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1 Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, South Australia 5041, Australia
2 Flinders University of South Australia, Bedford Park, South Australia 5042, Australia
3 University of Adelaide, Adelaide, South Australia 5005, Australia
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Abstract |
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I) during sleep in this group have not been assessed. We assessed I, breathing pattern, upper airway and total lung resistance (UAR, RL), intraoesohageal diaphragmatic EMG (EMGoes), intrinsic positive end-expiratory pressure (PEEPi), dynamic compliance (Cdyn), pressure–time product of oesophageal pressure (PTPoes), tension–time index of the diaphragm (TTIdi), end-expiratory lung volume (EELV) and respiratory drive (assessed as the slope of Poes versus time in the isovolumetric interval before PEEPi is overcome). Measurements were made in wakefulness and non-rapid eye movement (NREM) sleep, on 76%N2/24%O2 and on 76%He/24%O2 (heliox). Satisfactory data for analysis were obtained in 10 patients; five had measurements on heliox. I fell from (mean (S.E.M.)) 8.84(0.46) to 6.64(0.91 l min–1, P = 0.011) between wakefulness and stage II sleep, due to a fall in tidal volume. No changes were seen in PEEPi, Cdyn, EELV, PTPoes, TTIdi, EMGoes or respiratory drive. UAR increased (3.11(0.8) to 10.24(2.96) cmH2O l–1 s (P = 0.013) but RL was unchanged. UAR was reduced on heliox (5.20(1.67) to 3.45(1.35) cmH2O l–1 s, P = 0.049) but I during sleep did not increase. PTPoes (350.2(51.0) to 259.4(46.3) cmH2O s min–1, P = 0.016), TTIdi (0.13(0.02) to 0.10(0.02) P = 0.04), and respiratory drive (20.48(4.69) to 15.02(4.57) cmH2O s–1, P = 0.01) were all reduced. This suggests respiratory drive alters to maintain a preset I in sleep, irrespective of load, at least while the fatigue threshold of respiratory muscles is not exceeded.
(Received 18 April 2004;
accepted after revision 23 June 2004;
first published online 2 July 2004)
Corresponding author R. D. McEvoy: Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, South Australia 5041, Australia. Email: doug.mcevoy{at}rgh.sa.gov.au
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Introduction |
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I) is approximately 13–15% lower in stable-non-rapid eye movement (NREM) sleep than in wakefulness (Calverley, 1998). This is not entirely due to a fall in metabolic rate (White et al. 1985), since there is a concomitant increase in PCO2 of 2–4 mmHg (Calverley, 1998). The major reason for this relative hypoventilation appears to be a fall in respiratory drive (Morrell et al. 1995; Morrell et al. 1996), although the increase in upper airways resistance (UAR) at sleep onset also appears to contribute, particularly in snorers (Henke et al. 1990; Henke et al. 1992).
Hypercapnic chronic obstructice pulmonary disease (COPD) patients often have sustained increases in CO2 levels during sleep, with concomitant increases in wakeful PaCO2 between night and morning (O'Donoghue et al. 2003). It has been proposed (Hubmayr & Sieck, 1995; Mehta & Hill, 2001) that sleep hypoventilation may contribute to the development of chronic daytime hypercapnia in COPD. There have been no investigations of directly measured I in sleep in a hypercapnic COPD population. Investigations in normocapnic COPD have not shown a more profound fall in I in NREM sleep in COPD than in normal subjects (Ballard et al. 1995; Meurice et al. 1995). However, falls in minute ventilation were almost exclusively due to fall in tidal volume (VT), which would have a more pronounced effect on alveolar ventilation in COPD patients, due to greater dead space to tidal volume (VD/VT) ratios.
The detailed mechanisms of sleep hypoventilation are also uncertain. Ballard et al. (1995) documented reduced indices of respiratory drive and increased UAR in normocapnic COPD patients, and postulated that both contribute to the fall in ventilation during sleep. Other authors have shown that breath-by-breath variation in VT correlated with changes in supraglottic resistance in normocapnic COPD patients and normal subjects (Meurice et al. 1995). However, when continuous positive airways pressure (CPAP) was used to prevent the increase in upper airways resistance during sleep, there was still relative hypoventilation in a hypercapnic COPD group (Becker et al. 1999). No study has evaluated the possible influence of changes in intrinsic PEEP (PEEPi), dynamic lung compliance (Cdyn), respiratory muscle fatigue or the overall coordination of respiratory muscle interaction on directly measured minute ventilation.
Therefore this study aimed to (1) determine the magnitude of the fall in VI in stable NREM sleep in a hypercapnic COPD population; (2) elucidate the relative contribution of each of the above-mentioned elements to reduced VI. We hypothesized that (1) the sleep-related fall in ventilation would be more pronounced in this population when compared to historical normocapnic COPD controls; (2) the major factor contributing to the sleep-related fall in ventilation would be the increase in UAR during sleep. We simultaneously measured minute ventilation, upper airways resistance, respiratory mechanics, respiratory muscle effort and central drive during wakefulness and sleep. The inspiratory gas mixture was then changed to a less dense gas (Heliox: 76%He/24%O2) in order to reduce or eliminate the increase in UAR during sleep, to assess the effect on VI and the other measured parameters.
Hypoventilation in REM in COPD patients has received considerable attention in the past (Douglas, 1998), since hypoventilation in this stage is often more severe than in NREM. It was initially our intention to study REM as well as NREM sleep. However, pilot studies indicated that the degree of instrumentation required to make the above measurements precluded entry into REM in the vast majority of subjects. We therefore made the choice to continue with this level of instrumentation in the knowledge that we were unlikely to record sufficient quantities of REM for meaningful analysis.
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Methods |
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Seventeen patients with severe COPD were recruited from the respiratory medicine database of the Repatriation General Hospital, Daw Park.
Inclusion criteria were: (1) a clinical history consistent with stable COPD without an exacerbation of airways disease for at least 4 weeks at the time of evaluation; (2) irreversible airflow obstruction: forced expiratory volume in 1 s (FEV1) < 1.5 l or < 50% predicted, FEV1/FVC (forced vital capacity) < 65% and change in FEV1 (
FEV1) with bronchodilator < 15%, or if FEV1 < 1.5 l, FEV1 < 200 ml; (3) daytime awake PaCO2 > 45 mmHg while in a stable condition.
Exclusion criteria were: (1) significant obesity, defined as body mass index (BMI) 
33 kg m–2; (2) obstructive sleep apnoea (apnea/hypopnea index (AHI) > 10 h–1). No patient was taking theophylline at the time of the experiment, and patients refrained from taking benzodiazepines or other hypnotics, alcohol or caffeine on either the main experimental study night or at screening polysomnography.
All patients gave informed written consent, and the study was approved by the research and ethics committee of the Repatriation General Hospital, Daw Park. The study conformed to the Declaration of Helsinki.
Measurements
Height and weight were measured and BMI calculated. Spirometry pre- and post-bronchodilator, lung volumes and single breath carbon monoxide gas transfer (DLCO) were recorded (Jaeger ‘compact lab’, Warzberg, Germany).
Prior to the main experiment, attended screening polysomnography was performed (Compumedics S series, Abbotsford, VIC, Australia) while on prescribed oxygen flow delivered by nasal cannula. Measured parameters were EEG, left and right electro-oculogram (EOG), submental EMG, ECG, airflow (by nasal pressure cannula), thoracoabdominal movement by inductance plethysmography, leg movements, body position, and SaO2. Sleep was manually staged in 30 s epochs according to standard criteria (Rechtschafen & Kales, 1968; Sleep Disorders Atlas Task Force of the American Sleep Disorders Association, 1992), and respiratory events according to consensus conference recommendations (American Academy of Sleep Medicine Task Force, 1999).
On the experimental night, EEG, EOG, ECG and EMG electrodes were applied as for standard polysomnography. Upper and lower thoracic wall movements were monitored by uncalibrated respiratory inductance plethysmography (Ambulatory Monitoring Inc, Ardsley, NY, USA). Patients breathed through a nasal mask (Gel mask, Respironics, Murrysville, PA, USA) attached to a two-way breathing valve (series 2600, Hans Rudolph, Kansas City, MO, USA). A narrow perforated tube connected to a capnometer (POET II model 602-3 Criticare Systems, Waukesha, WI, USA) was positioned encircling the mask to detect leaks, and the mouth was taped (Douglas et al. 1982). The inspiratory side of the breathing valve was connected in series to a pneumotachograph (model PT36, Erich Jaeger, Würzburg, Germany) and a Gatlin-shape valve system (series 2440C, Hans Rudolph) for delivery of inspiratory gases. The Gatlin-shape valve consisted of one output port attached to the pneumotachograph and four inputs, two of which were connected to 300 l foil bags (Scholle Industries, Adelaide, Australia) containing the following inspiratory gas mixes: 76%N2/24%O2 or 76%He/24%O2. The other two ports were not utilized. Only one input port was open at a time, and all changes between ports were conducted remotely during expiration.
A catheter system constructed from a modified Swan–Ganz catheter as previously described (Javaheri et al. 1987), was inserted through the nose after decongestion (0.05% w/v oxymetazoline HCl) and local anaesthesia (2% lignocaine). Two of the channels were connected to gastric and oesophageal balloons. Six stainless steel insulated wires (316SS5T wire, Medwire, Mt Vernon, NY, USA) were inserted into a third channel, connected to stainless steel electrodes mounted at intervals of 1 cm for measurement of intraoesophageal diaphragmatic EMG (EMGoes). Electrodes were wired as four overlapping pairs (1 and 3, 2 and 4, 3 and 5, 4 and 6). The catheter was positioned so that the largest EMG signal was obtained in one of the middle electrode pairs. Oesophageal (Poes), gastric (Pga) and mask (Pmask) pressures were recorded using pressure transducers (Spectramed DTX, Oxnard, USA) calibrated against a water manometer. Epiglottic pressure (Pepi) was measured with a transducer-tipped catheter (model MPC-500, Millar, Houston, TX, USA) inserted through the same nostril and advanced 1 cm below the tongue base under direct visualization. In addition to EMGoes, scalene (EMGsca) EMG activity was recorded.
Calculated parameters
The inspiratory flow signal (pneumotachograph) was electronically integrated to give VT. Inspiratory (TI) and expiratory (TE) times, respiratory rate (FB) and I were determined from the flow and volume signals. The phase angle between peak inspiratory excursion of upper and lower chest wall was calculated.
The mean cardiac component of the Poes and Pga records (artifact) was recorded over a period of 3 min by ensemble averaging the recurrent pressure fluctuations centred on the R wave of the ECG. The cardiac artifact was found not to vary substantially within the tidal volume range. The mean artifact was then subtracted from the Poes and Pga traces at each cardiac cycle (Catcheside et al. 1999). Pdi (transdiaphragmatic pressure) was derived from the filtered signals. Upper airways resistance (UAR) was calculated from the slope of the plot of instantaneous pressure (Pmask – Pepi) against flow, sampled throughout inspiration. Only breaths where the coefficient of determination (r2) of the pressure versus flow regression line was greater than 0.5 were accepted. Total lung resistance (RL) was derived using the Mead–Whittenberger method (Mead & Whittenberger, 1953). The pressure–time product of the respiratory muscles (PTPoes), and of the diaphragm (PTPdi) were calculated between the initiation of effort and the end of inspiratory flow (Rochester & Bettini, 1976) and expressed per minute, and the tension–time index of the diaphragm calculated for each breath (Bellemare & Grassino, 1982) using the equation:
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Dynamic PEEPi was expressed as the negative deflection in Poes preceding the start of inspiratory flow, utilizing the correction for expiratory muscle activity validated by Zakynthinos et al. (2000) (Fig. 1). Dynamic lung compliance (Cdyn) was also calculated. Respiratory drive was assessed by the slope of the Poes against time trace during the interval between the initiation of inspiratory effort and the start of flow (slope Poes,isovol) (Conti et al. 1996; Brandolese & Andreose, 1998; Hamnegard et al. 1998)(Fig. 1).
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Sleep staging data were acquired on a standard commercial polysomnography system (Compumedics S series, Abbotsford, VIC, Australia). All other data were acquired on an IBM laptop computer using an analog-to-digital converter (DATAQ Instruments, Akron, OH, USA) and at a sampling rate of 200 Hz for all signals other than EMGs (1000 Hz). The two acquisition systems were time locked using a time-stamping system built in-house. Figure 2 depicts raw respiratory data over several breaths from a single patient, and Fig. 3 data from the same breaths after signal processing as detailed above.
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Subjects presented to the laboratory at 9 pm, having abstained from alcohol, sedative medications, caffeine and nicotine for 24 h. They were instrumented as described above, and lay supine with the bedhead angled at approximately 20 deg with one pillow. Maximal EMGoes, EMGsca, Poes and Pdi were determined by having the subject perform three of each of the following manoeuvres: slow inspiration from residual volume (RV) to total lung capacity (TLC), Muller manoeuvres and sniffs. The highest activity recorded was taken to be maximal. All EMG activity was then expressed as a percentage of maximal. The manoeuvres were repeated after the experimental night, and calibration of all pressure transducers (manometer) and of the pneumotachometer with each gas mixture (3 l syringe) was also performed before and after each study.
Subjects were allowed to fall asleep while breathing the N2/O2 mixture. During the night the inspirate was altered repeatedly between N2/O2 and He/O2, with the aim of obtaining approximately equal proportions of each sleep stage on each gas mixture.
Data analysis
Sleep was staged as on the screening night (Rechtschafen & Kales, 1968; Sleep Disorders Atlas Task Force of the American Sleep Disorders Association, 1992). Multiple periods in steady state were selected, defined as a 2 min period with no change in state (wake versus sleep) or in sleep stage in the preceding 5 min. Breath-by-breath parameters were calculated as above in each of these periods. Breaths during and for 5 s after arousals, and breaths exhibiting mask leaks, sighs and swallows were excluded from analysis.
Statistics
Paired samples Student's t tests were used to compare all parameters between wakefulness and sleep on each inspiratory gas mixture, and between each mixture during stable sleep. Data are expressed as means ± S.E.M. P < 0.05 was considered statistically significant.
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Results |
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Minute ventilation decreased significantly from 8.84 ± 0.46 l min–1 to 6.64 ± 0.91 l min–1 (P = 0.011), between wakefulness and stable stage II sleep. This was due to a fall in VT (0.53 ± 0.09 to 0.39 ± 0.07 l, P = 0.003) without a significant change in FB or other timing parameters. No changes were seen in muscle output as assessed by PTPoes, PTPdi, or TTIdi. Likewise respiratory drive (slope Poes,isovol) was unchanged as was EMGoes. Tonic EMGsca fell from 4.73 ± 0.77 to 2.48 ± 0.50% maximal (P = 0.014), but there was no change in phasic EMGsca. Lung mechanics as assessed by PEEPi, Cdyn, and RL were not significantly altered, though RL showed a strong trend to increase. Since Cdyn was unchanged, we were able to detect any change in end-expiratory lung volume (EELV) by calculating the product of transpulmonary pressure at the start of inspiratory flow and Cdyn. This also remained stable on transition to sleep. There was no change in the phase angle by which lower ribcage excursion lagged upper ribcage excursion, suggesting that, at least in this respect, respiratory muscle interaction did not change. The most striking change was an increase in UAR from 3.11 ± 0.80 to 10.24 ± 2.86 cmH2O l–1 s (P = 0013).
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Five patients contributed data to this comparison. Minute ventilation was no different on heliox than on N2/O2. Neither were there differences in VT or timing parameters. There was also no change in the phase angle between upper and lower chest wall movement. PTPoes (350.2 ± 51.0 to 259.4 ± 46.3 cmH2O s min–1 (P = 0.016)), PTPdi (382.4 ± 64.6 to 294.5 ± 52.9 cmH2O s min–1 (P = 0.040)) and TTIdi were all reduced significantly. There was also a significant fall in respiratory drive (20.48 ± 4.69 to 15.02 ± 4.57 cmH2O s–1 (P = 0.010)). There were no changes in EMG parameters, though both phasic EMGoes and EMGsca showed trends to decrease, which may have reached significance with greater numbers. Cdyn and EELV showed no change, but PEEPi (3.35 ± 0.95 to 2.31 ± 0.97 cmH2O (P = 0.039)), RL (21.05 ± 3.03 to 15.81 ± 2.24 cmH2O l–1 s (P = 0.010)) and UAR (5.20 ± 1.67 to 3.45 ± 1.35 cmH2O l–1 s (P = 0.049)) were all reduced.
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Discussion |
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I in stage II sleep compared to wakefulness in a hypercapnic COPD group. This was due solely to a drop in VT. Central drive, muscle output and lung mechanics were unchanged. The most striking change was a three-fold increase in UAR. Changing the inspired gas mixture to heliox resulted in a fall in UAR but also a fall in muscle output and central drive, with no change in I.
This is the first study to measure I in sleep in hypercapnic COPD. Studies in normal subjects have in general shown a fall in ventilation of 13–15% in sleep (Calverley, 1998), which is similar to the fall in normocapnic COPD patients (Ballard et al. 1995; Meurice et al. 1995). The greater fall in ventilation in the hypercapnic group is in agreement with our previous results (O'Donoghue et al. 2003), demonstrating frequent sleep hypoventilation in hypercapnic COPD, with increases in PaCO2 night to morning. It is also consistent with the earlier literature suggesting daytime PaCO2 is an independent predictive factor for episodes of desaturation during sleep (Bradley et al. 1990; Douglas, 1998). Taken together these results support the hypothesis that changes in ventilation during sleep are more profound in hypercapnic than normocapnic COPD or normal subjects.
Comparison of changes in UAR in stable sleep between studies is difficult, because of different methodologies used. We recorded an increase in UAR from 3.11 ± 0.80 to 10.24 ± 2.86 cmH2O l–1 s in our hypercapnic COPD population, comparable to the change from 5.9 ± 1.1 to 9.6 ± 2.1 cmH2O l–1 s (measured at 0.25 l s–1 inspiratory flow) found by Ballard et al. (1995) in a normocapnic COPD group. However, using an air-perfused catheter, Meurice et al. (1995) only found an increase from 3.6 ± 3.0 to 4.6 ± 2.5 cmH2O l–1 s at a flow of 0.2 l s–1, similar to their age-matched controls. In other studies in normal elderly subjects, Hudgel et al. (1984) found increases in UAR from (4.3 ± 0.7 to 7.2 ± 1.6 cmH2O l–1 s) while Thurnheer et al. (2001) found increases in older men from 8.4 ± 0.6 to 9.6 ± 1.2 cmH2O l–1 s in the lower 50% of the flow curve, and from 18.0 ± 3.0 to 26.4 ± 3.6 in the higher 50%. Our method of measurement excluded some breaths with highly alinear pressure–flow curves, and if applied to the Thurnheer's dataset, would be expected to produce values intermediate between their ‘low flow’ and ‘high flow’ conditions. We conclude that there is no evidence of a systematic difference between UAR values in our subjects and those in either normocapnic COPD patients or elderly normal subjects. However the data in each of these latter two groups are highly variable, and this variability is partly due to technical factors.
UAR increased three-fold during NREM sleep without changes in central drive, lung mechanics or muscle output. This would suggest that the increase in UAR is the major factor contributing to the fall in I during sleep, and would agree with the data of Meurice et al. (1995), who found that changes in ventilation on a breath-by-breath basis correlated with changes in UAR. On the other hand Ballard et al. (1995) found that there was a 60% increase in UAR in their subjects, but also a 25% fall in P0.1. Becker et al. (1999) described a 16% drop in I in a hypercapnic COPD group, some of whom had coexistent obstructive sleep apnoea (OSA), when CPAP was applied in sleep to eliminate increases in UAR. These authors concluded the major influence on I during sleep was a drop in respiratory drive, but I was not evaluated without CPAP.
In our study we reasoned that a simple comparison of wakefulness and sleep would not allow us to evaluate what might have happened to respiratory drive and muscle output in the absence of an increase in UAR. We therefore changed the inspired gas mixture to heliox with the intention of reducing UAR during sleep. Comparing stage II sleep on heliox and N2/O2, despite a decrease in UAR, RRS and PEEPi, there was no change in I but rather a fall in respiratory drive and muscle output, with trends to decreases in EMG parameters. Furthermore we found minimal correlation between changes in I and in UAR between wakefulness and sleep on N2/O2 (r = 0.21, P = 0.61). We interpret our data to indicate that central drive is adjusting to variations in load to maintain a preset level of I, and presumably PaCO2. This is in agreement with earlier studies in normal subjects who still show a drop in I during sleep when UAR is normalized to waking levels (Morrell et al. 1995), and in tracheostomized patients who also demonstrate a fall in I during sleep (Morrell et al. 1996). It suggests that in hypercapnic COPD patients, as in normal subjects, ventilation in NREM sleep is primarily controlled by chemoreceptor inputs and the imperative to maintain gas exchange homeostasis (Pack, 1995).
There was no change in TTIdi in sleep. TTIdi during wakefulness was close to the critical threshold of 0.15 identified by Bellemare & Grassino (1982). A TTIdi above this level cannot be sustained for longer than 45 min without muscle fatigue (Bellemare & Grassino, 1982). None of the 311 COPD patients with a wide range of PCO2 levels studied by Begin & Grassino (1991) had waking TTIdi levels above 0.15. It has been proposed that hypercapnic subjects hypoventilate in wakefulness rather than exceed the fatigue threshold (Begin & Grassino, 1991; Rochester, 1991). It is possible, if our patients had greater increases in UAR in sleep, that maintenance of I at the level required to maintain gas exchange homeostasis would have necessitated exceeding the critical TTIdi threshold. Our data do not preclude the possibility of such ‘central fatigue’ during sleep if greater loads are sustained.
We did not document any changes in Cdyn, RL or PEEPi in sleep. RL did show a strong trend to increase, but this was largely influenced by the increase in UAR. Ballard et al. (1995) also did not detect an effect of sleep on RL. To our knowledge ours is the first study to measure the effect of sleep on Cdyn and PEEPi. Based on this evidence we think it unlikely these factors play a significant role in the fall in I in NREM sleep in hypercapnic COPD patients.
EELV falls during sleep in normal subjects and in asthmatics (Ballard et al. 1990). We did not detect a fall in EELV in our COPD group. Previous studies by Hudgel et al. (1983), using respiratory inductance plethysmography, and by Ballard et al. (1995) using a supine body plethysmograph also found that EELV did not change in sleep in COPD. It would appear that waking EELV is maintained by tonic inspiratory muscle activity in normal and asthmatic individuals, but in severe COPD patients dynamic hyperinflation is the main determinant (Muller et al. 1981; Demedts, 1990; Ballard et al. 1995) which does not change during NREM sleep.
Chest wall paradox is known to occur during wakefulness in severe COPD, and to increase work of breathing (Goldman et al. 1976; Gilmartin & Gibson, 1984). We hypothesized that during sleep, relative atonia of the chest wall musculature would lead to worsening of chest wall paradox. A commonly observed form of paradox is that described by Hoover (1920), the indrawing of the lower rib cage during inspiration. We therefore assessed the phase lag between peak upper and lower chest wall excursion. However, no change in this phase lag was seen between wakefulness and sleep. White et al. (1995) reported that none of their 10 COPD patients who did not have lateral chest paradox in wakefulness developed this clinical sign during sleep.
Methodological limitations
Measurement of respiratory drive. We reasoned that during the interval between the initiation of inspiratory effort and the start of flow the respiratory system is almost isovolumetric, as inspiratory effort is expended in overcoming PEEPi (Brandolese & Andreose, 1998) (in fact during this interval there is very slow expiratory flow). Therefore during this interval, the rate of change of oesophageal pressure is a good index of respiratory drive as there are minimal pressure losses due to overcoming resistance or elastance. Experimental evidence to support this reasoning comes from the work of Conti et al. (1996) who showed in ventilated severe COPD patients that the slope of oesophageal pressure from initiation of effort to cessation of expiratory flow is the same as that from cessation of expiratory flow to opening of the demand valve of the ventilator. In the first part of this paper they demonstrated that the change in pressure during this latter interval was almost identical (r = 0.99, P < 0.001) to P0.1 as conventionally measured. Hamnegard et al. (1998) also found that the maximum rate of change of oesophageal pressure during unoccluded breaths was an adequate substitute for P0.1. We therefore believe our measurements provide a good estimate of respiratory drive.
Calculation of EELV. Since Cdyn did not change in our subjects, we were able to detect any change in EELV by calculating the product of transpulmonary pressure at the start of inspiratory flow and Cdyn (O'Donoghue et al. 2002). While we cannot be certain of the accuracy of our measurements, we believe they provide a good estimate of change in EELV.
Absence of data in REM sleep. Due to the invasive nature of the instrumentation required for this study, we were unable to collect sufficient data in REM to draw meaningful conclusions. Sleep hypoventilation tends to be most profound in REM in these patients (Douglas, 1998). It has been proposed (Hubmayr & Sieck, 1995; Mehta & Hill, 2001) that sleep hypoventilation may contribute to the development of daytime hypercapnia in COPD, through the mechanism of gradual renal retention of bicarbonate due to repeated episodes of nocturnal hypercapnia. If this is true, it seems unlikely that REM hypoventilation alone, lasting 1 h at most per night, would be sufficient to cause bicarbonate retention. Our own data (O'Donoghue et al. 2003) suggest that the change in PaCO2 night to morning is most strongly related to hypoventilation across the whole night, and less to REM-related hypoventilation alone. Therefore we believe study of the aetiology and magnitude of NREM hypoventilation is also important.
Conclusion
In conclusion, we have found that I fell by approximately 25% between wakefulness and NREM sleep in a hypercapnic COPD group. The most striking change in load was a three-fold increase in UAR, without a significant change in respiratory drive or muscle output. Nevertheless, when UAR was reduced in sleep by switching the inspirate to Heliox, rather than an increase in I there was a reduction in respiratory drive and muscle output. This suggests that respiratory drive is altered in order to maintain a target PCO2 in sleep, at least while attainment of the required I does not necessitate exceeding the fatigue threshold of the respiratory muscles.
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