This chapter is vaguely related to Section F12(ii) from the 2023 CICM Primary Syllabus, which expects the exam candidates to be able to "describe the principles of capnography, including calibration, sources of errors and limitations". Though the syllabus document does not explicitly state that this gap between PaCO2 and EtCO2 is essential knowledge, its constant appearance in the exams suggests that it probably is. It has featured in three SAQs, each of them essentially identical:
Of these, the college answer to Question 21 was the laziest ("Many candidates didn’t distinguish between the different types of dead space. In general this topic was not well understood."). The other two, however, were informative as to what was expected. Additionally, this topic has come up in the Part two exam papers, as Question 9.2 from the second paper of 2008, which at least listed some different causes for the gradient. As a result, the revision section from the Part Two exam has a brief entry on this topic, to help refresh the memories of senior trainees. Obviously, some occasional refreshing is called for, because none of the aforementioned SAQs had a pass rate higher than 30%.
- Normal PaCO2-EtCO2 difference is 2-5 mmHg (Satoh et al, 2015)
- This is due to alveolar dead space, which is small in healthy adults
- If there was no alveolar dead space, end-tidal CO2 would be identical to alveolar CO2
- Alveoli which are ventilated but not perfused (i.e. alveolar dead space) contain a gas mixture which is identical to inspired gas
- Thus, the addition of their content to expired gas dilutes the expired CO2 concentration and decreases the end-tidal CO2 value
- Anatomical dead space does not contribute to the end-tidal CO2 concentration because at the end of expiration all of the anatomical dead space volume has already emptied
- Where ventilation is "perfect" (i.e. alveoli empty maximally) and dead space is minimal, end-tidal CO2 may be lower than aterial CO2
- Factors which increase the PaCO2-EtCO2 difference include:
- Changes in pulmonary perfusion
- Regional decreases in pulmonary perfusion
- Pulmonary embolism
- Fat embolism
- Air embolism
- Globally reduced pulmonary perfusion:
- Pulmonary hypertension
- Cardiac failure (RHF)
- Cardiac arrest
- Extreme hypovolaemia (eg. haemorrhagic shock)
- Very high PEEP or positive inspiratory pressure
- Changes in ventilation
- Increased V/Q mismatch or increased alveolar dead space
- High PEEP or positive airway pressure
- High FiO2 (causing shunt into poorly ventilated alveoli)
- Oesophageal intubation
- Very large shunt fraction (>30%)
- Measurement error
- Dilution of expired gas, eg. the presence of helium
- The presence of nitrous oxide (N2O may be misinterpreted as CO2)
- The use of an inline HME filter can reduce the end-tidal CO2 concentration.
- The timing of the measurement may be wrong: the measurement is only valid if it is truly end-tidal, and so any scenario where the measurement is taken before the end of expiration would produce a falsely depressed value.
This gap is very well known, and is clearly a favourite among examiners in all sorts of critical care fields. As such, there are many good articles and it is difficult to make one specific recommendation from among multiple good resources. One stand-out reference is Michael Donnelan's chapter for Applied Technologies in Pulmonary Medicine (2011), which is somehow paywalled by Karger by available for free via Google Books. Another excellent resource is Capnography Outside the Operating Rooms by Bhavani Shankar Kodali (2013). Kodali is in fact a prolific FOAM author and his website (capnography.com) is an absolute goldmine of carefully referenced information, in essence a textbook on caphography for those unwilling or unable to pay full price for Capnography by Gravenstein et al (2011).
The college answer to Question 9 from the first paper of 2009 suggests we all go look at Power & Kam's "Physiology for the Anaesthetist" where apparently there is "an excellent graph... which helps understand alveolar dead space". Back in those days, the college was somewhat undersubscribed with trainees, making them a valuable resource worth investing in; as such the examiner's comments are even furnished with a page reference to the aforementioned graph, something unthinkable in the modern era of disposable multitudes. Thus, it is possible to track down the aforementioned excellent graph and reproduce it here with no permission whatsoever (this version comes from the 3rd edition of the textbook, p.89):
Without going into an excess of detail (again), it will suffice to say that:
So, basically, it's all to do with dead space. Alveolar dead space in particular is what affects the end-tidal CO2 measurement, which is taken at the end of expiration. By that stage, anatomical dead space has completely emptied, and is no longer contributing to the total expired CO2 value. One might correctly say that the anatomical dead space contributes to expired capnography, but not to end-tidal capnometry, as it affects the shape of the early capnography curve. The college felt strongly enough about this distinction to complain that "many incorrectly attributed anatomical dead space as a contributor to the PaCO2-ETCO2 gradient" in their answer to Question 3 from the second paper of 2018. Interestingly, though dead space is the major reason for the PaCO2-EtCO2 gap, according to the examiners "discussion of the various types of dead space did not score marks".
From the above, it follows that there is some normal value for the PaCO2-EtCO2 gap, which would correlate to the volume of alveolar dead space (normally, a very small volume in healthy adults). Most textbooks give a range of 2-5 mmHg, usually without a reference. When a reference is available, they usually give Nunn & Hill (1960), who actually measured a mean value of 4.6 mmHg (S.D. ± 2.5)
For some more detailed empirical data, Satoh et al (2015) measured this gap in a series of patients, all anaesthetised and supine, and of different ages. The authors found values of 2.4-4.3 mmHg, which was apparently "similar to the gradient of values previously reported for other clinical situations". The difference increases slightly with age, which the authors attributed to age-related decrease in FRC and increase in alveolar dead space. The difference was not massive: in the original image below (Satoh et al, 2015, Figure 1) groups A to G are decades of age, starting with age 16. As one can see, there was barely 1-2mmHg difference between the groups, and all groups up to the age of 76 had individuals with a 0mmHg gap (i.e. no alveolar dead space whatsoever).
There are multiple possible reasons for an increase in the normally small difference between. These generally fall into three major categories. Either something happened to the lung's perfusion, or something happened to the ventilation of the perfused alveoli, or there is some problem with the way the measurement is being performed.
Yes, it is also possible to have a negative PaCO2 - EtCO2 gap, i.e. scenarios where the arterial CO2 is actually lower than the end-tidal, leading to confusion and bewilderment. Never fear: this is, in fact, what is supposed to occur, if you think about it carefully. Consider: the blood arriving to the lungs contains more CO2 than the blood leaving the lungs (because respiratory gas exchange do be like that), and it would be logical to expect arterial blood to be CO2-depleted. In other words, there should be an arteriovenous CO2 gradient, and in fact that is what you usually see, with a difference of around 6mmHg on average. Alveolar CO2 is a bit unpredictable but generally supposed to be in equilibrium with end-pulmonary-capillary blood (which is basically the same as arterial blood, somewhere around 40 mmHg). However, because of the extremely rapid equlibration of CO2 across the capillary distance, alveolar CO2 can sometimes be more representative of mixed venous blood, which has a PvCO2 of 46mmHg or so. This can occur in several common scenarios: