Pathophysiological determinants of arterial carbon dioxide tension (PaCO2) in spontaneously breathing and mechanically ventilated patients

© Journal of Emergency and Critical Care Medicine. All rights reserved. J Emerg Crit Care Med 2021 | http://dx.doi.org/10.21037/jeccm-21-7 Changes in PaCO2 in hospitalised patients are common and associated with an increased risk of morbidity and mortality. Although many clinicians are aware of the physiological mechanisms for PaCO2 homeostasis, they often have difficulty understanding how different compensatory mechanisms interact, and why such interactions are not always successful in achieving normocapnia. Incorrect interpretation of PaCO2 level—even when it is within the normal range—can have dangerous consequences in a spontaneously breathing patient (1). In this correspondence, we briefly describe how we can visually interpret the interactions of different pathophysiological mechanisms in determining PaCO2 in a spontaneously breathing or mechanically ventilated patient. In a spontaneously breathing patient, there are two determinants of PaCO2. The respiratory drive from the brain is an active system (which can increase minute ventilation up to 10 L/min for every 3 mmHg PaCO2 increment unless PaCO2 is exceedingly high) (1); whilst the mathematical relationship between alveolar CO2 tension (or PaCO2 for simplicity), carbon dioxide production (VCO2 ~200 mL/min for an average adult that can increase up to 10 folds with vigorous exercise) and minute alveolar ventilation represents a passive system (Figure 1A) (2). Minute alveolar ventilation is equal to the minute ventilation minus the wasted ventilation due to the physiological dead space which is the sum of anatomical and alveolar dead space. The interaction between the active and passive systems defines the PaCO2. An increase in respiratory drive due to hypoxia or metabolic acidosis will increase the ‘slope’ of the active respiratory drive system, resulting in an increase in minute ventilation which will reduce PaCO2. As such, a PaCO2 within the normal range is actually abnormal in the presence of significant metabolic acidosis, and would signify concomitant respiratory drive depression (1). Respiratory depression due to opioids and sedatives will shift the active respiratory drive system to the right (Figure 1B), resulting in a lower minute ventilation and a higher PaCO2. An increase in VCO2 will shift the passive system upward, resulting in a higher PaCO2, until the active respiratory drive system shifts the slope upward to normalise the PaCO2 (Figure 1C). An increase in alveolar dead space—which can occur due to emphysema, reduced pulmonary blood flow without a corresponding reduction in ventilation or overventilating poorly perfused alveoli [i.e., ↑ overall ventilation to perfusion (V/Q) ratio], ↑ V/Q heterogeneity in acute respiratory distress syndrome (ARDS) and pneumonia (3), or attenuation of the normal hypoxic pulmonary vasoconstriction due to oxygen supplementation)—will shift the passive system to the right, resulting in a higher PaCO2 (Figure 1D). Acute pulmonary embolism would theoretically increase alveolar dead space; an elevation of PaCO2 is, however, often not observed. This is because any increase in PaCO2 and reduction in arterial oxygen tension (PaO2) will be sensed by the medullary and carotid Letter to the Editor