Polysomnographic Parameters Related to Daytime Sleepiness in Obstructive Sleep Apnea Syndrome: A Preliminary Study
Article information
Abstract
Background and Objective
Daytime sleepiness is frequently observed in patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study is to assess the parameters that are related to daytime sleepiness in OSAS.
Methods
We included patients with OSAS who underwent overnight polysomnography (PSG) followed by a next-day multiple sleep latency test (MSLT) and Epworth Sleepiness Scale (ESS) measurement. The respiratory disturbance index (RDI) was used for diagnosis and assessment of the disease severity.
Results
A total of 34 patients were evaluated, among whom 85.3% were male and the other 14.7% female. The mean value of the mean sleep latency (MSL) in the MSLT was 6.27 ± 3.67 minutes (range 1.70–13.40, median 5). We divided patients into two groups according to their median MSL value. The sleepier group exhibited a higher body-mass index (BMI; 27.04 ± 4.20 versus 24.59 ± 2.12), shorter rapid eye movement (REM) sleep latency (80.21 ± 28.61 min. versus 119.44 ± 55.91 min.), greater sleep efficiency (88.82 ± 6.37% versus 82.43 ± 10.43%), and higher respiratory event-related arousal index scores (RERAI; 3.92 ± 2.3/h versus 2.4 ± 1.85/h) than the less sleepy group. RDIs, apnea/hypopnea indices and oxygen saturations did not differ between the groups. Total ESS scores were also not different significantly.
Conclusions
A higher BMI, shorter REM latency, relatively higher sleep efficiency and a higher RERAI in the PSG were related to shorter MSL in the MSLT and thus daytime sleepiness in OSAS patients.
INTRODUCTION
Excessive daytime sleepiness (EDS) is a commonly observed symptom in patients with obstructive sleep apnea syndrome (OSAS).1,2 Because of the increased risk of accident,3,4 psychosocial morbidity5 and the substantial burden on quality of life,6,7 it is important to reveal the mechanism of this symptom as well as to improve diagnosis and treatment of the OSAS.8 It is not clear why only some patients with OSAS have EDS. Some authors have attributed the determinants of EDS to the sleep structural deterioration such as increased sleep fragmentation during the previous night,9,10 but others have failed to confirm this.11 Nocturnal hypoxemia has been also proposed as an explanation for EDS, but recent studies showed controversial results.12,13
Daytime sleepiness can be assessed both subjectively and objectively. Subjective methods include questionnaires such as the Epworth Sleepiness Scale (ESS)14 and the Stanford Sleepiness Scale,15 whereas objective methods include the multiple sleep latency test (MSLT)16 and the maintenance of wakefulness test (MWT).17 Subjective methods are less accurate and more difficult to quantify than the latter.18–22 The more convenient MSLT is more widely used than MWT. We thus chose to use MSLT to assess daytime sleepiness in this study.
The aim of the present study is to reveal the parameters that are related to daytime sleepiness in OSAS.
METHODS
Subjects
Thirty-four consecutive OSAS patients were prospectively included. A diagnosis of OSAS was made according to the second edition of the International Classification of Sleep Disorders. None of the participants suffered from chronic obstructive pulmonary disease, thyroid dysfunction, liver cirrhosis, chronic renal failure or congestive heart failure. Patients with a history of insomnia, periodic limb movement or cataplexy were excluded. Participants were not taking any sleep-related medication. The inclusion period was from July, 2010 to August, 2011. After administering structured questionnaires, including the ESS and Pittsburgh Sleep Quality Index (PSQI), overnight polysomnography (PSG) was performed. The next day, MSLT was conducted to evaluate daytime sleepiness. Among the examinees, we only included those whose respiratory disturbance index (RDI) was not less than 5/h. We divided these into two groups on the basis of the median value of mean sleep latency (MSL) assessed via the MSLT. The sleepier group (n = 17) comprised those OSAS patients with an MSL of MSLT not exceeding 5 minutes and the less sleepy group (n = 17) comprised those whose MSL of MSLT exceeded 5 minutes.
Overnight Polysomnography
Overnight PSG consisted of continuous recordings from 6 electroencephalographic (EEG) leads (F3-A2, F4-C1, C3-A2, C4-A1, O1-A2, and O2-A1 in the international 10–20 system), two electrooculographic leads (ROC-A1, LOC-A2), four electromyographic leads (two submental and bilateral tibialis anterior), thermistors for the nasal and the oral airflow, PTAF for the nasal air pressure, a mic for snore detection, strain gauges for thoracic and abdominal excursion, finger pulse oximetry, and leads for the electrocardiography. Each epoch was staged and scored according to the international criteria in the 2007 manual from the American Academy of Sleep Medicine.23 Apnea was defined as more than 90% reduction in airflow in the thermistor for at least 10 seconds; hypopnea as 50% or more reduction of airflow in the pressure transducer airflow (PTAF) for at least 10 seconds associated with 4% or more reduction in oxygen saturation. Respiratory effort-related arousal (RERA) was scored if there was a sequence of breaths lasting at last 10 seconds characterized by an increasing respiratory effort or a flattening of the nasal pressure waveform leading to an arousal from sleep when the sequence of breaths did not otherwise meet the criteria for apnea or hypopnea. Arousal was scored when the EEG frequency shift lasted three seconds following a 10-second stable sleep.
Multiple Sleep Latency Test
As recommended by the international guidelines,24 MSLT was carried out during the daytime of the day immediately following overnight PSG and was comprised of four 20-minute nap trials at intervals of 2 hours. The recording electrodes were those that were necessary for the sleep staging. A nap trial was terminated at 20 minutes if the subject had not achieved sleep, but was continued for 15 min after the onset of the sleep if it had occurred within 20 minutes. Sleep latency was defined as the duration in minutes from lights-out to the start of the first epoch of sleep in each nap trial. The mean sleep latency was calculated from the data of all five trials. Sleep onset REM periods (SOREMPs) were defined as a REM sleep occurring within 15 minutes of sleep onset.
Epworth Sleepiness Scale
All patients completed the Korean version of the ESS.14 ESS is a self-administered questionnaire designed to measure the general level of daytime sleepiness. Patients scored from 0–3 for each question related to their likelihood of falling asleep in eight different situations commonly encountered in daily life. The total ESS score ranges from 0 to 24; higher scores indicate more subjective sleepiness.
Statistical Analysis
Results were shown as mean ± SD. Comparisons between both groups were performed using independent t-tests and Mann-Whitney U tests for normally and abnormally distributed data, respectively. Statistical significance was defined using a p-value of 0.05. Statistical analyses were performed with SPSS for Windows.
RESULTS
Demographic Features
Subjects were 85.3% male and 14.7% female, with a mean age distribution of 47.63 ± 10.48 years, a median of 49 years and a range of 24–64 years. Table 1 shows the main comparative demographics and sleep questionnaire results of the sleepier and the less sleepy groups. The sleepier group had a significantly greater body mass index (BMI) but a lower MSL compared to the less sleepy group. No difference in the age, sex, ESS score and global PSQI was present between the groups.
Analysis of PSG
Mild OSAS (RDI 5–15) was present in 38.2% of cases, moderate (RDI 15–30) in 26.5%, and severe (RDI > 30) in 35.3%. Descriptive statistics for both groups are presented in Table 2. The sleepier group exhibited a significantly shorter REM latency and an increase in sleep efficiency. A tendency towards a longer total sleep time and shorter sleep latency was observed in this group without statistical significance. Comparison between the groups in absolute time spent and relative proportion of each sleep stage revealed no significant difference. Parameters related to disease severity such as RDI and apnea-hypopnea index (AHI) also did not differ between the groups. Arousal index seemed to be slightly higher in the sleepier group, but it was not statistically significant, either. Only RERA index differed between the groups. The sleepier group showed higher RERA index than the NEDS group.
Analysis of MSLT
Mean value for the MSL was 6.27 ± 3.67 minutes (with median of 5 minutes and range of 1.7–13.4 minutes) for all the patients. It was 3.33 ± 0.90 minutes in the sleepier group and 9.21 ± 2.94 minutes in the less sleepy group. Table 3 shows MSLT characteristics of the two groups. SOREMPs were present in 44.1% of patients. The number of SOREMPs recorded per MSLT was one in 23.5%, two in 17.6% and three in 5.9%. The frequency of the SOREMPs during the first nap was significantly higher in the sleepier group than in the less sleepy group.
DISCUSSION
The pathomechanism of EDS in patients suffering from OSAS is unclear. There are two hypotheses: sleep fragmentation and nocturnal hypoxemia. Several researchers have studied the effects of sleep fragmentation and nocturnal hypoxemia on EDS in patients with OSAS. Guilleminault et al.11 studied 100 patients with OSAS using MSLT. The sleepy patients had “sleep structure anomalies (higher stage 1 sleep, lower stage 3/4 sleep and lower REM sleep)”, higher RDI and higher number of awakenings. However, covariate and multiple stepwise regression analysis did not reveal any statistically significant relation. Bédard et al.13 suggested that nocturnal hypoxemia may play a primary role in EDS, whereas Colt et al.12 supported the hypothesis relating EDS to various measures of sleep disruption rather than to oxygen desaturation. Since then, several researchers have suggested that EDS is attributable to sleep fragmentation,25,26 whereas others have suggested there is a relationship between nocturnal hypoxemia and EDS,10 or indicated that hypoxemia and sleep fragmentation contribute independently.27,28 Recent studies using both MSLT and ESS revealed that the patients with EDS did not have only more severe nocturnal hypoxemia but also more severe sleep fragmentation.29,30
The present study is not completely compatible with any of above-mentioned studies. Our data showed that RERA index was significantly higher in the sleepier group, but that none of the RDI, apnea index, hypopnea index, or apnea/hypopnea index differed significantly between the groups. First, because of the small sample size, it is possible that we could not detect between-group differences. Second, the portion of RERA index in the RDI was too small to be reflected in daytime sleepiness. Third, our apnea criteria consisted of both arousal and desaturation as recommended. However, daytime sleepiness could have been expressed only through a final common cause of arousal. Thus, there is a possibility that the same apnea scoring could have had a different impact on the aspect of daytime sleepiness depending on the criterion we applied.
Relatively higher sleep efficiency was present in the sleepier group than in the less sleepy group. We suggest that this is a result but not a cause of daytime sleepiness. Several investigators also indicated a higher sleep efficiency in sleepy patients.11,29–31 They also found that these patients had increased number of arousals and longer total sleep time. As our study did not detect an increased arousal index in the sleepier group, we cannot fully support this. If more patients are recruited, we hope we see both increased sleep efficiency and increased arousal index in the sleepier group.
REM sleep latency was shorter in the sleepier group than in the less sleepy group in our study. This is compatible with the recent report of Sun et al.30 This revealed that shortened REM latency was an independent predictor of EDS and possibly associated with increased sleep drive pressure.
We postulate that the effect of BMI on the daytime sleepiness is an indirect one through sleep-disordered breathing accompanying arousal. Further confirmatory studies are needed.
Although two or more SOREMPs on a MSLT raise the possibility of narcolepsy, the percentage of patients with OSAS showing two or more SOREMPs was 23.5%. This is relatively high compared to Chervin and Aldrich.32 This found that four variables, male sex, sleepiness, nocturnal REM sleep latency, and extent of oxygen desaturation, could be related with two or more SOREMPs. Considering study differences in average MSL (3.33 in the current study vs. 5.3 in Chervin) and gender (male 85.3% vs. 70.1% in our and Chervin’s study, respectively) this discrepancy could be explained by selection bias. We will conduct further investigation after exclusion of patients compatible with a diagnosis of narcolepsy (MSL of MSLT ≤ 8 minutes and two or more SOREMPs) after completion of enrollment.
Several studies have suggested possible predictors of EDS in OSAS. However, these results remain confusing mainly due to the heterogeneity of the study design. In addition to the variety of the study designs and statistical methodology, the tools used to evaluate the EDS and the working definitions of the EDS were also heterogeneous. Among many possible tools, ESS and MSLT have been the most often used. Though ESS is a quick and inexpensive test and can reflect chronic sleepiness, its accuracy depends on patient interpretation and estimation. Additionally, there are many reports that ESS scores are affected by psychological variables,21 lack of energy, subjective perception of tiredness33 and even gender.19 On the contrary, MSLT is an objective measure and in spite of its cost, it is the gold standard for evaluating and quantifying sleepiness. Accordingly, we selected MSLT as objective measure of EDS in this study.
In the present study, a median MSL value of 5 minutes was used to divide subjects into two groups. The decision to include MSL of 5–10 minutes in the less sleepy group may be somewhat controversial. Some researchers have considered MSL of 5–8 minutes as obvious but mild EDS and MSL of 8–10 minutes as the grey zone.34 In this preliminary study, due to the small sample size, we could not categorize more than two groups. This may have caused some blurring effect on the discrimination of the relating parameters. After complete enrollment, we are going to re-categorise this grey zone and then reanalyze the data using multivariate and correlation studies.
Notes
Conflicts of Interest
The authors have no financial conflicts of interest.