II. Pathophysiology

  1. Hereditary Methemoglobinemia
  2. Acquired Methemoglobinemia
    1. Exposure to drugs with amino or nitro group
    2. Chemical exposure results in changed Hemoglobin iron
      1. Oxidizes ferrous Hemoglobin (Fe2+)
      2. Results in ferric Hemoglobin (Fe3+)
  3. Oxyhemoglobin becomes non-Oxygen carrying Methemoglobin
    1. Left Shifts Oxyhemoglobin Dissociation Curve
    2. Impairs oxygen unloading to tissues

III. Causes: Hereditary Methemoglobinemia

  1. Cytochrome b5 Reductase Deficiency
    1. Autosomal Recessive inheritance
    2. Two types
      1. Type I: Lifelong asymptomatic Cyanosis
      2. Type II: Cyanosis with Mental Retardation
    3. Associated conditions in some cases
      1. Mild Polycythemia
  2. M Hemoglobins (5 Hemoglobin variants)
    1. General
      1. Autosomal Dominant inheritance
      2. M Hemoglobins are asymptomatic except for Cyanosis
    2. Alpha chain variants (Cyanosis at birth)
      1. Hemoglobin M Boston
      2. Hemoglobin M Iwate
    3. Beta chain variants (Cyanosis at 4-6 months)
      1. Hemoglobin M Saskatoon
      2. Hemoglobin M Hyde Park
      3. Hemoglobin M Milwaukee

IV. Causes: Acquired Methemoglobinemia Causes (Oxidizing Agents)

  1. Nitrates and Nitrites
    1. Nitrate commonly contaminate well water
    2. Responsible for Blue Baby Syndrome (formula reconstituted in well water)
      1. Distinguish from Congenital Heart Disease
      2. Knobeloch (2000) Environ Health Perspect 108(7):675-8 [PubMed]
  2. Nitroglycerin
  3. Nitroprusside
  4. Aniline
  5. Paints
  6. Varnishes
  7. Inks
  8. Phenacetin
  9. Sulfonamides
  10. Pyridium
  11. Dapsone
  12. Primaquine
  13. Lidocaine
  14. Procaine
  15. Benzocaine
  16. Nitrophenol
  17. Toluidine
  18. Nitrobenzene
  19. Isobutyl nitrate
  20. Sodium Nitrite Ingestion
    1. Large Sodium Nitrite ingestions have been used for Suicide
    2. Also results in Tachypnea, acidosis and seziures

V. Findings: Signs and symptoms

  1. Methemoglobin >15%
    1. Cyanosis
    2. Asymptomatic
  2. Methemoglobin >30%
    1. Fatigue
    2. Headache
    3. Dizziness
    4. Tachycardia
    5. Weakness
  3. Methemoglobin >55%
    1. Dyspnea
    2. Bradycardia
    3. Hypoxia
    4. Acidosis
    5. Seizures
    6. Coma
    7. Arrhythmia
  4. Methemoglobin >70%
    1. Death

VI. Differential Diagnosis

VII. Complications

  1. Hyperkalemia
  2. Renal Failure
    1. Occurs 1-3 days after exposure

VIII. Labs

  1. Arterial Blood Gas (ABG)
    1. Normal arterial pO2
  2. Oxygen Saturation plateaus at 85%
    1. Overestimates the true blood oxygen level
    2. Oxygen Saturation remains 8% regardless of methemoglobin level
  3. Venipuncture
    1. "Chocolate brown" appearance to blood
    2. No change with exposure to oxygen
    3. Color fades with exposure to PotassiumCyanide 10%

IX. Management: Severe acquired Methemoglobinemia

  1. ABC Management
  2. Oxygen 100%
  3. See Toxin Ingestion Management
  4. Methylene Blue
    1. Dose: 1-2 mg/kg (1% solution) over 5 min
    2. Reduces Methemoglobin by 50% within 1 hour (by reduction back to Hemoglobin)
    3. Indications
      1. Methemoglobin > 20-30 g/L (20-30%)
      2. Methemoglobinemia with Hypoxia or other signficant symptoms (lethargy, confusion, Dyspnea)
    4. Contraindications
      1. G6PD Deficiency
      2. M Hemoglobin (not effective)
  5. Transfuse Packed Red Blood Cells
    1. Goal Hemoglobin: 15 g/dl
  6. Exchange Transfusion

X. References

  1. Wilson (1991) Harrison's Medicine, p. 1549

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Related Studies

Ontology: Methemoglobinemia (C0025637)

Definition (MSHCZE) Autointoxikační methemoglobinemie různé etiologie (část případů má familiární výskyt) projevující se temnou cyanózou, častými průjmy. V krvi je zvýšený obsah methemoglobinu a sulfhemoglobinu. Při dlouhodobějším trvání stavu se vyvíjejí paličkovité prsty. Též Stokvisův-Talmův syndrom. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI) An inherited or acquired condition characterized by abnormally increased levels of methemoglobin in the blood.
Definition (NCI_NCI-GLOSS) A condition in which a higher-than-normal amount of methemoglobin is found in the blood. Methemoglobin is a form of hemoglobin that cannot carry oxygen. In methemoglobinemia, tissues cannot get enough oxygen. Symptoms may include headache, dizziness, fatigue, shortness of breath, nausea, vomiting, rapid heartbeat, loss of muscle coordination, and blue-colored skin. Methemoglobinemia can be caused by injury or being exposed to certain drugs, chemicals, or foods. It can also be an inherited condition.
Definition (MSH) The presence of methemoglobin in the blood, resulting in cyanosis. A small amount of methemoglobin is present in the blood normally, but injury or toxic agents convert a larger proportion of hemoglobin into methemoglobin, which does not function reversibly as an oxygen carrier. Methemoglobinemia may be due to a defect in the enzyme NADH methemoglobin reductase (an autosomal recessive trait) or to an abnormality in hemoglobin M (an autosomal dominant trait). (Dorland, 27th ed)
Concepts Disease or Syndrome (T047)
MSH D008708
ICD9 289.7
ICD10 D74 , D74.9
SnomedCT 124965005, 191386007, 267549008, 191393006, 131171006, 38959009
English Methemoglobinemias, METHAEMOGLOBINAEMIA, METHEMOGLOBINEMIA, Methaemoglobinaemia, unspecified, Methemoglobinemia, unspecified, Methemoglobinemia NOS, Methemoglobinemia, Increased methemoglobin -RETIRED-, methemoglobinemia (diagnosis), methemoglobinemia, Methemoglobinemia [Disease/Finding], methaemoglobinaemia, Increased methemoglobin (biological function) (finding), Methaemoglobinaemia (disorder), Methemoglobinemia NOS (disorder), Methemoglobin concentration increased above normal, Methaemoglobinaemia, Increased methaemoglobin, Increased methemoglobin (finding), Increased methemoglobin, Methemoglobinemia (disorder), Methemoglobinemia, NOS, Increased methemoglobin (biological function), Methaemoglobinaemia [Ambiguous], Methaemoglobinaemia NOS
French METHEMOGLOBINEMIE, Méthémoglobinémie SAI, Méthémoglobinémie
Spanish METAHEMOGLOBINEMIA, Metahemoglobinemia NEOM, metahemoglobina aumentada (hallazgo), aumento del nivel de metahemoglobina (hallazgo), aumento del nivel de metahemoglobina, metahemoglobina aumentada, aumento del nivel de metahemoglobina (función biológica), aumento del nivel de metahemoglobina - RETIRADO -, metahemoglobinemia, SAI (trastorno), metahemoglobinemia, SAI, aumento del nivel de metahemoglobina - RETIRADO - (concepto no activo), metahemoglobinemia (trastorno), metahemoglobinemia, Metahemoglobinemia
German METHAEMOGLOBINAEMIE, Methaemoglobinaemia, Methaemoglobinaemie NNB, Methaemoglobinaemie, nicht naeher bezeichnet, Methämoglobinämie, Methaemoglobinaemie
Dutch methemoglobinemie, methemoglobinemie NAO, Methemoglobinemie, niet gespecificeerd, Methemoglobinemie
Italian Metaemoglobina nel sangue, Metaemoglobinemia NAS, Metemoglobinemia
Portuguese Metemoglobinema, Metemoglobinema NE, METAHEMOGLOBINEMIA, Metemoglobinemia
Japanese メトヘモグロビン血症NOS, メトヘモグロビン血症, メトヘモグロビンケツショウNOS, メトヘモグロビンケッショウNOS, メトヘモグロビンケッショウ
Swedish Methemoglobinemi
Czech methemoglobinémie, Methemoglobinemie, Methemoglobinemie NOS, Stokvisův-Talmův syndrom, cyanosis autotoxica, autointoxikační porucha, cyanosis enterogenes, methaemoglobinaemia idiopathica
Finnish Methemoglobinemia
Korean 메트헤모글로빈혈증, 상세불명의 메트헤모글로빈혈증
Polish Methemoglobinemia
Hungarian methaemoglobinaemia, methaemoglobinaemia k.m.n., Methaemoglobinemia
Norwegian Hemoglobinsykdom, Methemoglobinemi, Hb-sykdom

Ontology: Blue baby syndrome (C2721587)

Concepts Disease or Syndrome (T047)
English Blue baby syndrome
Spanish Síndrome del bebé azul
Portuguese Síndrome do bebé azul
French Syndrome du bébé bleu
Italian Sindrome del bambino blu
German Blaues Baby Syndrom
Dutch blauwe-babysyndroom
Czech Blue baby syndrom
Japanese セイショクジショウコウグン, 青色児症候群
Hungarian Kék csecsemő tünetegyüttes