TABLE 2.
Summary of studies on residual sleepiness (RES) after obstructive sleep apnoea (OSA) treatment
| First author, year [ref.] | Study type | Sample | Tests used | Results | Comments |
| Patel, 2003 [74] | Meta-analysis | 11 RCTs: subjective sleepiness (ESS) Eight RCTs: objective sleepiness (MSLT, MWT) |
CPAP treatment for 4–24 months | Greater decrease in ESS after CPAP in studies recruiting patients with severe OSA and EDS Sleep onset latency increased after CPAP by 1 min compared to placebo |
RES mentioned in the discussion but not analysed |
| Haba-Rubio, 2005 [58] | Observational study in OSA patients | 57 consecutive patients studied at baseline and after CPAP treatment | ESS, PLMS; 1 year of CPAP treatment | Prevalence of PLMS at follow-up: 38.5% PLMS not correlated with RES |
|
| Weaver, 2007 [5] | Multicentre observational study in OSA patients | 149 patients with severe OSA studied at baseline and after CPAP treatment | ESS (n=106), MSLT (n=85); FOSQ (n=120); 3 months | Prevalence of RES (ESS score >10): 77.4% at baseline and 34% post-CPAP Prevalence of RES decreased with increasing CPAP use About 20% of patients using CPAP for >8 h remained sleepy at follow-up |
Important paper reporting data on both subjective and objective sleepiness before/after treatment; MSLT results were in line with those obtained by ESS |
| Stradling, 2007 [52] | OSA versus community subjects | 525 controls versus 572 patients on CPAP | ESS, home sleep study, single time point | ESS >10 in 14.3% controls versus 16.1% in post-CPAP group p=0.54 | Non-matched controls, many sleepy subjects in the general population, causes of EDS not investigated |
| Antczak, 2007 [65] | PET study in OSA patients with persistent EDS post-CPAP treatment | Small observational study (seven out of 13 patients with RES) | FDG-PET scan; at least 12 months off CPAP treatment | Prevalence of RES (ESS >12): 7.8% (13/167 patients) Vigilance test abnormal in five out of seven patients studied Reduced glucose utilisation in the frontal area was the most common PET abnormality |
Small number of patients studied, no control group |
| Pépin, 2009 [54] | Multicentre observational study in OSA patients | 502 compliant CPAP users | ESS, QoL (NHP); 1 year | ESS ≥11 in 12% but 6% after exclusion of PLMS, depression, narcolepsy | Patients with residual EDS were younger and sleepier at time of OSA diagnosis |
| Koutsourelakis, 2008 [47] | Single-centre observational study in OSA patients | 208 compliant CPAP users | ESS; 6 months | Depression in 38.8% of patients with RES | Other predictors: diabetes, heart disease, higher ESS and lower RDI at baseline |
| Antic, 2011 [55] | Multicentre clinical effectiveness cohort study | 174 moderate to severe OSA on CPAP | ESS, MWT, SF36, FOSQ, neurocognitive function; 3 months | RES in 40%, MWT normal in 70%, vitality improved with adherence Vigilance (average reaction time) did not improve with CPAP |
% patients achieving normal ESS and FOSQ was correlated with hours of usage MWT did not improve with increased CPAP usage |
| Vernet, 2011 [63] | Single-centre observational case-control study in OSA patients | 20 OSA patients with RES on CPAP with good adherence, 20 age- and sex-matched OSA patients without RES, 20 healthy controls | ESS, several questionnaires including fatigue severity score, BDI, HAD score, PSG, MSLT, cognitive tests; CPAP for at least 6 months | RES associated with lower amount of nREM 3 sleep, higher PLM rate, and HAD and fatigue scores Central hypersomnia criteria in 15% of RES group, clinical profile of EDS different from narcoleptic patients (including poor response to modafinil) |
Exclusion criteria: abnormal sleep duration, use of sedative drugs or alcohol, night shift work, narcolepsy, severe RLS, neurological or psychiatric disease |
| Gasa, 2013 [56] | French National Sleep Registry | OSA patients treated with CPAP, exclusion of those using CPAP <3 h·night−1, with residual AHI ≥15 events·h−1 or major depression (n=1047) | RES: ESS ≥11; follow-up: 3–24 months | Prevalence of RES: 13% in the whole group (18% in patients with EDS at baseline); decreased with increasing CPAP use Higher prevalence of heart failure in the RES group; RES more frequent in moderate than in severe OSA |
No sleep study at follow-up |
| Lau, 2013 [59] | Single-centre observational study in OSA patients | Moderate to severe OSA patients on CPAP with good adherence (n=37) and healthy controls (n=27) | ESS, PSQI, BDI, POMS, FOSQ; ≥3 months (mean follow-up duration 18±11 months) | RES in 30% of the OSA sample versus 15% of controls (NS) Psychosocial and functional outcomes associated with EDS level and sleep quality post treatment |
RES-predicted psychosocial outcomes Predictors of RES not investigated |
| Verbruggen, 2014 [60] | Single-centre observational study in OSA patients | 185 OSA patients treated with MAD, 84 with complete response (45% with AHI >5 events·h−1) | PSG, ESS; 3 months | RES in 32% of patients with normalised AHI on MAD Less nREM 3 sleep in patients with RES Predictors of RES in this group: high baseline ESS score, younger age |
|
| Tippin, 2016 [53] | Single-centre observational study in OSA patients | Newly diagnosed OSA patients (n=80) and age- and education-matched controls from the general population (n=50) | Actigraphy, PSG, ESS, FOSQ, monthly visits for 3 months after start of CPAP | Prevalence of ESS score >10 decreased from 60% to 17% after CPAP for 3 months Actigraphic evidence of persistent sleep disruption on CPAP (high WASO, low sleep efficiency) and gradual improvement of ESS and FOSQ over time |
Incomplete normalisation of sleep on CPAP |
| Budhiraja, 2017 [62] | Prospective multicentre RCT (Apnoea Positive Pressure Long-term Efficacy Study) | 558 OSA patients randomised to active CPAP | PSG, MWT (n=380), ESS Follow-up: 6 months |
ESS score >10 in 22.3% of the sample at 6 months (18.1% in good CPAP users) Sleep latency at MWT <17 min in 23% |
Use of CPAP and ESS at baseline were the only significant predictors of EDS at 6 months |
| Xiong, 2017 [66] | Single-centre observational study in OSA patients | 29 male severe OSA patients aged 30–55 years, treated with CPAP for ≥6 h·night−1 | Sleepiness assessed by ESS and PVT; actigraphy, MRI scan; CPAP treatment for at least 30 days | RES prevalence: 41% (12/29) RES was associated with white matter changes, indicated by changes in median and radial diffusivity in whole brain and specific regions These changes correlated with PVT and ESS changes post CPAP |
|
| Schöbel, 2018 [61] | Prospective randomised crossover study | 49 consecutive OSA patients (39 male) on CPAP treatment | Six-channel PG versus WatchPat ESS, CPAP adherence Follow-up: 81±63 months |
RES in 12 patients (24.5% of the sample) Higher sensitivity of WatchPAT versus PG in detecting respiratory events (positive predictive value 41.7% versus 16.7%) |
Study centred on screening methods for RES WatchPAT more sensitive to autonomic events than PG |
| Zhang, 2019 [67] | Single-centre observational study in OSA patients | 27 male severe OSA patients aged 30–55 years, treated with CPAP for ≥6 h·night−1 | Sleepiness assessed by ESS and PVT; actigraphy, diffusion MRI scan; CPAP treatment for at least 30 days | RES prevalence: 33% (9/27); in the whole brain, temporal diffusion heterogeneity α and anomalous diffusion coefficient Dm in sleepy versus non-sleepy patients; differences in temporal and diffusion heterogeneity (α and β) and Dm in 12 fibre tracts between sleepy and non-sleepy patients | Extends previous results by Xiong et al. [66] |
| Foster, 2020 [64] | Retrospective clinical study | 29 OSA patients (23 male) with good adherence to CPAP and RES (ESS >10) | ESS, PSG, MSLT, actigraphy | AHI on CPAP <10 events·h−1 CPAP use: 7.0±0.9 h·night−1 Average ESS score: 16.3±2.3 SOL: <8 min in 31% (severe EDS), 8–11 min in 35% (moderate EDS), >11 min in 35% of the patients (no EDS) Short sleep excluded by actigraphy |
Relatively young subjects (mean age±sd: 41±11 years) No difference in ESS between SOL groups |
| Bonsignore, 2021 [57] | Retrospective multicentre study (ESADA Cohort) | 4853 OSA patients on CPAP at first follow-up visit; 2190 of them with sleep monitoring data | ESS, PSG or PG; median follow-up 5 months (IQR 3–13 months) | ESS >10 in 56% of patients at baseline, and in 28.2% of patients at follow-up (n=4853) ESS >10 on CPAP treatment was associated directly with ESS score at baseline, and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417) |
Highest prevalence of EDS (40%) in the first 3 months of treatment |
AHI: apnoea/hyponoea index; BDI: Beck Depression Inventory; CPAP: continuous positive airway pressure; EDS: excessive daytime sleepiness; ESS: Epworth Sleepiness Scale; FDG: fluorodeoxyglucose; FOSQ: functional outcomes of sleep questionnaire; HAD: hospital anxiety and depression; IQR: interquartile range; MAD: mandibular advancement device; MRI: magnetic resonance imaging; MSLT: multiple sleep latency test; MWT: maintenance of wakefulness test; NHP: Nottingham Health Profile; nREM: non-rapid eye movement; NS: not statistically significant; PET: positron emission tomography; PG: polygraphy; PLM: periodic leg movement; PLMS: periodic leg movements during sleep; POMS: profile of mood states; PSG: polysomnogram; PSQI: Pittsburgh Sleep Quality Index; PVT: psychomotor vigilance task; QoL: quality of life; RCT: randomised controlled trial; RDI: respiratory disturbance index; RLS: restless legs syndrome; SF36: short form 36; SOL: sleep onset latency; WASO: wakefulness after sleep onset.