End-tidal Oximetry Podcast Series

Hi, I am Dr. Robert Bilkovski. Welcome to this podcast series on end-tidal oximetry. In this podcast titled - Principles of Oxygen Exchange, which is the first in the series on the concept of end-tidal oximetry, we will focus on gaining a high-level understanding of oxygen transport basics and the concept of oxygen exchange within the alveolar unit. Future podcasts will dive into more detail including the concept of the oxygen gradient, end-tidal CO₂ and O₂ measurement and how end-tidal oximetry may be used clinically.

Before we review the application of respiratory gas measurement, we should first start with an overview 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. 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 ATP, which is essential for cellular function. As a byproduct of cellular metabolism, carbon dioxide is produced, which is transported from the tissue via the circulatory system back through the lungs is removed during gas exchange within the alveoli and exhalation.

Changes to lung ventilation that become clinically significant are commonly identified through measurement of respiratory gasses during exhalation or end-tidal measurements. For instance, under respiratory distress, where ventilation is rapid and deep, the amount of CO₂ being cleared during exhalation increases, and this is reflected as a low end-tidal CO₂ that corresponds with a low arterial CO₂ content. In contrast, when respiratory failure is imminent and ventilation is decreasing in depth and frequency, the amount of CO₂ being cleared falls and as a result the end-tidal CO₂ value will increase for the amount of CO₂ within the blood stream is accumulating.

Taking a closer look at gas exchange in the lungs, the simplest approach is to focus on a single alveolar unit that is part of innumerable alveolar units within the lungs. 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 oxygen and carbon dioxide occurs at the end-capillary portion of the alveolar unit. This gas exchange occurs as a result of diffusion gradients.   A diffusion gradient exists when the partial pressure of a gas, for instance oxygen, is different when separated by a permeable membrane, in this case at the alveolar. What results is equilibration via diffusion between the high and low concentrated compartments.

Under normal gas exchange, the partial pressure of oxygen in the alveolus is greater than that in mixed venous circulation. For CO₂, the opposite exists, where the partial pressure of CO₂ is greater in the mixed venous circulation.  The presence of diffusion gradients for O₂ and CO₂ will result in equilibration as blood traverses through the alveolar unit. The diffusion properties of CO₂ are greater than those of oxygen and as a result, the equilibration between the mixed venous capillary and alveolar compartments occurs sooner during transit of blood though the alveolar unit. To illustrate this difference in diffusion capability – when the partial pressure gradient of CO₂ is 5 mm Hg, an equal amount of CO₂ is exchanged compared to an oxygen partial pressure gradient that is 12 times greater at 60 mm Hg.^[1]  Therefore, within each alveolar unit, CO₂ equilibrates more quickly than O₂. This is an important factor in understanding how changes in ventilation or perfusion can impact arterial or end-tidal gases.

As a result, abnormalities in cardiopulmonary function can impact gas exchange and result in changes to the partial pressure of oxygen and carbon dioxide and can be observed via end-tidal measurements of these two gases in real-time.

This concludes the first podcast in the series of end-tidal oxygen monitoring with the next module focusing on the greater details around the concept of the “oxygen gradient.” Thank you for listening.

References

[1]     Johan Petersson and Robb W. Glenny, “Gas Exchange and Ventilation-Perfusion Relationships in the Lung,” The European Respiratory Journal 44, no. 4 (October 2014): 1023–41, https://doi.org/10.1183/09031936.00037014.

Hi, I am Dr. Robert Bilkovski. Welcome to this podcast series on end-tidal oximetry. In this podcast titled - Principles of End-Tidal Oximetry and the Oxygen Gradient, which is the second podcast in this series, we will take aim at the concept of end-tidal oximetry and the oxygen gradient and how it may be clinically applied.

The core measures associated with monitoring respiratory function include pulse oximetry and end-tidal CO₂. Both are non-invasive and provide minute-by-minute data that can inform the clinician of potentially serious perturbations in respiratory status. As was discussed in our first podcast in this series, end-tidal CO₂ can serve as an estimate for the arterial CO₂ content in the blood and thus inform clinicians on the ventilation and CO₂ elimination status of a patient.¹

However, changes in end-tidal CO₂ reflect the impact of carbon dioxide buffering that occurs within the blood and thus, reflects a delayed view of ventilatory changes.^2,3

A more novel concept is the measurement of end-tidal oxygen, and while the amount of clinical literature on this topic is small compared to end-tidal CO₂, there are some interesting avenues worthy of further study.

First, back in 1989, authors from Finland conducted a series of studies evaluating the association between end-tidal oxygen and the partial pressure of oxygen. From their studies, the term “oxygen gradient” was first used. Simply stated the oxygen gradient is the difference between the fraction of inspired oxygen and the end-tidal oxygen.^{2, 4}

These authors observed a relationship between the partial pressure of oxygen and end-tidal oxygen in their large animal study; notably when the fraction of inspired oxygen was at or below 40%. When ventilation was reduced in this animal study by 50% they observed a 23% decrease in the partial pressure of oxygen while the oxygen gradient increased 112%. More important was that there was no change in pulse oximetry, thereby suggesting that SpO₂ is a less sensitive indicator of hypoventilation than end-tidal oximetry. These authors conducted a human study in subjects undergoing abdominal surgery where similar observations were noted during periods of controlled hypoventilation.

In this 20-subject study, breath-by-breath recording of oxygen, carbon dioxide and oxygen saturation occurred during general anesthesia and immediately during recovery. During periods of apnea, the decreasing alveolar oxygen was detected earlier by the end-tidal oximetry than by SpO₂ or end-tidal capnography. Similarly, during hypoventilation, the end-tidal oximetry changes were identified more rapidly than changes in the other two continuous measures. The authors concluded that the oxygen gradient, which is FiO₂ minus end-tidal O₂, served as a more sensitive index of hypoventilation than either end-tidal CO₂ or pulse oximetry.

Granted, this data from Linko and colleagues is limited, and caution should be noted to avoid making broad conclusions on clinical utility. What is of interest is the potential areas of research and where additional data regarding end-tidal oximetry show promise.  That will be the focus of our next podcast. Until then, this concludes the second podcast in the series and thank you for listening.

References:

[1]J. F. Nunn, Applied Respiratory Physiology, 2d ed. (London, Boston: Butterworths, 1977).

[2]K Linko and M Paloheimo, “Inspiratory End-Tidal Oxygen Content Difference: A Sensitive Indicator of Hypoventilation,” Critical Care Medicine 17, no. 4 (April 1, 1989): 345–48, https://doi.org/10.1097/00003246-198904000-00009.

[3]Harvey A Zar et al., “Monitoring Pulmonary Function with Superimposed Pulmonary Gas Exchange Curves from Standard Analyzers,” n.d.

[4] Kai Link and Markku Paloheimo, "Monitoring of the Inspired and End-tidal Oxygen, Carbon Dioxide, and Nitrous Oxide Concentrations: Clinical Applications during Anesthesia and Recovery", Journal of Clinical Monitoring 5, no.3 (July 1, 1989): 149-56), https://doi.org/10.1007/BF01627446

Hi, I am Dr. Robert Bilkovski. Welcome to this podcast series on end-tidal oximetry. In this third and final podcast in this series, titled – Clinical Use Cases for End-Tidal Oximetry, we discuss areas where end-tidal O₂ measurements have been used to inform clinical decision making. Of note, we will pay particular attention to use during RSI, which is rapid sequence induction for intubation.

To start, let´s look at the potential application during weaning trials. One approach is to use a T-piece that requires the patient to breathe through the breathing circuit. Success during a T-piece breathing trial can inform the clinician that the patient is suitable to be extubated. In a small 10-subject trial, end-tidal oximetry was used along with end-tidal CO₂ to evaluate healthy volunteer response to changes in ventilation.^[1] Patients were guided to perform hyperventilation through a structured approach such that measurements at baseline, 2x and 3x minute ventilation occurred. This was followed by a period of relative hypoventilation as the patient’s minute ventilation returned to baseline levels. Of note, the oxygen gradient which is the difference between FiO₂ and end-tidal O₂ was found to be inversely related to minute ventilation and consistent between hyperventilation and hypoventilation. A 50% decrease in minute ventilation corresponded to an approximate 50% increase in oxygen difference. More importantly, as also published by Linko et al,^[2] the response in oxygen index was more quickly recognized than changes in end-tidal CO₂. Lastly, only modest changes in oxygen consumption and cardiac output were observed despite the oxygen gradient changes being recognized. This data shows that the oxygen gradient correlates with changes in minute ventilation, and it changes more quickly than changes in either end-tidal CO₂ or SpO₂.This implies that the oxygen gradient may support the clinician to an earlier warning of impending weaning trial failure, however this requires further study.

The other clinical scenario where end-tidal oximetry has demonstrated some clinical evidence during rapid sequence induction is during intubation, known as RSI.

The first step of RSI is to preoxygenate the patient. This involves the removal of nitrogen stored within the body, termed 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.

In the operating room guidelines state that a patient should be pre-oxygenated until the end-tidal oxygen be greater than or equal to 85%.^[3] In the emergency department, Caputo conducted a study of 100 patients to evaluate compliance with this 85% threshold that is applicable to anesthesia in the OR.^[4] In fact, only 25% of the patients evaluated attained the target preoxygenation target, 27% attained end-tidal O₂ between 50-69% and 11% failed to achieve a level above 50%. Desaturation as defined as SpO₂ less than 90% occurred in 18% of patients and in this sub-group only 11% achieved the 85% pre-oxygenation target at induction. The authors concludes that use of end-tidal oximetry may optimize pre-oxygenation during RSI in the emergency department.

Both of these clinical use cases highlight that there is a small body of evidence that suggests end-tidal oximetry may improve care delivery during weaning trials and RSI in the emergency department. There is a need for more clinical data before definitive conclusions can be made on the relevant patient populations and limitations around use.

This concludes the third and final podcast in this series on end-tidal oxygen monitoring and be on the lookout for other podcasts. Thank you for listening.

References

[1]     J. Bengtsson et al., “Effects of Hyperventilation on the Inspiratory to End-Tidal Oxygen Difference,” British Journal of Anaesthesia 73, no. 2 (August 1994): 140–44, https://doi.org/10.1093/bja/73.2.140.

[2]     Linko, Kai, and Markku Paloheimo. “Monitoring of the Inspired and End-Tidal Oxygen, Carbon Dioxide, and Nitrous Oxide Concentrations: Clinical Applications during Anesthesia and Recovery.” Journal of Clinical Monitoring 5, no. 3 (July 1, 1989): 149–56. https://doi.org/10.1007/BF01627446.

[3]     A. Higgs et al., “Guidelines for the Management of Tracheal Intubation in Critically Ill Adults,” British Journal of Anaesthesia 120, no. 2 (February 1, 2018): 323–52, https://doi.org/10.1016/j.bja.2017.10.021.

[4]     Nicholas D. Caputo et al., “Use of End Tidal Oxygen Monitoring to Assess Preoxygenation During Rapid Sequence Intubation in the Emergency Department,” Annals of Emergency Medicine 74, no. 3 (September 2019): 410–15, https://doi.org/10.1016/j.annemergmed.2019.01.038.