Non-invasive prospective targeting of arterial P(CO2) in subjects at rest.

Accurate measurement of arterial PCO2 (PaCO2) is important for the clinical assessment of patients and, in physiological studies, for the assessment of control of breathing and cerebral blood flow. Currently, the reference standard for measuring PaCO2 is analysis of arterial blood via direct arterial puncture. This invasive approach has a number of disadvantages for both the subject (discomfort and potential arterial wall damage) and investigator (restricted mobility of the catheter insertion site, cost, time delay for blood analysis, and limited temporal resolution of changes in PaCO2). As a result, investigators have long sought a suitable non-invasive method to measure PaCO2. Non-invasive methods of predicting PaCO2 from alveolar PCO2 (PACO2) consider the lung to be a tonometer in which CO2 equilibrates between alveolar gas and capillary blood. In reality, however, the lung is not a single homogeneous time-invariant gas exchange compartment. Rather, PCO2 varies in different regions of the lung as a result of differences in ventilation-to-perfusion matching throughout the lung and, in each lung region, throughout the respiratory cycle (Dubois et al. 1952; Lenfant, 1967). The contribution to the PaCO2 of blood passing each alveolus reflects the average PCO2 in that alveolus during the respiratory cycle (Jones et al. 1979; Robbins et al. 1990). PaCO2, then, reflects the time- and flow-weighted averages of all alveolar ventilatory fluctuations in all regions throughout the lung, i.e. the mean PaCO2 (Lenfant, 1967). As a result, the relation between the PCO2 in the exhaled gas and the PaCO2 is so obscured that one cannot calculate the PaCO2 from the PaCO2. We reasoned that if the regional variations of PCO2 in the lung could be reduced, then (a) the end-tidal PCO2 (PET,CO2) would accurately reflect the mean PaCO2 and (b) the PaCO2 would not be affected by the distribution of pulmonary blood flow. In other words, PET,CO2 should equal mean PaCO2, and, as mean PaCO2 is equal to PaCO2 (Jones et al. 1979; Robbins et al. 1990), PET,CO2 should equal PaCO2. In our laboratory, we have experimented with a method of controlling PET,CO2 by providing specific flows and concentrations of CO2 to a sequential gas delivery circuit (Slessarev et al. 2007). To the extent that minute ventilation exceeds such gas flow, previously expired gas, stored in an expiratory gas reservoir, enters the lung (Somogyi et al. 2005). This gas, we hypothesized, reduces both the regional variations and respiratory fluctuations of PaCO2 towards a mean PaCO2 (see Fig. 2 in Prisman et al. 2007). We tested this hypothesis using the method of Slessarev et al. (2007) to prospectively target a series of PET,CO2 values and measuring mean PaCO2 by analysing contemporaneously drawn arterial blood samples for PCO2. To test the robustness of the relation between PET,CO2 and PaCO2, we also varied the end-tidal PO2 values (PET,O2) and breathing frequencies (f) at each target PET,CO2. Figure 2 Example data