Nitrate/Nitrite Toxicity
What Laboratory Tests Can Help Diagnose Nitrate/Nitrite Toxicity?
Course: WB 1107
CE Original Date: September 24, 2007
CE Renewal Date: September 24, 2010
CE Expiration Date: September 24, 2012
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Learning Objectives |
Upon completion of this section, you will be able to
- identify the laboratory test results that indicate methemoglobinemia.
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Introduction |
Methemoglobinemia results in distinct changes in blood color and oxygen‑carrying capacity.
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Bedside Testing Instructions |
Place 1 or 2 drops of the patient's blood on white filter paper. The chocolate-brown appearance of methemoglobin does not change with time. In contrast, deoxyhemoglobin appears dark red/violet initially and then brightens after exposure to atmospheric oxygen. Gently blowing supplemental oxygen onto the filter paper hastens the reaction with deoxyhemoglobin, but does not affect methemoglobin (40, 67). A tube of methemoglobin-containing blood will not turn red when shaken in air or when oxygen is bubbled through it, whereas blood that is dark because of normal deoxyhemoglobin will turn red (68).
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Pulse Oximetry and Arterial Blood Gases |
Pulse-oximetry measurement of the oxygen saturation of hemoglobin does not provide accurate results in the presence of methemoglobinemia (69). Pulse oximetry underestimates oxygen saturation at low levels of methemoglobinemia and overestimates oxygen saturation when methemoglobinemia is severe. Arterial blood gas analysis will typically reveal a normal arterial oxygen tension (PO2) and may reveal a metabolic acidosis proportional to the severity and duration of tissue hypoxia. The profound and disproportionate metabolic acidosis seen in young infants with diarrheal illness and methemoglobinemia suggests that the acidosis is a cause or coexisting finding rather than a result of methemoglobinemia (48, 70).
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Co-Oximetry and MHg Levels |
Methemoglobin percentages can only be used to estimate oxygen-carrying capacity when interpreted with the total hemoglobin (49). Many hospital laboratories do not measure oxygen saturation directly on blood gas analysis. Instead, they derive it from a nomogram that is based on the measured PO2 and the presence of normal hemoglobin. In this case, the calculated oxygen saturation would be falsely elevated in the presence of methemoglobinemia. A “saturation gap” exists when the measured oxygen saturation of blood differs from the oxygen saturation calculated by routine blood gas analysis. A saturation gap of more than 5% suggests the presence of methemoglobin, carboxyhemoglobin, or sulfhemoglobin (20, 71).
Co-oximetry is an accurate method of measuring methemoglobin. A co-oximeter is a simplified spectrophotometer, but unlike a pulse oximeter, it measures light absorbance at four different wavelengths. These wavelengths correspond to specific absorbance characteristics of deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and hemoglobin. Interpreting the results from a blood gas analyzer without co-oximetry may lead to misdiagnosis because the oxygen saturation will have been calculated but not measured (72, 73).
Table 3. Suggested Lab Tests for Methemoglobinemia |
Screening Tests |
- Examination of blood color
- Determination of methemoglobin level
- Determination of the calculated versus measured arterial saturation gap using co-oximetry
- Hemoglobin and hematocrit
- Serum‑free hemoglobin (for hemolysis detection)
- Serum haptoglobin (for hemolysis detection)
- Heinz bodies on peripheral blood smear
- Urinalysis
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Specialized Tests |
- Tests for causes of congenital methemoglobinemia
- Hemoglobin electrophoresis
- Activity of NADH‑dependent methemoglobin reductase
- Activity of glucose‑6‑phosphate dehydrogenase (G6PD)
- Activity of NADPH‑dependent methemoglobin reductase
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Direct Biologic Indicators |
- Measurements of nitrates or nitrites in blood, urine, or saliva are not clinically useful.
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Indirect Biologic Indicators |
- The most useful diagnostic test for nitrate toxicity is a blood methemoglobin level.
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Key Points |
- Methemoglobinemia results in distinct changes in blood color and oxygen-carrying capacity.
- Pulse-oximetry measurement of the oxygen saturation of hemoglobin does not provide accurate results in the setting of methemoglobinemia (69).
- Co-oximetry is an accurate method of measuring methemoglobin.
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Progress Check |
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