No abstract

We measured arousal and ventilatory responses to rebreathing from a small bag, initially approximately 7% CO2 in 40% O2, via a nose mask in 13 normal human adults. With deepening non-rapid-eye-movement sleep (NREM), males aroused at increasing alveolar PCO2 (mean +/- SE: stage II 58.6 +/- 1.7, stage III 61.2 +/- 1.0, stage IV 63.8 +/- 0.8 Torr), whereas in rapid-eye-movement sleep (REM), arousal alveolar PCO2 was 57.7 +/- 0.7 Torr, i.e., much lower than in stage III and IV NREM. Females showed no significant change in arousal alveolar PCO2, (II 57.6 +/- 0.9, III 57.3 +/- 1.3, IV 59.4 +/- 0.9, REM 56.3 +/- 1.0 Torr). Male ventilatory response was 2.5 +/- 0.1 (SE) 1 X min-1 X Torr-1 and fell by 49% in NREM (1.29 +/- 0.13) and by 69% in REM (0.78 +/- 0.18). Female response was little affected by state, being similar to male NREM response (wake 1.39 +/- 0.14, NREM 1.40 +/- 0.13, REM 1.11 +/- 0.26 1 X min-1 X Torr-1). In NREM tests, there was no change in sleep state until arousal, whereas in REM, subjects awoke abruptly with the onset of rebreathing (11 cases), showed a transient arousal with onset but continued in REM until final arousal (21 cases), or changed to NREM at onset (2 cases). These arousal results contrast sharply with findings in tracheostomized dogs and in obstructive sleep apnea syndrome, where asphyxic arousal is later in REM than in NREM, suggesting that the events at test onset in REM in the present study may be related to upper airway sensitivity to CO2 specific to REM.

This study tested the effectiveness of the AutoSet self-titrating nasal continuous positive airway pressure (nCPAP) system in treating obstructive sleep apnea (OSA), and choosing a suitable pressure for subsequent conventional fixed-pressure nCPAP therapy. Twenty-one adult men with untreated OSA were studied with full polysomnography on each of four nights: diagnostic, manual and AutoSet nCPAP titration (in random order), and conventional fixed-pressure nCPAP at the pressure recommended by the AutoSet titration. Titration was satisfactorily performed in 20 of 21 subjects. Severe mask leak prevented automated titration in one subject and caused transient unnecessary increases in pressure in three subjects. In the 20 subjects, respiratory disturbance index (RDI) was 60.3 +/- 5.7 events/h (mean +/- SEM) on the diagnostic night. RDI was lower with manual titration (10.1 +/- 3.0, p < 0.001), and lower still with Autoset (2.8 +/- 0.9, p < 0.01) and fixed pressure (2.5 +/- 0.7, p = ns versus AutoSet) nCPAP. There were similar changes in the arousal index, which was 52.7 +/- 4.6 events/h on the diagnostic night, 14.2 +/- 2.4 with manual titration and 8.9 +/- 0.9 with AutoSet titration, and 9.5 +/- 1.0 on the night of conventional fixed-pressure CPAP (p < 0.001 versus diagnostic). We conclude that the AutoSet system is suitable for automated nCPAP pressure titration.

Nasal congestion, dry nose and throat, and sore throat affect approximately 40% of patients using nasal continuous positive airway pressure (CPAP). The mechanisms causing nasal symptoms are unclear, but mouth leaks causing high unidirectional nasal airflow may be important. We conducted a study to investigate the effects of mouth leak and the influence of humidification on nasal resistance in normal subjects. Nasal resistance was measured with posterior rhinomanometry in six normal subjects who deliberately produced a mouth leak for 10 min while using nasal CPAP. Nasal resistance was measured regularly for 20 min after the challenge. A series of tests were performed using air at differing temperatures and humidities. There was no change in nasal resistance when subjects breathed through their noses while on CPAP, but a mouth leak caused a large increase in resistance (at a flow of 0.5 L/s) from a baseline mean of 2.21 cm H2O/L/s to a maximum mean of 7.52 cm H2O/L/s at 1 min after the challenge. Use of a cold passover humidifier caused little change in the response (maximum mean: 8.27 cm H2O/L/s), but a hot water bath humidifier greatly attenuated the magnitude (maximum mean: 4.02 cm H2O/L/s) and duration of the response. Mouth leak with nasal CPAP leads to high unidirectional nasal airflow, which causes a large increase in nasal resistance. This response can be largely prevented by fully humidifying the inspired air.

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.

Mouth leak is common during nasal ventilatory assistance, but its effects on ventilatory support and on sleep architecture are unknown. The acute effect of sealing the mouth on sleep architecture and transcutaneous carbon dioxide tension (Ptc,CO 2 ) was tested in 9 patients (7 hypercapnic) on longterm nasal bilevel ventilation with symptomatic mouth leak.Patients slept with nasal bilevel ventilation at their usual settings on two nights in random order. On one night, the mouth was taped closed. Nocturnal nasal bilevel ventilatory support has become an important and successful therapy for respiratory failure during sleep [1±3]. At present, nasal masks are more common than mouthpieces, mouth-nose masks or full face masks (perhaps because of issues related to comfort, fit and deadspace) but a major practical problem is escape of air via the mouth, as has been well documented for nasal continuous positive airway pressure (CPAP) [4,5].In the only study to date to directly measure the effect of mouth leaks on effectiveness of ventilatory support, CAR-REY et al.[6] investigated the effect of voluntary mouth opening on diaphragm electromyogram (EMG) activity during awake nasal intermittent positive pressure ventilation in 5 subjects. With the mouth closed, diaphragm EMG dropped to 15% of unassisted control, but with the mouth open, returned to 98% of unassisted control, implying complete loss of ventilatory support.Mouth leak is ubiquitous during noninvasive ventilatory support in sleep. BACH et al. [7] demonstrated that during nasal intermittent positive pressure ventilation (NIPPV), severe leak (>33% of tidal volume escaping) was present for a median of 55% of sleep time, and was associated with 7.5 desaturations (of at least 4%) per hour of sleep.MEYER et al. [8] found severe mouth leak during most of sleep time and 100% of slow wave sleep.Mouth leak could lead to severe sleep fragmentation, either directly via airway irritation, or indirectly via a reduction in effectiveness of ventilation as discussed above. In the study by BACH et al. [7], there were a total of 34 arousals . h -1 and 74% of desaturations were terminated by either an arousal or a lightening of sleep stage. The authors concluded that leak was reducing ventilatory effectiveness and causing desaturation, and that arousal reversed the leak and desaturation. Similarly, in the study of MEYER et al. [8] there were 46 arousals . h -1 in stages I-II nonrapid eye movement (NREM) sleep, associated in time with mouth leak. However, association in time does not establish causality, and it is not known whether preventing the mouth leak would improve sleep quality.The purpose of the present paper was to directly assess the effect of mouth leak on sleep architecture and transcutaneous carbon dioxide tension (Ptc,CO 2 ) during nasal bilevel ventilatory support, by preventing the leak. To do this, the authors measured the first-night effect of taping the mouth closed, on sleep architecture and Ptc,CO 2 in patients already on long-term nasal bilevel venti...

To determine if a long-lasting increase in normoxic ventilatory drive is induced in conscious animals by repetitive hypoxia, we examined the normoxic [arterial O2 saturation (SaO2) > 93%] ventilatory response following successive episodes of 2-min eucapnic hypoxic challenges (SaO2 = 80%) in awake tracheotomized dogs. End-tidal CO2 was maintained at the resting level during and after repetitive hypoxia. The experimental protocol was performed twice in each of five dogs on separate days. To determine if changes in normoxic ventilation occurred between episodes of repetitive hypoxia, data were compared from six periods (epochs) for all experiments. The mean minute ventilation (VI) during three normoxic periods between episodes of intermittent hypoxia was 135, 154, and 169% of control (P < 0.05). VI during a 30-min recovery period was still higher at 183 and 172% of control (P < 0.05). Normoxic VI between hypoxic and recovery periods was significantly higher than the corresponding values in sham experiments. Our results indicate that a long-lasting increase in normoxic ventilation can be evoked in an awake unanesthetized dog by a short exposure to repetitive hypoxia.

Adaptive servo-ventilation (ASV) is a novel method of ventilatory support designed for Cheyne-Stokes respiration (CSR) in heart failure. The aim of our study was to compare the effect of one night of ASV on sleep and breathing with the effect of other treatments. Fourteen subjects with stable cardiac failure and receiving optimal medical treatment were tested untreated and on four treatment nights in random order: nasal oxygen (2 L/min), continuous positive airway pressure (CPAP) (mean 9.25 cm H(2)O), bilevel (mean 13.5/5.2 cm H(2)O), or ASV largely at the default settings (mean pressure 7 to 9 cm H(2)O) during polysomnography. Thermistor apnea + hypopnea index (AHI) declined from 44.5 +/- 3.4/h (SEM) untreated to 28.2 +/- 3.4/h oxygen and 26.8 +/- 4.6/h CPAP (both p < 0.001 versus control), 14.8 +/- 2.3/h bilevel, and 6.3 +/- 0.9/h ASV (p < 0.001 versus bilevel). Effort band AHI behaved similarly. Arousal index decreased from 65.1 +/- 3.9/h untreated to 29.8 +/- 2.8/h oxygen and 29.9 +/- 3.2/h CPAP, to 16.0 +/- 1.3/h bilevel and 14.7 +/- 1.8/h ASV (p < 0.01 versus all except bilevel). There were large increases in slow-wave and rapid eye movement (REM) sleep with ASV but not with oxygen or CPAP. All subjects preferred ASV to CPAP. One night ASV suppresses central sleep apnea and/or CSR (CSA/CSR) in heart failure and improves sleep quality better than CPAP or 2 L/min oxygen.