As discussed, traditional pulse oximetry may provide inaccurate oxygen saturation readings in patients with hemoglobinopathies. This limitation necessitates the use of alternative strategies and advanced monitoring technologies that can offer more reliable assessments of oxygenation. Anesthesia providers must be aware of these options to ensure safe perioperative care in this population. Below are several approaches and technologies that can complement or replace standard pulse oximetry when dealing with patients who have hemoglobinopathies.
Co-Oximetry: A Key Tool for Hemoglobin Variant Analysis
Co-oximetry is a more advanced technique than traditional pulse oximetry, designed to directly measure multiple hemoglobin species, including oxyhemoglobin (HbO2), deoxygenated hemoglobin (Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb). Unlike standard pulse oximeters, which use two wavelengths of light, co-oximeters use multiple wavelengths, enabling them to differentiate between normal and abnormal hemoglobin species. This yields the fractional saturation (oxyhemoglobin divided by all hemoglobin species), whereas a two-wavelength pulse oximeter estimates functional saturation (oxyhemoglobin divided by oxyhemoglobin plus deoxyhemoglobin). With 30% carboxyhemoglobin and 68% oxyhemoglobin, functional saturation is about 97% and fractional saturation is 68%. Modern blood gas co-oximeters use dozens of wavelengths on a hemolyzed arterial sample and are the reference standard against which pulse oximeters are validated.

In patients with conditions like methemoglobinemia or carboxyhemoglobinemia, co-oximetry provides accurate readings of the true oxygen saturation by accounting for the presence of these abnormal hemoglobins. This makes co-oximetry a critical tool in the management of patients with hemoglobinopathies where conventional pulse oximetry fails.
While co-oximeters are not typically used continuously in the operating room, they are valuable in perioperative and critical care settings where precise hemoglobin fraction analysis is required. Anesthesia providers should consider using co-oximetry when there is clinical suspicion of abnormal hemoglobins or when pulse oximetry readings are inconsistent with the patient’s clinical presentation.
Arterial Blood Gas (ABG) Analysis
Arterial blood gas (ABG) analysis remains a gold standard for directly measuring oxygenation, ventilation, and acid-base status. ABG measurements include the partial pressure of oxygen (PaO2), the oxygen dissolved in plasma, which is measured by an electrode and is therefore independent of hemoglobin variants. It is not a measure of oxygen content, which depends on hemoglobin concentration and saturation. The saturation printed on many blood gas reports is calculated from PaO2 assuming a normal dissociation curve and no dyshemoglobins; only an analyzer with a built-in co-oximeter measures it. A measured saturation well below the calculated one (the saturation gap) points to a dyshemoglobin or a variant.
In situations where pulse oximetry is unreliable, such as in patients with sickle cell disease or severe anemia, ABG analysis offers definitive information about a patient’s oxygenation status. However, because ABG involves intermittent, invasive sampling, it cannot replace the continuous monitoring capabilities of pulse oximetry. Therefore, ABG is most useful for confirming or refuting SpO2 readings and guiding oxygenation management in critical moments.
Near-Infrared Spectroscopy (NIRS)
Near-infrared spectroscopy (NIRS) is another technology that can offer additional insights into tissue oxygenation. NIRS measures tissue oxygen saturation (StO2) by analyzing light absorption in tissues like muscle or brain rather than in arterial blood, as pulse oximetry does. While not typically used to monitor systemic oxygenation, NIRS is particularly useful for assessing regional tissue oxygenation, especially in situations where global oxygen delivery may not reflect local tissue needs, such as in cases of shock or impaired microcirculation.
In patients with hemoglobinopathies, where pulse oximetry may fail to provide reliable systemic oxygenation data, NIRS can serve as a supplemental tool to assess whether specific tissues are receiving adequate oxygenation. It is often used in critical care and during complex surgeries where organ perfusion is a concern, though its routine use in anesthesia practice for monitoring oxygenation remains limited.
Transcutaneous Oxygen Monitoring
Transcutaneous oxygen (PtcO2) monitoring is another non-invasive technology that provides information about tissue oxygenation by measuring the diffusion of oxygen through the skin. This method involves placing a heated electrode on the skin, which promotes vasodilation and increased local blood flow, thereby allowing the measurement of oxygen tension in the underlying capillaries.
Transcutaneous monitoring has shown utility in neonatal care and in patients with peripheral vascular disease but can be considered as an adjunctive tool in patients with hemoglobinopathies when traditional pulse oximetry is unreliable. The readings provide a reflection of the tissue oxygenation rather than systemic oxygenation, which can be useful in assessing microcirculatory perfusion, particularly during surgery or in critically ill patients.
Multi-Wavelength Pulse Oximetry
While traditional pulse oximeters rely on two wavelengths of light (red and infrared), multi-wavelength pulse oximetry, often referred to as “rainbow” oximetry, uses additional wavelengths to measure more than just oxyhemoglobin and deoxygenated hemoglobin. This allows for the detection of abnormal hemoglobin species, such as carboxyhemoglobin and methemoglobin, without the need for co-oximetry or invasive sampling.
Commercial devices use seven or more wavelengths and display carboxyhemoglobin (SpCO) and methemoglobin (SpMet) continuously; in volunteer studies SpCO was accurate to within a few percent and SpMet to about 1%, but a raised methemoglobin degrades the SpCO reading, so an abnormal value should be confirmed by laboratory co-oximetry before major decisions rest on it (Barker et al., 2006). Though still less common in routine clinical practice, multi-wavelength oximeters are becoming more accessible, and the pulse CO-oximetry described next is the same device family. These devices have the potential to enhance accuracy in patients with hemoglobinopathies by offering real-time insights into hemoglobin variants and their impact on oxygen saturation. For anesthesia providers, the availability of this technology represents a significant advancement in non-invasive monitoring, particularly for patients with a known history of abnormal hemoglobins.
Pulse CO-Oximetry: Real-Time Hemoglobin Variant Detection
A specialized version of multiwavelength pulse oximetry, pulse CO-oximetry, allows for the continuous, non-invasive measurement of total hemoglobin (SpHb) as well as carboxyhemoglobin and methemoglobin levels in real time. This technology combines the benefits of traditional pulse oximetry with some of the analytical capabilities of co-oximetry.
Pulse CO-oximetry can be a game-changer in the perioperative management of patients with hemoglobinopathies, offering anesthesia providers a more complete picture of a patient’s oxygenation status. However, despite its promise, this technology is not yet universally available and may not replace the need for more established methods like ABG or co-oximetry in all clinical scenarios.
| Method | What it provides | Practical limits |
|---|---|---|
| Co-oximetry | Uses multiple wavelengths to measure oxyhemoglobin, deoxygenated hemoglobin, carboxyhemoglobin, and methemoglobin directly, giving true saturation where abnormal hemoglobins are present. | Not usually run continuously in the operating room; reserved for when a variant is suspected or the SpO2 does not match the clinical picture. |
| Arterial blood gas | Gold standard for oxygenation, ventilation, and acid-base status; PaO2 is measured by electrode and is independent of hemoglobin variants, but it is oxygen tension, not content, and the reported saturation is calculated unless the analyzer includes a co-oximeter. | Intermittent and invasive, so it confirms or refutes an SpO2 value rather than replacing continuous monitoring. |
| Near-infrared spectroscopy | Tissue oxygen saturation in muscle or brain, useful where global oxygen delivery does not reflect local need, as in shock or impaired microcirculation. | Regional rather than systemic; routine anesthesia use for oxygenation monitoring remains limited. |
| Transcutaneous oxygen monitoring | Oxygen tension in capillaries beneath a heated skin electrode that promotes local vasodilation and blood flow. | Reflects tissue rather than systemic oxygenation; established in neonatal care and peripheral vascular disease, adjunctive elsewhere. |
| Multi-wavelength (“rainbow”) pulse oximetry | Extra wavelengths detect abnormal hemoglobin species such as carboxyhemoglobin and methemoglobin without co-oximetry or invasive sampling. | Still less common in routine practice, though increasingly accessible. |
| Pulse CO-oximetry | Continuous non-invasive total hemoglobin along with carboxyhemoglobin and methemoglobin in real time. | Not yet universally available and does not remove the need for arterial blood gas or co-oximetry in every scenario. |