Copyright ©ERS Journals Ltd 2003 The role of mean inspiratory effort on daytime sleepinessSleep Disorders Unit, Dept of Neurology, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey CORRESPONDENCE: Z. Pelin, Bayar cad. 71/9, 81090, Kozyatagi, Istanbul, Turkey. Fax: 90 2163698925. E-mail: kzpelin@turk.net Keywords: daytime sleepiness, respiratory effort, sleep apnoea syndrome, upper airway resistance
Received: November 28, 2001
This study has investigated the role of average maximum inspiratory effort in excessive daytime sleepiness in patients with obstructive sleep apnoea syndrome (OSAS) and upper airway resistance syndrome (UARS).
Fifteen patients diagnosed with UARS and 32 patients with OSAS, with >5.5 h total sleep time (TST) during 8 h of nocturnal polygraphic recordings, were included in the study. Demographical data, polysomnographical data and data about daytime sleepiness, including Epworth sleepiness scale (ESS) and multiple sleep latency test (MSLT), were evaluated. In order to compute the average maximum inspiratory effort from oesophageal pressure (Poes) measurements, maximum Poes was obtained from 20 representative obstructive respiratory events (obstructive apnoeas, hypopnoeas or flow limitations) for each sleep stage in both supine and side positions. From Poes measurements during sleep, the increase in Poes (
The average maximum Poes, In conclusion, the data from this study indicate the possible important role of average inspiratory effort in determining subjective sleepiness in both obstructive sleep apnoea syndrome and upper airway resistance syndrome patients. Excessive daytime sleepiness (EDS) is one of the most prominent symptoms associated with obstructive upper airway disorders during sleep 1, 2. As a consequence of EDS, significant deterioration is observed in daily performance of patients, with impairment in psychosocial and cognitive functions 3. Besides affecting the quality of life, EDS also increases the risk of motor vehicle and industrial accidents 3, 4. In obstructive sleep apnoea syndrome (OSAS), many hypotheses have been proposed to explain EDS. Different aspects of polysomnographical evaluations, such as changes in breathing (i.e. apnoea/hypopnoea 58 or hypoxaemia 79), have been postulated as the main causes of EDS. In addition, reduction in the restorative nature of sleep by arousals 1012, fragmentation of sleep 13, 14, a lack of slow-wave sleep 15 and a reduction in total sleep time (TST) 16, have all been suggested as possible causes of EDS.
Patients with upper airway resistance syndrome (UARS) also complain of daytime sleepiness 17, 18, like patients with OSAS. Nocturnal polygraphical recordings, however, indicate differences between these two groups. During apnoeic or hypopnoeic events, OSAS patients show a substantial decrease in arterial oxygen saturation (Sa,O2). Conversely, in UARS, Sa,O2 may fluctuate somewhat, but it stays at In one study, Zamagni et al. 23 demonstrated that the degree of respiratory effort during obstructive apnoeas contributes to self-rated sleep propensity in patients with OSAS. In that study obstructive apnoeas selected only from nonrapid eye movement (NREM) sleep were evaluated. However, it was reported that among 34 patients with mild OSAS, the apnoea/hypopnoea index (AHI) during rapid eye movement (REM) sleep, but not the AHI for the entire night, was well correlated with the mean sleep latency on multiple sleep latency tests (MSLT) 24. However, Chervin and Aldrich 25 suggested that apnoeic events during REM and NREM sleep probably contribute equally to sleepiness as measured by the MSLT 25. Therefore, evaluating the effect of respiratory effort on sleepiness in different sleep stages might supply further information about daytime sleepiness in obstructive respiratory disorders. In the present study, the effects of inspiratory effort on daytime sleepiness, with the inclusion of the influences of sleeping position and sleep stages, were investigated in both UARS and OSAS. Other demographical and polysomnographical variables were also evaluated. In a previous study, the relationship between AHI supine sleep and daytime sleepiness was documented by Chervin and Aldrich 8. However, the influence of sleeping position on the amount of respiratory effort in the context of daytime sleepiness has not been investigated before. Only sleep stage dependent changes in respiratory effort were reported by Krieger et al. 26. They found that the respiratory effort was lower in REM than NREM sleep, but they did not establish a connection between this variability and EDS. In this study, testing for associations between Epworth sleepiness scale (ESS)- and MSLT-defined sleepiness, and inspiratory effort and other variables, was reported in patients with UARS as well as OSAS.
Subject selection From 150 consecutively selected patients, the clinical and polysomnographical data of 47 patients (11 females and 36 males) were evaluated. Inclusion criteria for the study included: 1) diagnosis of OSAS or UARS; and 2) >5.5 h of TST during 8 h polysomnographical recordings. Patients with restless leg syndrome and periodic leg movements during sleep were not included in the study. Fifteen patients were diagnosed as UARS with an AHI<10 and minimum Sa,O2>90%. For the diagnosis of UARS, the patient also had to have complained about excessive daytime sleepiness and have an increased number of arousals associated with increased respiratory effort. The other 32 patients were evaluated as OSAS with AHI>10 and minimum Sa,O2<90%. All patients underwent clinical interview before nocturnal polysomnography and these investigations were performed without any treatment.
Polysomnographical evaluations: sleep and respiratory variables
Nocturnal recordings were scored according to the standard criteria of Rechtschaffen and Kales 28, as epochs of 30 s, and the following sleep variables were calculated: TST, sleep efficiency index (TST/time in bed), sleep continuity index (TST/total sleep period), waketime after sleep onset, percentages of sleep stages, and awakening and arousal index. Awakening was defined as transition to awake state from any NREM or REM sleep stage for
Abnormal respiratory events were evaluated according to standard criteria of American Sleep Disorders Association (ASDA) 29. An apnoea was defined as a cessation of airflow with a duration of
Arousals were determined according to ASDA criteria 30 and the arousal index was computed as the number of arousals per hour of sleep.
Assessment of daytime vigilance The Turkish version of ESS was administered by two technicians. In the current authors' laboratory there are rules for the administration of ESS that limit subjective evaluations of technicians. For the ESS, 210 was accepted as normal and >10 was an indicator of pathological degree of sleepiness 33.
The MSLT was performed in the sleep laboratory the day following the polysomnographical examinations 32. The MSLT consisted of five naps scheduled at 10:00, 12:00, 14:00, 16:00 and 18:00 h. The mean sleep latency was calculated by averaging the individual latency scores of the five sleep latency tests. A mean latency to sleep onset of The cut-off points of excessive sleepiness for ESS (10 point) and MSLT (5 min) were not used for statistical analysis. They were only used for the evaluation of patients on an individual basis.
Assessment of respiratory efforts
In the different sleep stages and positions, maximum Poes was calculated by the average of 20 measured maximum Poes values of abnormal obstructive respiratory events. The Poes value for nocturnal polygraphic recording was calculated by using the following formula:
The same formula was also used for computing the average minimum Poes values. The difference between the average maximum and the minimum inspiratory effort was taken as a measurement of the overall increase in the inspiratory effort during obstructive respiratory event ( Poes values were reported as absolute values to facilitate interpretation of the results. Therefore, higher Poes reflected an increase in respiratory effort.
Statistical analysis For both UARS and OSAS patients, bivariate correlation analysis using Pearson's correlation coefficient was performed, using the ESS and MSLT scores as dependent variables and variables associated with sleep structure, respiratory events, respiratory effort and severity of hypoxaemia as independent variables. The parameters that were significantly correlated and very close to significance were included in multiple regression analysis.
The backward method was used for multiple regression analysis, taking the ESS scores and mean sleep latency of MSLT as dependent variables to identify significant models with the probability of F to remove p Statistical significance was accepted for a p-value of <0.05.
The patient population consisted of UARS and OSAS patients. Ten of 15 patients with UARS and 26 of 32 patients with OSAS were male. There were no significant overall differences in age (45±9 versus 48±10) and body mass index (30.3±4.9 versus 31.3±4.2) between UARS and OSAS patients, respectively.
The descriptive measurements of nocturnal sleep and respiratory parameters of OSAS and UARS patients are presented in table 1
The ESS score showed variability, ranging 120, in patients with both OSAS and UARS. The mean sleepiness score of UARS patients was 8.1±3.6 (range 116), while the mean score of OSAS patients was 10.6±5.2 (range 320). There were 16 OSAS and three UARS patients with an ESS score >10, which was defined as the upper point of normal range of sleepiness 33. The MSLT scores also showed a wide distribution, ranging 2.514 min (mean 7.0±3.3) in UARS patients and 110 min (mean 4.7±2.0) in OSAS patients. The pathological degree of sleepiness for the MSLT, which was defined as <5 min, was found in 22 OSAS and four UARS patients. ESS and MSLT scores showed that OSAS patients were significantly sleepier than UARS patients.
The maximum Poes calculated in each sleep stage and position are presented in table 2
The average maximum Poes showed a wide range of variability in UARS as well as in OSAS patients. The average maximum Poes was 27.7±8.3 (range 1653 cmH2O) and 44.9±13.7 (range 22.878.3 cmH2O) in UARS and OSAS patients, respectively. Other analyses of Poes between the two groups of patients are shown in table 3
The ESS and MSLT were not significantly correlated with each other in either UARS (r=0.27, p=0.32) or OSAS patients (r=0.32, p=0.07).
The results of bivariate correlation analysis for UARS and OSAS are presented in table 4
In OSAS patients, the multiple regression analysis, using the backward method, was performed to more clearly define the relationship of these correlated variables with the Epworth score. The selected model included number of stage variations and average Poes. The multiple correlation coefficient (R=0.51) was statistically significant (F=5.17, df=2, p=0.012). The only significant beta weight was for average Poes (ß=0.165, se of ß=0.06, p=0.01).
Excessive daytime sleepiness is a common complaint among patients with OSAS 1, 2. The association between daytime sleepiness and various respiratory and/or sleep-related factors has been investigated for many years. Among these factors, the most apparent association has been established with AHI 58, hypoxaemia severity 79 and sleep fragmentation 1014. The novelty in the current data is the demonstration that the average inspiratory effort during obstructive respiratory events, calculated with respect to sleep stages and positions, contributes to self-rated sleep propensity in both UARS and OSAS patients. The AHI, which is a commonly accepted indicator of disease severity, did not show a persistent relationship with daytime sleepiness. Although it has been suggested that there is a significant association between sleepiness and RDI 68, 34, in a study of Wisconsin state employees 35, 9% of females and 24% of males had an RDI of >5, while only 2% of females and 4% of males reported daytime sleepiness. A higher percentage of reported sleepiness was found even in patients with an RDI of <5 34, 35. In this study, RDI was significantly higher in patients with OSAS than with UARS. Furthermore, OSAS patients were sleepier than patients with UARS in both the subjective and objective evaluation of sleepiness. This finding might be explained by the findings of previous studies, which showed a linear association between sleepiness and RDI 33, 34. However, a very weak correlation between RDI and ESS score in OSAS patients, and no correlation with ESS in UARS and with MSLT in both UARS and OSAS patients did not support this explanation in the current study.
Another possible explanation of the difference in sleepiness between UARS and OSAS patients is the contribution of hypoxaemia to the sleepiness of OSAS patients. Several investigators 3638 have suggested that nocturnal hypoxaemia may be the primary cause of hypersomnolance in OSAS patients. In two separate reports, Mendelson 36, 37 has shown that measures of oxyhaemoglobin desaturation were the most significant predictors of daytime sleepiness as measured by MSLT. In support of these findings, there are further studies suggesting the importance of nocturnal hypoxaemia as an independent contributor to sleepiness in OSAS patients 7, 8. Interestingly, no correlation was found between measures of hypoxaemia severity and MSLT score in OSAS patients, which might be due to the difference in measure of hypoxaemia. Punjabl et al. 7 categorised the severity of oxyhaemoglobin desaturation as The average inspiratory effort, which was found as an explanatory variable to sleepiness in patients with UARS as well as OSAS, might be another confounding factor making OSAS patients more sleepy than patients with UARS. In this study, it was found that OSAS patients had more inspiratory effort throughout the night than the UARS patients. This finding could be accepted as one of the explanations of the difference in sleepiness between the two groups. This explanation would take into account the most currently accepted explanation of daytime sleepiness in patients with UARS as well as OSAS, which relates daytime sleepiness to the consequences of abnormal respiratory events on sleep structure, causing arousal reactions and sleep fragmentation 1012,14. However, Berg et al. 40 reported that nonapnoeic snorers complaining of excessive daytime sleepiness have similar total numbers of arousal to asymptomatic controls. It was also suggested that this difference in daytime symptom is created by the type of arousals (pure EEG versus respiratory). Roehrs et al. 13 also found a relationship between respiratory arousal index and daytime sleepiness. It has also been suggested that an increased effort of breathing is a more important stimuli for arousal than either hypercarbia or hypoxia 41. If daytime sleepiness was affected by arousals, especially respiratory arousals, there might be other determining factors identifying the arousal as a respiratory outcome. Therefore, inspiratory effort might be one of the designating factors for arousals. The lack of correlation between arousal index and any sleepiness index in patients with UARS and MSLT of OSAS patients was surprising. This may be due to the monitoring technique used or insufficiency of ASDA criteria for designating arousals rather than the actual absence of electrocortical activation. In the current study, central electrodes were used for EEG recordings and frontal electrodes were used to improve the detection of respiratory-related arousal reactions 42. This might be one explanation for the failure to note visible arousal reactions in this study. Conversely, it has been proposed that there are some microarousals 43 and non-EEG indices of arousal-like autonomic activation (i.e. changes in blood pressure and heart rate) 14, 43, and increasing the number of these type of arousals has been shown to impair daytime functions in normal subjects 15 and OSAS patients 14, 43. As a result it can be considered that detection of arousals according to ASDA criteria, as well as other parameters, would supply better information about the effects of arousals on daytime sleepiness. In this study, another point to be discussed is the evaluation of arousal reactions relating to lower leg movements. Mendelson 44 demonstrated that the index of periodic limb movement (PLM) with movement arousals was not different in patients with and without excessive daytime sleepiness. In addition, Coleman et al. 45 reported that there was no correlation between PLM index and MSLT in patients with primary insomnia and PLM during sleep (PLMS). Since the patients with restless leg syndrome and PLMS were excluded at the beginning of the study, it was expected that analysing the lower limb movement and associated movement arousals would not give any extra information about the sleepiness of patients with obstructive upper airway disorders during sleep. AHI as a determinant of EDS has been investigated previously within the aspects of body position 8 and sleep stages 24, 25. As a possible determinant of subjective sleepiness, inspiratory effort has been implicated by Zamagni et al. 23, who evaluated obstructive apnoeas during NREM sleep. However, evaluation of respiratory effort considering body position and sleep stages has not been performed previously. In the current study, inspiratory effort for all obstructive respiratory events, including flow limitations in all sleep stages and in different positions, were evaluated. Chervin and Aldrich 8 suggested that excessive daytime sleepiness was better explained if sleeping position, type and character of abnormal respiratory event were taken into consideration during the evaluation of apnoeas and hypopnoeas. In that study, it was reported that the rate of apnoeic events in the supine position correlated better with daytime sleepiness. In this study, no position-dependent change in respiratory effort was found within the same sleep stage, except slow-wave sleep of UARS patients. The findings indicate that respiratory effort in both the supine and nonsupine positions probably contribute equally to the role of respiratory effort on daytime sleepiness. Moreover, the importance of apnoeas and hypopnoeas during different sleep stages, either REM sleep alone 24 or REM sleep as well as NREM sleep 25, on the determination of daytime sleepiness, suggests a role for sleep stages in sleepiness. The authors found that inspiratory effort was lower in REM sleep than NREM sleep in patients with both UARS and OSAS. This conclusion is similar to previous findings 26. The authors consider that evaluation of inspiratory effort in such large aspects, including body position and sleep stages, supply enlarged vision to the evaluation of sleepiness in sleep disordered breathing. The significant correlation between average inspiratory effort and ESS in patients with UARS also supported its important role in daytime sleepiness. Some limitations of using Poes should be considered. Analysing the representative 20 obstructive respiratory events for each sleep stage and position totalled 80120 respiratory events for each patient. This selection and positional differences between patients may have created variability in mean inspiratory effort. Therefore, using this formula in a study over consecutive nights and using a randomised selection of abnormal respiratory events may provide more information about the validity of this formula. A possible explanation of the result of the current study is that inspiratory effort itself may increase sleepiness by way of energy expenditure throughout the night. The level of daytime sleepiness was described by Johns 46, 47 as a function of the total sleep drive to the total wake drive with which it competes, throughout the 24-h sleep/wake cycle. According to this theory, the majority of these drives are under the influence of the central nervous system. However, some behavioural and physical conditions, such as posture, feelings, mental and physical activity, have a role, especially on wake drive. Inspiratory effort, creating energy expenditure throughout the night, might be considered to affect the balance between sleep and wake drive in patients with UARS or OSAS. In contrast with the Epworth score, any parameter showed significant correlation with MSLT scores in both UARS and OSAS patients. The lack of association between MSLT and any polysomnographic variables is also supported by other studies in which such associations are absent 48, ambiguous 20 or weak 13, 49. The authors also failed to find a significant correlation between ESS and MSLT scores. Similarly, many investigators have reported poor or no association between sleep latency of MSLT and ESS and other subjective tests, such as Stanford sleepiness scale 50, 51. A possible explanation might be that subjective and objective tests evaluate different aspects of sleepiness. In fact MSLT measures the speed with which a sleep episode occurs under standardised laboratory conditions, whereas ESS evaluates the frequency of unwanted sleep episodes under naturalistic conditions of daily life 52. Under this definition, the term "average sleep propensity" might be more preferable for the parameter that ESS measures, as suggested by Johns 47. In conclusion, by taking into consideration the effect of sleep stages and body position, this study provides new evidence for average inspiratory effort as a contributing factor to the self-rated sleep propensity in patients with upper airway resistance syndrome as well as obstructive sleep apnoea syndrome. Finally, measuring sleepiness with a more reliable test may provide better information for understanding the relationship between respiratory effort and daytime sleepiness in obstructive breathing disorders during sleep.
This article has been cited by other articles:
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||