Tintinalli's Emergency Medicine - Just the Facts, 3ed.

119. DYSHEMOGLOBINEMIAS

Kristine L. Bott

images Dyshemoglobinemias are a group of disorders caused by functionally altered hemoglobin that is unable to bind to oxygen. The most clinically significant dyshemoglobinemias are methemoglobin, sulfhemoglobin, and carboxyhemoglobin.

METHEMOGLOBINEMIA

PATHOPHYSIOLOGY

images Methemoglobinemia can develop in the presence of oxidant stress caused by drugs or chemicals. There is also a hereditary form.

images Methemoglobinemia causes a shift of the oxyhemoglobin dissociation curve, causing more avid oxygen binding that leads to tissue hypoxia.

images Medications that can precipitate methemoglobinemia include phenazopyridine (Pyridium), benzocaine (a topical anesthetic) along with other local anesthetics, and dapsone (an antibiotic often used in HIV-related therapy). There may be a significant time delay from exposure to symptoms with some agents.

images Nitrates (in well water and vegetables) and nitrite salts can cause epidemic methemoglobinemia.

images All age groups are affected, but neonates and infants are more susceptible due to an underdeveloped methemoglobin reduction mechanism. Gastroenteritis can precipitate methemoglobinemia in infants.

CLINICAL FEATURES

images Clinical suspicion for methemoglobinemia should be raised when pulse oximetry approaches 80% to 85% without a response to supplemental oxygen. Patients may display gray discoloration of the skin.

images “Chocolate brown” discoloration of the blood is seen with methemoglobin levels above 20%.

images Patients with normal hemoglobin concentrations do not develop clinically significant effects until methemoglobin levels exceed 20%.

images Patients may seek evaluation for cyanosis that occurs when the methemoglobin level approaches 1.5 grams/dL; this is approximately 10% of the total hemoglobin in normal individuals.

images Patients with anemia require a higher percentage of methemoglobin to develop symptoms as the absolute concentration (1.5 grams/dL) determines cyanosis.

images Symptoms of anxiety, headache, weakness, and light-headedness develop when levels reach 20% to 30%. Tachypnea and sinus tachycardia may occur.

images Methemoglobin concentrations of 50% to 60% impair oxygen delivery to tissues, causing myocardial ischemia, dysrhythmias, depressed mental status (including coma), seizures, and lactic acidosis.

images Levels above 70% are typically fatal.

images Patients with anemia and those with preexisting diseases that impair oxygen delivery (eg, emphysema, congestive heart failure) may be symptomatic at lower concentrations of methemoglobin.

DIAGNOSIS AND DIFFERENTIAL

images Methemoglobinemia must be considered in any patient who presents with cyanosis, especially when unresponsive to supplemental oxygen.

images Pulse oximetry must be interpreted with caution, as it cannot properly differentiate oxyhemoglobin from methemoglobin and may therefore appear falsely elevated. Pulse oximetry trends toward 80% to 85% in those with methemoglobin levels above 30%.

images The oxygen saturation obtained from an arterial blood gas analysis is falsely reassuring, as it is calculated from dissolved oxygen tension rather than bound oxygen, and is typically normal.

images Definitive diagnosis of methemoglobinemia is made using co-oximetry, which is widely available and requires only venous blood (although arterial blood can be used). It can differentiate oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin.

EMERGENCY DEPARTMENT CARE AND DISPOSITION

images Treatment of patients with methemoglobinemia begins with supportive measures to ensure oxygen delivery.

images The effectiveness of gastric decontamination is limited since there is often a substantial delay between exposure and development of methemoglobin. If an ongoing source of exposure exists, a single dose of oral activated charcoal 1 gram/kg PO is indicated. Decontamination of the skin may also be necessary.

images Methylene blue therapy is reserved for patients with documented methemoglobinemia or a high clinical suspicion of disease. Unstable patients should receive methylene blue, but may require blood transfusion or exchange transfusion for immediate improvement of oxygen delivery.

images The initial dose of methylene blue is 1 to 2 milligrams/kg IV. It should be administered slowly over 15 minutes, as rapidly administered high doses (>7 milligrams/kg) may actually induce methemoglobin formation. Improvement should be seen within 20 minutes. Repeat dosing may be necessary.

images Treatment failures occur in some patients, including those with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other enzyme deficiencies, and may occur in the presence of hemolysis.

images Agents with long half-lives, such as dapsone, may require repetitive dosing of methylene blue.

images In patients with methemoglobinemia due to dapsone, inhibition of formation of the hydroxylamine metabolite with cimetidine will reduce toxicity

images Patients with methemoglobinemia unresponsive to methylene blue are treated supportively. In unstable patients, perform simple or exchange transfusions. If newly transfused red blood cell hemoglobin undergoes oxidation, it will likely respond to methylene blue therapy.

SULFHEMOGLOBINEMIA

images Sulfhemoglobinemia is caused by many of the same agents that cause methemoglobinemia, as well as metoclopromide and sumatriptan.

images Sulfhemoglobinemia is clinically less concerning than methemoglobinemia, as the oxygen dissociation curve is shifted rightward. This favors the release of oxygen in tissues and lessens the degree of tissue hypoxia.

images The pigmentation of blood by sulfhemoglobin is substantially more intense than in methemoglobinemia. The color of the blood on venipuncture has been described as dark greenish-black.

images Cyanosis may occur at levels of 0.5 gram/dL due to increased pigmentation.

images Standard pulse oximetry tends to report a falsely low value for arterial oxygen saturation.

images Standard co-oximetry may not differentiate sulfhemoglobin from methemoglobin because of similar spectral absorbance. Specialized testing is needed to confirm the diagnosis reliably.

images Sulfhemoglobinemia persists for the life of the red blood cell and patients do not respond to methylene blue. Supportive treatment is indicated, and blood transfusions may be required in cases of severe toxicity.


For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Guide, 7th ed., see Chapter 201, “Dyshemoglobinemias” by Brenna M. Farmer and Lewis S. Nelson.