Respiratory Muscle Function during Obstructive Sleep Apnea 1- 3
PEARCE G. WILCOX, 4 PETER D. PARE, JEREMY D. ROAD, 4 and JOHN A. FLEETHAM
Introduction
Obstructive sleep apnea (GSA) occurs because of recurrent upper airway occlusion during sleep. Repeated inspiratory efforts are made during an obstructive apnea until upper airway patency is restored. There is limited data on inspiratory and expiratory muscle function during obstructive apnea (1-4). Inspiratory muscles may be subjected to potentially fatiguing loads during an obstructive apnea, and Vincken and associates (4) have suggested that exceeding this fatigue threshold can trigger the termination of the apnea. Inspiratory pressure generation is influenced by respiratory timing and the relative contribution of the diaphragm and intercostal/accessory muscles. The inspiratory pressure generated by the diaphragm is also dependent on diaphragmatic length. Progressive recruitment of expiratory muscles, particularly the abdominal muscles during the expiratory phase of obstructive apnea, would cause diaphragm lengthening and optimize diaphragmatic function during inspiratory efforts. Wehave measured transdiaphragmatic pressure, breathing patterns, and chest wall motion in six male patients with GSA during sleep to characterize respiratory muscle function in GSA and to determine whether termination of obstructive apnea is consistently related to a pressure time index of the diaphragm (PTI) associated with respiratory muscle fatigue. Methods Subjects Six male subjects with OSA were recruited. No subject was using any medication and none had any clinical evidence of neuromuscular disease. All subjects gaveinformed consent to the study, which was approved by the university ethics committee. 'Techniques Lung function was assessed on the basis of the best of three expirations into a spirometer (CollinsModular Function Analyzer; Warren E. Collins, Braintree, MA). Detailed overnight polysomnograms were performed in a fully equipped sleep laboratory. Sleep and its
Obstructive sleep apnea (OSA) Is characterized by recurrent upper airway obstruction during sleep. Inspiratory muscles may be SUbjectedto potentially fatigUing loads during an obstructive apnea and this may be related to the termination of obstructive apnea. Wehave measured transdiaphragmatic pressure (Pdi) and breathing patterns In six male patients with OSA during sleep to characterize respiratory muscle function In OSA and determine whether apnea termination Is consistently related to a pressure time Index of the diaphragm (PTI) associated with respiratory muscle fatigue. There was a large intersubject variability In Pdl generation during apnea. No consistent level of PTI was associated with apnea termination. During prolonged apneas, the respiratory duty cycle plateaued, which Is suggestive of an Inhibitory reflex possibly mediated by chest wall afferents. There were Intersubject differences In both Inspiratory and expiratory muscle recruitment during apnea. In the majority of patients, the diaphragm appeared to be the primary Inspiratory muscle during apnea, but In some It appeared to be the Intercostal/accessory muscles. The majority of patients demonstrated an Increase In gastric pressure and Inward abdominal movement during the expiratory phases of an apnea, consistent with abdominal muscle recruitment stimulated by increased ventilatory drive. AM REV RESPIR DIS 1990; 142:533-539 SUMMARY
various stages were documented by standard electroencephalographic (EEG), electrooculographic (EOG), and electromyographic (EMG) criteria (5). Airflow was detected by an infrared CO, analyzer (Medical Gas Analyzer LB-2; Beckman Instruments, Fullerton, CA) recording continuously from the nose and mouth. Arterial oxygen saturation (Sao,) was monitored continuously with a pulse oximeter (Nellcor, Hayward, CA). Chest wall and abdominal movement were assessed by a respiratory inductive plethysmograph (Respitrace@; Ambulatory Monitoring, Inc., Ardsley, NY). The data were recorded on a 15channel polygraph recorder (Model 78; Grass Instruments, Quincy, MA) at a paper speed of 10 mm/s. Transdiaphragmatic pressure (Pdi) was measured with lO-cmlatex balloon catheters, one placed in the midesophagus and inflated with 0.5 ml of air (Pes) and the other placed in the stomach and inflated with 2 ml of air (Pga) (6). The catheters were coupled to individual pressure transducers (Model P23A; Statham Instruments, Oxnard, CA), and continuous overnight tracings of Pes and Pga were recorded with the other data. Maximal transdiaphragmatic pressure (Pdi max) was measured using the technique described by Laporta and Grassino (7). Patients were instructed to inspire maximally against an occluded airway from FRC. They were provided with a direct visualization of Pes and Pga recordings and instructed to maximize both pressure swings. The best of at least five efforts sustained for 1 s was selected as the Pdi max • All obstructive apneas (cessation of airflow > 10s with associated inspiratory effort) were analyzed for each patient. Apneas were ex-
eluded from analysis if there was significant artifact in either the Pes or the Pga tracings. The breath immediately preceding an apnea and all inspiratory efforts during an apnea were analyzed. Mean and peak ~Pdi (Pdi = Pga - Pes), inspiratory time (Ti) (from onset of pressure to zero pressure), and the time of the total respiratory cycle(not) weremeasured by tracing the simultaneous Pes and Pga measurements on a calibrated digitizer (GTCO Corp., Rockville, MD) interfaced to a microcomputer. The mean Pdi was measured by integrating the area under the inspiratory positive Pdi deflection. The respiratory duty cycle (Tr/Ttot) and the PTI (PTI = Pdi/Pdimax x Tr/Ttot) were derived for each inspiratory effort. Apnea duration, number of inspiratory efforts, mean and minimum Sao" and sleep stage were determined for each apnea.
Results
Individual anthropometric, awake lung
(Received in original form June 1, 1989 and in revised form February 27, 1990) t From the Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. , Supported by the Lung Association of British Columbia. 3 Correspondence and requests for reprints should be addressed to Dr. J. A. Fleetham, Respiratory Division, Department of Medicine, UniversityHospital, 2211 Wesbrook Mall, Vancouver, B. C. V6T 2B5, Canada. • Scholar of the British Columbia Health Care Research Foundation.
533
534
WILCOX, PARE, ROAD, AND FLEETHAM
TABLE 1 INDIVIDUAL ANTHROPOMETRIC, AWAKE LUNG FUNCTION AND POLYSOMNOGRAPHIC DATA FOR THE SIX SUBJECTS
SUbject No.
Age (yr)
Weight (kg)
1 2 3 4 5 6
51 61 52 52 52 52
140
rr
94
102 111 99
93 107 95 113
FVC (% pred)
84 54
FEV, (% pred)
Pdimax (em H2O)
Apnea Index (apnea/TST/h)
78 109 121 107 82
108 142 155 155 168 116
36
64
54
26 22 9 59
Sa02 (%)
Mean Apnea Duration (s)
Mean
Min
25 29 18 23 19 16
88 89 93 92 90 78
56 27 79 74 49 40
Definition of abbreviations: Pdi max = maximal transdiaphragmatic pressure; TST = total sleep time; Sao, = arterial oxygen saturation.
function, and polysomnographic data are presented for the six subjects in table 1. Their ages varied from 52 to 61 yr, and all subjects were obese with weights varying from 93 to 140 kg. Three subjects had a reduced vital capacity, but Pdimax was within the normal predicted range for all patients (7). Representative polygraphic recordings prior to and during an obstructive apnea in Patients 5 and 2, respectively, are shown in figure 1. Prior to the onset of the apnea, APdi during tidal breathing are relatively small with simultaneous positive Pga and negative Pes changes and outward rib cage and abdominal movement during inspiration. Patients 1, 3, 4, and 5 demonstrated paradoxical inward movement of the rib cage with outward movement of the abdomen during inspiratory efforts throughout obstructive apnea (figure 1, upper panel). Patients 2 and 6 consistently demonstrated a different pattern with a simultaneous inward movement of the abdomen and outward movement of the rib cage during inspiratory efforts during obstructive apnea (figure 1, lower panel). APdi during inspiration progressively increased in all patients during obstructive apnea. The APga were negligible during the initial inspiratory efforts in an apnea and increased minimally in comparison with APes during an apnea. In four patients (Patients 1, 3, 4, and 5), there was a progressive increase in APga during the expiratory phase with associated inward abdominal movement. Immediately after an apnea, there was a marked decrease in APdi; however, APdi remained larger for several breaths than during preapneic tidal breathing. The normal pattern of Pga (positive swing during inspiration returning to baseline during expiration) resumed immediately after an apnea. The pattern of
rib cage and abdominal motion during apnea remained consistent for each patient throughout the polysomnogram. The mean changes in APdi for each patient for the breath preceding an apnea and each inspiratory effort during the apnea are shown in figure 2. There was a large intersubject variability in Pdi generation during an apnea. The mean change in APdi in the final inspiratory effort varied from 25 ± 7 em H 20 (mean ± SD) for Patient 2 to 112 ± 43 em H 20 for Patient 5. The rate of increase of APdi during an apnea varied between patients. Patients 2 and 6 showed a gradual and slight increase, whereas Patient 5 had a large and rapid increase. Neither the rate of increase of APdi during an apnea or the mean APdi in the final inspiratory effort were related to Pdi max • The APdi during the final inspiratory effort in apneas of different durations are shown in table 2. The APdi during the final inspiratory effort were independent of the number of inspiratory efforts during an apnea in five of six patients. In Patient 5, the APdi increased progressively as the number of inspiratory efforts during an apnea increased. There was a linear increase in APes relative to APga during obstructive apnea in each patient, but the slope of this relationship varied between patients (figure 3). The mean changes in Tr, not, and Ti/Ttot for each patient for the breath preceding an apnea and each inspiratory effort during the apnea are shown in figure 4. n increased and Ttot progressively decreased during apnea, but both indices plateaued when the apnea exceeded five breaths despite a continued increase in APdi. Tt/Ttot for all patients increased from 0.37 ± 0.12 (mean ± SD) during the breath immediately before the onset ofthe apnea to 0.65 ± 0.07 during
the fourth inspiratory effort to 0.71 ± 0.1 during the final inspiratory effort of the apnea. The PTI progressively increased during obstructive apnea (figure 5). There was a large intersubject variability in PTI during apnea. In Patient 2, PTI increased by a factor of 3, whereas in Patient 5, PTI increased by a factor of 10. In Patients 1, 3, and 5, the mean PTI during the final inspiratory effort were greater than 0.15 (0.20 ± 0.07,0.16 ± 0.04,0.20 ± 0.08, respectively), which is the "fatigue threshold" of normal subjects (8). In Patients 2, 4, and 6, the mean PTI during the final inspiratory effort were less than 0.15 (0.06 ± 0.01, 0.10 ± 0.05, and 0.08 ± 0.03, respectively). The patients with the mean PTI less than 0.15 tended to have more severe OSA with higher apnea frequency (45 ± 20/h versus 24 ± 14/h, mean ± SD) and lower mean Sao, (86 ± 7"10 versus 90 ± 2"19). Apnea duration, APdi, and Tt/Ttot were not different between the different non-REM sleep stages. Only one patient (Patient 5) had sufficient REM sleep to allow comparison between apneas during non-REM and REM sleep (table 3). In this patient, apneas were longer (28 ± 12)and associated with lower Sao, (64 ± 8%) during REM sleep than during non-REM sleep (15 ± 7 s, 79 ± 6%). Although the rate of APdi and PTI during apneas were less during REM than during non-REM sleep, the APdi and PTI in the final inspiratory effort were similar between REM sleep and nonREM sleep. Discussion
This study demonstrates that in patients with OSA there is a variable response between patients in transdiaphragmatic pressure generation during an apnea. No consistent PTI of the diaphragm was associated with apnea termination though it tended to be lower in patients with more severe OSA. The respiratory duty cycle plateaued during prolonged apneas. There was intersubject variability in both inspiratory and expiratory muscle recruitment during apnea. In four ofthe six patients, the diaphragm appeared to be the primary inspiratory muscle during apnea, but the other two patients made weaker inspiratory efforts during apnea, with paradoxical abdominal wall motion, which suggests the intercostal/accessory muscles were more active. During the expiratory phase of apnea, the same four patients demonstrated an increase in Pga
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
_ .. ". .. .. . ~ J!. ... . ~-.I. ..,I.......,
...-
, _
" , .,#-.....
\O" ..
·. · .,· ,t
535
, r.4' " . .., .. , " ; ' ,'
.1. "" .. " .A....
•,••J ." ~
'~'.
EEG '~ J '
,. ....
~
r '0"" ' " " ,
..~ .. . .. ....( .. . .
•
4
.. _ _•
•·
'
•
•
... .. ...... .,
,+--/, ./"I
-.,...
'
.~
'r.. .
EOG
'f",',
",1:\' .
\ ~ ..J,.
E NG ..
..
~
I
,
..
•
"
t • ..,
j
...
j
...
of 'I
,
.,
,
I
"II
0.15. The effect of REM sleep on the relationship between respiratory muscle function and apnea termination was examined in the one patient in our study who had sufficient apnea during REM sleep to allow analysis. Apneas were longer, arterial oxygen desaturation was more marked, and the slope of the changes in L\Pdi and PTI were less during REM sleep. Despite this, the levels of L\Pdi and PTI achieved during the final inspiratory effort prior to apnea termination weresimilar between non-REM and REM sleep. This data further sup-
4
.t.Pga (em H20)
C'l
Fig. 2. Mean change in transdiaphragmatic pressure (Pdi)for the breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
2
0
... Patient6
Last
•
~
/
234
20
~
20
•
••
•
ports the hypothesis of a threshold of re• 10 spiratory muscle activity causing apnea •• termination. o+-~--r-~--r-~--r-~--r-~-r-~ We examined the Tr/Ttot to further o 2 4 6 8 10 characterizethe intersubject heterogeneity .t.Pga (em H20) of PTI response during apnea. The variability in PTI response during apnea could Fig. 3. Relationship beteween the mean change in not be accounted for by any differences esophageal (Pes)and gastric (Pga)pressure during each inspiratory effort during non-REM obstructive apnea in in respiratory timing. Wefound relatively Patient 1 (upper panel) and in Patient 6 (/cmer panel). consistent changes in 'Ir/Ttot during obstructive apnea in non-REM sleep. There was a progressive increase in 'Ir/Ttot during the initial inspiratory efforts of an an increase in II in the final inspiratory apnea because of both an increase in II effort prior to apnea termination. The and a decrease in Ttot. Tr/Ttot plateaued plateauing of the inspiratory duty cycle when the apnea exceeded five breaths. in the face of increased chemical drive Similar results were reported by Orem to breathe may represent a limitation of and coworkers (15) in a study of upper inspiratory time determined by the cenairway occlusion in anesthetized cats. tral control of breathing. Alternatively, Martin and associates (1) found a simi- it may be due to an inhibitory reflex, lar prolongation in 'Ir/Ttot in six patients which would have the beneficial effect during obstructive apnea, but they noted of preventing a progressive increase in inspiratory effort and the tendency for further upper airway obstruction. Reflexes known to reduce II have been ascribed TABLE 2 to afferents arising from the chest wall TRANSDIAPHRAGMATIC PRESSURE DURING THE FINAL INSPIRATORY (16,17). Afferents from intercostal musEFFORT IN APNEAS OF DIFFERENT DURATIONS cle tendon organs consistently reduce II Number of Inspiratory Efforts during the Apnea in anesthetized cats (18). Furthermore, Preceding the Final Inspiratory Effort' negativepressure applied to the upper airPatient No. 4 5 6 7 way has also been shown to decrease di3 8 aphragmatic activation (13, 14). Thus, 1 61.5 ± 4.7 62.3 ± 2.7 63.1 ± 2.9 67.5 ± 7.8 66.4 ± 3.5 70.8 ± 2.7 there is a physiologic basis for inspirato2 24.4 ± 2.3 25.4 ± 1.3 22.5 ± 3.7 21.7 ± 2.3 27.2 ± 1.6 23.1 ± 3.5 3 59.3 ± 2.6 58.4 ± 2.9 55.4 ± 4.5 60.6 ± 3.3 67.7 ± 22.1 ry muscle inhibition mediated by either 71.0 ± 4.3 4 24.7 ± 4.5 18.7 ± 7.2 23.5 ± 3.1 34.1 ± 6.9 31.6 ± 4.7 26.2 ± 5.8 chest wall or upper airway afferents. 5 79.8 ± 17.6 88.9 ± 8.0 158.9 ± 5.3 118.1 ± 8.1 The intersubject variability in PTI in 6 36.5 ± 2.1 33.3 ± 1.6 15.7 ± 1.2 33.4 ± 1.4 33.6 ± 1.8 32.8 ± 2.2 our study could be attributed to the dif• b.Pdi values (em H are mean ± SO. ferencesin diaphragmatic pressuregener20)
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
ation during apnea. Martin and coworkers (1) showed a similar variation in diaphragmatic pressure generation during apnea in six patients with OSA. This variability could potentially result from differences in respiratory drives, diaphragmatic weakness, or diaphragmatic fatigue, The heterogeneous changes in PTI reported by Vincken and associates (4) in five patients with OSA could be largelyaccounted for by intersubject variability in diaphragmatic strength. In contrast, in our study there was only minor variability in Pdimax between patients. In no patient was awake Pdi max in a range indicative of diaphragmatic weakness. Furthermore, there was no association between Pdimax and the pattern of L\Pdi changes during apnea. Diaphragmatic fatigue has been shown to develop when the PTI exceedsa threshold of 0.15 to 0.18 (8). Three of the six patients in our study and all the patients studied by Vincken and associates (4) exceeded this threshold during the last oceluded breath during an apnea. However, Bellemare and Grassino (8) have demonstrated that this level of effort must be maintained for as long as 60 min prior to overt failure of Pdi generation or fatigue. Clearly this did not occur in any of our patients. Although some of our patients had prolonged periods of snoring in between obstructive apnea, the PTI during these periods never exceeded 0.13. Vincken and associates (4) demonstrated no consistent change in EMGdi power spectral analysis during obstructive apnea to confirm diaphragmatic fatigue. A variable contribution of the intercostal/accessory muscles and the diaphragm to inspiratory effort between patients may influence generation of Pdi during obstructive apnea. We noted two different patterns of paradoxical motion in our study. In four patients, there was paradoxical motion of the rib cage, whereas in the other two, there was paradoxical motion of the abdomen during inspiratory efforts during apnea. Staats and coworkers (19) reported a similar dichotomy of chest wall paradox in a large study of patients with OSA. The diaphragm was increasingly recruited during successive inspiratory efforts dur-
537
; :z
3.0
2.5
2.0
~ 1.5
~-
1.0
0
Patient 1
• c •
Patient 2 Patient 3 Patient 4
6. Patient 5
0.5
.4 Patient 6 0
ss
, 2 3 4 5 Inspiratory effort number
6
I
Last
12
10
8 ~ I-
0
6
~
0
Patient 1
• c
Patient 2
4
•
Patient 4
2
6. Patient 5
Patient 3
.4 Patient 6
0
SS
, 2 4 3 5 Inspiratory effort number
6
I
Last
0.8
0.6
I-
0
~ 0.4 t-C-
0
Patient 1
•
Patient 2
•
0.2
Patient 3 Patient 4
6. Patient 5 Fig. 4. Meanchangesin inspiratory time (11) (upperpanel), total respiratorycycletime (Ttot)(middlepanel), and respiratory duty cycle(Tlmot) (Ic1Ner panel)forthe breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
.4 Patient 6 0.0
SS
,, 2
4 3 5 Inspiratory effort number
6
I
Last
538
WILCOX, PARE, ROAD, AND FLEETHAM
020
i= 0.15 Q..
x
(j)
"0
c
(j)
E 0.10 0
• 0.05
/
BB
234
5
6
Patient 1 Patient 2
0
Patient 3
•
Patient 4
/::,
Patient 5
•
Patient 6
I
Last
Inspiratory effort number Fig. 5. Mean changes in the pressure time index of the diaphragm (PTI) for the breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
ing apneas in all patients, as indicated by the positive relationship between Pes and Pga. During isovolumetric maneuvers (i.e.,inspiratory effort against an occluded upper airway), outward movement of the rib cage compartment must be balanced by inward movement of the abdominal compartment. The abdominal paradox noted in the two patients with the largest increase in Pes in relation to Pga may therefore be explained by a greater recruitment of the intercostal/accessory muscles. Alternatively, rib cage paradox, noted in the other four patients, might indicate predominant
recruitment of the diaphragm. Variability in the relationship between ~Pes and ~Pga could reflect differencesin abdominal and rib cage compliance. Reduced abdominal compliance is an unlikely cause of the decreased ~Pes/~Pga during apnea noted in our patients with rib cage paradox. In these patients, the sudden relaxation of the abdominal muscles at the onset of inspiratory efforts should have resulted in an increase in abdominal compliance in comparison with those patients with abdominal paradox. Expiratory muscle activity may also be of interest in patients with OSA. Sanders
Acknowledgment The writers thank Jemima Wasurakintu for her technical assistance and B. Robillard for her secretarial assistance.
TABLE 3 COMPARISON OF TRANSDIAPHRAGMATIC PRESSURE (aPdi), RESPIRATORY DUTY CYCLE (TIfTtot), AND PRESSURE TIME INDEX OF THE DIAPHRAGM (PTI) DURING APNEAS IN NONRAPID EYE MOVEMENT AND RAPID EYE MOVEMENT SLEEP IN PATIENT 5* Inspiratory Effort during Apnea
Sleep Stage
aPdi
References
TllTtot
PTI
Non-REM REM
26.2 ± 13.3 15.8 ± 5.4
0.26 ± 0.08 0.26 ± 0.15
0.023 ± 0.02 0.009 ± 0.003
2
Non-REM REM
37.4 ± 20.3 25.6 ± 7.8
0.51 ± 0.09 0.52 ± 0.08
0.052 ± 0.04 0.030 ± 0.008
3
Non-REM REM
63.8 ± 26.7 40.6 ± 18.5
0.62 ± 0.08 0.67 ± 0.11
0.100 ± 0.05 0.063 ± 0.02
4
Non-REM REM
84.9 ± 33.1 53.4 ± 29.9
0.66 ± 0.08 0.61 ± 0.13
0.140 ± 0.07 0.070 ± 0.04
Lastt
Non-REM REM
132.8 ± 45.3 171.8 ± 15.8
0.71 ± 0.08 0.69 ± 0.04
0.200 ± 0.06 0.290 ± 0.06
• All values are mean ± SO. Final inspiratory effort during apnea.
t
and coworkers (20)noted a prolonged expiratory phase in some patients with OSA, and they attributed this to increased upper airway resistance during expiration. Inspiratory pressure generation is dependent on diaphragmatic length. Progressive recruitment of abdominal muscles during the expiratory phase of an obstructive apnea and the resultant chest wall distortion would cause lengthening of the diaphragm and consequent optimization of diaphragmatic function during subsequent inspiratory efforts. In four of our patients, there was progressive recruitment of the abdominal muscles during the expiratory phases of the obstructive apnea as suggested by a phasic expiratory Pga and an end-expiratory decrease in Pga. Similar patterns of abdominal muscle recruitment have been observed in response to a variety of respiratory loads (21, 22) and with increased chemical drive to breathe (23). Abdominal muscle recruitment may help to explain the relatively greater increase in Pdi in comparison with EMGdi demonstrated during occluded inspiratory efforts (3). Interestingly, this recruitment was absent in the two patients in this study with the lowest ~Pdi responsesduring obstructive apnea and most severe OSA. Lack of abdominal muscle recruitment during obstructive apnea may be indicative of a reduced ventilatory response during apnea. In our study, patients with vigorous diaphragmatic and abdominal muscle responses during apnea tended to have less severe OSA. Whether these patients subsequently develop reduced ventilatory responses during apnea and more severe OSA remains to be determined.
1. Martin RJ, Pennock BE, Orr WC, Sanders MH, Rodgers RM. Respiratory mechanics and timing during sleep in occlusive sleep apnea. J Appl Physiol 1980; 48:432-7. 2. Onal E, Lopata M, O'Connor T. Pathogenesis of apneas in hypersomnia sleep apnea syndrome. Am Rev Respir Dis 1982; 125:167-74. 3. Onal E, Lopata M. Respiratory muscle interaction during NREM sleep in patients with occlusive apnea. J Appl Physiol 1986; 61:1891-5. 4. Vincken W, Guilleminault C, Silvestri L, Cosio M, Grassino A. Inspiratory muscle activity as a trigger causing the airways to open in obstructive sleep apnea. Am Rev Respir Dis 1987; 135:372-7. 5. Rechtschaffen A, Kales A, eds. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Bethesda: National Institute of Neurological Disease and
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
Blindness, 1968 (NIH publication no. 204). 6. Millo-Emili J, Mead J, Turner JM, Glauser EM. Improved technique for estimated pleural pressure from esophageal balloons. J Appl Physiol 1964; 19:207-11. 7. Laporta D, Grassino A. Assessment of transdiaphragmatic pressure in humans. J Appl Physiol 1985; 58:1469-76. 8. Bellemare F, Grassino A. Evaluation of human diaphragm fatigue. J Appl Physiol 1982; 53: 1196-206. 9. BowesG, Phillipson EA. Arousal responses to respiratory stimuli during sleep. In: Saunders NA, Sullivan CE, eds, Sleep and breathing. New York: Marcel Dekker, 1984; 137-61. 10. Hugelin A, Bonvallet M, Dell P. Activation reticulaire et corticale d'origine chemoceptive au course de I'hypoxie. Electroencephalogr Clin Neurophysiol 1959; 11:325-40. II. Berthon-Jones M, SullivanCEo Ventilatoryand arousal responses to hypoxia in sleeping humans. Am Rev Respir Dis 1982; 125:632-9.
12. F1eethamJ, WestP, Mezon B, ConwayW,Roth T, Kryger M. Sleep, arousals and oxygen desaturation in chronic obstructive pulmonary disease. Am Rev Respir Dis 1982; 126:429-33. 13. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on genioglossus muscle respiratory activity. J Appl Physiol 1982; 52:438-44. 14. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on respiratory frequency. Respir Physiol1982; 49:223-33. 15. Orem J, Dick T, Norris P. Laryngeal and diaphragmatic responses to airway occlusion in sleep and wakefulness. Electroencephalogr Clin Neurophysiol 1980; 50:151-64. 16. Knill R, Bryan AC. An intercostal-phrenic inhibitory reflex in human newborn infants. J Appl Physiol 1976; 40:352-6. 17. Read DJC, Freedman S, Kafer ER. Pressures developed by loaded inspiratory muscles in conscious and anesthetized man. J ApplPhysiol1974; 37:207-18.
539 18. Bolser DC, Lindsey BG, Shannon R. Medullary inspiratory activity: influence of intercostaltendon organs and muscle spindle endings. J Appl Physiol 1987; 62:1046-56. 19. Staats BA, Bonekat HW, Harris CD, Offord KP. Chest wall motion in obstructive sleep apnea. Am Rev Respir Dis 1984; 130:59-63. 20. Sanders M, Rogers R, Pennock B. Prolonged expiratory phase in sleep apnea. Am Rev Respir Dis 1985; 131:401-8. 21. Lopata M, Onal E, Ginzburg AS. Respiratory muscle function during CO, rebreathing. J Appl Physiol 1983; 54:475-82. 22. Lopata M, Onal E, Cromydas G. Respiratory load compensation in chronic airways obstruction. J Appl Physiol 1985; 59:1947-54. 23. Campbell EJM, Green JH. The variations in intra-abdominal pressure and the activity of the abdominal muscles during breathing: a study in man. J Physiol (Lond) 1953; 122:282-90.
PEARCE G. WILCOX, 4 PETER D. PARE, JEREMY D. ROAD, 4 and JOHN A. FLEETHAM
Introduction
Obstructive sleep apnea (GSA) occurs because of recurrent upper airway occlusion during sleep. Repeated inspiratory efforts are made during an obstructive apnea until upper airway patency is restored. There is limited data on inspiratory and expiratory muscle function during obstructive apnea (1-4). Inspiratory muscles may be subjected to potentially fatiguing loads during an obstructive apnea, and Vincken and associates (4) have suggested that exceeding this fatigue threshold can trigger the termination of the apnea. Inspiratory pressure generation is influenced by respiratory timing and the relative contribution of the diaphragm and intercostal/accessory muscles. The inspiratory pressure generated by the diaphragm is also dependent on diaphragmatic length. Progressive recruitment of expiratory muscles, particularly the abdominal muscles during the expiratory phase of obstructive apnea, would cause diaphragm lengthening and optimize diaphragmatic function during inspiratory efforts. Wehave measured transdiaphragmatic pressure, breathing patterns, and chest wall motion in six male patients with GSA during sleep to characterize respiratory muscle function in GSA and to determine whether termination of obstructive apnea is consistently related to a pressure time index of the diaphragm (PTI) associated with respiratory muscle fatigue. Methods Subjects Six male subjects with OSA were recruited. No subject was using any medication and none had any clinical evidence of neuromuscular disease. All subjects gaveinformed consent to the study, which was approved by the university ethics committee. 'Techniques Lung function was assessed on the basis of the best of three expirations into a spirometer (CollinsModular Function Analyzer; Warren E. Collins, Braintree, MA). Detailed overnight polysomnograms were performed in a fully equipped sleep laboratory. Sleep and its
Obstructive sleep apnea (OSA) Is characterized by recurrent upper airway obstruction during sleep. Inspiratory muscles may be SUbjectedto potentially fatigUing loads during an obstructive apnea and this may be related to the termination of obstructive apnea. Wehave measured transdiaphragmatic pressure (Pdi) and breathing patterns In six male patients with OSA during sleep to characterize respiratory muscle function In OSA and determine whether apnea termination Is consistently related to a pressure time Index of the diaphragm (PTI) associated with respiratory muscle fatigue. There was a large intersubject variability In Pdl generation during apnea. No consistent level of PTI was associated with apnea termination. During prolonged apneas, the respiratory duty cycle plateaued, which Is suggestive of an Inhibitory reflex possibly mediated by chest wall afferents. There were Intersubject differences In both Inspiratory and expiratory muscle recruitment during apnea. In the majority of patients, the diaphragm appeared to be the primary Inspiratory muscle during apnea, but In some It appeared to be the Intercostal/accessory muscles. The majority of patients demonstrated an Increase In gastric pressure and Inward abdominal movement during the expiratory phases of an apnea, consistent with abdominal muscle recruitment stimulated by increased ventilatory drive. AM REV RESPIR DIS 1990; 142:533-539 SUMMARY
various stages were documented by standard electroencephalographic (EEG), electrooculographic (EOG), and electromyographic (EMG) criteria (5). Airflow was detected by an infrared CO, analyzer (Medical Gas Analyzer LB-2; Beckman Instruments, Fullerton, CA) recording continuously from the nose and mouth. Arterial oxygen saturation (Sao,) was monitored continuously with a pulse oximeter (Nellcor, Hayward, CA). Chest wall and abdominal movement were assessed by a respiratory inductive plethysmograph (Respitrace@; Ambulatory Monitoring, Inc., Ardsley, NY). The data were recorded on a 15channel polygraph recorder (Model 78; Grass Instruments, Quincy, MA) at a paper speed of 10 mm/s. Transdiaphragmatic pressure (Pdi) was measured with lO-cmlatex balloon catheters, one placed in the midesophagus and inflated with 0.5 ml of air (Pes) and the other placed in the stomach and inflated with 2 ml of air (Pga) (6). The catheters were coupled to individual pressure transducers (Model P23A; Statham Instruments, Oxnard, CA), and continuous overnight tracings of Pes and Pga were recorded with the other data. Maximal transdiaphragmatic pressure (Pdi max) was measured using the technique described by Laporta and Grassino (7). Patients were instructed to inspire maximally against an occluded airway from FRC. They were provided with a direct visualization of Pes and Pga recordings and instructed to maximize both pressure swings. The best of at least five efforts sustained for 1 s was selected as the Pdi max • All obstructive apneas (cessation of airflow > 10s with associated inspiratory effort) were analyzed for each patient. Apneas were ex-
eluded from analysis if there was significant artifact in either the Pes or the Pga tracings. The breath immediately preceding an apnea and all inspiratory efforts during an apnea were analyzed. Mean and peak ~Pdi (Pdi = Pga - Pes), inspiratory time (Ti) (from onset of pressure to zero pressure), and the time of the total respiratory cycle(not) weremeasured by tracing the simultaneous Pes and Pga measurements on a calibrated digitizer (GTCO Corp., Rockville, MD) interfaced to a microcomputer. The mean Pdi was measured by integrating the area under the inspiratory positive Pdi deflection. The respiratory duty cycle (Tr/Ttot) and the PTI (PTI = Pdi/Pdimax x Tr/Ttot) were derived for each inspiratory effort. Apnea duration, number of inspiratory efforts, mean and minimum Sao" and sleep stage were determined for each apnea.
Results
Individual anthropometric, awake lung
(Received in original form June 1, 1989 and in revised form February 27, 1990) t From the Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. , Supported by the Lung Association of British Columbia. 3 Correspondence and requests for reprints should be addressed to Dr. J. A. Fleetham, Respiratory Division, Department of Medicine, UniversityHospital, 2211 Wesbrook Mall, Vancouver, B. C. V6T 2B5, Canada. • Scholar of the British Columbia Health Care Research Foundation.
533
534
WILCOX, PARE, ROAD, AND FLEETHAM
TABLE 1 INDIVIDUAL ANTHROPOMETRIC, AWAKE LUNG FUNCTION AND POLYSOMNOGRAPHIC DATA FOR THE SIX SUBJECTS
SUbject No.
Age (yr)
Weight (kg)
1 2 3 4 5 6
51 61 52 52 52 52
140
rr
94
102 111 99
93 107 95 113
FVC (% pred)
84 54
FEV, (% pred)
Pdimax (em H2O)
Apnea Index (apnea/TST/h)
78 109 121 107 82
108 142 155 155 168 116
36
64
54
26 22 9 59
Sa02 (%)
Mean Apnea Duration (s)
Mean
Min
25 29 18 23 19 16
88 89 93 92 90 78
56 27 79 74 49 40
Definition of abbreviations: Pdi max = maximal transdiaphragmatic pressure; TST = total sleep time; Sao, = arterial oxygen saturation.
function, and polysomnographic data are presented for the six subjects in table 1. Their ages varied from 52 to 61 yr, and all subjects were obese with weights varying from 93 to 140 kg. Three subjects had a reduced vital capacity, but Pdimax was within the normal predicted range for all patients (7). Representative polygraphic recordings prior to and during an obstructive apnea in Patients 5 and 2, respectively, are shown in figure 1. Prior to the onset of the apnea, APdi during tidal breathing are relatively small with simultaneous positive Pga and negative Pes changes and outward rib cage and abdominal movement during inspiration. Patients 1, 3, 4, and 5 demonstrated paradoxical inward movement of the rib cage with outward movement of the abdomen during inspiratory efforts throughout obstructive apnea (figure 1, upper panel). Patients 2 and 6 consistently demonstrated a different pattern with a simultaneous inward movement of the abdomen and outward movement of the rib cage during inspiratory efforts during obstructive apnea (figure 1, lower panel). APdi during inspiration progressively increased in all patients during obstructive apnea. The APga were negligible during the initial inspiratory efforts in an apnea and increased minimally in comparison with APes during an apnea. In four patients (Patients 1, 3, 4, and 5), there was a progressive increase in APga during the expiratory phase with associated inward abdominal movement. Immediately after an apnea, there was a marked decrease in APdi; however, APdi remained larger for several breaths than during preapneic tidal breathing. The normal pattern of Pga (positive swing during inspiration returning to baseline during expiration) resumed immediately after an apnea. The pattern of
rib cage and abdominal motion during apnea remained consistent for each patient throughout the polysomnogram. The mean changes in APdi for each patient for the breath preceding an apnea and each inspiratory effort during the apnea are shown in figure 2. There was a large intersubject variability in Pdi generation during an apnea. The mean change in APdi in the final inspiratory effort varied from 25 ± 7 em H 20 (mean ± SD) for Patient 2 to 112 ± 43 em H 20 for Patient 5. The rate of increase of APdi during an apnea varied between patients. Patients 2 and 6 showed a gradual and slight increase, whereas Patient 5 had a large and rapid increase. Neither the rate of increase of APdi during an apnea or the mean APdi in the final inspiratory effort were related to Pdi max • The APdi during the final inspiratory effort in apneas of different durations are shown in table 2. The APdi during the final inspiratory effort were independent of the number of inspiratory efforts during an apnea in five of six patients. In Patient 5, the APdi increased progressively as the number of inspiratory efforts during an apnea increased. There was a linear increase in APes relative to APga during obstructive apnea in each patient, but the slope of this relationship varied between patients (figure 3). The mean changes in Tr, not, and Ti/Ttot for each patient for the breath preceding an apnea and each inspiratory effort during the apnea are shown in figure 4. n increased and Ttot progressively decreased during apnea, but both indices plateaued when the apnea exceeded five breaths despite a continued increase in APdi. Tt/Ttot for all patients increased from 0.37 ± 0.12 (mean ± SD) during the breath immediately before the onset ofthe apnea to 0.65 ± 0.07 during
the fourth inspiratory effort to 0.71 ± 0.1 during the final inspiratory effort of the apnea. The PTI progressively increased during obstructive apnea (figure 5). There was a large intersubject variability in PTI during apnea. In Patient 2, PTI increased by a factor of 3, whereas in Patient 5, PTI increased by a factor of 10. In Patients 1, 3, and 5, the mean PTI during the final inspiratory effort were greater than 0.15 (0.20 ± 0.07,0.16 ± 0.04,0.20 ± 0.08, respectively), which is the "fatigue threshold" of normal subjects (8). In Patients 2, 4, and 6, the mean PTI during the final inspiratory effort were less than 0.15 (0.06 ± 0.01, 0.10 ± 0.05, and 0.08 ± 0.03, respectively). The patients with the mean PTI less than 0.15 tended to have more severe OSA with higher apnea frequency (45 ± 20/h versus 24 ± 14/h, mean ± SD) and lower mean Sao, (86 ± 7"10 versus 90 ± 2"19). Apnea duration, APdi, and Tt/Ttot were not different between the different non-REM sleep stages. Only one patient (Patient 5) had sufficient REM sleep to allow comparison between apneas during non-REM and REM sleep (table 3). In this patient, apneas were longer (28 ± 12)and associated with lower Sao, (64 ± 8%) during REM sleep than during non-REM sleep (15 ± 7 s, 79 ± 6%). Although the rate of APdi and PTI during apneas were less during REM than during non-REM sleep, the APdi and PTI in the final inspiratory effort were similar between REM sleep and nonREM sleep. Discussion
This study demonstrates that in patients with OSA there is a variable response between patients in transdiaphragmatic pressure generation during an apnea. No consistent PTI of the diaphragm was associated with apnea termination though it tended to be lower in patients with more severe OSA. The respiratory duty cycle plateaued during prolonged apneas. There was intersubject variability in both inspiratory and expiratory muscle recruitment during apnea. In four ofthe six patients, the diaphragm appeared to be the primary inspiratory muscle during apnea, but the other two patients made weaker inspiratory efforts during apnea, with paradoxical abdominal wall motion, which suggests the intercostal/accessory muscles were more active. During the expiratory phase of apnea, the same four patients demonstrated an increase in Pga
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
_ .. ". .. .. . ~ J!. ... . ~-.I. ..,I.......,
...-
, _
" , .,#-.....
\O" ..
·. · .,· ,t
535
, r.4' " . .., .. , " ; ' ,'
.1. "" .. " .A....
•,••J ." ~
'~'.
EEG '~ J '
,. ....
~
r '0"" ' " " ,
..~ .. . .. ....( .. . .
•
4
.. _ _•
•·
'
•
•
... .. ...... .,
,+--/, ./"I
-.,...
'
.~
'r.. .
EOG
'f",',
",1:\' .
\ ~ ..J,.
E NG ..
..
~
I
,
..
•
"
t • ..,
j
...
j
...
of 'I
,
.,
,
I
"II
0.15. The effect of REM sleep on the relationship between respiratory muscle function and apnea termination was examined in the one patient in our study who had sufficient apnea during REM sleep to allow analysis. Apneas were longer, arterial oxygen desaturation was more marked, and the slope of the changes in L\Pdi and PTI were less during REM sleep. Despite this, the levels of L\Pdi and PTI achieved during the final inspiratory effort prior to apnea termination weresimilar between non-REM and REM sleep. This data further sup-
4
.t.Pga (em H20)
C'l
Fig. 2. Mean change in transdiaphragmatic pressure (Pdi)for the breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
2
0
... Patient6
Last
•
~
/
234
20
~
20
•
••
•
ports the hypothesis of a threshold of re• 10 spiratory muscle activity causing apnea •• termination. o+-~--r-~--r-~--r-~--r-~-r-~ We examined the Tr/Ttot to further o 2 4 6 8 10 characterizethe intersubject heterogeneity .t.Pga (em H20) of PTI response during apnea. The variability in PTI response during apnea could Fig. 3. Relationship beteween the mean change in not be accounted for by any differences esophageal (Pes)and gastric (Pga)pressure during each inspiratory effort during non-REM obstructive apnea in in respiratory timing. Wefound relatively Patient 1 (upper panel) and in Patient 6 (/cmer panel). consistent changes in 'Ir/Ttot during obstructive apnea in non-REM sleep. There was a progressive increase in 'Ir/Ttot during the initial inspiratory efforts of an an increase in II in the final inspiratory apnea because of both an increase in II effort prior to apnea termination. The and a decrease in Ttot. Tr/Ttot plateaued plateauing of the inspiratory duty cycle when the apnea exceeded five breaths. in the face of increased chemical drive Similar results were reported by Orem to breathe may represent a limitation of and coworkers (15) in a study of upper inspiratory time determined by the cenairway occlusion in anesthetized cats. tral control of breathing. Alternatively, Martin and associates (1) found a simi- it may be due to an inhibitory reflex, lar prolongation in 'Ir/Ttot in six patients which would have the beneficial effect during obstructive apnea, but they noted of preventing a progressive increase in inspiratory effort and the tendency for further upper airway obstruction. Reflexes known to reduce II have been ascribed TABLE 2 to afferents arising from the chest wall TRANSDIAPHRAGMATIC PRESSURE DURING THE FINAL INSPIRATORY (16,17). Afferents from intercostal musEFFORT IN APNEAS OF DIFFERENT DURATIONS cle tendon organs consistently reduce II Number of Inspiratory Efforts during the Apnea in anesthetized cats (18). Furthermore, Preceding the Final Inspiratory Effort' negativepressure applied to the upper airPatient No. 4 5 6 7 way has also been shown to decrease di3 8 aphragmatic activation (13, 14). Thus, 1 61.5 ± 4.7 62.3 ± 2.7 63.1 ± 2.9 67.5 ± 7.8 66.4 ± 3.5 70.8 ± 2.7 there is a physiologic basis for inspirato2 24.4 ± 2.3 25.4 ± 1.3 22.5 ± 3.7 21.7 ± 2.3 27.2 ± 1.6 23.1 ± 3.5 3 59.3 ± 2.6 58.4 ± 2.9 55.4 ± 4.5 60.6 ± 3.3 67.7 ± 22.1 ry muscle inhibition mediated by either 71.0 ± 4.3 4 24.7 ± 4.5 18.7 ± 7.2 23.5 ± 3.1 34.1 ± 6.9 31.6 ± 4.7 26.2 ± 5.8 chest wall or upper airway afferents. 5 79.8 ± 17.6 88.9 ± 8.0 158.9 ± 5.3 118.1 ± 8.1 The intersubject variability in PTI in 6 36.5 ± 2.1 33.3 ± 1.6 15.7 ± 1.2 33.4 ± 1.4 33.6 ± 1.8 32.8 ± 2.2 our study could be attributed to the dif• b.Pdi values (em H are mean ± SO. ferencesin diaphragmatic pressuregener20)
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
ation during apnea. Martin and coworkers (1) showed a similar variation in diaphragmatic pressure generation during apnea in six patients with OSA. This variability could potentially result from differences in respiratory drives, diaphragmatic weakness, or diaphragmatic fatigue, The heterogeneous changes in PTI reported by Vincken and associates (4) in five patients with OSA could be largelyaccounted for by intersubject variability in diaphragmatic strength. In contrast, in our study there was only minor variability in Pdimax between patients. In no patient was awake Pdi max in a range indicative of diaphragmatic weakness. Furthermore, there was no association between Pdimax and the pattern of L\Pdi changes during apnea. Diaphragmatic fatigue has been shown to develop when the PTI exceedsa threshold of 0.15 to 0.18 (8). Three of the six patients in our study and all the patients studied by Vincken and associates (4) exceeded this threshold during the last oceluded breath during an apnea. However, Bellemare and Grassino (8) have demonstrated that this level of effort must be maintained for as long as 60 min prior to overt failure of Pdi generation or fatigue. Clearly this did not occur in any of our patients. Although some of our patients had prolonged periods of snoring in between obstructive apnea, the PTI during these periods never exceeded 0.13. Vincken and associates (4) demonstrated no consistent change in EMGdi power spectral analysis during obstructive apnea to confirm diaphragmatic fatigue. A variable contribution of the intercostal/accessory muscles and the diaphragm to inspiratory effort between patients may influence generation of Pdi during obstructive apnea. We noted two different patterns of paradoxical motion in our study. In four patients, there was paradoxical motion of the rib cage, whereas in the other two, there was paradoxical motion of the abdomen during inspiratory efforts during apnea. Staats and coworkers (19) reported a similar dichotomy of chest wall paradox in a large study of patients with OSA. The diaphragm was increasingly recruited during successive inspiratory efforts dur-
537
; :z
3.0
2.5
2.0
~ 1.5
~-
1.0
0
Patient 1
• c •
Patient 2 Patient 3 Patient 4
6. Patient 5
0.5
.4 Patient 6 0
ss
, 2 3 4 5 Inspiratory effort number
6
I
Last
12
10
8 ~ I-
0
6
~
0
Patient 1
• c
Patient 2
4
•
Patient 4
2
6. Patient 5
Patient 3
.4 Patient 6
0
SS
, 2 4 3 5 Inspiratory effort number
6
I
Last
0.8
0.6
I-
0
~ 0.4 t-C-
0
Patient 1
•
Patient 2
•
0.2
Patient 3 Patient 4
6. Patient 5 Fig. 4. Meanchangesin inspiratory time (11) (upperpanel), total respiratorycycletime (Ttot)(middlepanel), and respiratory duty cycle(Tlmot) (Ic1Ner panel)forthe breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
.4 Patient 6 0.0
SS
,, 2
4 3 5 Inspiratory effort number
6
I
Last
538
WILCOX, PARE, ROAD, AND FLEETHAM
020
i= 0.15 Q..
x
(j)
"0
c
(j)
E 0.10 0
• 0.05
/
BB
234
5
6
Patient 1 Patient 2
0
Patient 3
•
Patient 4
/::,
Patient 5
•
Patient 6
I
Last
Inspiratory effort number Fig. 5. Mean changes in the pressure time index of the diaphragm (PTI) for the breath before the apnea (BB) and each inspiratory effort during the apnea. Each patient is represented by a different symbol.
ing apneas in all patients, as indicated by the positive relationship between Pes and Pga. During isovolumetric maneuvers (i.e.,inspiratory effort against an occluded upper airway), outward movement of the rib cage compartment must be balanced by inward movement of the abdominal compartment. The abdominal paradox noted in the two patients with the largest increase in Pes in relation to Pga may therefore be explained by a greater recruitment of the intercostal/accessory muscles. Alternatively, rib cage paradox, noted in the other four patients, might indicate predominant
recruitment of the diaphragm. Variability in the relationship between ~Pes and ~Pga could reflect differencesin abdominal and rib cage compliance. Reduced abdominal compliance is an unlikely cause of the decreased ~Pes/~Pga during apnea noted in our patients with rib cage paradox. In these patients, the sudden relaxation of the abdominal muscles at the onset of inspiratory efforts should have resulted in an increase in abdominal compliance in comparison with those patients with abdominal paradox. Expiratory muscle activity may also be of interest in patients with OSA. Sanders
Acknowledgment The writers thank Jemima Wasurakintu for her technical assistance and B. Robillard for her secretarial assistance.
TABLE 3 COMPARISON OF TRANSDIAPHRAGMATIC PRESSURE (aPdi), RESPIRATORY DUTY CYCLE (TIfTtot), AND PRESSURE TIME INDEX OF THE DIAPHRAGM (PTI) DURING APNEAS IN NONRAPID EYE MOVEMENT AND RAPID EYE MOVEMENT SLEEP IN PATIENT 5* Inspiratory Effort during Apnea
Sleep Stage
aPdi
References
TllTtot
PTI
Non-REM REM
26.2 ± 13.3 15.8 ± 5.4
0.26 ± 0.08 0.26 ± 0.15
0.023 ± 0.02 0.009 ± 0.003
2
Non-REM REM
37.4 ± 20.3 25.6 ± 7.8
0.51 ± 0.09 0.52 ± 0.08
0.052 ± 0.04 0.030 ± 0.008
3
Non-REM REM
63.8 ± 26.7 40.6 ± 18.5
0.62 ± 0.08 0.67 ± 0.11
0.100 ± 0.05 0.063 ± 0.02
4
Non-REM REM
84.9 ± 33.1 53.4 ± 29.9
0.66 ± 0.08 0.61 ± 0.13
0.140 ± 0.07 0.070 ± 0.04
Lastt
Non-REM REM
132.8 ± 45.3 171.8 ± 15.8
0.71 ± 0.08 0.69 ± 0.04
0.200 ± 0.06 0.290 ± 0.06
• All values are mean ± SO. Final inspiratory effort during apnea.
t
and coworkers (20)noted a prolonged expiratory phase in some patients with OSA, and they attributed this to increased upper airway resistance during expiration. Inspiratory pressure generation is dependent on diaphragmatic length. Progressive recruitment of abdominal muscles during the expiratory phase of an obstructive apnea and the resultant chest wall distortion would cause lengthening of the diaphragm and consequent optimization of diaphragmatic function during subsequent inspiratory efforts. In four of our patients, there was progressive recruitment of the abdominal muscles during the expiratory phases of the obstructive apnea as suggested by a phasic expiratory Pga and an end-expiratory decrease in Pga. Similar patterns of abdominal muscle recruitment have been observed in response to a variety of respiratory loads (21, 22) and with increased chemical drive to breathe (23). Abdominal muscle recruitment may help to explain the relatively greater increase in Pdi in comparison with EMGdi demonstrated during occluded inspiratory efforts (3). Interestingly, this recruitment was absent in the two patients in this study with the lowest ~Pdi responsesduring obstructive apnea and most severe OSA. Lack of abdominal muscle recruitment during obstructive apnea may be indicative of a reduced ventilatory response during apnea. In our study, patients with vigorous diaphragmatic and abdominal muscle responses during apnea tended to have less severe OSA. Whether these patients subsequently develop reduced ventilatory responses during apnea and more severe OSA remains to be determined.
1. Martin RJ, Pennock BE, Orr WC, Sanders MH, Rodgers RM. Respiratory mechanics and timing during sleep in occlusive sleep apnea. J Appl Physiol 1980; 48:432-7. 2. Onal E, Lopata M, O'Connor T. Pathogenesis of apneas in hypersomnia sleep apnea syndrome. Am Rev Respir Dis 1982; 125:167-74. 3. Onal E, Lopata M. Respiratory muscle interaction during NREM sleep in patients with occlusive apnea. J Appl Physiol 1986; 61:1891-5. 4. Vincken W, Guilleminault C, Silvestri L, Cosio M, Grassino A. Inspiratory muscle activity as a trigger causing the airways to open in obstructive sleep apnea. Am Rev Respir Dis 1987; 135:372-7. 5. Rechtschaffen A, Kales A, eds. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Bethesda: National Institute of Neurological Disease and
RESPIRATORY MUSCLE FUNCTION DURING OBSTRUCTIVE SLEEP APNEA
Blindness, 1968 (NIH publication no. 204). 6. Millo-Emili J, Mead J, Turner JM, Glauser EM. Improved technique for estimated pleural pressure from esophageal balloons. J Appl Physiol 1964; 19:207-11. 7. Laporta D, Grassino A. Assessment of transdiaphragmatic pressure in humans. J Appl Physiol 1985; 58:1469-76. 8. Bellemare F, Grassino A. Evaluation of human diaphragm fatigue. J Appl Physiol 1982; 53: 1196-206. 9. BowesG, Phillipson EA. Arousal responses to respiratory stimuli during sleep. In: Saunders NA, Sullivan CE, eds, Sleep and breathing. New York: Marcel Dekker, 1984; 137-61. 10. Hugelin A, Bonvallet M, Dell P. Activation reticulaire et corticale d'origine chemoceptive au course de I'hypoxie. Electroencephalogr Clin Neurophysiol 1959; 11:325-40. II. Berthon-Jones M, SullivanCEo Ventilatoryand arousal responses to hypoxia in sleeping humans. Am Rev Respir Dis 1982; 125:632-9.
12. F1eethamJ, WestP, Mezon B, ConwayW,Roth T, Kryger M. Sleep, arousals and oxygen desaturation in chronic obstructive pulmonary disease. Am Rev Respir Dis 1982; 126:429-33. 13. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on genioglossus muscle respiratory activity. J Appl Physiol 1982; 52:438-44. 14. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on respiratory frequency. Respir Physiol1982; 49:223-33. 15. Orem J, Dick T, Norris P. Laryngeal and diaphragmatic responses to airway occlusion in sleep and wakefulness. Electroencephalogr Clin Neurophysiol 1980; 50:151-64. 16. Knill R, Bryan AC. An intercostal-phrenic inhibitory reflex in human newborn infants. J Appl Physiol 1976; 40:352-6. 17. Read DJC, Freedman S, Kafer ER. Pressures developed by loaded inspiratory muscles in conscious and anesthetized man. J ApplPhysiol1974; 37:207-18.
539 18. Bolser DC, Lindsey BG, Shannon R. Medullary inspiratory activity: influence of intercostaltendon organs and muscle spindle endings. J Appl Physiol 1987; 62:1046-56. 19. Staats BA, Bonekat HW, Harris CD, Offord KP. Chest wall motion in obstructive sleep apnea. Am Rev Respir Dis 1984; 130:59-63. 20. Sanders M, Rogers R, Pennock B. Prolonged expiratory phase in sleep apnea. Am Rev Respir Dis 1985; 131:401-8. 21. Lopata M, Onal E, Ginzburg AS. Respiratory muscle function during CO, rebreathing. J Appl Physiol 1983; 54:475-82. 22. Lopata M, Onal E, Cromydas G. Respiratory load compensation in chronic airways obstruction. J Appl Physiol 1985; 59:1947-54. 23. Campbell EJM, Green JH. The variations in intra-abdominal pressure and the activity of the abdominal muscles during breathing: a study in man. J Physiol (Lond) 1953; 122:282-90.
