Good Morning and Welcome Applicants February 3, 2010

Methemoglobinemia Normal Fe+2 to Fe3+ Rare cause of cyanosis Oxidation Fe3+ is unable to bind oxygen Remaining Fe has higher O2 affinity Impaired O2 delivery to tissues Rare cause of cyanosis

Methemoglobinemia Hereditary NADH cytochrome b5 reductase deficiency Hemoglobin M disease AD Structural alteration of alpha or beta globin chains NADH – physiologic pathway to reduce methemoglobin back to hemoglobin, patients that are heterozygous can develop symptoms as well M disease – forms metHb that resists reduction, will not be cured by methylene blue

Methemoglobinemia Acquired Exogenous agents that increase methemoglobin formation Topical anesthetic agents Benzocaine Acute diarrhea and metabolic acidosis Babies 2-6 months Abnormal absorption of nitrites

Methemoglobinemia Presentation Cyanosis (8-12%) 30-50% Dyspnea Dizziness Tachycardia Fatigue HA Cyanosis – different absorbance spectrum of methemoglobin compared with oxyhemoglobin

Methemoglobinemia Presentation Congenital 50-70% >70% Asymptomatic Severe lethargy Stupor >70% Death Congenital Asymptomatic

Methemoglobinemia Suspicion Clinical cyanosis Normal arterial pO2 “chocolate brown blood” Pulse oximetry unreliable Calculated saturation on the gas may be significantly different from the pulse oximetry

Methemoglobinemia Diagnosis Co-oximetry Genetic testing Respiratory therapy False positives with methylene blue with some methods Genetic testing

Methemoglobinemia Treatment - Acquired Recognition and discontinuation of offending agents Symptomatic or >20% Methylene blue 1-2mg/kg May repeat 1 hr later (max dose 7mg/kg) Reducing agents Ascorbid acid Glutathione Riboflavin Treatment for acquired

The major pathway for methemoglobin reduction is via cytochrome b5 reductase (thick arrows). An alternative pathway, which requires an exogenous electron acceptor such as methylene blue, is via NADPH methemoglobin reductase. Only a small amount of methemoglobin is reduced via nonenzymatic pathways (dashed arrow).

Methemoglobinemia Treatment G6PD deficiency Other May not respond to treatment Other Hyperbaric oxygen Exchange Transfusion G6PD – G6PD def patients cannot produce NADPH which is needed to reduce methemoglobin, needs methylene blue or riboflavin as cofactors to react. Also MB may induce hemolysis in these patients.

Methemoglobinemia Lessons Always consider in differential diagnosis of cyanosis Caution with use of topical anesthetics History Cyanosis Blue nail beds Blue lips Family History