Methemoglobinemia: Difference between revisions
 
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==Background==
==Background==
[[File:methemoglobinemia.JPG|thumbnail]]
*Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
*Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
*Suspect in any patient with cyanosis not responsive to supplemental O2
*Suspect in any patient with cyanosis not responsive to supplemental O2
*Causes<ref>Fernandez-Frackelton M, Bocock J: Cyanosis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 29:p 211-216.</ref><ref>Mody, A., Silverman, B.: Problems in the Early Neonatal Period, In Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, Lippincott, WIlliams and Wilkins 2010, Page 995.</ref>
**Consider in pediatric patient (<6 months) with diarrhe and low oxygen saturation
**Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe<sup>3+</sup> → Fe<sup>2+</sup>)
 
**Exposure to oxidizing agent
===Causes===
***Benzocaine and other local anesthetics
*Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe<sup>3+</sup> → Fe<sup>2+</sup>)
***cyanide kit, nitrites, nitrates, well water (nitrates)
*Exposure to oxidizing agent<ref>Fernandez-Frackelton M, Bocock J: Cyanosis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 29:p 211-216.</ref><ref>Mody, A., Silverman, B.: Problems in the Early Neonatal Period, In Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, Lippincott, WIlliams and Wilkins 2010, Page 995.</ref>
***Antimalarials
**[[Benzocaine]] and other local anesthetics
***Quinolones
**[[Cyanokit]], nitrites, nitrates, well water (nitrates)
***Dapsone (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
**[[Antimalarials]]
***Aniline dyes
**[[Quinolones]]
***Phenazopyridine<ref>Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9.</ref>
**[[Dapsone]] (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
**Aniline dyes
**Phenazopyridine<ref>Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9.</ref>


==Clinical Features==
==Clinical Features==
*Depends on level of metHb
[[File:Eplasty16ic18 fig1.jpg|thumb|Cyanosis from methemoglobinemia.]]
**''Pts with anemia or preexisting cardiopulmonary disease will show symptoms sooner''
[[File:Eplasty16ic18 fig3.jpg|thumb|Cyanosis resolved after methylene blue.]]
**<20%: asymptomatic, gray-blue cyanosis
[[File:PMC4987464 CRIEM2016-9013816.001.png|thumb|Severe methemoglobinemia.]]
**20-30%: anxiety, HA, weakness, light-headedness, tachycardia
[[File:ChocolateBrownBlood (cropped)2.jpg|thumb|Chocolate-brown blood due to methemoglobinemia.]]
**50-60%: myocardial ischemia, dysrhythmias, depressed mental status, seizure
{| {{table}}
**>70%: usually fatal
| align="center" style="background:#f0f0f0;"|'''MetHb level (%)'''
*Ask about family or personal hx of G6PD deficiency as methylene blue contraindicated<ref>Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview</ref>
| align="center" style="background:#f0f0f0;"|'''Signs & Symptoms^'''
[[File:methemoglobinemia.JPG|thumbnail]]
|-
| <3||None
|-
| 3-15||Blue/slate-gray skin
|-
| 15-30||Cyanosis, chocolate-brown blood
|-
| 30-50||[[Breathlessness]], [[headache]], [[dizziness]], [[syncope]]
|-
| 50-70||Tachypnea, [[myocardial ischemia]], [[lactic acidosis]], [[arrythmia]], [[seizure]], [[CNS depression]], [[coma]]
|-
| >70||Death
|}
^''Patients with [[anemia]] or preexisting cardiopulmonary disease will show symptoms sooner''
 
*Ask about family or personal history of [[G6PD deficiency]] as [[methylene blue]] contraindicated<ref>Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview</ref>


==Differential Diagnosis==
==Differential Diagnosis==
*Consider rare entity of [[sulfhemoglobinemia]]
*Consider rare entity of [[sulfhemoglobinemia]]
**Sulfonamides, sulfasalazine, phenazopyridine
**[[Sulfonamides]], [[sulfasalazine]], [[phenazopyridine]]
**Occupational exposure
**Occupational exposure
**Conventional co-oximerty misidentifies sulfhemoglobin as methemoglobin so diagnosis is suspected when patient does not respond to methylene blue
**Typically requires no treatment other than removal of offending agent
**Blue-green discoloration of blood
**Blue-green discoloration of blood
{{SOB DDX}}
{{SOB DDX}}


==Diagnosis==
==Evaluation==
[[File:ChocolateBrownBlood (cropped).jpg|thumb|Chocolate-brown blood due to methemoglobinemia.]]
[[File:MethemoglobinDiag.jpg|thumb|Color chart for the detection of the amount of methemoglobin in the blood.]]
*Diagnosis requires high index of suspicion; lack of improvement in oxygen saturation with high-flow oxygen plus discrepancy in oxygen saturation >5% between measurements by ABG vs pulse oximetry ("saturation gap") should raise suspicion. Diagnosis is then confirmed by measuring level of methemoglobin in blood
*Co-oximetry
*Co-oximetry
**Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
**Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
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==Management==
==Management==
*Methylene Blue
 
*[[High-Flow Oxygen]]
** All patients warrant supplemental oxygen. Symptoms may improve with a non-rebreather but the pulse oximeter reading will remain unchanged and patients may remain cyanotic. This is a diagnostic clue.
*[[Methylene blue]]
**Treat if symptomatic '''OR''' asymptomatic with MetHb >25%
**Treat if symptomatic '''OR''' asymptomatic with MetHb >25%
**1-2mg/kg Methylene Blue IV over 5min; repeat dose if no effect
**1-2mg/kg [[Methylene blue]] IV over 5min; repeat dose if no effect
**Improvement seen within 20min
**Improvement seen within 20min
**'''Contraindicated in G6PD deficiency'''
**'''Contraindicated in [[G6PD]] deficiency'''
***May induce acute [[hemolytic anemia]]
***Instead use moderate dose of ascorbic acid (vitamin C),  300 to 1000 mg/day orally in divided doses
*Other treatment modalities<ref>Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview</ref>
*Other treatment modalities<ref>Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview</ref>
**Exchange transfusion for symptomatic methemoglobinemia in patient with G6PD deficiency
**[[Exchange transfusion]] for symptomatic methemoglobinemia in patient with G6PD deficiency
**Hyperbaric O2 when methylene blue ineffective or contraindicated
**Hyperbaric O2 when methylene blue ineffective or contraindicated
**IV hydration and bicarbonate for metabolic acidosis
**IV hydration and [[bicarbonate]] for metabolic acidosis
 
==Disposition==
*Will vary depending on response to the antidote and persistence of symptoms. Discuss with toxicologist/[[poison control]]


==See Also==
==See Also==
*[[Toxicology (Main)]]
*[[Toxidromes]]
*[[Toxidromes]]
*[[Dyshemoglobinemia]]
*[[Carbon monoxide]]
*[[Cyanide toxicity]]
==External Links==
*http://www.emdocs.net/tox-card-methemoglobinemia/


==References==
==References==

Latest revision as of 18:46, 15 March 2023

Background

Methemoglobinemia.JPG
  • Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
  • Suspect in any patient with cyanosis not responsive to supplemental O2
    • Consider in pediatric patient (<6 months) with diarrhe and low oxygen saturation

Causes

  • Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe3+ → Fe2+)
  • Exposure to oxidizing agent[1][2]
    • Benzocaine and other local anesthetics
    • Cyanokit, nitrites, nitrates, well water (nitrates)
    • Antimalarials
    • Quinolones
    • Dapsone (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
    • Aniline dyes
    • Phenazopyridine[3]

Clinical Features

Cyanosis from methemoglobinemia.
Cyanosis resolved after methylene blue.
Severe methemoglobinemia.
Chocolate-brown blood due to methemoglobinemia.
MetHb level (%) Signs & Symptoms^
<3 None
3-15 Blue/slate-gray skin
15-30 Cyanosis, chocolate-brown blood
30-50 Breathlessness, headache, dizziness, syncope
50-70 Tachypnea, myocardial ischemia, lactic acidosis, arrythmia, seizure, CNS depression, coma
>70 Death

^Patients with anemia or preexisting cardiopulmonary disease will show symptoms sooner

Differential Diagnosis

  • Consider rare entity of sulfhemoglobinemia
    • Sulfonamides, sulfasalazine, phenazopyridine
    • Occupational exposure
    • Conventional co-oximerty misidentifies sulfhemoglobin as methemoglobin so diagnosis is suspected when patient does not respond to methylene blue
    • Typically requires no treatment other than removal of offending agent
    • Blue-green discoloration of blood

Acute dyspnea

Emergent

Non-Emergent

Evaluation

Chocolate-brown blood due to methemoglobinemia.
Color chart for the detection of the amount of methemoglobin in the blood.
  • Diagnosis requires high index of suspicion; lack of improvement in oxygen saturation with high-flow oxygen plus discrepancy in oxygen saturation >5% between measurements by ABG vs pulse oximetry ("saturation gap") should raise suspicion. Diagnosis is then confirmed by measuring level of methemoglobin in blood
  • Co-oximetry
    • Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
    • Usually performed on arterial blood sample, but fingertip CO-oximeter devices are available
  • Normal PaO2
  • SpO2 will initially be falsely elevated
    • Once MetHb >30% → SpO2 will fall to 80-85%
    • Mid-80s SpO2 due to light absorption of both oxyHb and deoxyHb
  • "Chocolate brown" color of blood

Management

  • High-Flow Oxygen
    • All patients warrant supplemental oxygen. Symptoms may improve with a non-rebreather but the pulse oximeter reading will remain unchanged and patients may remain cyanotic. This is a diagnostic clue.
  • Methylene blue
    • Treat if symptomatic OR asymptomatic with MetHb >25%
    • 1-2mg/kg Methylene blue IV over 5min; repeat dose if no effect
    • Improvement seen within 20min
    • Contraindicated in G6PD deficiency
      • May induce acute hemolytic anemia
      • Instead use moderate dose of ascorbic acid (vitamin C), 300 to 1000 mg/day orally in divided doses
  • Other treatment modalities[5]
    • Exchange transfusion for symptomatic methemoglobinemia in patient with G6PD deficiency
    • Hyperbaric O2 when methylene blue ineffective or contraindicated
    • IV hydration and bicarbonate for metabolic acidosis

Disposition

  • Will vary depending on response to the antidote and persistence of symptoms. Discuss with toxicologist/poison control

See Also

External Links

References

  1. ↑ Fernandez-Frackelton M, Bocock J: Cyanosis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 29:p 211-216.
  2. ↑ Mody, A., Silverman, B.: Problems in the Early Neonatal Period, In Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, Lippincott, WIlliams and Wilkins 2010, Page 995.
  3. ↑ Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9.
  4. ↑ Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview
  5. ↑ Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview
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