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| ==Overview== | | ==Overview== |
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| * The risk factors for the formation of [[methemoglobinemia]] can be divided into two groups: congenital risk factors and acquired risk factors.
| | Some of the risk factors for the formation of [[methemoglobinemia] include topical use of various anesthetics, drinking contaminated with nitrates water or eating solid food contaminated with nitrates. |
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| '''Congenital Risk Factors for Methemoglobinemia'''
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| *There are three main [[congenital]] conditions that lead to [[methemoglobinemia]]:
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| 1. [[Cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]]
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| 2. [[G6PD deficiency]]
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| 3. Presence of abnormal hemoglobin ([[Hb M]])
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| '''Acquired Risk Factors for Methemoglobinemia'''
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| *Some of the most common risk factors include different [[oxidant drugs]], [[toxins]] and [[chemicals]].
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| ==Risk Factors== | | ==Risk Factors== |
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| '''Congenital Risk Factors for Methemoglobinemia''' | | '''1. Anesthetics''' |
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| *There are three main congenital risk factors that lead to methemoglobinemia:
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| 1. [[Cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]] | |
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| 2. [[G6PD deficiency]]
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| 3. Presence of abnormal hemoglobin ([[Hb M]])
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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.
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| 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>
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| *The second type, which is much less common, is the [[IIb5R deficiency]], where [[MetHb]] levels vary between 10% and 15% and the [[cyt
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| 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>
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| *[[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>
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| *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>
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| '''Acquired Risk Factors for Methemoglobinemia'''
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| *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>
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| '''1.''' '''Drug Induced'''
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| • [[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>
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| • [[Methylene blue]]
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| • [[Nitric oxide]]
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| • [[Amyl Nitrate]]
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| • [[Nitroglycerin]]
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| • [[Antimalarial drugs]] like [[Primaquine phosphate]] (in [[nicotinamide adenine dinucleotide]] ([[NADH]]) methemoglobin reductase deficient individuals)
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| • [[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>
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| • [[Sulfasalazine]]
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| • [[Dapsone]]
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| • [[Trimethoprim]]
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| • [[Sulfonamides]]
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| • [[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>
| | Topical [[benzocaine]] and [[lidocaine]] are commonly used in general anesthesia to facilitate the intubation in awake patients and can cause [[methemoglobinemia]].<ref name="pmid9305310">{{cite journal| author=Cooper HA| title=Methemoglobinemia caused by benzocaine topical spray. | journal=South Med J | year= 1997 | volume= 90 | issue= 9 | pages= 946-8 | pmid=9305310 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9305310 }} </ref> <ref name="pmid17694687">{{cite journal| author=Lin SK, Wu JL, Lee YL, Tsao SL| title=Methemoglobinemia induced by exposure to topical benzocaine for an awake nasal intubation--a case report. | journal=Acta Anaesthesiol Taiwan | year= 2007 | volume= 45 | issue= 2 | pages= 111-6 | pmid=17694687 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17694687 }} </ref> <ref name="pmid27139292">{{cite journal| author=Lipton M, Szlam SM, Barker K, Benitez JG| title=Methemoglobinemia Secondary to Topical Benzocaine Application to Gastrostomy Site. | journal=Pediatr Emerg Care | year= 2016 | volume= 32 | issue= 5 | pages= 312-4 | pmid=27139292 | doi=10.1097/PEC.0000000000000800 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27139292 }} </ref> |
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| • [[Metoclopramide]]
| | '''2. Contaminated well water''' |
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| • [[Chlorates and Bromates]]
| | In premature infants and infants younger than 4 months, contaminated with nitrates water can induce [[methemoglobinemia]]. Most cases occur due to contaminated well water by nitrates sprayed on different vegetables etc. <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> |
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| '''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> | | '''3. Solid foods''' |
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| '''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>
| | Solid foods that are not well cooked, like vegetables high in nitrates, can induce [[methemoglobinemia]] 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> |
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| ==References== | | ==References== |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aksiniya Stevasarova, M.D.
Overview
Some of the risk factors for the formation of [[methemoglobinemia] include topical use of various anesthetics, drinking contaminated with nitrates water or eating solid food contaminated with nitrates.
Risk Factors
1. Anesthetics
Topical benzocaine and lidocaine are commonly used in general anesthesia to facilitate the intubation in awake patients and can cause methemoglobinemia.[1] [2] [3]
2. Contaminated well water
In premature infants and infants younger than 4 months, contaminated with nitrates water can induce methemoglobinemia. Most cases occur due to contaminated well water by nitrates sprayed on different vegetables etc. [4]ref> [www.epa.gov/dwstandardsregulations]</ref>
3. Solid foods
Solid foods that are not well cooked, like vegetables high in nitrates, can induce methemoglobinemia in premature infants and infants younger than 4 months.
[5] [6]
References
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