Continuous positive airway pressure in patients with rapid eye movement (REM)-specific obstructive sleep apnea, a retrospective match-controlled chart review

Introduction

The prevalence of obstructive sleep apnea (OSA) in adults in the Wisconsin Sleep Cohort study was estimated to be between 1% to 2% in women and 3% to 4% in men¹. OSA is associated with increased cardiovascular mortality and it is considered an independent risk factor for all-cause mortality^2–4. The severity of the disease is usually expressed using the apnea hypopnea index (AHI)⁵.

In a subset of those with OSA, respiratory events happen predominantly or exclusively during rapid eye movement (REM) sleep; this condition is referred to as “REM-related OSA (REM OSA)”. Its prevalence among patients with OSA is 13 to 35% depending on the criteria used to define AHIs^6–8. REM OSA has been a topic of debate in the sleep medicine community since we do not know if this form of sleep apnea is part of the spectrum of “general” sleep apnea or a completely different entity with unique risk factors and different treatment needs⁹.

REM OSA does not have a male predilection; in fact, it may be even more common in women. Unlike OSA the likelihood of REM OSA decreases with age^8,9. REM OSA is not associated with daytime sleepiness or diminished quality of life (QOL)¹⁰.

It is, however, linked to increased incidence of hypertension¹¹ and type 2 diabetes¹².

CPAP is the gold standard for treatment of both REM and NREM OSA, and both forms of sleep apnea seem to respond in similar ways to CPAP therapy. Su and colleagues reported CPAP titration needs in individuals with REM OSA but their study did not use gender, AHI, and BMI matched controls¹³. We still don’t know if CPAP pressures required to control REM OSA are significantly different than those needed for OSA in general.

We designed this study with the initial hypothesis that individuals with REM OSA would require a lower CPAP pressure than controls. This hypothesis was based on day-to-day observations at our sleep center.

Methods

The Institutional Review Board (IRB) at HealthEast care system approved this study (IRB #HE1511002). The search included all polysomnography (PSG) tests that were completed from January 1^st 2014 to December 31^st 2014. We searched all patients older than 18 years old who had a baseline evaluation as well as a CPAP titration. REM OSA subjects and controls were required to have NREM and REM sleep during the baseline test and a minimum of 10 minutes of stage REM sleep during the titration.

Identification of individuals and controls

We first identified individuals that met criteria for REM OSA using the sleep center’s database. Data was extracted by reviewing the database manually, record by record, and reviewing the polysomnography report; all the variables that were needed for this study were already part of the reports. The dataset that is provided, was used to collect the information on an MS Excel 2013 spreadsheet (Dataset 1¹⁴). No information regarding CPAP pressure recommendations was accessed during this phase to avoid selection bias. The database was searched a second time in order to identify gender, BMI, and AHI matching controls. Individuals were considered a matching control if the BMI and the AHI were within 5 kg/m² and 5 events/hour respectively.

Sample Size and controls

Based on preliminary sample-size calculations, we aimed to identify 50 individuals with REM OSA and 50 controls in order to detect a pressure difference of 1 cm H₂O with a significance level of 0.05 Power 0.8. This was based on a separate estimate of the mean CPAP pressure recommended at the lab (9 cm H₂O; SD=2.45; D=0.41). We only found 16 matching controls.

Polysomnography (PSG) values and definitions

PSG tests were scored by a certified PSG technologist the night of the test using the American Academy of Sleep Medicine Scoring Manual v 2.0⁵.

REM OSA definition

Individuals were considered to have REM OSA if the REM AHI was greater than 5 events/hour, and the ratio of REM AHI / non-rapid eye movement (NREM) AHI was greater than 2. REM sleep duration had to be greater than 15 minutes.

OSA definition for controls

Individuals were considered appropriate controls if they had an AHI greater than 5 events/hour and within 5 events/hour of the REM OSA match. The NREM AHI had to be greater than 5 events/hour and the ratio of REM AHI to NREM AHI had to be 1 or less. REM sleep duration had to be greater than 15 minutes.

CPAP pressure

The recommended CPAP pressure was obtained during a manual in-lab titration and was the lowest pressure that eliminated respiratory events during the test, including supine REM sleep. The polysomnography technician followed a CPAP titration protocol that was designed to eliminate obstructive respiratory events. The interpreting sleep medicine physician reviewed the titration polysomnography EPOCH by EPOCH and made the final recommendation for a CPAP pressure.

Other variables

We collected demographic, clinical, and polysomnographical variables such as age, gender, Body mass index (BMI), presence of diabetes, presence of hypertension, recording time, total sleep time, Epworth score (to assess daytime sleepiness), STOP BANG Score (to assess risk for OSA), and percentage of each sleep stage.

Statistical analysis

Descriptive characteristics for demographic information were summarized as mean with standard deviation for continuous variables and as frequency for categorical variables.

Continuous and categorical variables were compared using paired Student’s T-Tests and Chi-square tests, respectively. All hypothesis tests were 2-sided, with a significance level of 0.05. All analyses were performed using R® for Mac OS X GUI version 1.67.

Results

We were able to identify a total of 16 individuals with REM OSA who had gender, AHI, and BMI matching controls for a total of 32 subjects in the study. Table 1 summarizes the demographic and clinical characteristics of individuals with REM OSA and controls.

Both groups were very similar in terms of age, daytime sleepiness, diabetes, hypertension, and sleep architecture parameters. Subjects with REM-OSA had a slightly lower score in the STOP-BANG questionnaire (3.5 vs. 4.0 p= 0.03).

Figure 1 shows the recommended CPAP pressure for the REM OSA group and controls. There was no significant difference between the groups.

Figure 1. Recommended Continuous positive airway pressure (CPAP).

Discussion

To our knowledge our study is the first comparing nPAP treatment requirements for individuals with REM OSA using gender, AHI, and BMI matched controls. We found that individuals with REM OSA required similar nCPAP pressures as gender, AHI, and BMI matched controls.

This was a very simple and limited study that was designed to test our hypothesis that individuals with REM OSA required lower CPAP pressures than controls. Su and colleagues found that individuals with REM-OSA were titrated to lower CPAP pressures than individuals with OSA that was not restricted to REM sleep (9.7 Vs. 10.3 cm H₂O P= 0.035) but in their study, the REM OSA group had a much higher proportion of women and previous data have shown that women require lower CPAP pressures^13,15. There has been debate about whether REM OSA constitutes a different phenomenon or is just very similar to any other form of OSA. Our results suggest that, regarding CPAP pressure needs, REM OSA could be similar to NREM OSA.

Age, gender, and AHI have been identified as predictors of CPAP pressure needs but none of those studies have looked at the stage in which the respiratory events happen.^16,17. Since REM OSA has a different gender and BMI association than the general OSA population, we were able to isolate the effect of the REM component by looking at gender, AHI, and BMI matched controls^15,18.

Our study had the limitation of a small sample size because it was difficult to identify an adequate number of matching controls. With our small sample size, the study was underpowered to detect smaller differences in CPAP pressure needs. We still think that publishing our results could be important because there are no other studies, regardless of sample size, that have looked into this topic.

Data availability

F1000Research: Dataset 1. Rapid eye movement related obstructive sleep apnea (REM OSA) dataset, https://doi.org/10.5256/f1000research.16688.d226331¹⁴