Methemoglobinemia risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Template:Aksiniya K. Stevasarova, M.D.

Overview

  • The risk factors for the formation of methemoglobinemia can be divided into two groups: congenital risk factors and acquired risk factors.

Congenital Risk Factors for Methemoglobinemia

1. Cytochrome b5 reductase deficiency and pyruvate kinase deficiency

2. G6PD deficiency

3. Presence of abnormal hemoglobin (Hb M)


Acquired Risk Factors for Methemoglobinemia

Risk Factors

Congenital Risk Factors for Methemoglobinemia

  • There are three main congenital risk factors that lead to methemoglobinemia:

1. Cytochrome b5 reductase deficiency and pyruvate kinase deficiency

2. G6PD deficiency

3. Presence of abnormal hemoglobin (Hb M)


The most common form, is the Ib5R deficiency, where cyt b5 reductase is absent only in RBCs, and the levels of MetHb are around 10% to 35%. [1]

  • The second type, which is much less common, is the IIb5R deficiency, where MetHb levels vary between 10% and 15% and the [[cyt

b5 reductase]] is absent in all cells. This form is associated with mental retardation, microcephaly, and other neurologic problems. The lifespan of the affected individuals is greatly affected and patients usually die very young. [2]


Acquired Risk Factors for Methemoglobinemia

1. Drug Induced

Anesthetics[8] like benzocaine[9], lidocaine[10], prilocaine[11]

Methylene blue

Nitric oxide

Amyl Nitrate

Nitroglycerin

Antimalarial drugs like Primaquine phosphate (in nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficient individuals)

Rasburicase [12]

Sulfasalazine

Dapsone

Trimethoprim

Sulfonamides

Aniline dyes[13]

Metoclopramide

Chlorates and Bromates

2. Contaminated well water (in premature infants and infants younger than 4 months) [14] [15]

3. Solid foods (not well cooked vegetables high in nitrates in premature infants and infants younger than 4 months) [16] [17]

References

  1. {{Rev Bras Anestesiol. 2008 Nov-Dec;58(6):651-64. Methemoglobinemia: from diagnosis to treatment. [Article in English, Portuguese] do Nascimento TS1, Pereira RO, de Mello HL, Costa J. pmid=PMID:19082413 }}
  2. {{J Pediatr Hematol Oncol. 2012 Aug;34(6):457-60. doi: 10.1097/MPH.0b013e318257a492. Methemoglobin reductase deficiency: novel mutation is associated with a disease phenotype of intermediate severity. Percy MJ1, Barnes C, Crighton G, Leventer RJ, Wynn R, Lappin TR. PMID: 22627575 }}
  3. {{BMJ Case Rep. 2018 Mar 28;2018. pii: bcr-2017-223369. doi: 10.1136/bcr-2017-223369. Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man. Rehman A1,2, Shehadeh M2, Khirfan D2, Jones A2. PMID: 29592989 }}
  4. {{J Pediatr Hematol Oncol. 2016 Apr;38(3):173-5. doi: 10.1097/MPH.0000000000000489. Hemoglobin M Disease as a Cause of Cyanosis in a Newborn. Alonso-Ojembarrena A1, Lubián-López SP. pmid=PMID:26694193 }}
  5. Template:Med Toxicol. 1986 Jul-Aug;1(4):253-60. Drug- and chemical-induced methaemoglobinaemia. Clinical features and management. Hall AH, Kulig KW, Rumack BH.pmid=PMID: 3537620
  6. {{Rev Bras Anestesiol. 2008 Nov-Dec;58(6):651-64. Methemoglobinemia: from diagnosis to treatment. [Article in English, Portuguese] do Nascimento TS1, Pereira RO, de Mello HL, Costa J. pmid=19082413}}
  7. {{Rev Bras Anestesiol. 2008 Nov-Dec;58(6):651-64. Methemoglobinemia: from diagnosis to treatment. [Article in English, Portuguese] do Nascimento TS1, Pereira RO, de Mello HL, Costa J. pmid=19082413}}
  8. {{ J Emerg Med. 2018 Mar 5. pii: S0736-4679(18)30095-7. doi: 10.1016/j.jemermed.2018.01.039. [Epub ahead of print] Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options. Faust AC1, Guy E1, Baby N2, Ortegon A3.pmid=29519718}}
  9. {{ Ann Pharmacother. 1994 May;28(5):643-9. Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. Rodriguez LF1, Smolik LM, Zbehlik AJ.pmid=8069004 }}
  10. {{Drug Saf Case Rep. 2018 Apr 7;5(1):15. doi: 10.1007/s40800-018-0081-4. Acquired Methemoglobinemia Associated with Topical Lidocaine Administration: A Case Report. Gay HC1,2, Amaral AP3. pmid=PMID: 29627919 }}
  11. {{Isr Med Assoc J. 2014 Apr;16(4):250-4. Methemoglobinemia induced by lidocaine-prilocaine cream. Shamriz O, Cohen-Glickman I, Reif S, Shteyer E.pmid=24834764}}
  12. {{Curr Drug Saf. 2017;12(1):13-18. doi: 10.2174/1574886312666170111151246. Rasburicase-Induced Methemoglobinemia in a Patient with Glucose-6- Phosphate Dehydrogenase Deficiency. Khan M, Paul S, Farooq S, Oo TH, Ramshesh P, Jain N1. pmid=28078984}}
  13. {{Case Rep Emerg Med. 2015;2015:208732. doi: 10.1155/2015/208732. Epub 2015 Mar 12. P-chloroaniline poisoning causing methemoglobinemia: a case report and review of the literature. Messmer AS1, Nickel CH1, Bareiss D1. pmid=25861488 PMCID: PMC4377359 }}
  14. {{Eur J Emerg Med. 2003 Dec;10(4):326-30. A severe methaemoglobinemia induced by nitrates: a case report. Brunato F1, Garziera MG, Briguglio E. pmid=14676514 }}
  15. [www.epa.gov/dwstandardsregulations]
  16. [www.fda.gov/Drugs/DrugSafety/ucm250024.htm]
  17. [www.fda.gov/forconsumers/consumerupdates/ucm306062.htm]

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