prompt immediate blood-gas co-oximetry. [7][19][23]", "columns": [ "Finding", "Interpretation", "Next action" ], "rows": [ [ "Cyanosis with low SpO2 and no major cardiac or pulmonary explanation", "Dyshemoglobinemia is a key alternative to cardiopulmonary hypoxemia. [19][23]", "Obtain venous or arterial blood gas with co-oximetry. [7][23]" ], [ "Low SpO2 with normal PaO2", "Supports impaired hemoglobin oxygen carriage rather than impaired dissolved oxygen tension. [23]", "Quantify methemoglobin by co-oximetry and review oxidant exposures. [7][12]" ], [ "Chocolate-brown blood", "Characteristic visual clue but not a quantitative test. [19][23]", "Confirm with co-oximetry; begin exposure removal and oxygen support. [7][19]" ], [ "Recent dapsone, benzocaine, lidocaine, prilocaine, nitrate/nitrite, or rasburicase exposure", "Acquired oxidant methemoglobinemia is likely until proved otherwise. [3][4][16][19]", "Stop the agent, assess for hemolysis when relevant, and obtain serial co-oximetry. [1][16]" ] ] } }, { "id": "confirm-and-interpret", "eyebrow": "Diagnostic testing", "heading": "Confirm with co-oximetry and interpret the saturation gap correctly", "intro": "Co-oximetry establishes the diagnosis and guides treatment intensity.", "paragraphs": [ "Obtain co-oximetry on an arterial or venous blood gas in every patient with a credible clinical syndrome. Co-oximetry spectrophotometrically measures hemoglobin derivatives, including oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin, and is the preferred confirmatory test. [7][12][13][23]", "Do not rely on calculated arterial oxygen saturation, routine pulse oximetry, or PaO2 to exclude disease. A saturation gap—difference between SpO2 and co-oximetry-derived SaO2—greater than 5% suggests an abnormal hemoglobin species, including methemoglobin, carboxyhemoglobin, or sulfhemoglobin. [13]", "Interpret the methemoglobin percentage in clinical context rather than as an isolated antidote trigger. Acute acquired disease is generally less well tolerated than congenital disease because the rate of rise matters; congenital patients may have baseline concentrations of 20% to 40% with chronic cyanosis and relatively limited symptoms. [7][21]" ], "bullets": [ "At methemoglobin concentrations above 20%, early symptoms may include headache, lightheadedness, fatigue, dyspnea, lethargy, tachycardia, and pallor. [7]", "Concentrations above 70% are potentially lethal, although individual tolerance varies with acuity and oxygen-delivery reserve. [7][21]", "Obtain a CBC when anemia is possible; methemoglobinemia functions as anemia, and a lower baseline hemoglobin reduces the total amount of functional hemoglobin at any given methemoglobin percentage. [7][8]" ], "subsections": [], "table": { "caption": "Treatment-relevant interpretation of methemoglobin results in acquired disease. [21]", "columns": [ "Clinical setting", "Methemoglobin result", "Decision" ], "rows": [ [ "Symptomatic acquired methemoglobinemia", "20% or higher. [21]", "Give antidotal treatment after stopping the oxidant exposure and providing oxygen support. [21]" ], [ "Asymptomatic acquired methemoglobinemia", "30% or higher. [21]", "Treat and monitor with serial co-oximetry. [21]" ], [ "Symptoms or impaired oxygen delivery from anemia, cardiac disease, lung disease, or carbon monoxide poisoning", "10% to 30%. [21]", "Use a lower treatment threshold based on clinical severity and oxygen-delivery risk. [21]" ], [ "Chronic hereditary methemoglobinemia", "Higher concentrations may be tolerated than in acute acquired disease. [7][21]", "Avoid applying acquired-disease thresholds without considering baseline status and symptoms. [21]" ] ] } }, { "id": "identify-the-cause", "eyebrow": "Etiologic branch point", "heading": "Distinguish acquired oxidant exposure from hereditary methemoglobinemia", "intro": "The exposure timeline determines acute management and the subsequent diagnostic pathway.", "paragraphs": [ "Classify most new presentations as acquired when cyanosis begins recently after a medication, toxin, or environmental exposure. High-yield exposures include dapsone; benzocaine and other local anesthetics; nitrates and nitrites; nitroprusside and nitric oxide; sulfonamides; nitrofurantoin; antimalarials; rasburicase; and aniline dyes. [3][4][16][19][21]", "Pursue hereditary evaluation after acquired triggers have been excluded or when cyanosis is longstanding, began in infancy, recurs without exposure, or occurs in relatives. Family history of dusky skin or blue sclera and consanguinity favor congenital disease; cardiac and pulmonary right-to-left shunting remain competing causes of central cyanosis that require independent evaluation. [18][21][24]", "Measure cytochrome b5 reductase activity to distinguish hereditary CYB5R3 deficiency from acquired disease; it is the reference test for this branch point. Confirm congenital disease with molecular testing, which can identify CYB5R3-related disease and globin-gene variants causing HbM disease. Hemoglobin electrophoresis can help identify HbM variants. [18][21][24]", "Before rasburicase, obtain G6PD testing because G6PD-deficient patients are at risk for both hemolysis and methemoglobinemia. If methemoglobinemia follows rasburicase, monitor for delayed hemolysis; in one reported pattern, hemolysis developed more than 30 hours after methemoglobinemia. [16]" ], "bullets": [ "CYB5R activity less than 20% of normal supports congenital CYB5R3 deficiency. [24]", "HbM disease is associated with globin-gene variants and is inherited differently from autosomal recessive CYB5R3 deficiency; molecular testing clarifies the diagnosis when the phenotype is persistent. [22][24]", "Patients with known hereditary or acquired methemoglobinemia should avoid precipitating oxidant factors, including before surgery or during pregnancy planning. [18]" ], "subsections": [], "table": { "caption": "Etiologic patterns and the next diagnostic action. [18][21][24]", "columns": [ "Pattern", "Most likely branch", "Tests or actions that change management" ], "rows": [ [ "Abrupt cyanosis after a new drug, anesthetic, nitrate/nitrite, or toxin", "Acquired oxidant methemoglobinemia. [3][4][19][21]", "Stop exposure; quantify methemoglobin with co-oximetry; treat according to symptoms and concentration. [7][21]" ], [ "Lifelong cyanosis, family history, blue sclera, or consanguinity", "Hereditary methemoglobinemia. [18][21][24]", "Measure CYB5R activity and obtain molecular testing; consider hemoglobin electrophoresis for HbM. [18][24]" ], [ "Rasburicase exposure with methemoglobinemia or hemolysis", "Oxidant event in possible G6PD deficiency. [16]", "Check G6PD status and avoid methylene blue when deficiency is present or strongly suspected. [1][16]" ], [ "Persistent cyanosis with no elevated methemoglobin", "Alternative dyshemoglobinemia or cardiopulmonary disease.", "Evaluate carboxyhemoglobin and sulfhemoglobin on co-oximetry when available; reassess for cardiac or pulmonary shunt disease. [13][21]" ] ] } }, { "id": "treat-acquired-disease", "eyebrow": "Antidotal treatment", "heading": "Treat acquired methemoglobinemia without causing hemolysis", "intro": "Choose methylene blue by clinical severity and avoid it when its redox mechanism is unsafe.", "paragraphs": [ "For acquired methemoglobinemia meeting treatment thresholds, give intravenous methylene blue as first-line antidotal therapy unless contraindicated. Treatment is indicated at 20% methemoglobin in symptomatic patients and at 30% in asymptomatic patients; use lower thresholds in patients with reduced oxygen-delivery reserve. [13][21]", "Do not give methylene blue to patients with G6PD deficiency. FDA labeling identifies G6PD deficiency as a contraindication because treatment can cause severe hemolysis and severe anemia; methylene blue may also be ineffective because its reduction to the active form depends on adequate reducing capacity. [1][16]", "Avoid excessive cumulative methylene blue exposure. Doses greater than 7 mg/kg can themselves act as an oxidant and induce or worsen methemoglobinemia in susceptible patients. If severe hemolysis occurs, discontinue methylene blue and pursue alternative management. [1][7][14]", "Use serial co-oximetry to document response and identify rebound. Rebound or incomplete resolution is specifically described after aryl-amine exposures such as aniline and sulfa drugs such as dapsone; continue monitoring through clinical and laboratory resolution rather than relying on transient improvement in cyanosis. [1]" ], "bullets": [ "In G6PD deficiency or when methylene blue cannot be used, ascorbic acid is a slower direct reducer of methemoglobin and has been used in hereditary disease and in selected nonsevere presentations. [6][13][15]", "Consider exchange transfusion or hyperbaric oxygen as rescue options when the patient does not improve or methylene blue is contraindicated or cannot be used. [2][15]", "For dapsone-associated disease, do not assume a single response ends the episode; repeat methemoglobin measurements because rebound may occur. [1]" ], "subsections": [ { "heading": "Medication safety and exposure prevention", "paragraphs": [ "When a local anesthetic is necessary in a patient at increased risk—G6PD deficiency, congenital methemoglobinemia, infant age under 6 months, cardiopulmonary compromise, or concurrent oxidant drug exposure—use close clinical monitoring for cyanosis and abnormal blood color. [3][4]", "After liposomal bupivacaine administration, avoid additional local anesthetics for 96 hours because concurrent local anesthetic exposure can increase methemoglobinemia risk. [4]" ], "bullets": [] } ], "table": { "caption": "Treatment selection and monitoring for acquired methemoglobinemia. [1][13][15][16][21]", "columns": [ "Scenario", "Action", "Monitoring or escalation" ], "rows": [ [ "Symptomatic patient with methemoglobin 20% or higher", "Stop oxidant exposure, provide oxygen support, and use intravenous methylene blue unless contraindicated. [13][21]", "Repeat co-oximetry to document decline and clinical response. [1]" ], [ "Asymptomatic patient with methemoglobin 30% or higher", "Treat with methylene blue unless contraindicated. [21]", "Follow serial methemoglobin until resolution. [1]" ], [ "G6PD deficiency or strong suspicion of deficiency", "Avoid methylene blue because of severe hemolysis risk and potential lack of efficacy. [1][16]", "Use oxygen support; consider ascorbic acid and rescue exchange transfusion or hyperbaric oxygen when clinically necessary. [6][13][15]" ], [ "Dapsone, aniline, or sulfa-associated disease", "Remove exposure and treat by severity threshold. [1][21]", "Monitor for rebound after initial response. [1]" ], [ "No improvement or methylene blue cannot be used", "Escalate to exchange transfusion or hyperbaric oxygen as second-line rescue therapy. [2][15]", "Continue serial co-oximetry and organ-supportive care. [1][15]" ] ] } }, { "id": "long-term-management", "eyebrow": "After stabilization", "heading": "Long-term management of hereditary and recurrent methemoglobinemia", "intro": "Document the mechanism, establish a baseline, and prevent repeat oxidant injury.", "paragraphs": [ "After stabilization, patients with persistent elevation or a history consistent with congenital disease should have CYB5R activity measurement and molecular confirmation when available. This distinguishes CYB5R3 deficiency from HbM disease and provides the basis for counseling about inheritance, baseline cyanosis, and oxidant avoidance. [18][21][24]", "Do not treat chronic cyanosis solely to normalize a laboratory value. Patients with congenital methemoglobinemia can tolerate higher baseline methemoglobin concentrations than patients with acute acquired disease; treatment decisions should instead incorporate symptoms, baseline concentration, and comorbid conditions that impair oxygen delivery. [7][21]", "Oral methylene blue has been used as maintenance therapy in congenital disease, while oral ascorbic acid reduces methemoglobin slowly and has been used in hereditary disease. Long-term pharmacologic decisions require individualized hematology input because the available evidence is largely based on reports and small series. [6][13][20]" ], "bullets": [ "Record confirmed G6PD deficiency prominently because methylene blue is contraindicated and oxidant drugs may cause hemolysis and methemoglobinemia. [1][16]", "Before procedures, review exposure to topical anesthetics and other oxidant drugs; patients with congenital disease or G6PD deficiency warrant heightened monitoring if local anesthetics are unavoidable. [3][4][18]", "Advise patients with a confirmed hereditary diagnosis to avoid known precipitating oxidants and to disclose the diagnosis during emergency care, surgery, and pregnancy-related care. [18]" ], "subsections": [], "table": { "caption": "Follow-up priorities after an episode of methemoglobinemia. [1][18][21][24]", "columns": [ "Clinical situation", "Follow-up action", "Purpose" ], "rows": [ [ "Single clear acquired exposure with normalization", "Document culprit drug or toxin and avoid re-exposure. [1][19]", "Prevents recurrent oxidant injury." ], [ "Persistent or recurrent cyanosis without a clear exposure", "Measure CYB5R activity; obtain molecular testing and consider hemoglobin electrophoresis. [18][24]", "Identifies CYB5R3 deficiency or HbM disease." ], [ "Rasburicase-associated event", "Confirm G6PD status and monitor for hemolysis after the methemoglobinemia episode. [16]", "Guides future drug avoidance and detects delayed hemolytic complications. [16]" ], [ "Known hereditary disease", "Establish baseline symptoms and methemoglobin level; review oxidant avoidance before surgery or pregnancy. [18][21]", "Avoids unnecessary acute-style treatment and reduces preventable exacerbations. [18]" ] ] } } ], "faq": [], "references": [ { "number": 1, "title": "[PDF] Table of Pharmacogenomic Biomarkers in Drug Labeling - FDA", "detail": "www.fda.gov", "url": "https://www.fda.gov/media/122407/download", "authors": "www.fda.gov", "host": "www.fda.gov" }, { "number": 2, "title": "4169829 This label may not be the latest approved by FDA ...", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201444s019lbl.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov" }, { "number": 3, "title": "[PDF] 209511Orig1s000 - accessdata.fda.gov", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/209511Orig1s000Lbl.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov" }, { "number": 4, "title": "[PDF] CENTER FOR DRUG EVALUATION AND RESEARCH", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/22496Orig1s037.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov" }, { "number": 5, "title": "An Update to the American Heart Association Guidelines for ...", "detail": "www.ahajournals.org", "url": "https://www.ahajournals.org/doi/10.1161/CIR.0000000000001161", "authors": "www.ahajournals.org", "host": "www.ahajournals.org" }, { "number": 6, "title": "A rare cause of cyanosis: Congenital methemoglobinemia - 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Abstract", "detail": "pubmed.ncbi.nlm.nih.gov", "url": "https://pubmed.ncbi.nlm.nih.gov/34467556", "authors": "pubmed.ncbi.nlm.nih.gov", "host": "pubmed.ncbi.nlm.nih.gov" }, { "number": 23, "title": "Methemoglobinemia: from diagnosis to treatment - PubMed", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19082413", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov" }, { "number": 24, "title": "A blue blood toddler– a case report of methemoglobinemia and literature review - PMC", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11846283", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov" } ], "editorialNote": "Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.", "citations": [ { "number": 1, "title": "[PDF] Table of Pharmacogenomic Biomarkers in Drug Labeling - FDA", "detail": "www.fda.gov", "url": "https://www.fda.gov/media/122407/download", "authors": "www.fda.gov", "host": "www.fda.gov", "snippet": "204630, 04/08/2016 Methylene Blue Hematology G6PD Contraindications, Warnings and Precautions 4 CONTRAINDICATIONS PROVAYBLUE™ is contraindicated in the following conditions: • Severe hypersensitivity reactions to methylene blue or any other thiazine dye [see Warnings and Precautions (5.2)]. • Patien", "score": 0.7004242 }, { "number": 2, "title": "4169829 This label may not be the latest approved by FDA ...", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201444s019lbl.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov", "snippet": "guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Monitor serum methemoglobin levels dur", "score": 0.56460327 }, { "number": 3, "title": "[PDF] 209511Orig1s000 - accessdata.fda.gov", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/209511Orig1s000Lbl.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov", "snippet": "for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Overdosage (10)]. 7.2 Drugs Associated with Methemoglobinemia Patients who are administered local anesthetics may be at increased risk of deve", "score": 0.6964752 }, { "number": 4, "title": "[PDF] CENTER FOR DRUG EVALUATION AND RESEARCH", "detail": "www.accessdata.fda.gov", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/22496Orig1s037.pdf", "authors": "www.accessdata.fda.gov", "host": "www.accessdata.fda.gov", "snippet": "anesthetics within 96 hours following administration of EXPAREL. Patients who are administered local anesthetics, including EXPAREL, may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Class Examples ", "score": 0.69199765 }, { "number": 5, "title": "An Update to the American Heart Association Guidelines for ...", "detail": "www.ahajournals.org", "url": "https://www.ahajournals.org/doi/10.1161/CIR.0000000000001161", "authors": "www.ahajournals.org", "host": "www.ahajournals.org", "snippet": "sodium nitrite, LA poisoning can also produce methemoglobinemia; Long-acting local anesthetic drugs and convulsions with hypoxia and acidosis.", "score": 0.5082762 }, { "number": 6, "title": "A rare cause of cyanosis: Congenital methemoglobinemia - Guedri - 2021 - Clinical Case Reports - Wiley Online Library", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/full/10.1002/ccr3.4422", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "# A rare cause of cyanosis: Congenital methemoglobinemia. Congenital Methemoglobinemia is a rare condition that may mimic congenital heart diseases. There are two types of congenital Methemoglobinemia. Methemoglobinemia can be acquired or, more rarely, congenital. In this article, we report a case o", "score": 0.76152116 }, { "number": 7, "title": "Methemoglobinemia: When to Suspect and How to Treat : Current Medical Issues", "detail": "journals.lww.com", "url": "https://journals.lww.com/cmii/fulltext/2019/17040/methemoglobinemia__when_to_suspect_and_how_to.7.aspx", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "Title: Methemoglobinemia: When to Suspect and How to Treat : Current Medical Issues\n# Methemoglobinemia. Effectively, patients with acutely increased levels of methemoglobin have a functional anemia, wherein the amount of functional hemoglobin capable of oxygen delivery to the tissues is less than t", "score": 0.7474137 }, { "number": 8, "title": "Acquired methemoglobinemia: A systematic review of reported cases - ScienceDirect", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/science/article/pii/S1473050221002998", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Title: Acquired methemoglobinemia: A systematic review of reported cases - ScienceDirect\n# Acquired methemoglobinemia: A systematic review of reported cases. ### Introduction. Acquired methemoglobinemia may cause cyanosis and tissue ischemia unresponsive to oxygen supplementation. We performed a lit", "score": 0.7373288 }, { "number": 9, "title": "Methemoglobinemia - an overview | ScienceDirect Topics", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/medicine-and-dentistry/methemoglobinemia", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Methemoglobinemia refers to the oxidation of ferrous iron (Fe++) to ferric iron (Fe+++) within the hemoglobin molecule.1 This reaction impairs the ability of hemoglobin to transport oxygen and carbon dioxide, leading to tissue hypoxemia and in severe cases, death. Methemoglobinemia most commonly res", "score": 0.67321366 }, { "number": 10, "title": "Acquired methemoglobinemia induced by dapsone in... : Medicine", "detail": "journals.lww.com", "url": "https://journals.lww.com/md-journal/fulltext/2025/07250/acquired_methemoglobinemia_induced_by_dapsone_in_a.103.aspx", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "in teenagers, emphasizing the need for clinicians to be vigilant when prescribing dapsone-containing medications and to promptly intervene in suspected cases to prevent adverse outcomes. This study is important as acquired methemoglobinemia, especially induced by dapsone, is a rare but life-threaten", "score": 0.6175132 }, { "number": 11, "title": "A Case of Rapid Methemoglobinemia Following Topical Anesthetics", "detail": "academic.oup.com", "url": "https://academic.oup.com/ajrccm/article/211/Supplement_1/A2586/8334794", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "... co-oximetry confirmed a methemoglobin level of 24.6%. Methylene blue was administered, and within 1 hour, her methemoglobin level dropped to 1.7", "score": 0.6847074 }, { "number": 12, "title": "Laboratory Assessment of Oxygenation in Methemoglobinemia", "detail": "academic.oup.com", "url": "https://academic.oup.com/clinchem/article-abstract/51/2/434/5629640", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "CO-oximetry is a more complex and reliable method that measures the concentration of hemoglobin derivatives in the blood from which various quantities such as", "score": 0.64639384 }, { "number": 13, "title": "Successful management of methemoglobinemia with oral... : MRIMS Journal of Health Sciences", "detail": "journals.lww.com", "url": "https://journals.lww.com/mjhs/fulltext/2025/10000/successful_management_of_methemoglobinemia_with.15.aspx", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "This article presents two unique cases of methemoglobinemia successfully managed with oral ascorbic acid, showcasing an alternative treatment approach for mild cases. Both patients, an adult male and female with unexplained, persistent desaturation and central cyanosis, were diagnosed with congenita", "score": 0.7738498 }, { "number": 14, "title": "Methylene blue-induced Hemolysis in a patient with lidocaine-induced Methemoglobinemia: a case report | Oxford Medical Case Reports | Oxford Academic", "detail": "academic.oup.com", "url": "https://academic.oup.com/omcr/article/2025/12/omaf264/8404891", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "# Methylene blue-induced Hemolysis in a patient with lidocaine-induced Methemoglobinemia: a case report *Open Access*. Murad Mehmood, Fatema Jaber A Almarri, Methylene blue-induced Hemolysis in a patient with lidocaine-induced Methemoglobinemia: a case report, *Oxford Medical Case Reports*, Volume 2", "score": 0.7557276 }, { "number": 15, "title": "Acute methemoglobinemia due to ingestion of MAHIA... : Annals of African Medicine", "detail": "journals.lww.com", "url": "https://journals.lww.com/aoam/fulltext/2016/15040/acute_methemoglobinemia_due_to_ingestion_of_mahia.9.aspx", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "The transfusion or hyperbaric oxygen should be used.[1][2][3][4][5][6] Therefore, large doses of methylene blue might result in higher levels of methylene blue than leucomethylene blue, which will result in hemolysis and paradoxically, methemoglobinemia in patients with G6PD deficiency. Although ascorbic", "score": 0.7371019 }, { "number": 16, "title": "Methemoglobinemia and hemolysis in a patient with G6PD deficiency treated with rasburicase", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.23182", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "# Methemoglobinemia and hemolysis in a patient with G6PD deficiency treated with rasburicase. Laboratory Data from a Case of Rasburicase-Induced Methemoglobinemia and Hemolysis in a Patient with G6PD Deficiency and Anemia. A glucose-6-phosphatase dehydrogenase (G6PD) level is usually obtained in pat", "score": 0.5559422 }, { "number": 17, "title": "Pulse Fiction: The Sp O 2 –Sa O 2 Gap in Methemoglobinemia", "detail": "academic.oup.com", "url": "https://academic.oup.com/annalsats/article/21/11/1610/8380734", "authors": "academic.oup.com", "host": "academic.oup.com", "snippet": "The cause of her methemoglobinemia was attributed to dapsone, commonly associated with methemoglobinemia. Local anesthetics Prilocaine", "score": 0.56517935 }, { "number": 18, "title": "Summary of Joint European Hematology Association (EHA) and EuroBloodNet Recommendations on Diagnosis and Treatment of Methemoglobinemia - PMC", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8598222", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "The diagnosis of methemoglobinemia should be suspected in the case of unexplained cyanosis and hypoxemia; however, the clinical presentation is variable from mildly symptomatic to severe cases.5 Cytochrome b5 reductase activity measurement is the gold standard test to discriminate hereditary CYB5R3 ", "score": 0.8437023 }, { "number": 19, "title": "Methemoglobinemia - StatPearls - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/portal/utils/pageresolver.fcgi?recordid=69535b8d003dc56acd1231a8", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov", "snippet": "Methemoglobinemia is a potentially life-threatening condition characterized by impaired oxygen delivery due to oxidation of hemoglobin iron from the ferrous (Fe2+) to the ferric (Fe3+) state. Acquired methemoglobinemia typically arises after exposure to oxidizing agents, including topical anesthetic", "score": 0.8215175 }, { "number": 20, "title": "Congenital Methemoglobinemia in a 33-Year-Old Patient: A Case Report on a Rare Presentation and a Review of the Literature - PMC", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10082972", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "Cyanosis and dyspnea are common complaints in adults and have broad differential diagnoses, of which rare ones such as congenital methemoglobinemia should always be considered in the differential diagnosis. Methemoglobinemia might be acquired or congenital. Patients' symptoms vary from severe shortn", "score": 0.82117355 }, { "number": 21, "title": "Recommendations for diagnosis and treatment of methemoglobinemia - PMC", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9291883", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "### 1.4. Diagnostic approaches and differential diagnosis\n\nGiven the different pathogenic basis of this group of diseases, an accurate clinical and family history, evaluation of consanguinity (more common in CYB5R3 deficiency), as well as review of environmental and drug exposure, is fundamental in ", "score": 0.81770587 }, { "number": 22, "title": "Recommendations for diagnosis and treatment of methemoglobinemia. - Abstract", "detail": "pubmed.ncbi.nlm.nih.gov", "url": "https://pubmed.ncbi.nlm.nih.gov/34467556", "authors": "pubmed.ncbi.nlm.nih.gov", "host": "pubmed.ncbi.nlm.nih.gov", "snippet": "Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances th", "score": 0.8033131 }, { "number": 23, "title": "Methemoglobinemia: from diagnosis to treatment - PubMed", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19082413", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov", "snippet": "Title: Methemoglobinemia: from diagnosis to treatment - PubMed\nAn official website of the United States government. **The .gov means it’s official.**. Federal government websites often end in .gov or .mil. sharing sensitive information, make sure you’re on a federal. The **https://** ensures that yo", "score": 0.77487355 }, { "number": 24, "title": "A blue blood toddler– a case report of methemoglobinemia and literature review - PMC", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11846283", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "### Clinical features and diagnostic approach\n\nTo diagnose this disease and distinguish between hereditary and acquired forms, it is crucial to obtain a detailed clinical and family history, assess for consanguinity, and review environmental and drug exposures. For acquired forms, the cyanosis is ty", "score": 0.76194656 } ], "publishedAt": "2026-09-16T00:07:11.915416+00:00", "updatedAt": "2026-09-16T00:07:11.915416+00:00", "readingMinutes": 6, "slug": "methemoglobinemia" }