CO-Oximetry: Principles, Uses, and Clinical Applications

CO-oximetry, also called hemoximetry, is a laboratory method used to evaluate the different forms of hemoglobin present in blood. It provides information that cannot be obtained reliably from arterial oxygen tension or conventional pulse oximetry alone.

By directly measuring oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, methemoglobin, and other hemoglobin species, CO-oximetry helps determine whether hemoglobin is actually capable of transporting oxygen effectively.

It is especially important when carbon monoxide poisoning, methemoglobinemia, smoke inhalation, or unexplained tissue hypoxia is suspected.

 

What Is CO-Oximetry?

CO-oximetry is a blood-analysis technique designed to identify and quantify different forms of hemoglobin. It may also be referred to as hemoximetry, and the instrument used for testing may be called a CO-oximeter, hemoximeter, or spectrophotometric oximeter.

The primary advantage of CO-oximetry is that it does more than estimate oxygen saturation. It directly evaluates the composition of hemoglobin within the blood. This allows clinicians to distinguish functional hemoglobin from abnormal forms that are unable to participate normally in oxygen transport.

The major hemoglobin species commonly measured include:

• Oxyhemoglobin
• Reduced or deoxygenated hemoglobin
• Carboxyhemoglobin
• Methemoglobin

Some instruments may also account for sulfhemoglobin and fetal hemoglobin.

CO-oximetry is particularly useful when routine oxygenation measurements do not match the patient’s clinical appearance. For example, a patient may have a normal PaO₂ and an apparently acceptable pulse oximetry reading while still experiencing impaired oxygen delivery because a significant portion of the hemoglobin is dysfunctional.

Why Hemoglobin Matters in Oxygen Transport

Most oxygen in arterial blood is transported by hemoglobin. Only a small amount remains physically dissolved in plasma.

This distinction is important because arterial blood gas analysis measures the partial pressure of oxygen dissolved in plasma, reported as PaO₂. PaO₂ provides valuable information about pulmonary oxygen transfer, but it does not directly reveal how much hemoglobin is carrying oxygen or whether that hemoglobin is functioning normally.

A patient can therefore have a normal PaO₂ while still having severely impaired oxygen transport.

Carbon monoxide poisoning provides a classic example. Oxygen may enter the bloodstream normally and produce an adequate PaO₂, yet carbon monoxide may occupy a substantial percentage of hemoglobin-binding sites. The oxygen-carrying capacity of the blood is reduced even though the dissolved oxygen tension remains normal.

Note: Similar problems can occur with methemoglobinemia and severe anemia.

Arterial Oxygen Content

A more complete understanding of oxygen transport can be obtained by considering arterial oxygen content.

Arterial oxygen content, or CaO₂, is estimated using the following equation:

CaO₂ = (Hb × 1.34 × SaO₂) + (PaO₂ × 0.003)

The first part of the equation represents oxygen carried by hemoglobin. The second represents oxygen dissolved in plasma.

The hemoglobin-bound portion contributes the overwhelming majority of arterial oxygen content under normal circumstances. This explains why hemoglobin concentration and function are so important.

A patient with severe anemia may have a normal PaO₂ and a normal oxygen saturation but reduced oxygen content because there is not enough hemoglobin available to carry oxygen.

Likewise, a patient with elevated carboxyhemoglobin or methemoglobin may have sufficient hemoglobin concentration but reduced functional hemoglobin. CO-oximetry helps identify these situations by providing information about the actual forms of hemoglobin present.

Principle of CO-Oximetry

CO-oximetry works according to the principles of spectrophotometry. Different substances absorb light in characteristic patterns. Hemoglobin species are no exception. Oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin each absorb light differently at specific wavelengths.

By exposing a blood sample to multiple wavelengths and measuring the amount of light absorbed or transmitted, a CO-oximeter can determine the relative amount of each hemoglobin species.

The relationship between light absorption and substance concentration follows the Lambert-Beer law. As the concentration of a particular substance increases, predictable changes occur in light absorption. This principle makes it possible for the analyzer to separate different hemoglobin forms from one another.

Multiple Wavelengths

Conventional pulse oximeters generally use two wavelengths of light. These wavelengths are primarily intended to distinguish oxyhemoglobin from reduced hemoglobin.

CO-oximeters use four or more wavelengths because additional wavelengths are required to differentiate additional hemoglobin species. More advanced systems may use many wavelengths.

For example, a pulse CO-oximeter may use seven or more wavelengths to estimate oxyhemoglobin, carboxyhemoglobin, methemoglobin, and total hemoglobin noninvasively. The greater number of wavelengths allows the device to evaluate hemoglobin species that conventional pulse oximetry cannot reliably distinguish.

CO-Oximeter Components

A laboratory CO-oximeter typically contains several major components that work together to analyze a blood sample.

These may include:

• Light source
• Lenses
• Optical filters
• Beam splitter
• Blood sample cuvette
• Photodetectors
• Microprocessor
• Sampling and flushing system

Light produced by the instrument passes through optical components that generate the wavelengths needed for analysis. A beam splitter may divide the light so that one portion travels through a reference solution while another passes through the patient’s blood sample.

Photodetectors measure the amount of transmitted light. The analyzer then compares the sample and reference measurements. The microprocessor interprets the light absorption pattern and calculates the concentration of each hemoglobin species.

Blood Sample Processing

Modern CO-oximeters are generally automated. Blood may be introduced into the analyzer through aspiration or injection. The exact volume required depends on the instrument and may range from approximately 40 to 200 microliters.

Before optical measurement occurs, red blood cells are hemolyzed. Hemolysis releases hemoglobin into solution so that light can pass through the sample in a predictable manner. The hemolyzed sample enters a cuvette, where its optical properties are measured.

After testing, the analyzer flushes and cleans the sample tubing and cuvette to prepare the system for the next specimen. Proper sample preparation is important because incomplete hemolysis, clots, air bubbles, or contamination may interfere with the measurement.

Hemoglobin Species Measured by CO-Oximetry

CO-oximetry provides detailed information about the forms of hemoglobin circulating in the blood.

Oxyhemoglobin

Oxyhemoglobin, often abbreviated HbO₂ or O₂Hb, is hemoglobin with oxygen bound to it. It represents the functional hemoglobin responsible for transporting oxygen from the lungs to tissues. In healthy arterial blood, most functional hemoglobin is present as oxyhemoglobin.

Reduced Hemoglobin

Reduced hemoglobin, also called deoxyhemoglobin, is hemoglobin that is not currently bound to oxygen. After hemoglobin releases oxygen to tissues, it becomes reduced hemoglobin.

Reduced hemoglobin remains physiologically functional because it can bind oxygen again when blood returns to the lungs.

Carboxyhemoglobin

Carboxyhemoglobin forms when carbon monoxide binds to hemoglobin. Unlike reduced hemoglobin, carboxyhemoglobin is considered dysfunctional because hemoglobin occupied by carbon monoxide cannot transport oxygen normally.

Elevated carboxyhemoglobin is one of the most important reasons for obtaining CO-oximetry.

Methemoglobin

Methemoglobin forms when the iron in hemoglobin is oxidized from the normal ferrous state to the ferric state. Methemoglobin cannot bind oxygen normally.

Elevated concentrations therefore reduce functional oxygen-carrying capacity and interfere with tissue oxygen delivery.

Sulfhemoglobin

Sulfhemoglobin is another abnormal form of hemoglobin. It may occur after exposure to certain medications or sulfur-containing compounds. It is not reversible in the same way as normal oxygen binding and may interfere with oxygen transport.

Not all analyzers measure sulfhemoglobin directly, but its presence may influence interpretation of other measurements.

CO-Oximetry and Carbon Monoxide Poisoning

One of the most important clinical applications of CO-oximetry is the diagnosis of carbon monoxide poisoning. Carbon monoxide is a colorless, odorless, and tasteless gas produced by incomplete combustion of carbon-containing materials.

Potential sources include:

• House fires
• Enclosed garage fires
• Vehicle exhaust
• Fuel-burning heaters
• Generators
• Furnaces
• Charcoal grills
• Smoke inhalation

Note: Because carbon monoxide cannot be detected reliably by sight, smell, or taste, exposure may occur without the patient realizing it.

Why Carbon Monoxide Is Dangerous

Carbon monoxide has a much stronger affinity for hemoglobin than oxygen. Its affinity has been estimated at approximately 200 to 250 times greater than that of oxygen.

When carbon monoxide enters the bloodstream, it competes with oxygen for hemoglobin-binding sites. Hemoglobin occupied by carbon monoxide forms carboxyhemoglobin and becomes unavailable for normal oxygen transport. This creates functional anemia.

The total amount of hemoglobin may be normal, but a portion of it is effectively removed from oxygen transport. Carbon monoxide also causes the remaining functional hemoglobin to hold onto oxygen more tightly. This shifts the oxyhemoglobin dissociation curve to the left.

As a result, oxygen that remains attached to hemoglobin is more difficult to release to the tissues. Carbon monoxide therefore impairs tissue oxygenation in two major ways:

• It reduces the number of available oxygen-binding sites.
• It interferes with release of oxygen from remaining oxyhemoglobin.

Carboxyhemoglobin Levels

Small amounts of carboxyhemoglobin may normally be present. Nonsmokers generally have low COHb concentrations, often below approximately 1.5% to 2%.

Smokers may have substantially higher baseline concentrations. Values approaching approximately 9% to 10% may occur, and heavy smokers can occasionally have even higher levels. Interpretation should therefore consider smoking history and possible environmental exposure.

As COHb rises, the amount of hemoglobin available for oxygen transport falls. Significant elevations may cause headache, dizziness, weakness, confusion, nausea, cardiovascular dysfunction, loss of consciousness, and other manifestations of tissue hypoxia. Very high levels can be life-threatening.

Why PaO₂ Can Be Normal in Carbon Monoxide Poisoning

A major clinical point is that PaO₂ can remain normal in carbon monoxide poisoning. PaO₂ reflects oxygen dissolved in plasma. Carbon monoxide primarily interferes with oxygen carried by hemoglobin.

Therefore, an arterial blood gas may show an acceptable PaO₂ even when a large percentage of hemoglobin is occupied by carbon monoxide. This is why PaO₂ alone cannot rule out carbon monoxide poisoning.

When carbon monoxide exposure is suspected, direct measurement of carboxyhemoglobin with CO-oximetry is needed.

CO-Oximetry After Smoke Inhalation

Patients exposed to smoke in an enclosed environment should raise immediate concern for carbon monoxide exposure.

Examples include patients removed from:

• Burning houses
• Enclosed garages
• Industrial fires
• Vehicles with engines running
• Poorly ventilated areas involving combustion

Note: A standard SpO₂ reading may look acceptable even when COHb is substantially elevated. For this reason, CO-oximetry should be considered whenever the history and clinical findings suggest significant carbon monoxide exposure.

CO-Oximetry and Methemoglobinemia

Methemoglobinemia is another important indication for CO-oximetry. Normal hemoglobin contains iron in the ferrous state. In methemoglobin, iron becomes oxidized to the ferric state. Ferric hemoglobin cannot bind oxygen normally.

As methemoglobin concentration rises, the amount of functional hemoglobin falls. The remaining normal hemoglobin may also hold onto oxygen more tightly, shifting the oxyhemoglobin dissociation curve to the left and impairing oxygen unloading.

Causes of Methemoglobinemia

Methemoglobinemia may be congenital, but acquired forms are more commonly encountered clinically. Several oxidizing drugs and chemicals can produce methemoglobinemia.

Common examples include certain local anesthetics, such as:

• Benzocaine
• Lidocaine
• Prilocaine

Note: Other oxidizing substances may also cause the disorder. A patient who develops unexplained cyanosis after receiving benzocaine or another oxidizing medication should be evaluated for possible methemoglobinemia.

Clinical Clues to Methemoglobinemia

A classic presentation includes cyanosis that does not improve normally with supplemental oxygen. Pulse oximetry may remain around 85% despite increasing the inspired oxygen concentration.

At the same time, PaO₂ may be normal or even elevated because oxygen is still entering and dissolving in plasma. The blood may have a characteristic chocolate-brown appearance.

Important clues include:

• Cyanosis
• SpO₂ around 85%
• Minimal improvement in SpO₂ with oxygen
• Normal or high PaO₂
• Chocolate-brown blood
• Recent exposure to an oxidizing drug or chemical

Note: CO-oximetry can directly measure methemoglobin and help confirm the diagnosis.

CO-Oximetry Versus Conventional Pulse Oximetry

Conventional pulse oximetry is useful for continuous, noninvasive monitoring of arterial oxygen saturation. However, pulse oximetry and CO-oximetry do not measure the same thing.

Standard pulse oximetry generally uses two wavelengths to distinguish oxyhemoglobin from reduced hemoglobin. It reports SpO₂, which is an estimate of arterial oxygen saturation.

CO-oximetry uses multiple wavelengths and directly measures several hemoglobin species. This distinction becomes important when abnormal hemoglobins are present.

Carbon Monoxide and False SpO₂ Readings

Carboxyhemoglobin can cause conventional pulse oximetry to produce a falsely reassuring saturation. The pulse oximeter may interpret some carboxyhemoglobin as oxyhemoglobin.

A patient with significant carbon monoxide poisoning may therefore have an SpO₂ that appears relatively normal. This means standard pulse oximetry should not be used to rule out carbon monoxide poisoning. A blood sample analyzed with CO-oximetry is required for direct COHb measurement.

Methemoglobin and the 85% Saturation Pattern

Methemoglobin also interferes with conventional pulse oximetry. As the methemoglobin concentration increases, the SpO₂ reading tends to drift toward approximately 85%.

When significant methemoglobinemia is present, the pulse oximeter may remain close to this value regardless of the true arterial oxygen status.

This produces a characteristic pattern in which supplemental oxygen may substantially increase PaO₂ while the SpO₂ remains close to 85%. The discrepancy should prompt consideration of methemoglobinemia.

The Saturation Gap

A discrepancy between different oxygen saturation measurements can provide an important diagnostic clue. For example, the clinician may observe a difference between conventional pulse oximetry and a laboratory saturation measurement.

When the values do not agree as expected, abnormal hemoglobin species should be considered.

Potential causes include:

• Carboxyhemoglobinemia
• Methemoglobinemia
• Measurement artifact
• Poor peripheral perfusion
• Vascular dyes

Note: CO-oximetry can help determine whether an abnormal hemoglobin species is responsible for the discrepancy.

Pulse CO-Oximetry

Pulse CO-oximetry is a noninvasive technology that expands upon conventional pulse oximetry. Instead of using only two wavelengths, these systems use several wavelengths to estimate multiple hemoglobin species.

Depending on the device, measurements may include:

• SpO₂
• SpCO
• SpMet
• SpHb

SpCO estimates carboxyhemoglobin. SpMet estimates methemoglobin. SpHb provides an estimate of total hemoglobin. These devices may be useful for screening or following trends during treatment.

However, noninvasive pulse CO-oximetry may not provide the same accuracy as laboratory CO-oximetry. If the noninvasive result conflicts with the patient’s clinical condition, laboratory analysis of a blood sample may be required.

Monitoring Carbon Monoxide Treatment

Once carbon monoxide poisoning has been identified, pulse CO-oximetry may sometimes be used to follow the decline in carboxyhemoglobin during treatment. This can provide continuous information without requiring repeated arterial blood sampling.

However, clinical decisions should not rely solely on a noninvasive measurement when accuracy is uncertain. Laboratory CO-oximetry remains the more definitive method for measuring carboxyhemoglobin.

CO-Oximetry and Blood Gas Analysis

Blood gas analysis and CO-oximetry provide different but complementary information.

A standard arterial blood gas directly measures:

• pH
• PaCO₂
• PaO₂

These values are used to evaluate acid-base balance, ventilation, and pulmonary oxygenation. A blood gas analyzer may calculate oxygen saturation from the PaO₂ and other assumptions. However, calculated oxygen saturation does not directly identify dyshemoglobins.

CO-oximetry directly measures the different hemoglobin species. Modern laboratory systems may combine blood gas analysis and CO-oximetry in the same instrument, allowing both measurements to be obtained from a single specimen.

When CO-Oximetry Should Be Considered

CO-oximetry is particularly useful when hemoglobin dysfunction is suspected.

Clinical situations may include:

• Suspected carbon monoxide poisoning
• Smoke inhalation
• Enclosed-space fire exposure
• Cyanosis with normal PaO₂
• Suspected methemoglobinemia
• SpO₂ around 85% that does not respond normally to oxygen
• Unexplained tissue hypoxia
• Discrepancy between SpO₂ and other oxygenation measurements
• Monitoring patients at risk for methemoglobinemia
• Evaluation of abnormal hemoglobin species

Note: The decision should be based on the entire clinical picture rather than a single oxygenation value.

CO-Oximetry and Inhaled Nitric Oxide

Patients receiving inhaled nitric oxide may require monitoring for methemoglobin formation. Nitric oxide may be administered to reduce pulmonary vascular resistance in selected patients.

Because nitric oxide can oxidize hemoglobin, methemoglobin concentrations may rise during therapy. CO-oximetry allows direct measurement of methemoglobin and can help determine whether clinically significant accumulation is occurring.

Unexplained Tissue Hypoxia

CO-oximetry may be valuable when signs of tissue hypoxia occur despite apparently acceptable conventional oxygen measurements. Possible findings could include altered mental status, elevated lactate, cardiovascular instability, or other signs of impaired oxygen delivery.

A normal PaO₂ does not guarantee adequate oxygen delivery. The clinician should consider several factors, including:

• Hemoglobin concentration
• Functional hemoglobin saturation
• Cardiac output
• Tissue perfusion
• Abnormal hemoglobin species
• Cellular oxygen utilization

Note: CO-oximetry addresses the hemoglobin component of this assessment.

Hypoxemia vs. Hypoxia

Hypoxemia and hypoxia are related but different concepts. Hypoxemia refers to reduced oxygen in arterial blood and is commonly evaluated using PaO₂. Hypoxia refers to inadequate oxygen at the tissue level.

Hypoxia can occur without hypoxemia. For example, anemic hypoxia can occur when hemoglobin is reduced or dysfunctional even though PaO₂ remains normal.

Carbon monoxide poisoning is an example of functional anemic hypoxia. Circulatory hypoxia may occur when blood flow is inadequate, such as with reduced cardiac output.

Histotoxic hypoxia may occur when tissues cannot properly use delivered oxygen, as in cyanide poisoning. CO-oximetry is primarily useful when abnormal hemoglobin contributes to impaired oxygen transport.

Oxygen Delivery and Cardiac Output

Oxygen delivery depends on more than oxygen saturation. It is determined by the interaction between arterial oxygen content and cardiac output. Even when CaO₂ is adequate, a severe reduction in cardiac output can decrease tissue oxygen delivery.

Likewise, normal cardiac output cannot completely compensate for severe loss of functional hemoglobin. This reinforces the importance of evaluating oxygen transport as a complete process rather than relying on one isolated value.

Normal Hemoglobin Measurements

Reference ranges vary by laboratory and patient population. Approximate adult total hemoglobin values may include:

• Adult men: approximately 13.5 to 18.0 g/dL
• Adult women: approximately 12.0 to 16.0 g/dL

Oxyhemoglobin may normally account for approximately 94% to 100% of total hemoglobin in arterial blood. Carboxyhemoglobin is generally very low in nonsmokers but may be elevated in smokers. Methemoglobin normally represents only a small percentage of total hemoglobin.

Note: Values should always be interpreted according to the laboratory’s reference ranges and the patient’s clinical circumstances.

Sample Collection and Handling

Accurate CO-oximetry depends on proper collection and handling of the blood sample.

Potential problems include:

• Air bubbles
• Clotted samples
• Incomplete mixing
• Delayed analysis
• Incorrect storage
• Sample contamination
• Incomplete hemolysis

Blood gas and hemoximetry specimens should be labeled correctly and handled according to laboratory and manufacturer recommendations.

Plastic-syringe blood gas samples are generally analyzed promptly, often within approximately 30 minutes when kept at room temperature. Specific handling requirements may differ depending on the analyzer and institutional procedures.

Sources of Measurement Error

Several substances and sample conditions can interfere with CO-oximetry.

Incomplete Hemolysis

Red blood cells must be adequately hemolyzed before spectrophotometric analysis. Incomplete hemolysis can interfere with the optical measurement and may produce falsely low total hemoglobin or oxyhemoglobin results.

Sickle cells may be more difficult to hemolyze completely, potentially interfering with measurements.

Hyperlipidemia

High lipid concentrations can scatter light. Depending on the analyzer, hyperlipidemia may alter total hemoglobin, oxyhemoglobin, carboxyhemoglobin, or methemoglobin measurements.

Vascular Dyes

Certain dyes absorb light at wavelengths used by the CO-oximeter.

Examples include:

• Methylene blue
• Evans blue
• Indocyanine green

Note: These substances may produce erroneous hemoglobin measurements.

Bilirubin

Marked hyperbilirubinemia may interfere with light absorption and may alter measurements of total hemoglobin, oxyhemoglobin, and methemoglobin.

Fetal Hemoglobin

Fetal hemoglobin has different optical characteristics from adult hemoglobin. High fetal hemoglobin concentrations may affect measurements, including carboxyhemoglobin. When testing infants, the analyzer may need to be configured appropriately for fetal hemoglobin.

Sulfhemoglobin

Sulfhemoglobin may interfere with certain measurements and may be difficult for some analyzers to distinguish from other dyshemoglobins.

Cuvette Contamination

The sample cuvette must remain clean for accurate spectrophotometric measurement. Clouding, residue, or contamination of the cuvette walls alters light transmission and can produce erroneous results.

Routine maintenance and cleaning are therefore important parts of CO-oximetry quality assurance.

Calibration and Quality Control

Reliable measurements depend on proper calibration, maintenance, and quality-control procedures.

Calibration may be required:

• During initial analyzer installation
• At manufacturer-recommended intervals
• After replacement of sample tubing
• After cuvette replacement or disassembly
• Following maintenance
• When results appear inconsistent or suspicious

Personnel should be trained in:

• Sample collection
• Sample handling
• Calibration
• Preventive maintenance
• Troubleshooting
• Quality-control procedures
• Recognition of analytical errors

Note: Unexpected results should always be interpreted in relation to the patient’s clinical condition.

Clinical Interpretation

CO-oximetry should not be interpreted in isolation. The results should be considered together with:

• Patient history
• Exposure history
• Physical examination
• PaO₂
• PaCO₂
• pH
• SpO₂
• Hemoglobin concentration
• Lactate
• Cardiovascular status

For example, a normal PaO₂ does not exclude carbon monoxide poisoning. An SpO₂ of approximately 85% that fails to improve despite a high PaO₂ may suggest methemoglobinemia.

An apparently normal saturation in a smoke-inhalation patient should not eliminate concern for elevated carboxyhemoglobin. The relationship among the measurements is often more informative than any individual number.

Clinical Example: Carbon Monoxide Exposure

Consider a patient rescued from an enclosed garage fire. The patient has soot around the mouth, headache, dizziness, and confusion.

Pulse oximetry reads 98%, and PaO₂ is within the normal range. These measurements might initially appear reassuring.

However, neither measurement reliably excludes significant carbon monoxide poisoning.

The high SpO₂ may be misleading because conventional pulse oximetry cannot distinguish oxyhemoglobin from carboxyhemoglobin adequately.

The PaO₂ reflects dissolved oxygen and does not indicate how much hemoglobin is occupied by carbon monoxide. CO-oximetry should therefore be used to measure COHb directly.

Clinical Example: Methemoglobinemia

Consider a patient who becomes cyanotic after receiving topical benzocaine. The SpO₂ remains around 85% despite supplemental oxygen.

An arterial blood gas reveals a high PaO₂. The blood appears dark or chocolate brown. This pattern should raise suspicion for methemoglobinemia.

The PaO₂ indicates that oxygen is entering the plasma, yet hemoglobin is not transporting oxygen normally. CO-oximetry can directly measure methemoglobin and confirm the abnormality.

Key Differences Among Oxygenation Measurements

PaO₂, SpO₂, SaO₂, and CO-oximetry provide related but different information.

• PaO₂ measures the partial pressure of oxygen dissolved in arterial plasma.
• SpO₂ is a noninvasive estimate of arterial oxygen saturation obtained by conventional pulse oximetry.
• SaO₂ refers to arterial hemoglobin oxygen saturation and may be measured or calculated depending on the testing method.
• CO-oximetry directly measures different hemoglobin species using multiple wavelengths of light.

Note: Understanding these distinctions is essential when interpreting abnormal oxygenation findings.

Importance for Respiratory Care

Respiratory therapists frequently evaluate patients using pulse oximetry and arterial blood gases. These tools provide important information, but neither alone can reliably identify all causes of impaired oxygen transport. Recognizing situations that require CO-oximetry is therefore important.

Smoke inhalation, unexplained cyanosis, suspected carbon monoxide poisoning, abnormal saturation patterns, and suspected methemoglobinemia should prompt consideration of hemoximetry.

The central concept is that oxygenation depends not only on oxygen entering the lungs and dissolving in plasma but also on functional hemoglobin being available to carry and release oxygen.

CO-Oximetry Practice Questions

1. What is another term for CO-oximetry?
Hemoximetry

2. What is the primary purpose of CO-oximetry?
To measure and differentiate the various forms of hemoglobin present in the blood.

3. Which principle is used by a CO-oximeter to identify different hemoglobin species?
Spectrophotometry

4. What law describes the relationship between light absorption and the concentration of a substance in a sample?
The Lambert-Beer law

5. Which four major hemoglobin species can be measured by CO-oximetry?
Oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin

6. Why does a CO-oximeter use multiple wavelengths of light?
Different hemoglobin species have different light absorption patterns, so multiple wavelengths allow them to be distinguished from one another.

7. What does oxyhemoglobin represent?
Hemoglobin that is bound to oxygen and capable of transporting oxygen to the tissues.

8. What is reduced hemoglobin?
Hemoglobin that is not currently bound to oxygen but remains capable of binding oxygen again.

9. What abnormal hemoglobin forms when carbon monoxide binds to hemoglobin?
Carboxyhemoglobin

10. Why is carboxyhemoglobin considered nonfunctional for oxygen transport?
Carbon monoxide occupies hemoglobin-binding sites and prevents those sites from carrying oxygen normally.

11. Approximately how much greater is carbon monoxide’s affinity for hemoglobin compared with oxygen?
Approximately 200 to 250 times greater

12. How does carbon monoxide affect the oxyhemoglobin dissociation curve?
It shifts the curve to the left, making oxygen more difficult to unload to the tissues.

13. Why can a patient with severe carbon monoxide poisoning have a normal PaO₂?
PaO₂ measures oxygen dissolved in plasma rather than the amount of oxygen carried by functional hemoglobin.

14. Which test should be used to directly measure carboxyhemoglobin in a patient with suspected carbon monoxide poisoning?
CO-oximetry

15. Why should conventional pulse oximetry not be used to rule out carbon monoxide poisoning?
Carboxyhemoglobin can cause the pulse oximeter to display a falsely reassuring SpO₂ value.

16. What type of exposure should prompt consideration of carbon monoxide poisoning and CO-oximetry?
Smoke inhalation or exposure to combustion products in an enclosed space

17. What is generally considered a typical carboxyhemoglobin level in a nonsmoker?
Approximately 2% or less

18. Why may smokers normally have higher carboxyhemoglobin levels than nonsmokers?
Cigarette smoke contains carbon monoxide that binds to hemoglobin.

19. What abnormal hemoglobin forms when hemoglobin iron is oxidized from the ferrous state to the ferric state?
Methemoglobin

20. How does methemoglobin affect oxygen transport?
It cannot bind oxygen normally and causes the remaining functional hemoglobin to hold oxygen more tightly.

21. Which local anesthetic is commonly associated with acquired methemoglobinemia?
Benzocaine

22. A cyanotic patient has an SpO₂ of 85% that changes very little with supplemental oxygen, while the PaO₂ is high. What condition should be suspected?
Methemoglobinemia

23. What characteristic appearance may blood have in a patient with significant methemoglobinemia?
Chocolate-brown

24. What tends to happen to the conventional pulse oximetry reading as methemoglobin levels become significantly elevated?
The SpO₂ tends to move toward and remain near approximately 85%.

25. Why is CO-oximetry more useful than PaO₂ alone when dyshemoglobinemia is suspected?
CO-oximetry directly measures abnormal hemoglobin species, while PaO₂ reflects only the oxygen dissolved in plasma.

26. What does a standard arterial blood gas directly measure that differs from CO-oximetry?
pH, PaCO₂, and PaO₂

27. Why is a calculated oxygen saturation from a blood gas analyzer not sufficient when dyshemoglobins are suspected?
It does not directly identify abnormal hemoglobin species such as carboxyhemoglobin or methemoglobin.

28. What does arterial oxygen content primarily depend on?
Hemoglobin concentration and hemoglobin oxygen saturation

29. Which portion of the arterial oxygen content equation represents oxygen dissolved in plasma?
PaO₂ × 0.003

30. Which portion of the arterial oxygen content equation represents oxygen carried by hemoglobin?
Hb × 1.34 × SaO₂

31. Why can severe anemia cause tissue hypoxia even when PaO₂ is normal?
There may be too little hemoglobin available to carry an adequate amount of oxygen.

32. What is the normal approximate range for arterial oxygen content?
About 16 to 22 mL/dL

33. What is the difference between hypoxemia and hypoxia?
Hypoxemia refers to low arterial oxygen, while hypoxia refers to inadequate oxygen at the tissue level.

34. What type of hypoxia can occur with carbon monoxide poisoning?
Anemic hypoxia

35. What type of hypoxia can occur when cardiac output is severely reduced?
Circulatory hypoxia

36. What type of hypoxia can occur when tissues cannot properly use delivered oxygen?
Histotoxic hypoxia

37. What is a major advantage of combining blood gas analysis and CO-oximetry in one analyzer?
Both gas measurements and hemoglobin species can be assessed from the same blood specimen.

38. Why are red blood cells hemolyzed before CO-oximetry analysis?
To release hemoglobin into solution so its light absorption can be measured accurately.

39. What effect can incomplete hemolysis have on CO-oximetry results?
It can produce inaccurate measurements, including falsely low total hemoglobin and oxyhemoglobin values.

40. Why can sickle cell disease interfere with CO-oximetry?
Sickle cells may be difficult to hemolyze completely, which can distort hemoglobin measurements.

41. How can hyperlipidemia interfere with CO-oximetry?
High lipid concentrations can scatter light and produce erroneous hemoglobin measurements.

42. Which dye can interfere with CO-oximetry by absorbing light at wavelengths used by the analyzer?
Methylene blue

43. What effect can markedly elevated bilirubin have on CO-oximetry?
It may interfere with light absorption and falsely alter total hemoglobin, oxyhemoglobin, or methemoglobin measurements.

44. Why can fetal hemoglobin affect CO-oximetry results?
Its optical characteristics differ from adult hemoglobin and may interfere with some measured hemoglobin fractions.

45. What should be considered when performing CO-oximetry on a young infant?
The analyzer may need to be configured appropriately for fetal hemoglobin.

46. Why must the CO-oximeter cuvette be kept clean?
Clouding or contamination can alter light transmission and cause inaccurate results.

47. What should be done when a CO-oximetry result does not match the patient’s clinical condition?
The sample, analyzer, calibration, and possible sources of interference should be evaluated.

48. What does SpCO represent on a pulse CO-oximeter?
A noninvasive estimate of carboxyhemoglobin

49. What does SpMet represent on a pulse CO-oximeter?
A noninvasive estimate of methemoglobin

50. What does SpHb represent on a pulse CO-oximeter?
A noninvasive estimate of total hemoglobin

51. What does SpO₂ represent on a conventional pulse oximeter?
An estimate of arterial oxyhemoglobin saturation

52. Why is conventional pulse oximetry limited when abnormal hemoglobin species are present?
It cannot reliably distinguish oxyhemoglobin from dyshemoglobins such as carboxyhemoglobin and methemoglobin.

53. What is one major advantage of pulse CO-oximetry over laboratory CO-oximetry?
It can provide continuous, noninvasive estimates of abnormal hemoglobin species.

54. Why should laboratory CO-oximetry be used when a pulse CO-oximeter result conflicts with the clinical picture?
Laboratory CO-oximetry generally provides a more definitive measurement of hemoglobin species.

55. How can pulse CO-oximetry be useful after carbon monoxide poisoning has been diagnosed?
It can help follow the decline in carboxyhemoglobin during treatment.

56. What type of sample is commonly used for laboratory CO-oximetry when carbon monoxide poisoning is suspected?
A blood sample, often arterial blood

57. Why should blood samples for CO-oximetry be thoroughly mixed before analysis?
To ensure the sample is uniform and representative when hemoglobin measurements are performed.

58. How can air bubbles affect a blood sample used for CO-oximetry?
They can interfere with accurate analysis and contribute to erroneous results.

59. How can blood clots interfere with CO-oximetry?
They may obstruct sampling tubing or prevent the specimen from reaching the measurement chamber properly.

60. Why should blood gas and hemoximetry samples be analyzed promptly?
Delays can alter specimen characteristics and reduce the reliability of the measurements.

61. What is the purpose of calibration in a CO-oximeter?
To ensure the analyzer accurately relates measured light absorption to hemoglobin concentrations.

62. When might a CO-oximeter require recalibration in addition to routine scheduled calibration?
After maintenance, component replacement, or when results appear suspicious.

63. What role do photodetectors play in a CO-oximeter?
They measure the amount of light transmitted through the sample and reference pathways.

64. What is the function of the microprocessor in a CO-oximeter?
It analyzes optical measurements and calculates the concentrations of the different hemoglobin species.

65. What is the purpose of a reference solution in some CO-oximeters?
It provides a comparison for evaluating light transmission through the patient’s blood sample.

66. Why are several wavelengths required to measure multiple hemoglobin species?
Each hemoglobin species has a different light absorption spectrum that must be distinguished from the others.

67. What is an isosbestic point in spectrophotometric analysis?
A wavelength at which certain hemoglobin species absorb light equally.

68. Why can vascular dyes produce inaccurate CO-oximetry measurements?
They may absorb light at wavelengths used by the analyzer and interfere with spectrophotometric calculations.

69. Besides methylene blue, what are two other dyes that may interfere with CO-oximetry?
Evans blue and indocyanine green

70. Why may sulfhemoglobin complicate CO-oximetry interpretation?
Its absorption characteristics may interfere with the measurement of other abnormal hemoglobin species.

71. Why can oxygen delivery be inadequate even when arterial oxygen content is normal?
A reduction in cardiac output can limit the amount of oxygen delivered to the tissues.

72. What two major factors determine overall oxygen delivery to the tissues?
Arterial oxygen content and cardiac output

73. How can positive-pressure ventilation potentially reduce oxygen delivery?
It can decrease venous return and cardiac output by increasing intrathoracic pressure.

74. What laboratory finding may support the presence of tissue hypoxia when oxygen delivery is inadequate?
An elevated lactate level

75. What is the central reason CO-oximetry is valuable when routine oxygenation measurements appear normal?
It can reveal abnormal or dysfunctional hemoglobin that prevents effective oxygen transport despite apparently normal PaO₂ or SpO₂ values.

76. Why is total hemoglobin concentration important when evaluating oxygen transport?
Because the amount of hemoglobin available directly affects how much oxygen the blood can carry.

77. Can a patient with normal oxygen saturation still have reduced arterial oxygen content?
Yes, if the hemoglobin concentration is significantly decreased.

78. Why is PaO₂ only a small contributor to total arterial oxygen content?
Because only a small amount of oxygen is dissolved in plasma compared with the amount bound to hemoglobin.

79. What does a leftward shift of the oxyhemoglobin dissociation curve mean for tissue oxygen delivery?
Hemoglobin holds oxygen more tightly, making oxygen less available for release to tissues.

80. Why is carbon monoxide poisoning considered a problem of both oxygen-carrying capacity and oxygen unloading?
It occupies hemoglobin-binding sites and also causes the remaining oxyhemoglobin to release oxygen less readily.

81. Why can cyanosis occur in methemoglobinemia despite an adequate PaO₂?
Because methemoglobin is unable to carry oxygen normally even though dissolved oxygen in plasma may be adequate.

82. What general finding should raise suspicion when oxygen saturation measurements do not match the patient’s appearance?
A possible dyshemoglobinemia or measurement interference

83. What is meant by dysfunctional hemoglobin?
Hemoglobin that is present in the blood but cannot participate normally in oxygen transport.

84. Why is exposure history important when interpreting CO-oximetry results?
It can help identify possible sources of carbon monoxide, oxidizing drugs, or other causes of abnormal hemoglobin.

85. What environmental condition increases concern for carbon monoxide accumulation during combustion?
Poor ventilation in an enclosed space

86. Why is carbon monoxide difficult for exposed patients to detect?
It is colorless, odorless, and tasteless.

87. What happens to functional hemoglobin as the percentage of carboxyhemoglobin increases?
The amount of hemoglobin available to carry oxygen decreases.

88. What happens to functional hemoglobin as the percentage of methemoglobin increases?
The amount of hemoglobin capable of normal oxygen binding decreases.

89. Why should smoking status be considered when interpreting an elevated COHb level?
Smokers may have higher baseline carboxyhemoglobin levels than nonsmokers.

90. Why is a normal SpO₂ potentially misleading after smoke inhalation?
Conventional pulse oximetry may not recognize carboxyhemoglobin and can overestimate effective oxygen saturation.

91. What finding after topical benzocaine use should increase suspicion for methemoglobinemia?
New-onset cyanosis with an SpO₂ near 85% despite supplemental oxygen

92. What is the main difference between laboratory CO-oximetry and pulse CO-oximetry?
Laboratory CO-oximetry analyzes a blood sample directly, while pulse CO-oximetry estimates hemoglobin species noninvasively.

93. What type of information does a conventional two-wavelength pulse oximeter primarily use?
Differences in light absorption between oxyhemoglobin and reduced hemoglobin

94. Why are additional wavelengths needed to identify carboxyhemoglobin and methemoglobin?
Their absorption patterns cannot be reliably separated using only the two wavelengths of conventional pulse oximetry.

95. What should be checked if an analyzer produces an unexpectedly abnormal CO-oximetry result?
Sample quality, calibration, instrument maintenance, and possible interfering substances

96. Why can contamination of optical components affect CO-oximetry accuracy?
It changes the amount of light reaching the detectors and can distort calculated hemoglobin concentrations.

97. Why should CO-oximetry results be interpreted with the patient’s cardiovascular status?
Adequate hemoglobin oxygenation does not guarantee adequate tissue oxygen delivery if cardiac output is poor.

98. What clinical problem may be present when lactate is elevated despite acceptable PaO₂ values?
Inadequate tissue oxygen delivery or utilization

99. Why is CO-oximetry useful in patients receiving inhaled nitric oxide?
It can monitor for the development of elevated methemoglobin levels.

100. What is the most important reason to understand the differences among PaO₂, SpO₂, and CO-oximetry?
Each evaluates a different aspect of oxygenation, so relying on only one measurement can miss impaired oxygen transport.

Final Thoughts

CO-oximetry provides a detailed assessment of hemoglobin that conventional pulse oximetry and PaO₂ cannot provide alone. By directly measuring oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, methemoglobin, and other hemoglobin species, it helps identify abnormalities that can severely impair oxygen transport despite apparently acceptable routine oxygen measurements.

Its most important uses include suspected carbon monoxide poisoning, methemoglobinemia, smoke inhalation, and unexplained tissue hypoxia.

Understanding the relationship among PaO₂, oxygen saturation, hemoglobin function, arterial oxygen content, and tissue oxygen delivery allows clinicians to recognize when CO-oximetry is necessary for a more complete assessment.