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Methemoglobinemia - Emergency Management

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General Information

General Information

Background

  • Methemoglobin (MetHb) is a stable, oxidized ferric (Fe3+) form of hemoglobin that causes a functional anemia and tissue hypoxia
  • MetHb is present normally at levels < 1%, and maintained at a low level due to innate antioxidant mechanisms in the body

Mechanism of Toxicity

  • Methemoglobin (MetHb) may be acquired from oxidant stress, such as an illness or medications, or congenital due to genetic polymorphisms
  • Oxidant stress oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+)1,2,3
  • MetHb has reduced oxygen-carrying capacity and shifts the oxygen hemoglobin dissociation curve to the left, limiting oxygen release from hemoglobin, and therefore delivery to tissue, causing functional anemia and tissue hypoxia

Pharmacokinetics

  • Assuming no congenital hemoglobinopathy, methemoglobin (MetHb)’s half-life is 1-3 hours4,5
    • May be longer with continued exposure to oxidant
      • The classic example is dapsone, which has a long half-life
  • Infants (especially age < 4-6 months) are more susceptible to MetHb formation
    • Immature innate protective mechanisms against oxidation6,7
    • Increased susceptibility of fetal hemoglobin to oxidation6,7
    • Increased gastric pH facilitates conversion of nitrates to nitrates (potent oxidizers)6,7
    • Gastrointestinal illness, metabolic acidosis, and well water (nitrate) exposure are classic causes of methemoglobinemia in infants6,7

References

References

General References Used

  1. Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003;22(1):13-27OpenInNew
  2. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). 2004 Sep;83(5):265-73OpenInNew
  3. Hartmann AF, Perley AM, Barnett HL. A study of some of the physiological effects of sulfanilamide. II. Methemoglobin formation and its control. J Clin Invest. 1938 Nov;17(6):699-710OpenInNewPDFPictureAsPdf
  4. Knobeloch L, Salna B, Hogan A, Postle J, Anderson H. Blue babies and nitrate-contaminated well water. Environ Health Perspect. 2000 Jul;108(7):675-8OpenInNewPDFPictureAsPdf
  5. Darling RC, Roughton FJW: The effect of methemoglobin on the equilibrium between oxygen and hemoglobin. Am J Physiol. 1942;137:56-66 PDFPictureAsPdf
  6. Lebby T, Roco JJ, Arcinue EL. Infantile methemoglobinemia associated with acute diarrheal illness. Am J Emerg Med. 1993 Sep;11(5):471-2OpenInNew
  7. Rehman HU. Methemoglobinemia. West J Med. 2001 Sep;175(3):193-6OpenInNewfull-textOpenInNew
  8. Barker SJ, Tremper KK, Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology. 1989 Jan;70(1):112-7OpenInNew
  9. El-Husseini A, Azarov N. Is threshold for treatment of methemoglobinemia the same for all? A case report and literature review. Am J Emerg Med. 2010 Jul;28(6):748.e5-748.e10OpenInNew
  10. Faust AC, Guy E, Baby N, Ortegon A. Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options. J Emerg Med. 2018 May;54(5):681-684OpenInNew
  11. Wendel WB. The control of Methemoglobinemia with methylene blue. J Clin Invest. 1939 Mar;18(2):179-85OpenInNewPDFPictureAsPdf
  12. Dawson AH, Whyte IM. Management of dapsone poisoning complicated by methaemoglobinaemia. Med Toxicol Adverse Drug Exp. 1989 Sep-Oct;4(5):387-92OpenInNew
  13. Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Saf. 2010 Sep 1;33(9):713-26OpenInNew
  14. Kellermeyer RW, Tarlov AR, Brewer GJ, Carson PE, Alving AS. Hemolytic effect of therapeutic drugs. Clinical considerations of the primaquine-type hemolysis. JAMA. 1962 May 5;180:388-94OpenInNew
  15. Jang DH, Nelson LS, Hoffman RS. Methylene blue for distributive shock: a potential new use of an old antidote. J Med Toxicol. 2013 Sep;9(3):242-9OpenInNewfull-textOpenInNew
  16. Lo JC, Darracq MA, Clark RF. A review of methylene blue treatment for cardiovascular collapse. J Emerg Med. 2014 May;46(5):670-9OpenInNew, commentary can be found in J Emerg Med 2016 Jan;50(1):126OpenInNew
  17. Park SY, Lee KW, Kang TS. High-dose vitamin C management in dapsone-induced methemoglobinemia. Am J Emerg Med. 2014 Jun;32(6):684.e1-3OpenInNew, commentary can be found in Am J Emerg Med 2014 Aug;32(8):935OpenInNew

DynaMed Editorial Process

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T908624, Methemoglobinemia - Emergency Management; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T908624. Registration and login required.
  • Related Summaries

  • Critical Points

  • KeyboardArrowRight

    General Information

    • Background

    • Mechanism of Toxicity

    • Pharmacokinetics

  • KeyboardArrowRight

    History and Physical

    • History

    • Physical

  • KeyboardArrowRight

    Diagnostic Studies

    • Lab Tests

    • Imaging Tests

    • Other Diagnostic Tests

  • Making the Diagnosis

  • KeyboardArrowRight

    Management

    • Overview

    • Medications

  • KeyboardArrowRight

    Disposition

    • KeyboardArrowRight

      Prognosis and Complications

      • Prognosis

      • Complications

      • Associated Conditions

    • Indications for Hospital Admission

    • Discharge Planning

  • Consultations

  • KeyboardArrowRight

    References

    • General References Used

    • DynaMed Editorial Process

    • How to cite

Author
Robert Goodnough MD
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Affiliations

Emergency Medicine Physician, Toxicology Fellow, University of California, San Francisco General Hospital; California, United States; Emergency Medicine Physician, Kaiser Permanente San Leandro Emergency Department; California, United States

Conflicts of Interest

Dr. Goodnough declares no relevant financial conflicts of interest.

Deputy Editor
Rachel Chin MD
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Affiliations

Professor of Emergency Medicine, University of California; California, United States

Conflicts of Interest

Dr. Chin declares no relevant financial conflicts of interest.

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