A quick and easy method of measuring the hypercapnic ventilatory response in patients with COPD.

BACKGROUND: Hypercapnic ventilatory response (HCVR) techniques have not previously been adequately validated in patients with chronic obstructive pulmonary disease (COPD). We have tested the hypothesis that end-tidal PCO(2) may be used to test the HCVR in COPD during non-steady-state rebreathing, despite the fact that large (arterial-end-tidal) PCO(2) differences (P(a-et)CO(2)) exist during air breathing. METHODS: Eight patients and 11 healthy volunteers underwent steady-state HCVR testing and non-steady-state rebreathing HCVR testing, using Pa and PetCO(2). RESULTS: In COPD patients, PetCO(2) was lower than PaCO(2) by a constant amount throughout steady-state HCVR, but equalised with PaCO(2) during non-steady-state HCVR. Consequently there were no differences in HCVR slope using either method (steady-state p=0.91; rebreathing p=0.73), or HCVR intercept in rebreathing (p=0.68) whether PaCO(2) or PetCO(2) was used. The steady-state HCVR intercept using PetCO(2) was greater than that using PaCO(2) (p=0.02). In healthy volunteers PetCO(2) equalised with PaCO(2) during steady-state HCVR, but was progressively greater than PaCO(2) during non-steady-state. Consequently, there was no difference in HCVR slope (p=0.21) or intercept (p=0.46) whether PaCO(2) or PetCO(2) was used. During non-steady-state there was a P(a-et)CO(2) difference in slope (p=0.03) and intercept (p=0.04). CONCLUSIONS: In COPD patients non-steady-state HCVR using PetCO(2) is well tolerated, which is as accurate as PaCO(2). HCVR slope may be derived using PetCO(2) during steady-state testing, though there may be errors in intercept compared to use of PaCO(2). In healthy volunteers PetCO(2) may be used to estimate PaCO(2) during steady-state but not rebreathing HCVR.

CO2 retention in lung disease; could there be a pre-existing difference in respiratory physiology.

Some patients with lung disease retain CO(2), while others with similar lung function do not. This could be explained if CO(2) retainers had a pre-existing low hypercapnic ventilatory response (HCVR) and, from this, a tendency to retain CO(2). To test if such a phenomenon exists in healthy people, we determined the change in end-tidal P(CO(2)) (deltaPET(CO(2))) produced by the addition of a dead-space (DS), during wakefulness and sleep, and related this to the HCVR measured awake. The group mean (n=14) HCVR slope was 2.2+/-1.1 (S.D.) L min(-1) mmHg(-1). The deltaPET(CO(2)) with the application of DS was 1.6+/-1.6 mmHg awake and 2.6+/-2.2 mmHg asleep. During wakefulness the deltaPET(CO(2)) with DS did not correlate with the HCVR slope. However, during sleep, four subjects had a marked increase in the deltaPET(CO(2)) (3.7, 4.3, 6.2, 8.0 mmHg) and a relatively low HCVR (slope 1.5, 1.7, 1.5, 1.7 L min(-1) mmHg(-1), respectively). We speculate that such individuals, should they develop lung disease, may be predisposed to retain CO(2).

Hypercapnic cerebral vascular reactivity is decreased, in humans, during sleep compared with wakefulness.

During wakefulness, increases in the partial pressure of arterial CO(2) result in marked rises in cortical blood flow. However, during stage III-IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III-IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III-IV NREM sleep. The end-tidal Pco(2) (Pet(CO(2))) was elevated during the awake and sleep states by regulating the inspired CO(2) load. The cerebral vascular reactivity to CO(2) was calculated from the relationship between Pet(CO(2)) and MCAV by using linear regression. From wakefulness to sleep, the Pet(CO(2)) increased by 3.4 Torr (P < 0.001) and the MCAV fell by 11.7% (P < 0.001). A marked decrease in cerebral vascular reactivity was noted in all subjects, with an average fall of 70.1% (P = 0.001). This decrease in hypercapnic cerebral vascular reactivity may, at least in part, explain the stage III-IV NREM sleep-related reduction in cortical blood flow.