Current methods of forcing end‐tidal P_CO2 (P_ETCO2) and P_O2 (P_ETO2) rely on breath‐by‐breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo‐control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath‐by‐breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P_ETCO2 and P_ETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P_ETCO2 from control (40 mmHg for P_ETCO2 and 100 mmHg for P_ETO2) to two target P_ETCO2 values (45 and 50 mmHg) at iso‐oxia (100 mmHg), P_ETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P_ETCO2 with P_ETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P_ETCO2 and P_ETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P_ETCO2 was ± 1 mmHg, and for P_ETO2 was ± 4 mmHg. P_ETCO2 varied by ± 1 mmHg and P_ETO2 by ± 5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min⁻¹). We conclude that targeted end‐tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed‐forward, low gas flow system.

Accurate measurements of arterial P (P) currently require blood sampling because the end‐tidal P (P) of the expired gas often does not accurately reflect the mean alveolar P and P . Differences between P and P 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 from P . We tested this hypothesis in five healthy middle‐aged men by comparing their P values with P values at various combinations of P (between 35 and 50 mmHg), P (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 was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P and average P 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 was −0.1 ± 1.6 mmHg (95% CI −3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P and P over the ranges of P , f and target P . We conclude that when breathing via a sequential gas delivery circuit, P provides as accurate a measurement of P as the actual analysis of arterial blood.

Cerebrovascular reactivity (CVR) studies have elucidated the physiology and pathophysiology of cerebral blood flow regulation. A non-invasive, high spatial resolution approach uses carbon dioxide (CO₂) as the vasoactive stimulus and magnetic resonance techniques to estimate the cerebral blood flow response. CVR is assessed as the ratio response change to stimulus change. Precise control of the stimulus is sought to minimize CVR variability between tests, and show functional differences. Computerized methods targeting end-tidal CO₂ partial pressures are precise, but expensive. Simpler, improvised methods that fix the inspired CO₂ concentrations have been recommended as less expensive, and so more widely accessible. However, these methods have drawbacks that have not been previously presented by those that advocate their use, or those that employ them in their studies. As one of the developers of a computerized method, I provide my perspective on the trade-offs between these two methods. The main concern is that declaring the precision of fixed inspired concentration of CO₂ is misleading: it does not, as implied, translate to precise control of the actual vasoactive stimulus – the arterial partial pressure of CO₂. The inherent test-to-test, and therefore subject-to-subject variability, precludes clinical application of findings. Moreover, improvised methods imply widespread duplication of development, assembly time and costs, yet lack uniformity and quality control. A tabular comparison between approaches is provided.