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 ETIOLOGY 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 DIAGNOSIS 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