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Dyshemoglobinemias result from the alteration of the hemoglobin molecule, which prevents it from carrying oxygen. Carboxyhemoglobin is created following exposure to carbon monoxide, which is usually considered an environmental emergency and is discussed in Chapter 127. Table 117-1 lists common pharmaceuticals capable of causing the formation of methemoglobin.

Table 117-1

Drugs Commonly Implicated in Patients with Methemoglobinemia


Methemoglobinemia presents with grayish-brown discoloration of the skin that is recognized as cyanosis. Children up to the age of 4 months lack the enzyme activity that normally reduces methemoglobin, thus making them susceptible to oxidant stress-induced methemoglobinemia. Three scenarios occur with some frequency: children with acute gastroenteritis and increased nitrate production from bacteria in the GI tract; children exposed to nitrates in water of agricultural areas where fertilizer runoff contaminates water sources; and overconsumption of nitrogenous vegetables such as spinach.

In drug-induced methemoglobinemia, the slate-gray to blue discoloration of the skin is apparent with levels of 10% to 15%. Symptoms occur in proportion to declining oxygen delivery. Headache, nausea, and fatigue occur at lower levels (20% to 30%). Levels above 50% can cause loss of consciousness, myocardial ischemia, dysrhythmias, seizures, and metabolic acidosis. Levels above 70% may be lethal. In patients with cardiopulmonary disease in which there is impaired oxygen delivery, the symptoms will be manifested at lower methemoglobin levels.


The diagnosis of methemoglobinemia 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 give an erroneously high oxygen saturation level at approximately 85% and does not change despite administration of 100% oxygen. Pulse co-oximeters are available that can noninvasively measure both methemoglobin and carboxyhemoglobin.


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 ...

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