eMedicine Specialties > Pediatrics: General Medicine > Hematology

Methemoglobinemia: Differential Diagnoses & Workup

Author: Michael J Verive, MD, Medical Director, Pediatric Intensive Care, Department of Pediatrics, St Mary's Hospital for Women and Children
Coauthor(s): Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 6, 2009

Differential Diagnoses

Acrodermatitis Enteropathica

Other Problems to Be Considered

Pulmonary disease
Cyanotic heart disease (right-to-left shunts)
Hemoglobin variants with altered oxygen affinity
Sulfhemoglobinemia
Chronic/massive blue dye ingestion

Workup

Laboratory Studies

  • An arterial blood sample from a patient with methemoglobinemia is characteristically chocolate brown.

    Note the chocolate brown color of methemoglobinem...

    Note the chocolate brown color of methemoglobinemia. Tube 1 and tube 2 have a methemoglobin concentration of 70%; tube 3, a concentration of 20%; and tube 4, a normal concentration.

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    Note the chocolate brown color of methemoglobinem...

    Note the chocolate brown color of methemoglobinemia. Tube 1 and tube 2 have a methemoglobin concentration of 70%; tube 3, a concentration of 20%; and tube 4, a normal concentration.


    • Blood that is cyanotic or dark in color due to cardiopulmonary disease turns red upon exposure to oxygen, whereas blood with methemoglobin does not.
    • A quick and easy bedside test is to bubble 100% oxygen in a tube that contains the dark blood. Blood that remains dark likely does so because of the presence of methemoglobin.
    • Another simple test (and one that is less likely to splash potentially infectious blood) is to place 1-2 drops of blood on white filter paper, then evaluate for color change upon exposure to oxygen (this test can be accelerated by gently blowing supplemental oxygen onto the filter paper). Deoxygenated hemoglobin changes from dark red or violet to bright red, whereas methemoglobin remains brown.
  • Serum methemoglobin levels of more than 1% are considered abnormal, although higher levels are commonly encountered in smokers (and patients with long-term exposure to second-hand smoke). Symptomatic individuals usually have levels of more than 40-50%.
  • Serum levels of nitrites or other offending drugs may be determined; however, most of these results are not immediately available, and treatment must not be withheld or delayed pending test results.
  • Nicotinamide adenine dinucleotide (NADH) reductase levels should be checked.
  • Hemoglobin electrophoresis may be needed to confirm hemoglobin M disease.
  • Pulse oximetry may be a useful tool in patient with cyanosis, although its results must be interpreted with caution.
    • The blood is exposed to light using a small probe placed across a capillary bed, usually on a finger or toe. Light wavelengths of 660 nm and 940 nm are used, and the ratio of absorption of light at each of these wavelengths is converted into oxygen saturation using calibration curves.
    • A pulse oximetry reading in a child with respiratory or cardiac disease reflects the degree of hypoxia and is proportionate to the amount of reduced hemoglobin.
    • Methemoglobin increases absorption of light at both wavelengths (more at 940 nm) and, therefore, offers optical interference to the pulse oximetry by falsely absorbing light. This leads to the plateau in the oxygen saturation at 85%.
    • In a patient with methemoglobinemia, the severity of the cyanosis does not correspond to the pulse oximetry reading. The patient may appear extremely cyanotic but have a pulse oximetry reading in the high 80s.
    • In methemoglobinemia, the oxygen saturations (as determined by pulse oximetry) plateau at around 85%; therefore, a patient with a methemoglobin level of 5% and a patient with a methemoglobin level of 40% both have pulse oximetry readings of around 85%.
  • Co-oximetry should be performed to evaluate for methemoglobinemia (although some equipment does not differentiate between sulfhemoglobin and methemoglobin).

Imaging Studies

  • Chest radiography may be helpful to exclude pulmonary or cardiac disease.
  • If needed, use echocardiography to determine the presence of congenital heart disease with right-left (pulmonary-systemic) shunt.

More on Methemoglobinemia

Overview: Methemoglobinemia
Differential Diagnoses & Workup: Methemoglobinemia
Treatment & Medication: Methemoglobinemia
Follow-up: Methemoglobinemia
Multimedia: Methemoglobinemia
References
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References

  1. Jolly BT, Monico EP, McDevitt B. Methemoglobinemia in an infant: case report and review of the literature. Pediatr Emerg Care. Oct 1995;11(5):294-7. [Medline].

  2. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). Sep 2004;83(5):265-73. [Medline].

  3. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: Etiology, Pharmacology, and Clinical Management. Annals of Emergency Medicine. 1999;34:646-656. [Medline].

  4. Yano SS, Danish EH, Hsia YE. Transient methemoglobinemia with acidosis in infants. J Pediatr. Mar 1982;100(3):415-8. [Medline].

  5. Erkekoglu P, Baydar T. Evaluation of nitrite contamination in baby foods and infant formulas marketed in Turkey. Int J Food Sci Nutr. May 2009;60(3):206-9. [Medline].

  6. [Guideline] Greer FR, Shannon M. Infant methemoglobinemia: the role of dietary nitrate in food and water. Pediatrics. Sep 2005;116(3):784-6. [Medline]. [Full Text].

  7. Fung HT, Lai CH, Wong OF, Lam KK, Kam CW. Two cases of methemoglobinemia following zopiclone ingestion. Clin Toxicol (Phila). Feb 2008;46(2):167-70. [Medline].

  8. Carstairs SD, Tanen DA. Case studies in pediatric toxicology. Pediatr Ann. Dec 2005;34(12):973-8, 981. [Medline].

  9. Dahshan A, Donovan GK. Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature. Pediatrics. Apr 2006;117(4):e806-9.

  10. Geller RJ, Barthold C, Saiers JA, Hall AH. Pediatric cyanide poisoning: causes, manifestations, management, and unmet needs. Pediatrics. Nov 2006;118(5):2146-58. [Medline].

  11. Hjelt K, Lund JT, Scherling B, et al. Methaemoglobinaemia among neonates in a neonatal intensive care unit. Acta Paediatr. Apr 1995;84(4):365-70. [Medline].

  12. Jacka MJ, Kruger M, Glick N. Methemoglobinemia after transesophageal echocardiography: a life-threatening complication. J Clin Anesth. 2006;18(1):52-54. [Medline]. [Full Text].

  13. Jaffe ER. Methemoglobin pathophysiology. Prog Clin Biol Res. 1981;51:133-51. [Medline].

  14. Lebby T, Roco JJ, Arcinue EL. Infantile methemoglobinemia associated with acute diarrheal illness. Am J Emerg Med. Sep 1993;11(5):471-2. [Medline].

  15. Lindenmann J, Matzi V, Kaufmann P, et al. Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report. Inhal Toxicol. Dec 2006;18(13):1047-9. [Medline].

  16. Mansouri A, Lurie AA. Concise review: methemoglobinemia. Am J Hematol. Jan 1993;42(1):7-12. [Medline].

  17. McMullen SE, Casanova JA, Gross LK, Schenck FJ. Ion chromatographic determination of nitrate and nitrite in vegetable and fruit baby foods. J AOAC Int. Nov-Dec 2005;88(6):1793-6. [Medline].

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Further Reading

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Keywords

methemoglobinemia, methemoglobin, cyanosis, glucose-6-phosphate dehydrogenase deficiency, cytochrome b5 oxidase deficiency, acquired methemoglobinemia, congenital methemoglobinemia, encephalopathy, microcephaly, hypertonia, athetosis, opisthotonus, strabismus, mental retardation, growth retardation, diagnosis, treatment

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Contributor Information and Disclosures

Author

Michael J Verive, MD, Medical Director, Pediatric Intensive Care, Department of Pediatrics, St Mary's Hospital for Women and Children
Michael J Verive, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Mudra Kumar, MD, MBBS, MRCP is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MBBS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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