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

Abstract

Accurate measurements of arterial P(CO(2)) (P(a,CO(2))) currently require blood sampling because the end-tidal P(CO(2)) (P(ET,CO(2))) of the expired gas often does not accurately reflect the mean alveolar P(CO(2)) and P(a,CO(2)). Differences between P(ET,CO(2)) and P(a,CO(2)) result from regional inhomogeneities in perfusion and gas exchange. We hypothesized that breathing via a sequential gas delivery circuit would reduce these inhomogeneities sufficiently to allow accurate prediction of P(a,CO(2)) from P(ET,CO(2)). We tested this hypothesis in five healthy middle-aged men by comparing their P(ET,CO(2)) values with P(a,CO(2)) values at various combinations of P(ET,CO(2)) (between 35 and 50 mmHg), P(O(2)) (between 70 and 300 mmHg), and breathing frequencies (f; between 6 and 24 breaths min(-1)). Once each individual was in a steady state, P(a,CO(2)) was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P(ET,CO(2)) and average P(a,CO(2)) was 0.5 +/- 1.7 mmHg (P = 0.53; 95% CI -2.8, 3.8 mmHg) whereas the mean difference between the two measurements of P(a,CO(2)) was -0.1 +/- 1.6 mmHg (95% CI -3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P(ET,CO(2)) and P(a,CO(2)) over the ranges of P(O(2)), f and target P(ET,CO(2)). We conclude that when breathing via a sequential gas delivery circuit, P(ET,CO(2)) provides as accurate a measurement of P(a,CO(2)) as the actual analysis of arterial blood.

Figures

Figure 2. Example data

A, PET,O2 and PET,CO2 from one subject during Phase I of the protocol. Each end-tidal value is represented by a filled circle. Averages of two PaCO2 values at end of each 3 min test interval are represented by open triangles. Horizontal arrows designate the time during which f was maintained by breathing in synchrony with a metronome. Subjects were administered room air in the intervals between fixed f. Reductions in PCO2 between tests can be partly attributed to a rebound hyperventilation after hypercarbia, as was previously reported by Wise et al. (2007) and partly to artifact as the face mask was flooded with air at high flows between tests. In Phase I, before each period of breathing at controlled f, subjects were encouraged to hyperventilate for about 1–2 min to below a PET,CO2 of 35 mmHg so they could undergo a sharp step up to the new target PCO2. This was done to minimize the time to attain target end-tidal values and thereby shorten the duration of the protocol. PET,CO2 measurements and arterial blood sampling were performed only after a steady state was achieved. The increases in PET,O2 between periods of fixed f were the result of hyperventilation on room air. B, PET,O2 and PET,CO2 from one subject during Phase II of the protocol. Between periods of fixed f, subjects breathed room air without restriction.

Figure 1. Experimental protocol

Time course showing target end-tidal PO2 (PT,O2) and target end-tidal PCO2 (PT,CO2). In Phase I, PT,O2 was kept constant and PT,CO2 was set to three different levels for each of four different frequencies (f). In Phase II, PT,CO2 was kept constant and PT,O2 was set to three different levels for each of four different f. Upward pointing arrowheads indicate time for duplicate arterial blood sampling. Horizontal arrows indicate period of constant f.

Figure 3. Bland–Altman plots

The limits of agreement between PET,CO2 and PaCO2 (A) and the repeatability coefficient for repeat PaCO2 measurements (B).