Nasal Continuous Positive Airway Pressure Facilitates Respiratory Muscle Function during Sleep in Severe Chronic Obstructive Pulmonary Disease':'

BASIL J. PETROF,5 R. JOHN KIMOFF, ROBERT D. LEVY, 6 MANUEL G. COSIO, and STEWART B. GOTTFRIED7

Introduction

Patients with advanced chronic obstructive pulmonary disease (COPD) breathe against an increased mechanical load on a continual basis. In addition, several factors, including hyperinflation, hypoxemia, hypercarbia, and malnutrition, may contribute either directly or indirectly to impaired respiratory muscle function in these individuals (1). This constellation of pathophysiologic abnormalities could predispose to the development of respiratory muscle fatigue (1-3). Indeed, it has been hypothesized that certain patients with severe COPD and persistent ventilatory insufficiency suffer from a state of chronic respiratory muscle fatigue (1,4-6). Recent work indicates that such patients may demonstrate improved respiratory muscle function following treatment aimed at decreasing the energy expenditure of the ventilatory muscles (4-6). Presumably the observed amelioration in respiratory muscle performance is related to recovery from the fatigue state subsequent to resting of chronically fatigued respiratory muscles (7). A number of studies have demonstrated the ability of continuous positive airway pressure (CPAP) to substantially reduce inspiratory muscle effort and dyspnea in patients with severe COPD. Such improvement has been shown to occur both at rest (8) and during exercise (9, 10) in stable ambulatory patients as well as during weaning from mechanical ventilation in patients with acute respiratory failure (11). Under these conditions CPAP facilitates respiratory muscle function by counterbalancing the positive end-expiratory elastic recoil pressure that occurs in the setting of dynamic hyperinflation, referred to as auto or intrinsic PEEP (PEEPi) (10-14). To the extent that CPAP is capable of decreasing the burden imposed on the in928

SUMMARY Patients with chronic respiratory insufficiency due to severe chronic obstructive pulmonary disease (COPO) and presumed respiratory muscle fatigue may benefit from therapeutic maneuvers aimed at reducing the magnitude of inspiratory muscle effort. Recent work has demonstrated that continuous positive airway pressure (CPAP)can significantly reduce Inspiratory effort and work of breathing in COPOpatients with acute respiratory failure. Accordingly it was reasoned that prolonged CPAP administration may similarly reduce the work of breathing in stable COPO patients with chronic respiratory insufficiency, thereby allowing recovery from respiratory muscle fatigue. The purpose of this study was to determine the feasibility of employing nasal CPAPduring sleep as a means of Implementing this approach to reducing inspiratory muscle effort in such patients. Standard polysomnographlc parameters were recorded during nocturnal administration of nasal CPAPIn eight stable patients with severe COPO(FEV, 26.7 ± 3.9% of predicted). Esophageal pressure, diaphragmatic (EMGdi) and parasternal intercostal (EMGlc) electromyographlc activity, arterial oxyhemoglobin saturation (Sa02), and transcutaneous pe0 2 (Ptce02) were also measured. Breathing pattern was determined by respiratory inductive plethysmography. In each patient an optimum level of nasal CPAPcould be determined that produced consistent reductions In Indices of inspiratory muscle effort without changing tidal volume or breathing frequency. Highly significant reductions in the tidal excursions of esophageal pressure and the pressure-time Integral for the inspiratory muscles occurred at the optimum CPAP level In all patients. EMGdi and EMGic were similarly reduced. Sa02and Ptce02 were unaffected by CPAP. These results indicate that nasal CPAP can effectively reduce inspiratory muscle effort during sleep In patients with severe COPO. Future work is required to determine whether long-term nasal CPAPadministration can sufficiently reduce inspiratory effort to produce sustained improvement in muscle function in patients with severe COPO AM REV RESPIR DIS 1991; 143:928-935 and presumed chronic respiratory muscle fatigue.

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spiratory muscles of COPD patients, it was reasoned that the use of CPAP could be considered a form of ventilatory muscle rest therapy (7). Administration of nasal CPAP (nCPAP) during sleep would be well suited to this purpose due to its ease of application and the ability to provide therapy for several hours without interfering with daytime activities. The purpose of the present study was to examine the feasibility of this approach and to determine the efficacy of nCPAP administration in reducing inspiratory muscle effort during sleep in patients with severe COPD. Methods A group of eight patients (six male and two female) from the Respiratory Disease Clinics of the Montreal General and Royal Victoria Hospitals were recruited to participate in the

(Received in original form April 27, 1990 and in revised form January 2, 1991) 1 From the Department of Medicine, Montreal General Hospital, the Desmond N. Stoker Sleep Laboratory, Royal Victoria Hospital, and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada. 2 Supported in part by the Medical Research Council of Canada and the Canadian Cystic Fibrosis Foundation. 3 Presented in part at the Annual Meeting of the American Thoracic Society in Cincinnati, Ohio, May 17, 1989. 4 Correspondence and requests for reprints should be addressed to S. B. Gottfried, M.D., Respiratory Division, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G lA4. 5 Recipient of a Clinician-Scientist Award from the Medical Research Council of Canada. 6 Supported in part by the Quebec Lung Association. 7 Medical Research Scholar of the Fonds de la Recherche en Sante du Quebec.

929

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study.All had clinical, radiographic, and physiologic evidence of severe, irreversible airway obstruction. There was no history of daytime hypersomnolence, excessivesnoring, or other symptoms suggestive of obstructive sleep apnea syndrome in any patient. Anthropometric and pulmonary function data (15, 16) are shown in table 1. Patients were stable and without change in symptomatology or clinical status for at least 1 month before evaluation. The investigative protocol was approved by the institutional ethics committee on human research, and written informed consent was obtained in all cases. Patients werestudied overnight in the Royal Victoria Hospital Sleep Laboratory. Electroencephalogram, electro-oculogram, and submental electromyogram were continuously recorded and sleep state determined using standard criteria (17). An airtight nasal mask (Respironics Inc., Monroeville, PA) was strapped to the face and mask pressure (Pmask) was directly measured using a differential pressure transducer (MP-45, ± 100 ern H 20 ; Validyne Corp., Northridge, CA) connected by rigid tubing to a sideport of the mask. The nasal mask was fitted with a large T connector, one end of which was attached to a two-way respiratory valve (Respironics NRV) and a standard nCPAP device (Respironics Sleep Easy® II). The other end of the T connector contained a rubber balloon that upon inflation provided rapid and silent occlusion of its opening, thus allowing the CPAP device to instantly achieve a given level of pressure within the mask. Conversely, deflation of the balloon caused an immediate return of Pmask to atmospheric pressure. The dead space of the nasal mask and Tconnector system was approximately 80 ml. Esophageal pressure (Pes) was measured in all patients using a lO-cmlatex balloon connected by a polyethylenecatheter to a differential pressure transducer (Validyne MP-45, ± 100em H 20 ). The esophageal balloon was properly positioned using the "occlusion test" as previously described (18). In Patients 1, 2, 5,6, and 7 diaphragmatic electromyographic (EMOdi) activity was recorded from surface electrodes placed over the right 6th and 7th intercostal spaces near the costal margin (19). Intercostal muscle electromyographic (EMOic) activity was also obtained from surface electrodes placed at the second intercostal space parasternally in Patients 1-7 (20). All EMO signals were processed by a moving time averager (CWE Inc., Ardmore, PA) with a time constant of 100 ms after amplification, band-pass filtering (0.03 to 10 kHz), and rectification. A DC-coupled respiratory inductive plethysmograph (Respitrace"; Ambulatory Monitoring Inc., Ardsley, NY) was employed to determine breathing pattern as wellas changes in end-expiratory lung volume (21, 22). The bands were placed circumferentially around the rib cage (RC) and abdomen (AB) such that their midpositions were aligned with the nipples and umbilicus, respectively. Care was taken to avoid overlap of the AB band with

the lower rib cage, and the bands were held in place with adhesive tape. A thermistor placed at the mouth provided a semiquantitative index of changes in oral airflow during the study. In all patients arterial oxyhemoglobin saturation (Sao 2) was continuously monitored with a digital pulse oximeter (N200-PB; Nellcor Inc., Haywood, CA). Transcutaneous Pco, (Ptceo2) wasalso recorded (Kontron 634; Kontron Cardiovascular Inc., Everett, MA) throughout the night in patients 1 through 6. The Ptcc02 device was calibrated according to the manufacturer's specifications using standard calibration gases (5 and 10% CO 2), To determine the importance of the upper airway in the response to nocturnal CPAP two patients with severe COPD (FEV1 = 30 and 42% of predicted) and permanent tracheostomies were also evaluated. Flow was measured with a heated pneumotachygraph (Fleisch #1)and a differential pressure transducer (Validyne MP-45, ± 2 em H 20 ) connected directly to a cuffed tracheostomy tube (Shiley#8)whilevolume was obtained by electrical integration of the flow signal. CPAP was applied by attaching the T connector and CPAP circuit directly to the distal end of the pneumotachygraph. Tracheal pressure was recorded proximal to the pneumotachygraph using a differential pressure transducer (Validyne MP-45, ± 100 em H 2O). All the respiratory signals were recorded on an eight-channelstrip-chart recorder(7718A system recorder; Hewlett-Packard Co., Waltham, MA) as well as on FM magnetic tape (Model D; A. R. Vetter Co., Roseburg, PA). Signals werelater played back to a microcomputer (Compaq 386) through a 12-bitanalogto-digital converter (Data Translation 2801A; Data Translation Inc., Marlborough, MA) at a sampling rate of 100Hz for subsequent data analysis.

Procedure and Data Analysis Patients reported to the sleep laboratory approximately 2 h before their usual bedtime, and the recording equipment was attached as described previously. Once the patient had fallen asleep nCPAP was intermittently applied throughout the night. In each patient an optimum level of nCPAP was sought, defined as that level of applied pressure that would produce the greatest reduction in inspiratory muscle effort without altering tidal volume and breathing frequency. This was accomplished by increasing the levelof nCPAP during individual trials in 1- to 2-cm H 2O increments over a 2 to 10em H 20 range. Each level of nCPAP was applied for a minimum of 3 min and preceded by a control period of similar duration. Measurements were obtained for each experimental condition (control and optimum nCPAP) from 20 to 30 consecutive breaths. Any trial in which there was a change in either body position or sleep state between the control and nCPAP periods was excluded from analysis.The tidal excursions of Pes were determined as the change in pressure from

PETROF, KIMOFF, LEVY, COSIO, AND GOTTFRIED

930

the onset of inspiratory effort to the peak negative value obtained during inspiration. Phasic diaphragmatic and intercostal muscle activity wereassessed by measuring the peak inspiratory amplitude of the moving timeaverage EMG signal from the expiratory baseline in arbitrary units. The rate of rise in EMGdi and EMGic was also determined by dividing the peak amplitude of the moving time-average signal by the time from the onset of phasic EMG activity to its peak. The EMG valuesrecorded during nCPAP wereexpressed as a percentage of the mean values acquired during the preceding control period. The pressure-time integral for the inspiratory muscles (j'Pes-dt) was obtained by measuring the area under the Pes versus time relationship and computed for a l-min period (23). The respiratory inductive plethysmograph (RIP) was calibrated by having patients perform an isovolume maneuver (21, 22). This was done after patients had assumed the body position in which they chose to sleep (supine or lateral decubitus) and was repeated at the end of the night. The isovolume maneuver was also repeated if patients changed body position during the course of the study. No attempt was made to determine absolute volumes, the summed RC and AB excursions being measured in arbitrary units. Tidal volume (VT) and changes in end-expiratory lung volume measured during the use of nCPAP were expressed as a percentage of the mean VT value obtained during the immediately preceding control period. The summed RC and AB signals from the RIP were also analyzed to determine the duration of inspiration (11), expiration (IE), and the total breathing cycle (not). Values for Sa02 and Ptcoo, were also recorded at the end of each experimental condition. Results are expressed as mean values ± standard error of the mean (SEM). All data reported werecollectedduring non-rapid-eyemovement (REM) sleep, as REM sleep was rarely observed (24). Comparisons between periods of non-REM sleep before and during the use of nCPAP were made using the Student's t test for paired data. P values < 0.05 were considered statistically significant.

Results None of the patients snored or exhibited either central or obstructive apneic episodes. The effects of nCPAP on respiration during non-REM sleep in a representative patient (Patient 5) are shown in figure 1. After a number of control breaths, nCPAP was applied as indicated by the sudden increase in Pmask. As can be seen, this produced a substantial and persistent reduction in the tidal excursions of Pes. Marked reductions were also observed in the peak amplitudes of the diaphragmatic and intercostal EMG signals. Tidal volume and breathing frequency were essentially unchanged but there was a slight increase in end-expi-

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Fig. 1. Effects of nasal CPAP during non-REM sleep in a representative COPO patient. From top to bottom, tracings represent mask (Pmask) and esophageal pressure (Pes), moving time average of diaphragm (EMGdi) and parasternal intercostal (EMGic) electromyographic activity, rib cage (RC) and abdomen (AS) displacement (inspiratory deflections are downward as indicated by the arrows), and oral thermistor airflow. See text for interpretation.

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ratory lung volume. Oral airflow as determined by the thermistor was virtually absent during the use of nCPAP, indicating that ventilation was occurring primarily through the nasal route. In this particular patient the optimum level of nCPAP (shown here) amounted to approximately 5 em H 2 0 . Although not shown here, qualitatively similar results were obtained at lower levels of nCPAP. It should be noted, however, that the application of nCPAP at levels substantially exceeding the optimum level tended to result in either arousal from sleep or a decrease in minute ventilation (primarily through reductions in tidal volume). Similar findings were obtained in the other patients studied. For the group as a whole, the optimum nCPAP level ranged from approximately 3 to 8 cm H 20 (mean = 4.9 ± 0.7 cm H 20). Figure 2 illustrates the effect ofnCPAP on breathing pattern parameters for all patients. It is readily apparent from the idealized spirograms shown that tidal volume, breathing frequency, and hence

minute ventilation were virtually identical during the control and optimum nCPAP periods. In addition, TI, TE, and Tr/Ttot were not significantly altered by the use of nCPAP. The mean inspiratory (VT/TI) and expiratory (VT/TE) flow rates were also unaffected. An increase in end-expiratory lung volume was observed for the group during the optimum nCPAP level, amounting to 26 ± 8070 of the control VT value (p < 0.05). Sao, during non-REM sleep was reduced below normal values for the group as a whole. This amounted to 89.8 ± 0.9070 and was unaltered by nCPAP (90.5 ± 0.7070). Ptcco2 averaged 50.0 ± 4.5 mm Hg during the control period and was also not affected by nCPAP (50.0 ± 4.3 mm Hg), consistent with the observed lack of alteration in breathing pattern and minute ventilation. Figure 3 demonstrates the effects of the optimum level of nCPAP on inspiratory muscle effort during non-REM sleep in individual patients. Tidal excursions of Pes were considerable during the con-

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Fig. 2. Idealized spirograms depicting group mean values ± SEM for breathing pattern parameters in all patients. The dashed line indicates results from the nasal CPAP trials; the solid line represents values from the preceding control periods. As can be seen, there was a small increase in end-expiratory lung volume during nasal CPAP but the pattern of breathing was otherwise no different between the control and nasal CPAP periods.

CPAP DURING SLEEP IN COPD

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TABLE 2 EFFECT OF NASAL CPAP ON INSPIRATORY MUSCLE ACTIVATION·

EMGdi (n = 5) EMGic (n = 7)

Peak Amplitude (% Control)

p Value t

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p Valuet

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< 0.02

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Definitionof abbreviations: EMGdi = surface electromyogram of diaphragm; EMGic = surface electromyogram of parasternal intercostal muscle. * Values are means ± SEM. t Nasal CPAP versus control, paired t test.

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