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Dyshemoglobinemias result from the alteration of the hemoglobin molecule, which prevent it from carrying oxygen. Carboxyhemoglobin is created following exposure to carbon monoxide and is discussed in Chapter 127. Table 117-1 lists common pharmaceuticals capable of causing toxicity.

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Table Graphic Jump Location
Table 117-1 Drugs Commonly Implicated in Patients with Methemoglobinemia
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Methemoglobinemia presents with cyanosis. Children up to the age of 4 months lack the key enzyme for normally reducing methemoglobin. These children are susceptible to oxidant stress-induced methemoglobinemia. Three scenarios occur with some frequency: children with acute febrile illness, especially with diarrhea and dehydration; children with exposure to benzocaine in over-the-counter teething gels; and children with exposure to nitrates in agricultural areas with fertilizer runoff into the water aquifer.

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In drug-induced methemoglobinemia, patients present with slate-grey to blue discoloration of the skin when levels exceed 15%. Symptoms occur in proportion to declining oxygen delivery. Headache, nausea, and fatigue occur at low levels (20% to 30%). In those with coronary artery disease, dyspnea, angina, and dysrhythmias may result. Levels above 50% can cause loss of consciousness and metabolic acidosis, and above 70% may be lethal.

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The diagnosis of methemoglobin should be considered in patients presenting with cyanosis that does not improve with administration of oxygen. During venipuncture blood may appear chocolate brown, a visible effect that is easily identified when the blood is placed on filter paper with a normal patient's blood for comparison. Levels are measured by co-oximetry on an arterial blood gas analyzer, with either an arterial or venous sample. Standard pulse oximetry will almost always generate a reading of 85% that does not change despite administration of 100% oxygen. Newer generation pulse oximeters have been developed that can accurately measure abnormal hemoglobin (both methemoglobin and carboxyhemoglobin) noninvasively.

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Methemoglobinemia should be treated initially with close monitoring and high concentrations of inspired oxygen (Table 117-2). Methemoglobinemia at levels above 25%, and symptomatic patients with lower levels should be treated with methylene blue. The initial dose of methylene blue is 1 to 2 milligrams/kilogram as a 10% solution IV, given over 15 min, which may be repeated. Failure to respond to a second dose is usually due to 1 of 5 causes (in order or likelihood of occurrence):

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  1. Glucose-6-phosphate dehydrogenase deficiency (G6PD): ...

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