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Updated: Mar 14 2021


  • Snapshot
    • A 20-year-old woman with a history of celiac disease presents to the dermatologist with pruritic papules on her bilateral extensor elbows. She is started on dapsone for dermatitis herpetiformis, an itchy rash commonly seen in patients with celiac disease. A few weeks later, she reports feeling very tired, with frequent episodes of lightheadedness. At an urgent care clinic, she is noted to have pulse oximetry readings of 90% with no improvement on supplemental oxygen. A methemoglobin level is found to be > 3%. She is sent to the emergency room for treatment.
  • Introduction
    • Overview
      • 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, and bupivacaine
          • 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
    • Arterial blood gas
      • normal pO2
        • this indicates dissolved oxygen in the blood
    • Pulse oximetry
      • oxygen saturation 85-90%
    • Methemoglobin level
      • > 3% (normal values < 1%)
      • measured with CO-oximetry device
  • 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
  • Treatment
    • Medical
      • 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
      • 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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