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


==Overview==
==Overview==


'''Congenital (Hereditary) Methemoglobinemia'''
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.
 
There are three main [[congenital]] conditions that lead to [[methemoglobinemia]]:
 
1. [[Cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]]
 
2. [[G6PD deficiency]]
 
3. Presence of abnormal hemoglobin ([[Hb M]])
 
 
'''Acquired or Acute Methemoglobinemia'''
 
Some of the most common causes include different [[oxidant drugs]], [[toxins]] and [[chemicals]]


==Risk Factors==   
==Risk Factors==   
<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>
'''Congenital (Hereditary) Methemoglobinemia'''
There are three main congenital conditions that lead to methemoglobinemia:
1. [[Cytochrome b5 reductase deficiency]] and [[pyruvate kinase deficiency]]
2. [[G6PD deficiency]]
3. Presence of abnormal hemoglobin ([[Hb M]])
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%.
The second type, which is much less common, is the [[IIb5R]], where [[MetHb]] varies 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.
[[Congenital]] deficiency in [[G6PD]] can lead to decreased levels of [[NADPH]] and thus compromising the function of the [[diaphorase II enzyme]] system.
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 [[cyanosi]]s at birth, and infants with beta chain amino acid substitution will present with [[cyanosis]] later around 4-6 months of age.
'''Acquired methemoglobinemia'''
The acquired methemoglobinemia is significantly more common than the congenital one. It is associated with exposure to or ingestion of [[oxidant drugs]], toxins or chemicals, that cause acute increment in [[methemoglobin]] levels, by overwhelming the normal physiologic protective [[enzyme]] mechanisms. The most common agents are [[anesthetics]] like [[benzocaine]], [[lidocaine]], [[prilocaine]], used locally or topically, [[antibiotics]] like [[dapsone]] (used for the treatment of [[Brown Recluse spider]] bites, [[Leprosy]], [[PCP]] prophylaxis, ecc) [[trimethoprim]], [[sulfonamides]], [[nitrates]]([[amynitrate])), [[nitroglycerin]] ([[NG]]), [[aniline dyes)], [[metoclopramide]], [[chlorates]] and [[bromates]].
'''Drug Induced'''
• [[Anesthetics]] like [[benzocaine]], [[lidocaine]], [[prilocaine ]]
• [[Methylene blue]]
• [[Nitric oxide]]
• [[Amilnitrate]]
• [[Nitroglycerin]]
• Antimalarial drugs like [[Primaquine phosphate]] (in [[nicotinamide adenine dinucleotide]] ([[NADH]]) methemoglobin reductase deficient individuals)
• [[Rasburicase]]
• [[Sulfasalazine]]
• [[Dapsone]]
• [[Trimethoprim]]
• [[Sulfonamides]]


• [[Aniline dyes]]
'''1. Anesthetics'''


• [[Metoclopramide]]
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>


• [[Chlorates]] and [[Bromates]] and others
'''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. <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>


'''Contaminated well water''' (in premature infants and infants younger than 4 months)
'''3. Solid foods'''  


'''Solid foods''' (not well cooked vegetables high in [[nitrates]] in premature infants and infants younger than 4 months)
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>


==References==
==References==

Latest revision as of 13:56, 15 August 2018

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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

  1. ↑ Cooper HA (1997). "Methemoglobinemia caused by benzocaine topical spray". South Med J. 90 (9): 946–8. PMID 9305310.
  2. ↑ Lin SK, Wu JL, Lee YL, Tsao SL (2007). "Methemoglobinemia induced by exposure to topical benzocaine for an awake nasal intubation--a case report". Acta Anaesthesiol Taiwan. 45 (2): 111–6. PMID 17694687.
  3. ↑ Lipton M, Szlam SM, Barker K, Benitez JG (2016). "Methemoglobinemia Secondary to Topical Benzocaine Application to Gastrostomy Site". Pediatr Emerg Care. 32 (5): 312–4. doi:10.1097/PEC.0000000000000800. PMID 27139292.
  4. ↑ 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.
  5. ↑ [www.fda.gov/Drugs/DrugSafety/ucm250024.htm]
  6. ↑ [www.fda.gov/forconsumers/consumerupdates/ucm306062.htm]

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