Question: How do the presence of methemoglobin and carboxyhemoglobin affect InSpectra™ StO₂ Measurements?

Summary

Carboxyhemoglobin and methemoglobin are variants of normal hemoglobin that are not capable of effectively carrying oxygen. They also will both cause erroneous elevations in apparent StO₂ levels as measured by the InSpectra™ StO₂ Tissue Oxygenation Monitor, with the effect due to methemoglobin being larger than that of carboxyhemoglobin. This is important as we have (rarely) seen cases during evaluations in which the SpO₂ is lower than StO₂. This is, of course, not possible physically, and should be an alert that there is an artifact in the StO₂ and/or SpO₂ measurement.¹

Background

Carboxyhemoglobin

What is it? Carboxyhemoglobin (COHgb) is hemoglobin that has carbon monoxide bound to it instead of oxygen. Hemoglobin has an affinity for carbon monoxide that is 200-times stronger than for oxygen, so that it can very effectively displace oxygen from the hemoglobin molecule and thus interfere with oxygen delivery.

What is the normal range? Normal carboxyhemoglobin levels in the blood are from 1% to 3% of total hemoglobin. Overt toxic signs of carbon monoxide poisoning usually appear when carboxyhemoglobin levels reach 15% to 20%. Levels over 40% are associated with hallucination and a shock state.

How does it affect StO₂ measurements? The presence of carboxyhemoglobin contributes a slight artifactual increase in reported StO₂ levels. The effect is not large, as a carboxyhemoglobin level of 15% increases reported StO₂ only 2 to 3 percentage units at true StO₂ levels between 35% and 85%, regardless of THI level. Carboxyhemoglobin levels of 45% (which is quite high) contribute only a 3% to 7% false elevation in reported StO₂ at true StO₂ levels of 85% and 35%, respectively and THI levels of 14.² This is shown in more detail in the table below.

What causes carboxyhemoglobinemia? Higher levels can arise from carbon monoxide poisoning from automobile exhaust or faulty furnace combustion gas exhaust, for example. Burn patients may also have elevated carboxyhemoglobin levels as a result of smoke inhalation. In addition, cigarette smoking is reported to increase carboxyhemoglobin levels by an average of 5% per pack of cigarettes smoked per day.

StO₂ Error Due To COHgb²

Methemoglobin

What is it? Methemoglobin (metHgb) is an altered form of hemoglobin in which the iron atom in the molecule (a critical part of the oxygen-binding site) has been converted to a higher oxidation state. This renders it incapable of binding oxygen. High blood levels of metHgb (called methemoglobinemia) in a patient can impair delivery of oxygen within the body.

What is the normal range? In normal, healthy individuals metHgb levels are usually less than 1% of the total hemoglobin. If the metHgb level exceeds 1% or 2% of total hemoglobin (the threshold varies somewhat between different institutions), the patient is said to have methemoglobinemia.

How does it affect StO₂ measurements? High levels of metHgb will falsely elevate StO₂ values. The size of the error in reported StO₂ depends on the concentration of metHgb and on the true StO₂ level in the blood, with the error being greatest at low StO₂ levels. For example, at an StO₂ of 35%, the presence of 5% metHgb causes the StO₂ to be reported high by about 9 percentage points (i.e., the InSpectra™ StO₂ System will report 44% rather than 35%). Higher metHgb levels will cause correspondingly higher errors: a metHgb level of 15% will increase the reported StO₂ by 23 points to around 58%.² High StO₂ measurements are not affected quite as strongly. See the table on the next page for more details.

The methemoglobin-induced error in StO₂ is not affected significantly by the THI level.

What causes methemoglobinemia? Methemoglobinemia has both congenital and external (environmental) origins.

Congenital causes include defects in certain enzymes that would otherwise convert methemoglobin back into normal hemoglobin. In addition, an abnormal hemoglobin called hemoglobin M is associated with elevated metHgb levels. These congenital causes of methemoglobinemia, which can cause metHgb levels of up to 35%, are rare, but if present also cause increased susceptibility to the effects of external causes of methemoglobinemia. In addition, certain ethnic groups, including Navajo and Alaska Athabascan Native Americans, have higher frequencies of these genetic defects.

Methemoglobinemia is more commonly caused by exposure to environmental or pharmaceutical chemicals, with the primary culprits being oxidizing agents. This includes nitrates and nitrites, resorcinol, nitric oxide, nitroglycerin, dapsone, and the anesthetic “-caines” such as Benzocaine, Prilocaine, etc. Dapsone is an antibiotic used in treatment of Hansen’s disease (leprosy) and is also given prophylactically to immunosuppressed patients (e.g. transplant recipients or patients receiving chemotherapy) to prevent pneumocystis carinii pneumonia. Nitric oxide (INOmax) is an inhaled gas that is used to dilate blood vessels in lungs of patients with severe respiratory distress. It is delivered by a ventilator and treatment lasts for 2 to 3 days. It will also convert normal hemoglobin into metHgb, but if given at recommended doses (less than 20 ppm in inhaled gases) should not cause metHgb levels to exceed 1% of total hemoglobin. MetHgb blood levels are normally monitored whenever the patient is on nitric oxide.

StO₂ Error Due To MetHgb²

1 Many of the commonly used pulse oximeters will report an SpO₂ of 85% on pure methemoglobin, so that increased methemoglobin levels will also tend to lower the SpO₂ reading towards 85% from their customary values near 98-100%, contributing to this “impossible” situation.

2 McGraw and Myers, internal HTI study. These results supersede those from the Myers et al. 2005 publication in J Biomed Optics. This earlier work which showed a larger error due to dyshemoglobins, was conducted prior to the introduction of the model 650.