Methemoglobinemia risk factors: Difference between revisions

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*Both [[cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]] can lead to [[NADH deficiency]] which in turn will lead to decreased ability to remove MetHb from the blood. [[Cytochrome b5 reductase deficiency]] is an [[autosomal recessive disorder]] with at least 2 forms that we know of.  
*Both [[cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]] can lead to [[NADH deficiency]] which in turn will lead to decreased ability to remove MetHb from the blood. [[Cytochrome b5 reductase deficiency]] is an [[autosomal recessive disorder]] with at least 2 forms that we know of.  
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%. <ref>{{Rev Bras Anestesiol. 2008 Nov-Dec;58(6):651-64.
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%. <ref name="pmid19082413">{{cite journal| author=do Nascimento TS, Pereira RO, de Mello HL, Costa J| title=Methemoglobinemia: from diagnosis to treatment. | journal=Rev Bras Anestesiol | year= 2008 | volume= 58 | issue= 6 | pages= 651-64 | pmid=19082413 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19082413 }} </ref>
Methemoglobinemia: from diagnosis to treatment.
[Article in English, Portuguese]
do Nascimento TS1, Pereira RO, de Mello HL, Costa J. pmid=PMID:19082413 }}</ref>


*The second type, which is much less common, is the [[IIb5R deficiency]], where [[MetHb]] levels vary between 10% and 15% and the [[cyt  
*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.  <ref>{{J Pediatr Hematol Oncol. 2012 Aug;34(6):457-60. doi: 10.1097/MPH.0b013e318257a492.
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.  <ref name="pmid22627575">{{cite journal| author=Percy MJ, Barnes C, Crighton G, Leventer RJ, Wynn R, Lappin TR| title=Methemoglobin reductase deficiency:  novel mutation is associated with a disease phenotype of intermediate severity. | journal=J Pediatr Hematol Oncol | year= 2012 | volume= 34 | issue= 6 | pages= 457-60 | pmid=22627575 | doi=10.1097/MPH.0b013e318257a492 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22627575 }} </ref>
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 }}</ref>


*[[Congenital]] deficiency in [[G6PD]] can lead to decreased levels of [[NADPH]] and thus compromising the function of the [[diaphorase II enzyme]] system. <ref>{{BMJ Case Rep. 2018 Mar 28;2018. pii: bcr-2017-223369. doi: 10.1136/bcr-2017-223369.
*[[Congenital]] deficiency in [[G6PD]] can lead to decreased levels of [[NADPH]] and thus compromising the function of the [[diaphorase II enzyme]] system. <ref name="pmid29592989">{{cite journal| author=Rehman A, Shehadeh M, Khirfan D, Jones A| title=Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man. | journal=BMJ Case Rep | year= 2018 | volume= 2018 | issue=  | pages=  | pmid=29592989 | doi=10.1136/bcr-2017-223369 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29592989 }} </ref>
Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man.
Rehman A1,2, Shehadeh M2, Khirfan D2, Jones A2. PMID: 29592989 }}</ref>


*Abnormal hemoglobins like [[Hb M]], including [[Hb Ms]], [[Hb MIwate]], [[Hb MBoston]], [[Hb MHyde Park]], and [[Hb MSaskatoon]], an [[autosomal dominant condition]], can also lead to [[methemoglobinemia]]. In case of [[amino acid]] substitution in the [[alpha-chain of hemoglobin]], we observe [[cyanosis]] at birth, and infants with [[beta chain amino acid]] substitution will present with [[cyanosis]] later around 4-6 months of age. <ref>{{J Pediatr Hematol Oncol. 2016 Apr;38(3):173-5. doi: 10.1097/MPH.0000000000000489.
*Abnormal hemoglobins like [[Hb M]], including [[Hb Ms]], [[Hb MIwate]], [[Hb MBoston]], [[Hb MHyde Park]], and [[Hb MSaskatoon]], an [[autosomal dominant condition]], can also lead to [[methemoglobinemia]]. In case of [[amino acid]] substitution in the [[alpha-chain of hemoglobin]], we observe [[cyanosis]] at birth, and infants with [[beta chain amino acid]] substitution will present with [[cyanosis]] later around 4-6 months of age. <ref name="pmid26694193">{{cite journal| author=Alonso-Ojembarrena A, Lubián-López SP| title=Hemoglobin M Disease as a Cause of Cyanosis in a Newborn. | journal=J Pediatr Hematol Oncol | year= 2016 | volume= 38 | issue= 3 | pages= 173-5 | pmid=26694193 | doi=10.1097/MPH.0000000000000489 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26694193  }} </ref>
Hemoglobin M Disease as a Cause of Cyanosis in a Newborn.
Alonso-Ojembarrena A1, Lubián-López SP. pmid=PMID:26694193  }}</ref>




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'''Acquired Risk Factors for Methemoglobinemia'''
'''Acquired Risk Factors for Methemoglobinemia'''


*Some of the most common risk factors that can cause excessive formation of methemoglobin include different [[oxidant drugs]], [[toxins]] and [[chemicals]].<ref>{{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}}</ref> <ref>{{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}}</ref>    <ref>{{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}}</ref>
*Some of the most common risk factors that can cause excessive formation of methemoglobin include different [[oxidant drugs]], [[toxins]] and [[chemicals]].<ref name="pmid3537620">{{cite journal| author=Hall AH, Kulig KW, Rumack BH| title=Drug- and chemical-induced methaemoglobinaemia. Clinical features and management. | journal=Med Toxicol | year= 1986 | volume= 1 | issue= 4 | pages= 253-60 | pmid=3537620 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3537620 }} </ref> <ref name="pmid19082413">{{cite journal| author=do Nascimento TS, Pereira RO, de Mello HL, Costa J| title=Methemoglobinemia: from diagnosis to treatment. | journal=Rev Bras Anestesiol | year= 2008 | volume= 58 | issue= 6 | pages= 651-64 | pmid=19082413 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19082413 }} </ref>  


'''1.''' '''Drug Induced'''  
'''1.''' '''Drug Induced'''  


• [[Anesthetics]]<ref>{{ J Emerg Med. 2018 Mar 5. pii: S0736-4679(18)30095-7. doi: 10.1016/j.jemermed.2018.01.039. [Epub ahead of print]
• [[Anesthetics]]<ref name="pmid29519718">{{cite journal| author=Faust AC, Guy E, Baby N, Ortegon A| title=Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options. | journal=J Emerg Med | year= 2018 | volume= 54 | issue= 5 | pages= 681-684 | pmid=29519718 | doi=10.1016/j.jemermed.2018.01.039 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29519718 }} </ref> like [[benzocaine]]<ref name="pmid8069004">{{cite journal| author=Rodriguez LF, Smolik LM, Zbehlik AJ| title=Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. | journal=Ann Pharmacother | year= 1994 | volume= 28 | issue= 5 | pages= 643-9 | pmid=8069004 | doi=10.1177/106002809402800515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8069004 }} </ref>, [[lidocaine]]<ref name="pmid29627919">{{cite journal| author=Gay HC, Amaral AP| title=Acquired Methemoglobinemia Associated with Topical Lidocaine Administration: A Case Report. | journal=Drug Saf Case Rep | year= 2018 | volume= 5 | issue= 1 | pages= 15 | pmid=29627919 | doi=10.1007/s40800-018-0081-4 | pmc=5889764 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29627919 }} </ref>, [[prilocaine]]<ref name="pmid24834764">{{cite journal| author=Shamriz O, Cohen-Glickman I, Reif S, Shteyer E| title=Methemoglobinemia induced by lidocaine-prilocaine cream. | journal=Isr Med Assoc J | year= 2014 | volume= 16 | issue= 4 | pages= 250-4 | pmid=24834764 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24834764  }} </ref>
Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options.
Faust AC1, Guy E1, Baby N2, Ortegon A3.pmid=29519718}}</ref> like [[benzocaine]]<ref>{{ 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 }}</ref>, [[lidocaine]]<ref>{{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 }}</ref>, [[prilocaine]]<ref>{{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}}</ref>


• [[Methylene blue]]
• [[Methylene blue]]
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• [[Antimalarial drugs]] like [[Primaquine phosphate]] (in [[nicotinamide adenine dinucleotide]] ([[NADH]]) methemoglobin reductase deficient individuals)
• [[Antimalarial drugs]] like [[Primaquine phosphate]] (in [[nicotinamide adenine dinucleotide]] ([[NADH]]) methemoglobin reductase deficient individuals)


• [[Rasburicase]]  <ref>{{Curr Drug Saf. 2017;12(1):13-18. doi: 10.2174/1574886312666170111151246.
• [[Rasburicase]]  <ref name="pmid28078984">{{cite journal| author=Khan M, Paul S, Farooq S, Oo TH, Ramshesh P, Jain N| title=Rasburicase-Induced Methemoglobinemia in a Patient with Glucose-6- Phosphate Dehydrogenase Deficiency. | journal=Curr Drug Saf | year= 2017 | volume= 12 | issue= 1 | pages= 13-18 | pmid=28078984 | doi=10.2174/1574886312666170111151246 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28078984 }} </ref>
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}}</ref>


• [[Sulfasalazine]]
• [[Sulfasalazine]]
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• [[Sulfonamides]]
• [[Sulfonamides]]


• [[Aniline dyes]]<ref>{{Case Rep Emerg Med. 2015;2015:208732. doi: 10.1155/2015/208732. Epub 2015 Mar 12.
• [[Aniline dyes]]<ref name="pmid25861488">{{cite journal| author=Messmer AS, Nickel CH, Bareiss D| title=P-chloroaniline poisoning causing methemoglobinemia: a case report and review of the literature. | journal=Case Rep Emerg Med | year= 2015 | volume= 2015 | issue=  | pages= 208732 | pmid=25861488 | doi=10.1155/2015/208732 | pmc=4377359 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25861488 }} </ref>
P-chloroaniline poisoning causing methemoglobinemia: a case report and review of the literature.
Messmer AS1, Nickel CH1, Bareiss D1. pmid=25861488 PMCID: PMC4377359 }}</ref>  


• [[Metoclopramide]]
• [[Metoclopramide]]
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• [[Chlorates and Bromates]]
• [[Chlorates and Bromates]]


'''2. Contaminated well water''' (in premature infants and infants younger than 4 months) <ref>{{Eur J Emerg Med. 2003 Dec;10(4):326-30.
'''2. Contaminated well water''' (in premature infants and infants younger than 4 months) <ref name="pmid14676514">{{cite journal| author=Brunato F, Garziera MG, Briguglio E| title=A severe methaemoglobinemia induced by nitrates: a case report. | journal=Eur J Emerg Med | year= 2003 | volume= 10 | issue= 4 | pages= 326-30 | pmid=14676514 | doi=10.1097/01.mej.0000103472.32882.db | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14676514 }} </ref>ref> [www.epa.gov/dwstandardsregulations]</ref>
A severe methaemoglobinemia induced by nitrates: a case report.
Brunato F1, Garziera MG, Briguglio E. pmid=14676514 }}</ref>   <ref> [www.epa.gov/dwstandardsregulations]</ref>


'''3. Solid foods''' (not well cooked vegetables high in nitrates in premature infants and infants younger than 4 months)  <ref> [www.fda.gov/Drugs/DrugSafety/ucm250024.htm]</ref>  <ref> [www.fda.gov/forconsumers/consumerupdates/ucm306062.htm]</ref>
'''3. Solid foods''' (not well cooked vegetables high in nitrates in premature infants and infants younger than 4 months)  <ref> [www.fda.gov/Drugs/DrugSafety/ucm250024.htm]</ref>  <ref> [www.fda.gov/forconsumers/consumerupdates/ucm306062.htm]</ref>

Revision as of 13:03, 15 June 2018

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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[6] like benzocaine[7], lidocaine[8], prilocaine[9]

• Methylene blue

• Nitric oxide

• Amyl Nitrate

• Nitroglycerin

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

• Rasburicase [10]

• Sulfasalazine

• Dapsone

• Trimethoprim

• Sulfonamides

• Aniline dyes[11]

• Metoclopramide

• Chlorates and Bromates

2. Contaminated well water (in premature infants and infants younger than 4 months) [12]ref> [www.epa.gov/dwstandardsregulations]</ref>

3. Solid foods (not well cooked vegetables high in nitrates in premature infants and infants younger than 4 months) [13] [14]

References

  1. ↑ 1.0 1.1 do Nascimento TS, Pereira RO, de Mello HL, Costa J (2008). "Methemoglobinemia: from diagnosis to treatment". Rev Bras Anestesiol. 58 (6): 651–64. PMID 19082413.
  2. ↑ Percy MJ, Barnes C, Crighton G, Leventer RJ, Wynn R, Lappin TR (2012). "Methemoglobin reductase deficiency: novel mutation is associated with a disease phenotype of intermediate severity". J Pediatr Hematol Oncol. 34 (6): 457–60. doi:10.1097/MPH.0b013e318257a492. PMID 22627575.
  3. ↑ Rehman A, Shehadeh M, Khirfan D, Jones A (2018). "Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man". BMJ Case Rep. 2018. doi:10.1136/bcr-2017-223369. PMID 29592989.
  4. ↑ Alonso-Ojembarrena A, Lubián-López SP (2016). "Hemoglobin M Disease as a Cause of Cyanosis in a Newborn". J Pediatr Hematol Oncol. 38 (3): 173–5. doi:10.1097/MPH.0000000000000489. PMID 26694193.
  5. ↑ Hall AH, Kulig KW, Rumack BH (1986). "Drug- and chemical-induced methaemoglobinaemia. Clinical features and management". Med Toxicol. 1 (4): 253–60. PMID 3537620.
  6. ↑ Faust AC, Guy E, Baby N, Ortegon A (2018). "Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options". J Emerg Med. 54 (5): 681–684. doi:10.1016/j.jemermed.2018.01.039. PMID 29519718.
  7. ↑ Rodriguez LF, Smolik LM, Zbehlik AJ (1994). "Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature". Ann Pharmacother. 28 (5): 643–9. doi:10.1177/106002809402800515. PMID 8069004.
  8. ↑ Gay HC, Amaral AP (2018). "Acquired Methemoglobinemia Associated with Topical Lidocaine Administration: A Case Report". Drug Saf Case Rep. 5 (1): 15. doi:10.1007/s40800-018-0081-4. PMC 5889764. PMID 29627919.
  9. ↑ Shamriz O, Cohen-Glickman I, Reif S, Shteyer E (2014). "Methemoglobinemia induced by lidocaine-prilocaine cream". Isr Med Assoc J. 16 (4): 250–4. PMID 24834764.
  10. ↑ Khan M, Paul S, Farooq S, Oo TH, Ramshesh P, Jain N (2017). "Rasburicase-Induced Methemoglobinemia in a Patient with Glucose-6- Phosphate Dehydrogenase Deficiency". Curr Drug Saf. 12 (1): 13–18. doi:10.2174/1574886312666170111151246. PMID 28078984.
  11. ↑ Messmer AS, Nickel CH, Bareiss D (2015). "P-chloroaniline poisoning causing methemoglobinemia: a case report and review of the literature". Case Rep Emerg Med. 2015: 208732. doi:10.1155/2015/208732. PMC 4377359. PMID 25861488.
  12. ↑ Brunato F, Garziera MG, Briguglio E (2003). "A severe methaemoglobinemia induced by nitrates: a case report". Eur J Emerg Med. 10 (4): 326–30. doi:10.1097/01.mej.0000103472.32882.db. PMID 14676514.
  13. ↑ [www.fda.gov/Drugs/DrugSafety/ucm250024.htm]
  14. ↑ [www.fda.gov/forconsumers/consumerupdates/ucm306062.htm]

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