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| __NOTOC__ | | __NOTOC__ |
| {{Methemoglobinemia}} | | {{Methemoglobinemia}} |
| {{CMG}}; {{AE}}{{Aksiniya K. Stevasarova, M.D.}} | | {{CMG}}; {{AE}}{{AKS}} |
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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== |