Clinical Research Applications for End-Tidal Oxygen Measurement

Clinical medical practice has used end-tidal CO₂ measurement for several decades for purposes that include procedural sedation, adequacy of laryngeal intubation, pediatric critical care, and cardiopulmonary resuscitation. In contrast, there have been few use cases for monitoring end-tidal oxygen. Now research has identified emerging opportunities for further clinical research on the use of end-tidal oxygen measurement as an alternative to end-tidal CO₂ and pulse oximetry. Researchers have found potential utility for end-tidal oxygen measurement in ventilation assessment, and in emergency department procedures including procedural sedation, assessment of ventilation/perfusion mismatch, pre-oxygenation during rapid sequence intubation, and prediction of central venous oxygen saturation.

Oxygen transport

Oxygen Utilization Basics

An exploration of the utility of respiratory gas measurement starts with an understanding of the basics of oxygenation and oxygen transport.

Oxygenation involves a series of steps that include inhalation, gas exchange, oxygen transport, oxygen delivery, oxygen extraction and exhalation. This paper provides an overview of the key steps along this path. Oxygen is central to the proper functioning of the human body, which functions optimally under aerobic conditions. The reason is that the conversion of glucose, the dominant fuel for cells, requires a high amount of oxygen to produce energy the body can utilize. This energy is more commonly referenced as adenosine triphosphate (ATP).

When oxygen is lacking (i.e. under anaerobic conditions), the metabolic processes become hampered, and alternative fuel sources are utilized to generate ATP. When tissue is exposed to anaerobic conditions for prolonged periods, tissue necrosis may ensue. For example, both stroke and myocardial infarction involve tissue necrosis as a direct result of tissue hypoxia resulting from obstructed blood flow.

The metabolic byproduct of tissue metabolism is carbon dioxide (CO₂), which is transported from the tissue via blood circulation and is removed during exhalation. Abnormalities affecting carbon dioxide are assessed via measurements of partial pressures within the circulation (i.e. PCO₂) or end-tidal measurements (i.e. etCO₂) collected during exhalation. Changes to lung ventilation that become clinically significant are commonly identified through these measurement modalities. For instance, under respiratory distress, where ventilation is rapid and deep, the amount of CO₂ cleared during exhalation increases, and this is reflected as low PCO₂ and low etCO₂. In contrast, when respiratory failure is imminent, ventilation decreases and is reflected by increasing PCO₂ and etCO₂ values.

Oxygen Uptake

The air we breathe contains 21% oxygen and is commonly denoted as the fractional inspired oxygen concentration (FiO₂). Under medical care, the minimal FiO₂ that can be delivered is room air (FiO₂=21%). But with supplemental oxygen, the FiO₂ can be increased to 40% or higher with use of nasal prongs, a face mask, or forms of mechanical ventilation. In contrast, the atmospheric concentration of CO₂ is negligible (FiCO₂ = ~0%). As oxygen enters an alveolar unit during inhalation, mixed venous blood enters through capillaries that originate from the pulmonary artery. As the capillary blood traverses the alveolar unit, gas exchange occurs so that equilibration of gases occurs at the end-capillary portion of the alveolar unit.

Under normal gas exchange, the partial pressure of oxygen in the alveolus is greater than within the mixed venous circulation. For CO₂, the opposite exists: the mixed venous partial pressure of CO₂ is greater than within the alveoli. These diffusion gradients result in equilibration through the alveolar unit (Figure 1). The diffusion properties of CO₂ are greater than those of oxygen; as a result the equilibration between the mix-venous capillary and alveolar compartments occurs sooner during transit of blood through the alveolar unit. As much CO₂ is exchanged for a partial pressure difference of 5 mmHg between mixed venous and alveolar space as O₂ is exchanged when the partial pressure difference is 60 mmHg.¹  Therefore, within each alveolar unit, CO₂ equilibrates sooner than O₂. This is an important factor in understanding how changes in ventilation or perfusion can impact arterial or end-tidal gases.

When oxygen crosses from the alveolus into the mixed-venous capillary of the alveolar unit, that oxygen will bind to hemoglobin and be transported to the heart via the pulmonary vein. Once the oxygenated blood enters the heart, it is distributed to the tissue during each contraction of the ventricles. The oxygenated blood leaving the heart is carried predominantly bound to hemoglobin; a fraction is freely dissolved within the plasma. Abnormalities to cardiopulmonary function can impact gas exchange and result in perturbations in PaO₂, PaCO₂, etO2 and etCO₂. Arterial hypoxemia can manifest, for example, as a result of hypoventilation.

In cases of hypoventilation, minute ventilation (VE) is reduced, impairing gas exchange at the alveolar unit. Mixed venous blood flow is not affected, while oxygen delivered into each alveolar unit is diminished; the ventilation/perfusion ratio is reduced compared to normal. What then manifests is a reduction in PaO₂ and etO₂ and an accumulation of carbon dioxide as reflected in an increased PaCO₂ and etCO₂. The oxygen gradient, which is the difference between the FiO₂ and etO₂ (e.g. FiO₂ - etO₂) is a newer concept that has been shown to correlate closely with changes in ventilation (described in more detail in a later section). The change in the oxygen gradient is the result of a static FiO₂ in concert with ventilatory changes that impact etO₂; hypoventilation will result in an increasing gradient while hyperventilation will see the gradient decrease. The partial pressure of oxygen and etO₂ will increase, but the hallmark finding is a decrease in PaCO₂ and etCO₂.

In the presence of a perfusion shunt (Figure 2), ventilation to the alveolar unit is unaffected, but the number of mixed-venous capillaries participating in gas exchange (i.e. alveolar units not receiving mixed-venous blood) is decreased. This results in unique changes to the gas-exchange relationship. Notably, the alveolar units affected by a perfusion shunt make no contribution to gas exchange, and the mixed-venous and end-capillary O₂ and CO₂ will be the same. Given that the lung is comprised of many alveolar units, the degree of shunt will affect PaO₂ levels (decrease) and PaCO₂ levels (increase). The magnitude of changes to O₂ and CO₂ depends on the size (or relative percentage) of alveolar units affected.

The percentage of oxygen bound to hemoglobin corresponds to the degree of oxygen saturation (SaO₂) within the artery. The oxygen saturation dissociation curve (Graph 1) illustrates the degree of oxygen saturation for each step change in the partial pressure of oxygen (PaO₂). The curve is sigmoid in shape with the steepest portion in the middle of the curve. The significance of this is that minor changes in PaO₂ impart different changes to SaO₂ depending on the position along the curve. When oxygen saturation is above 92%, changes in PaO₂ are difficult to recognize without invasive testing such as blood gas analysis, given the flat nature of the dissociation curve.

Oxygen saturation is depicted as SaO₂ and can range from 0-100%; normal saturation is 92% or greater. Conventional patient monitors measure peripheral oxygen saturation (SpO₂) and are frequently used interchangeably. Mixed venous oxygen saturation follows the same oxygen dissociation principles and is depicted as SvO₂.

Oxygen Delivery

The delivery of oxygen (DO₂) to the tissue is the product of oxygen content (CaO₂) of the blood and cardiac output (CO). The delivery of oxygen to the tissue is derived from the following equation(s):

• CO = HR x SV (HR = heart rate, SV = stroke volume)
• CaO₂ = SaO₂ x Hb x 1.34 + PaO₂ x 0.003 (Hb = hemoglobin)
• DO₂ = CaO₂ x CO

Once blood is transported to the tissues, oxygen is extracted from hemoglobin in a ratio corresponding to oxygen consumption (VO₂); under aerobic conditions the normal extraction ratio is 25%. The oxygen extraction ratio (OER) can be represented as a relationship between oxygen delivery and oxygen consumption (Graph 2).

• OER = VO₂/DO₂ = (SaO₂ -SvO₂) /SaO₂

As oxygen consumption increases or oxygen delivery falls, the OER will rise in order to maintain aerobic metabolism. At the threshold where oxygen delivery can no longer fulfill oxygen consumption, anaerobic metabolism develops and there is an accumulation of oxygen debt. Oxygen debt commences when the maximum OER is attained (e.g. between 60-70%). As blood returns to the heart for re-oxygenation, the mixed venous (or central venous) oxygen saturation can be measured invasively. This measure can provide an inference to the balance between oxygen delivery and oxygen consumption.

To summarize, there exists a balance between oxygen intake, oxygen delivery and oxygen consumption. The figure below (Figure 3) provides a visual representation of this balance. The expiratory phase of the oxygen transport process affords the opportunity to measure end-tidal gases. Clinical practice has used end-tidal CO₂ for several decades. Indications for use include but are not limited to procedural sedation,²  adequacy of laryngeal intubation,³  pediatric critical care⁴  and cardiopulmonary resuscitation.⁵  In contrast, there has been a paucity of use cases for monitoring end-tidal oxygen. The subsequent sections aim to illustrate emerging opportunities for further clinical research for use of end-tidal oxygen measurements.

Emerging topics on end-tidal oxygen measurement

Recent research has explored the utility of end-tidal oxygen measurement in a variety of clinical scenarios. Here are several applications for which end-tidal oxygen measurement has shown potential for clinical benefit.

Ventilation Assessment

Historically, the core measures associated with monitoring respiratory function included pulse oximetry (SpO₂) and end-tidal CO₂ (etCO₂). Both are available noninvasively and provide minute-by-minute data streams that can inform the clinician of potentially serious perturbations in respiratory status. It has been established that end-tidal CO₂ can serve as an estimate for PaCO₂ and thus inform clinicians on the ventilation and CO₂ elimination status of a patient.6  However, changes in end-tidal CO₂ incorporate the impact of buffering of CO₂ within the blood and reflect a delayed view of ventilatory changes.^{7, 8} In the future, breath-by-breath analysis of oxygen concentration may support enhanced ventilatory status monitoring.

A study by Linko et al. aimed to evaluate relationships that may exist between end-tidal oxygen and arterial gas measurements during periods of hypoventilation.⁸  The authors conducted a large animal study in pigs during a series of planned hypoventilation conditions. Minute ventilation was decreased by 50% and 75% from the baseline in order to measure the utility of etO₂ through these changes in minute ventilation. In addition, FiO₂ was changed through five step increments (20%, 40%, 60%, 80% and 100%).

The researchers observed an association between etO₂ and PaO₂ when the FiO₂ was 40% or less. As hypoventilation worsened, both etO₂ and PaO₂ decreased, and the relationship was more robust when the FiO₂ approximated room air. The authors introduced a gradient measure between FiO₂ and etO₂, from here on termed as the oxygen gradient. When ventilation was reduced by 50%, the PaO₂ fell by 23% and the FiO₂ – etO₂ (oxygen gradient) increased 112%, but no change in SpO₂ was observed. This further supports the hypothesis that SpO₂ as measured by pulse oximetry is an insensitive indicator of hypoventilation. The authors concluded that FiO₂ – etO₂ is the most sensitive parameter for detection of hypoventilation. Furthermore, increases in the FiO₂ – etO₂ gradient indicated an imbalance between oxygen delivery (DO₂) and oxygen consumption (VO₂), and changes in FiO₂ – etO₂ predicted the onset of hypoxemia earlier than SpO₂.

Building off of these animal results, the same authors conducted a human study during general anesthesia.⁹  In this clinical study (n=20 patients), they performed breath-by-breath recording of oxygen, carbon dioxide and oxygen saturation during general anesthesia and immediately during recovery. During periods of apnea, the decreasing alveolar oxygen was detected earlier by the oxygram (etO₂) than by SpO₂. During hypoventilation, the end-tidal O₂ changes were identified more rapidly than changes in etCO₂. More important, the FiO₂-etO₂ gradient served as a more sensitive index of hypoventilation than either end-tidal CO₂ or pulse oximetry.

Changes in the oxygram and specifically the oxygen gradient during periods of hyperventilation have also shown promise. A study was conducted in spontaneously breathing healthy volunteers (n=10) using a T-piece system designed to attain non-rebreathing conditions.10  Inspiratory oxygen (FiO₂) and carbon dioxide (FiCO₂) were measured along with expired oxygen (etO₂) and carbon dioxide (etCO₂) fractions and oxygen saturation (SpO₂). Each of the volunteers underwent a standardized sequence of ventilation (minute ventilation, VE) changes based on resting respiratory status. The first step of hyperventilation was to double VE from the baseline; five minutes thereafter the VE was tripled and held for five minutes. A simulated hypoventilation occurred thereafter - the patients were instructed to return to resting ventilation for another five minutes. This aimed to reflect a relative hypoventilation condition. There was no change to the FiO₂ during this sequence of ventilation interventions.

The oxygen gradient (FiO₂-etO₂) was tracked during each change in ventilation VE. The minute ventilation changed from 3.3 liters m-2 min-1 at rest, to 6.4 at 5 minutes (p<0.01), 8.4 at 10 minutes (p<0.01) and 2.5 (p<0.01) at 15 minutes. This latter measure reflected the relative hypoventilation state when compared to the 10-minute mark of 3x VE.

In summary, there is limited evidence to suggest that end-tidal oxygen measurement has clinical utility in the assessment of hypoventilation that trumps the use of pulse oximetry. The utility of etO2 monitoring is optimal when the FiO₂ is between 21-40%. The use of supplemental oxygen beyond 40% does not provide clinically meaningful information because the sensitivity of the FiO₂ – etO₂ relationship degrades. In the study, the oxygen gradient (FiO₂-etO₂) changed from a baseline value of 48 mm Hg to 29 mm Hg at 5 min and 22 mm Hg at 10 min (all p<0.01)*. During the period of relative hypoventilation, the oxygen gradient increased to 62 mm Hg (p<0.05). End-tidal CO₂ changes during the experiment showed a resting value of 45 mm Hg, decreasing to 34 mm Hg at 5 minutes, 27 mm Hg at 10 minutes, and increasing to 40 mm Hg at 15 minutes (all p<0.01). Pulse oximetry showed modest changes of 96.3%, 97.2%, 97.6% and 92.9% at rest and at 5, 10 and 15 minutes, respectively.

In this study, the oxygen gradient (FiO₂-etO₂) showed an inverse relationship to VE, and for a 50% decrease in VE the oxygen gradient increased by 50%. The changes in oxygen gradient were more rapid than changes in end-tidal CO₂. In addition, the relative change in oxygen gradient was larger than that of etCO₂. In contrast, oxygen saturation showed modest changes during the sequence of hyperventilation steps. Therefore, the authors concluded that the oxygen gradient (FiO₂-etO₂) could provide earlier indications of changes to ventilation than conventional measurements of etCO₂ and SpO₂, especially when FiO₂ was ≤40%. Extrapolation to the use of the FiO₂-etO₂ gradient in spontaneous weaning trials appears to be a logical avenue for future exploration. The gradient has shown the ability to correlate with changes in minute ventilation, and it changes more quickly than changes in either etCO₂ or SpO₂. Use of the oxygen gradient may provide clinicians with an added layer of detail that can better indicate when patients are suitable for weaning.

* Data was originally presented in kPa but was converted to mm Hg using publicly available conversion calculators https://www.checkyourmath.com/convert/pressure/kilopascals_mmhg.php

ED applications of the capnograph and oxygraph

Procedural Sedation

Procedural sedation involves the use of intravenous agents used to induce a level of sedation and analgesia in order to facilitate painful procedures. In the emergency department (ED), representative procedures would include laceration repair, fracture reduction, incision and drainage, and cardioversion. Adverse events are known to occur and, while rare, some can be serious, such as apnea, bradycardia, hypotension and aspiration. Advances in procedural sedation have evolved from use exclusively within the operating theater to use more broadly within the hospital setting, including the ED.

Cardiopulmonary complications that occur during procedural sedation are often related to respiratory depression that cascades into hypoxia and cardiac decompensation. Respiratory depression can occur in up to 44% of ED cases undergoing procedural sedation.²  Standard monitoring has included continuous pulse oximetry and cardiac monitoring throughout the procedure to provide a layer of patient safety. More recently, the use of end-tidal CO₂ capnography has grown in adoption to further augment patient safety. End-tidal capnography has the benefit of recognizing respiratory depression earlier than pulse oximetry and has been found to be more sensitive than clinical evaluation. In fact, compromised respiratory function was detected 5 to 240 seconds earlier with continuous etCO₂ monitoring when compared to changes in pulse oximetry.^{11, 12}

The premise of end-tidal capnography relies on the understanding of the ventilation and gas exchange principles that were described earlier. When intravenous agents that induce sedation or analgesia result in respiratory depression, changes in ventilation (decreased VE) will result in a decreased release of carbon dioxide during exhalation. Over time, systemic carbon dioxide will accumulate and result in an upward deflection in the CO₂ capnograph. When increases in CO₂ are observed, the clinician can be alerted to reassess the patient’s airway and breathing status in order to prevent desaturation or more serious complications.

In a meta-analysis, end-tidal capnography demonstrated a significant reduction in the incidence of mild desaturation (relative risk = 0.77, 95% CI = 0.67-0.89).¹³  The odds of severe desaturation (SpO₂ ≤85%) were also significantly reduced (RR = 0.59, 95% CI = 0.38-0.78). Assisted ventilation, which requires the use of a bag-valve mask, was shown to be favorably impacted by using etCO₂ monitoring; the odds ratio was significantly lower at 0.47 (95% CI = 0.23-0.95) when compared to SpO₂. On the whole, this meta-analysis supported the conclusion that use of end-tidal CO₂ capnography during procedure sedation can improve patient safety via reductions in mild desaturation, severe desaturation and assisted ventilation rates.

Building from there is the potential application of the oxygen gradient (FiO₂-etO₂), which shows a strong correlation to changes in minute ventilation as described earlier. Furthermore, the oxygen gradient has been reported to change more rapidly than etCO₂ and SpO₂ in response to hypoventilation. Could this measure add an incremental layer of patient safety to a procedure known to have the risk for respiratory complications?

Ventilation/Perfusion Mismatch

Efficient gas exchange at the alveoli is dependent upon matching alveolar ventilation (V) and perfusion (Q). An imbalance between these two can result from impaired ventilation or reduced perfusion and is termed a ventilation-perfusion (V/Q) mismatch. This mismatch results in suboptimal oxygenation of blood in the pulmonary artery and in turn negatively affects oxygen delivery (DO₂). As stated earlier, impairment in DO₂ can progress into anaerobic metabolism and organ damage. The hallmark condition associated with a V/Q mismatch is a pulmonary embolism, which results in a subtotal obstruction within the pulmonary arterial circulation and can be fatal depending on the degree of obstruction.

Pulmonary embolism is a medical condition that commonly presents with a combination of chest pain, shortness of breath and hypoxemia.¹⁴  The clinical presentation can be diverse, and many diagnostic and imaging modalities have been deployed with the aim to improve the diagnostic accuracy. Diagnostic algorithms have been introduced in order to enhance the diagnostic precision of pulmonary embolism through the combination of clinical presentation, laboratory tests and diagnostic imaging modalities.¹⁵  Paoletti et al. illustrated that end-tidal CO₂ was significantly lower while end-tidal O₂ was significantly higher in patients with pulmonary embolism compared to normal patients, or patients with chronic obstructive lung disease.¹⁶  This led to the hypothesis that end-tidal CO₂/O₂ ratio will be lower in patients with pulmonary embolism.

Kline et al. conducted a study to assess the clinical utility of end-tidal PCO₂ and PO₂ as noninvasive diagnostic tools in the assessment of patients with suspected pulmonary embolism (PE).¹⁷  Furthermore, they assessed deep exhalation or 30-second averaged end-tidal measurements obtained during normal tidal breathing. The PO₂, PCO₂ and PCO₂/PO₂ ratio remained stable during repeated measures across both breathing techniques. There was clear separation in PCO₂/PO₂ ratio between PE-positive patients compared to PE-negatives; that was observed with both deep exhalation and 30-second averaged tidal breathing measurements. Furthermore, receiver operating characteristic curves were plotted and were robust for both end-tidal breath assessments. The area under the curve (AUC) for deep exhalation was 0.728 compared to 0.803 for 30-second tidal breathing. The PCO₂/PO₂ cutoff that yielded a sensitivity of 95% was 0.40. Lastly, the authors combined pre-test probability with the PCO₂/PO₂ cutoff and concluded that this approach could provide a definite rule-in for 67.4% of patients.

This single-center study builds off of previous evidence that suggests end-tidal measurements of both oxygen and carbon dioxide can serve as an effective screening tool for suspected pulmonary embolism. This solution would be noninvasive, simple and rapid to obtain. A multi-center study conducting similar assessments would add weight to the potential clinical utility of this diagnostic approach.

Preoxygenation During Rapid Sequence Intubation

Another intervention central to emergency medicine practice is rapid sequence induction (RSI) and intubation to place a patient on mechanical ventilation. The first step of RSI is to preoxygenate the patient. This involves the removal of nitrogen stored within the body (denitrogenization) and replacement with oxygen. The basis for denitrogenization is to create a reservoir of oxygen within the pulmonary system that prevents hypoxia during the apneic phase of intubation. Common practice in the ED is to measure continuous SpO₂ during RSI; use of gas analyzers remains uncommon. Present-day gas analyzers can measure etCO₂ and etO₂ levels in real time to provide clinicians with another layer of data that informs respiratory function.

The premise of using etO₂ was first used in the operating theater for optimizing preoxygenation.^{18, 19}  Guidelines recommend that critically ill patients undergoing RSI be preoxygenated until the etO₂ level reaches ≥ 85%.²⁰  A study by Caputo et al. was the first conducted in the ED addressing etO₂ measurements in patients undergoing RSI.²¹  In this two-center prospective study in patients requiring RSI, a total of 100 patients were enrolled. At the initiation of preoxygenation, the median etO₂ was 53%, and at the induction phase the etO₂ was 78%; there was no difference between use of a nonrebreather mask compared to bag-valve-mask ventilation. Only 25% (n=26) of the patients achieved a target etO₂ level of 85%, while 36% achieved levels between 70-85% and 27% attained levels of 50-69%. In addition, 11% did not achieve an etO₂ level > 50%. Desaturation below 90% occurred in 18% of patients and marked desaturation (<80%) occurred in 2% of the cases. Among the cases that experienced desaturation, only 11% had an etO₂ >85% at the time of induction. These authors concluded that measurement of etO₂ in the ED may be a valuable adjunct to optimize preoxygenation during emergency airway management requiring RSI.

Another study conducted in the ED assessed the reliability of end-tidal oxygen measurement to predict arterial oxygen (PaO₂) during RSI.²²  The authors specifically examined the relationship between FiO₂ and etO₂ at the time of induction to predict PaO₂. In this single-center prospective study, 75 patients were enrolled who required RSI for emergency airway support. Preoxygenation was controlled with a mean time of 12.5 minutes and a mean apnea time of 59 seconds. The predicted and actual PaO₂ were recorded within 3 minutes of intubation; the predicted PaO₂ was derived from an equation using FiO₂ and etO₂ values. The Pearson correlation coefficient was strong: r=0.89 (95% CI 85-92%) and the Bland-Altman plots suggested no substantial bias affecting correlation. The authors summarized that use of a gas analyzer to measure FiO₂ and etO₂ can provide a reliable measure of the minimum PaO₂ during RSI. Future research should explore other uses of end-tidal oximetry, this PaO₂ prediction equation, and other relationships to further optimize patient respiratory function.

Prediction of Central Venous Oxygen Saturation

Mixed venous oxygen saturation (SvO₂) is used commonly within the intensive care unit (ICU) and for high risk surgery (i.e. liver transplant or cardiothoracic surgery). The central venous oxygen saturation (ScvO₂) is commonly used in the acute care setting (ED, ICU) as a surrogate for SvO₂ because it is less invasive. The SvO₂ requires placement of a highly invasive pulmonary artery catheter within the pulmonary artery while ScvO₂ needs the placement of a central venous catheter within the right atrium. In both the central and mixed venous saturation, the measure is used as a surrogate for cardiac output and thus oxygen delivery (DO₂). Understanding oxygen delivery is critical when managing a patient with sepsis or other serious illnesses that can compromise the balance between oxygen delivery and oxygen consumption. In shock states like sepsis, the patient’s DO₂ may be imbalanced compared to oxygen consumption (VO₂), and that can contribute to oxygen debt that manifests as an elevation in serum lactate. A noninvasive surrogate marker for ScvO₂ would be desired, especially in the ED where the majority of sepsis cases first present.

The premise behind this is the understanding of the oxygen-hemoglobin disassociation curve, where the percentage of red blood cells bound to oxygen varies with the partial pressure of oxygen in the plasma and follows a sigmoidal curve. Equilibration of the partial pressure of oxygen between the alveolus and pulmonary mixed venous capillaries (alveolar unit) occurs rapidly throughout the respiratory cycle. Therefore, one can surmise that the partial pressure of oxygen in the central blood would correlate directly with the nadir partial pressure of oxygen in a deep expired breath. This could serve as a noninvasive means to estimate ScvO₂.

A study conducted by Singer et al. aimed to assess the agreement between end-tidal oxygenation and ScvO₂ in critically ill patients managed in an ED setting with a central venous catheter in place.²³  This study enrolled 27 patients in a prospective observational study where etO₂ was measured at the time blood was drawn from a central venous line for the purpose of measuring ScvO₂. Modest agreement was observed via Bland-Altman plots demonstrated with bias towards etO2 under-representing ScvO₂.

Leveraging the potential association between etO₂ and ScvO₂, a separate study was conducted by Jones et al.²⁴ in a convenience sample of patients with end-stage renal disease undergoing elective hemodialysis managed through a pre-existing central venous catheter. A side-stream analyzer was used to measure etO₂ and etCO₂ immediately after central venous blood was drawn for ScvO₂ analysis. Patients were instructed to perform repeated deep exhalation breathing in order to obtain an average etO₂ measure. In total, 21 patients were prospectively enrolled, and no significant correlation between etO₂ and ScvO₂ was identified. A linear equation incorporating etO₂ and ScvO₂ had modest predictive accuracy. Despite the lackluster findings, one limitation deserves attention. This study used a side-stream measurement technology that could have resulted in inaccurate measurements and deep expiratory breathing may not be representative of the ScvO₂. In addition, a methodological design that considers the use of tidal breathing over 30 seconds to measure the average nadir etO₂ could be more predictive.

Clinicians for years have explored noninvasive means to evaluate patients with or at-risk of critical illness, and these include end-tidal oxygen measurements. While no strong association has been identified between etO₂ and ScvO₂ at this time, future research to examine alternate measurement techniques and waveform analysis leveraging etO₂ may provide additional details on clinical utility for this application.

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