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Updated: Dec 24 2021


  • Snapshot
    • An infant is brought to the emergency room for increasing cyanosis around the lips. His mother’s pregnancy was uncomplicated and he was born at 39 weeks without complications. His parents started feeding him water from their backyard well, which they have been using for years. A pulse oximetry reading shows oxygen saturation of 86%, despite supplemental oxygen administration. He is also found to be tachycardic. A CO-oximetry shows methemoglobinemia level of 15%. The patient is started on methylene blue. (Well water contaminated with nitrates)
  • Introduction
    • Clinical definition
      • methemoglobinemia causes tissue hypoxia due to accumulation of methemoglobin in the blood
        • methemoglobin
          • hemoglobin (Hb) that contains ferric form of iron (Fe3+)
  • Epidemiology
    • Demographics
      • infants are at increased risk
    • Risk factors
      • drugs
        • nitrates
        • anesthetics
        • dapsone
        • lidocaine, benzocaine, bupivacaine, etc.
        • nitroglycerin
      • infants are more susceptible to hemoglobin oxidation
      • food
      • well water
    • Pathogenesis
      • methemoglobin is the oxidized form of Hb, which has an affinity for cyanide
        • oxygen does not bind as easily to the heme subunit with the ferric form of iron
        • remaining heme sites has increased affinity for oxygen
          • results in decreased ability to release oxygen to tissues
        • causes left-shift of the oxygen-hemoglobin dissociation curve
          • tissue hypoxia
          • functional anemia
  • Presentation
    • Symptoms
      • may be asymptomatic if levels are low
      • headache
      • lightheadedness
      • fatigue
      • shortness of breath
      • seizures or coma
        • at very high levels of methemoglobinemia
    • Physical exam
      • pulse oximetry shows decreased oxygen saturation level (< 90%)
        • supplemental oxygen will not improve pulse oximetry reading
      • tachycardia
      • cyanosis
      • altered mental status
      • “chocolate brown” or blue blood
  • Studies
    • Diagnostic testing
      • studies
        • arterial blood gas
          • normal pO2
            • this indicates dissolved oxygen in the blood
        • pulse oximetry
          • oxygen saturation 85-90%
        • methemoglobin level > %
          • measured via CO-oximetry device
          • normally < 1%
  • Differential
    • Cyanide poisoning
      • distinguishing factor
        • arterial blood gas shows metabolic acidosis from the accumulation of lactic acid
        • CO-oximetry is normal
        • does not respond to methylene blue
    • Making the diagnosis
      • based on clinical presentation and laboratory studies
        • methemoglobin levels > 3%
  • Treatment
    • Management approach
      • supplemental oxygen alone will not alleviate the hypoxia
      • administration of 100% oxygen and methylene blue is the first-line treatment
    • First-line
      • 100% oxygen + methylene blue
        • mechanism
          • reduces hemoglobin to non-oxidized form
        • contraindications
          • pregnancy
            • methylene blue is a teratogen
          • G6PD deficiency
            • may cause hemolytic anemia
          • patients taking an SSRI
            • may precipitate serotonin syndrome as methylene blue has some monoamine oxidase inhibitor activity, which increases levels of neurotransmitters such as serotonin
    • Other treatments
      • vitamin C
        • indication
          • in patients with contraindications to methylene blue
          • failure of methylene blue treatment
  • Complications
    • End-organ failure
    • Acute respiratory distress syndrome
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