BACKGROUND: The prevalence of sleep-disordered breathing (SDB) in stroke is
high. One study showed SDB had a negative impact on the functional capacity of
stroke patients on discharge and another that SDB was associated with a higher
mortality rate. However, these findings are disputed. The impact of SDB in stroke
patients on cognition and health-related quality of life is also not clear. The one
randomized controlled trial of nasal continuous positive airway pressure (CPAP) in
stroke patients with SDB showed CPAP improved wellbeing but not other outcomes.
I hypothesised that: (1) SDB is related to stroke outcome and (2) treatment of SDB in
stroke patients with CPAP would improve functional outcome.METHODS: There are three parts of the thesis: (1) a study of the prevalence of SDB
after stroke; (2) a randomized controlled trial (RCT) of CPAP after stroke and (3) a
longitudinal cohort study to investigate the impact of SDB on outcome after stroke.
On day 14-19 after stroke, recruited patients underwent a limited sleep study using a
validated system (Embletta PDS, Medcare Flaga, Iceland). Baseline assessments
were performed on the morning following the sleep study. On day 21-25 following
stroke, patients who had (A+H)-h⁻¹ ≥ 30 with < 30% of central events were
randomized to 8 weeks of CPAP treatment with Autoset T (ResMed, SanDiego
USA) or conservative treatment for SDB. All outcomes were recorded in the 8th week
after randomization or 3 months after stroke for non-randomized patients. All
recruited patients received follow-up at six months after stroke. If available, patients
also received 12 months and 18 months follow-up until the last recruited patient had
had his 6 months follow-up. The Nottingham Extended ADL Index (EADL) was
chosen as the primary outcome measure. Secondary outcome measures included:
Subscales of EADL, NIH Stroke Scale (NIHSS), Barthel Index (BI), Stanford
Sleepiness Scale (SSS), Addenbrooke's Cognitive Examination (ACE) and Mini-
Mental State Examination (MMSE), Hospital Anxiety and Depression Scale
(HADS), MOS Short Form 36 Health Survey (SF-36) and ambulatory blood pressure
- measured with Spacelabs 90207 (Spacelabs, Redmond, USA).RESULTS: We screened 658 patients with recent strokes and excluded those with
dementia, confusion, severe dysphasia or insufficient hand function to use CPAP.
Only 96 of 658 patients remained eligible of whom 25 declined to give informed
consent. 71 patients were thus successfully recruited for overnight limited sleep study
14-19 days following stroke. Sixty-six patients with adequate recording were
included in the study: 45 men and 21 women, median age 74yrs. The sleep study
showed 50% of patients had more than 30 apnoeas + hypopnoeas per hour in bed
[expressed as (A+H)-h⁻¹]. Pulse oximetry alone had lower sensitivity (70%) but high
specificity (90%) to predict (A+H)-h⁻¹ ≥ 30. A combination of age, body mass index,
snoring and excessive daytime sleepiness based on logistic regression model is useful
as a screening tool at the bedside (sensitivity = 85%, specificity = 70%) to predict
(A+H)-h⁻¹ ≥ 30 in stroke before referring patients for overnight sleep study.
Interaction of lowest oxygen saturation and lowest heart rate is independently
associated with stroke during sleep in patients with (A+H)-h⁻¹ < 30 (p = 0.023).
Patients with (A+H)-h⁻¹ ≥ 30 more often had their stroke during daytime than patients
with (A+H)-h⁻¹ < 30 (p = 0.006). Thirty patients who had (A+H)-h⁻¹ ≥ 30, with < 30%
central apnoea or Cheyne-Stokes respiration, proceeded to a randomized controlled
trial starting from the 4th week after stroke with 15 patients randomized to CPAP and
15 to conservative treatment for SDB. Conventional stroke treatment was maintained
in all patients. Duration of treatment was 8 weeks and blind outcome assessment was
performed at 3 months and 6 month after stroke. The result showed compliance with
CPAP was poor with mean 1.40 hours and median 0.16 hours per night. There was
no statistically significant difference in the outcomes, sleepiness and ambulatory
blood pressure with CPAP therapy. Increased length of keeping CPAP was correlated
with higher score of language subscale in the Addenbrooke's Cognitive Examination
(Spearman's rho = 0.544, p = 0.036) and lower score in the depression subscale of
the Hospital Anxiety and Depression Scale (HADS, Spearman's rho = -0.538, p =
0.039). All 66 patients with adequate sleep studies received longitudinal follow-up at
3, 6 12 and 18 months following stroke. The patients with (A+H)-h⁻¹ ≥ 30 had a trend
to worse functional capacity in both Barthel Index and Nottingham Extended ADL
Index (EADL) than patients with (A+H)-h⁻¹ < 30 but there was only a statistically
significant difference in the mobility subscale of EADL. The negative influence of
(A+H)-h⁻¹ ≥ 30 on functional capacity and health-related quality of life following
stroke was only statistically significant in patients with mild stroke (NIH Stroke
Scale, NIHSS < 7) at both 3 and 6 months, lesser emotional distress (HADS < 8) at
both 3 and 6 months and lesser cognitive impairment (Mini Mental State
Examination ≥ 28) at 6 months after stroke in subgroup analysis. The difference of
Modified Rankin Scale between groups was significant at 6 months after stroke (p =
0.026). There was no difference in cognitive or emotional outcome. No significant
difference of mortality rate was noted.CONCLUSIONS: We focused on a group of patients with mild to moderate stroke
(median NIHSS = 6) within a narrow time span (14-19 days) and confirmed a high
prevalence of SDB in stroke. CPAP compliance was a major problem but might be
enhanced by selecting patients with higher functional capacity, higher cognitive
function especially language and less depression in the acute or subacute phase of
stroke. We also found that sleep-disordered breathing had little or no effect on
cognitive and emotional outcomes, health-related quality of life and mortality in
stroke patients. Many other factors resulting from brain damage or complications of
stroke have stronger influences on stroke outcome than SDB
