Methemoglobinemia

Source: Wikipedia, the free encyclopedia.
Not to be confused with Argyria.
Methemoglobinemia
Other names
Blood gas[3]
Differential diagnosisArgyria, sulfhemoglobinemia, heart failure[3]
TreatmentOxygen therapy, methylene blue[3]
PrognosisGenerally good with treatment[3]
FrequencyRelatively uncommon[3]

Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated

heart arrhythmias.[3][4]

Methemoglobinemia can be due to certain medications, chemicals, or food or it can be inherited.

blood gas.[3]

Treatment is generally with

hyperbaric oxygen therapy.[3] Outcomes are generally good with treatment.[3] Methemoglobinemia is relatively uncommon, with most cases being acquired rather than genetic.[3]

Signs and symptoms

Chocolate-brown blood due to methemoglobinemia

Signs and symptoms of methemoglobinemia (methemoglobin level above 10%) include shortness of breath, cyanosis, mental status changes (~50%), headache, fatigue, exercise intolerance, dizziness, and loss of consciousness.[5]

People with severe methemoglobinemia (methemoglobin level above 50%) may exhibit

sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5–8%).[citation needed
]

Cause

Acquired

Methemoglobinemia may be acquired.[7] Classical drug causes of methemoglobinaemia include various antibiotics (trimethoprim, sulfonamides, and dapsone[8]), local anesthetics (especially articaine, benzocaine, prilocaine,[9] and lidocaine[10]), and aniline dyes, metoclopramide, rasburicase, umbellulone, chlorates, bromates, and nitrites.[11] Nitrates are suspected to cause methemoglobinemia.[12]

In otherwise healthy individuals, the protective enzyme systems normally present in red blood cells rapidly reduce the methemoglobin back to hemoglobin and hence maintain methemoglobin levels at less than one percent of the total hemoglobin concentration. Exposure to exogenous oxidizing drugs and their metabolites (such as benzocaine, dapsone, and nitrates) may lead to an increase of up to a thousandfold of the methemoglobin formation rate, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels.[citation needed]

Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme (NADH-cytochrome b5 reductase) in their red blood cells. This results in a major risk of methemoglobinemia caused by nitrates ingested in drinking water,[13] dehydration (usually caused by gastroenteritis with diarrhea), sepsis, or topical anesthetics containing benzocaine or prilocaine resulting in blue baby syndrome. Nitrates used in agricultural fertilizers may leak into the ground and may contaminate well water. The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically set to protect infants.[13] Benzocaine applied to the gums or throat (as commonly used in baby teething gels, or sore throat lozenges) can cause methemoglobinemia.[14][15]

Genetic

autosomal recessive
pattern of inheritance.

Due to a deficiency of the

recessive gene. If only one parent has this gene, offspring will have normal-hued skin, but if both parents carry the gene, there is a chance the offspring will have blue-hued skin.[citation needed
]

Another cause of congenital methemoglobinemia is seen in patients with abnormal hemoglobin variants such as

hemoglobin H (HbH), which are not amenable to reduction despite intact enzyme systems.[citation needed
]

Methemoglobinemia can also arise in patients with

NADPH.[16]

Pathophysiology

The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methemoglobin results in an increased affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric hemoglobin unit.

tissue hypoxia may occur.[18]

Normally, methemoglobin levels are <1%, as measured by the

cytochrome-b5 reductase) (major pathway), NADPH methemoglobin reductase (minor pathway) and to a lesser extent the ascorbic acid and glutathione enzyme systems. Disruptions with these enzyme systems lead to methemoglobinemia. Hypoxia occurs due to the decreased oxygen-binding capacity of methemoglobin, as well as the increased oxygen-binding affinity of other subunits in the same hemoglobin molecule, which prevents them from releasing oxygen at normal tissue oxygen levels.[citation needed
]

Diagnosis

Color chart for the detection of the amount of methemoglobin in the blood

The diagnosis of methemoglobinemia is made with the typical symptoms, a suggestive history, low oxygen saturation on pulse oximetry measurements (SpO2) and these symptoms (cyanosis and hypoxia) failing to improve on oxygen treatment. The definitive test would be obtaining either CO-oximeter or a methemoglobin level on an arterial blood gas test.[3] Arterial blood with an elevated methemoglobin level has a characteristic chocolate-brown color as compared to normal bright red oxygen-containing arterial blood; the color can be compared with reference charts.[6]

The SaO2 calculation in the arterial blood gas analysis is falsely normal, as it is calculated under the premise of hemoglobin either being

distinguish the methemoglobin concentration and percentage of hemoglobin.[3]
At the same time, the SpO2 concentration as measured by pulse ox is false high, because methemoglobin absorbs the pulse ox light at the 2 wavelengths it uses to calculate the ratio of oxyhemoglobin and deoxyhemoglobin. For example with a methemoglobin level of 30–35%, this ratio of light absorbance is 1.0, which translates into a false high SpO2 of 85%.[3]

Differential diagnosis

Other conditions that can cause bluish skin include argyria, sulfhemoglobinemia, heart failure,[3] amiodarone-induced bluish skin pigmentation and acrodermatitis enteropathica.[3]

Treatment

Cyanosis from methemoglobinemia
Resolved after methylene blue

Methemoglobinemia can be treated with supplemental oxygen and methylene blue.[19] Methylene blue is given as a 1% solution (10 mg/ml) 1 to 2 mg/kg administered intravenously slowly over five minutes. Although the response is usually rapid, the dose may be repeated in one hour if the level of methemoglobin is still high one hour after the initial infusion. Methylene blue inhibits monoamine oxidase, and serotonin toxicity can occur if taken with an SSRI (selective serotonin reuptake inhibitor) medicine.[20]

Methylene blue restores the iron in hemoglobin to its normal (

hexose monophosphate shunt
.

Genetically induced chronic low-level methemoglobinemia may be treated with oral methylene blue daily. Also, vitamin C can occasionally reduce cyanosis associated with chronic methemoglobinemia, and may be helpful in settings in which methylene blue is unavailable or contraindicated (e.g., in an individual with G6PD deficiency).[22] Diaphorase (cytochrome b5 reductase) normally contributes only a small percentage of the red blood cell's reducing capacity, but can be pharmacologically activated by exogenous cofactors (such as methylene blue) to five times its normal level of activity.[citation needed]

Epidemiology

Methemoglobinemia mostly affects infants under 6 months of age (particularly those under 4 months) due to low hepatic production of

nitrates, such as wells and other water that is not monitored or treated by a water treatment facility. The nitrates can be hazardous to the infants.[25][26] The link between blue baby syndrome in infants and high nitrate levels is well established for waters exceeding the normal limit of 10 mg/L.[27][28] However, there is also evidence that breastfeeding is protective in exposed populations.[29]

Society and culture

Blue Fugates

Main article: Blue Fugates

The Fugates, a family that lived in the hills of

recessive methemoglobinemia (met-H) gene, as was a nearby clan with whom the Fugates descendants intermarried. As a result, many descendants of the Fugates were born with met-H.[31][32][33][34]

Blue Men of Lurgan

The "blue men of

ascorbic acid and sodium bicarbonate. In case one, by the eighth day of treatments, there was a marked change in appearance, and by the twelfth day of treatment, the patient's complexion was normal. In case two, the patient's complexion reached normality over a month-long duration of treatment.[35]

See also

References

  1. ^ "Methemoglobinemia". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. Retrieved 8 June 2019.
  2. ^ a b c d "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved 21 December 2019.
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  5. ^ Oiseth S, Jones L, Maza E (eds.). "Methemoglobinemia". The Lecturio Medical Concept Library. Retrieved 10 August 2021.
  6. ^ a b Khanapara DB, Sacher RA, Kumar MDenshaw-Burke M, Savior DC, Curran AL, DelGiacco E, Abouelezz KF (7 December 2023). Besa EC (ed.). "Methemoglobinemia". eMedicine. Retrieved 2008-09-13.
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  13. ^ a b "Basic Information about Nitrate in Drinking Water". United States Environmental Protection Agency. Retrieved 10 May 2013.
  14. ^ "FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth". U.S. Food and Drug Administration. 7 April 2011. Retrieved 10 May 2013.
  15. ^ "Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics". U.S. FDA. May 23, 2018. Retrieved May 24, 2018.
  16. ^ Oiseth S, Jones L, Maza E, eds. (3 September 2020). "Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency". The Lecturio Medical Concept Library. Retrieved 23 July 2021.
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  22. ^ Prchal JT. Burns MM, Takemoto CM (eds.). "Methemoglobinemia". UpToDate.
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  24. ^ "Nitrates and drinking water". www.bfhd.wa.gov. Retrieved 10 December 2016.
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  27. ^ "Nitrate and Nitrite in Drinking-Water" (PDF). www.who.int. WHO Press. 2011. Retrieved December 10, 2016.
  28. ^ "Table of Regulated Drinking Water Contaminants". www.epa.gov. 30 November 2015. Retrieved 2016-12-12.
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  30. ^ "Blue-skinned family baffled science for 150 years". MSN. 24 February 2012. Archived from the original on 22 January 2013. Retrieved 10 May 2013.
  31. ^ Adams C (24 July 1998). "Is there really a race of blue people?". Straight Dope.
  32. ^ "Appalachia's Blue People". Tri City Herald. 7 November 1974. p. 32.
  33. ^ Fugates of Kentucky: Skin Bluer than Lake Louise
  34. ^ "Martin Fuqatenin nəsli: genetik problemə görə dünyaya gələn mavi uşaqlar — Mavi Fuqatelər" [Generation of Martin Fugaten: Blue Children born according to genetic problem - blue fuqates]. YouTube (in Azerbaijani).
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External links
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