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).
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).
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).
