Sleep-disordered breathing after stroke: a randomised controlled trial of continuous positive airway pressure.

BACKGROUND: Sleep-disordered breathing (SDB) is common after stroke, but it is unclear whether it should be treated. OBJECTIVE: To conduct a randomised controlled trial of continuous positive airway pressure (CPAP) after stroke. METHODS: Patients with stroke with > or = 30 apnoeas and hypopnoeas per hour ((A+H)/h) with predominant obstructive sleep apnoea or hypopnoea were randomised to either CPAP treatment or conservative treatment for 8 weeks. Outcomes were measured blind to treatment allocation at 8 weeks and 6 months after the stroke. The primary outcome was physical function on the Nottingham Extended Activities of Daily Living Scale. RESULTS: Of 658 patients with stroke screened, only 71 (10.7%) were eligible and consented to a sleep study 14-19 days after stroke. 66 patients completed the sleep study (21 women; mean age 72 years), 33 (50%) had > or = 30 (A+H)/h that were predominantly obstructive. 15 were randomised to CPAP treatment and 15 to conventional treatment. Despite intensive efforts, objective use of CPAP was poor, averaging 1.4 h a night. CPAP treatment resulted in no significant improvements (p>0.1) in the primary outcome or in neurological function or sleepiness, and in poorer health status on some measures. CONCLUSIONS: This trial showed no benefit from CPAP treatment, the relevance of the observed detrimental effects is questionable. Even in our highly selected patients with stroke, use of CPAP was poor. At present, CPAP treatment should be advocated for patients with stroke only if they have symptoms of SDB.

Can psychological factors help us to determine adherence to CPAP? A prospective study.

The present study objective was to establish whether pretreatment social cognitive variables may contribute to the explanation of variance in adherence to continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). A total of 119 of 180 consecutive OSAHS patients were recruited to the study prior to initial CPAP titration. Patients completed psychological measures of health value, health locus of control (incorporating internality, chance, powerful others) and self-efficacy prior to CPAP titration. Objective adherence data were measured by CPAP unit time clocks and collected at 3-month follow-up. Average nightly use was calculated over this period. Logistic regression of prospective predictors of adherence produced a model comprising psychological (health value, internality, powerful others), as well as clinical variables (Epworth score, body mass index, apnoea/hypopnoea index, CPAP pressure). This model explained 24% of the variance in CPAP use, and correctly identified 75% of adherers and 53% of nonadherers. Although the psychological variables explained only a small amount of the overall variance in adherence behaviour, this result provides further support for the hypothesis that psychological variables contribute, in part, to continuous positive airway pressure adherence. Future research should focus on highlighting discrete variables, which may helpfully inform psychologically based interventions aimed at improving the use of continuous positive airway pressure by patients with obstructive sleep apnoea/hypopnoea syndrome at risk of discontinuance.

Sleep. 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome.

Sleepiness, cognitive performance, and quality of life are overlapping aspects of daytime function that may be affected in patients with obstructive sleep apnoea/hypopnoea syndrome. The evidence is compatible with hypotheses that these deficits are reversible with treatment, particularly for patients with severe disease.

Partners of patients with sleep apnoea/hypopnoea syndrome: effect of CPAP treatment on sleep quality and quality of life.

BACKGROUND: The sleep apnoea/hypopnoea syndrome (SAHS) causes snoring, apnoeas, and restlessness during sleep which partners frequently complain about. A study was undertaken to determine the impact on partners of SAHS and of treatment of the patient with continuous positive airway pressure (CPAP). METHODS: Forty nine partners and patients with SAHS booked for CPAP treatment completed in house and validated questionnaires (Pittsburgh sleep quality index, Short Form 36 self-reported health status) before the patient started treatment. Twenty three couples in whom the index SAHS patient had no driving problems were recruited to a randomised crossover trial with 1 month limbs of CPAP and placebo capsule. At the end of each limb the partners' sleep was monitored by home polysomnography (PSG) and questionnaires were completed. RESULTS: Before treatment partners frequently reported moderate to severe disturbance from patient snoring/apnoeas/restlessness and had poor sleep quality and self-reported health status. In the crossover study (22 completed) the partners' objective sleep quality did not differ between CPAP and placebo, but they reported benefit from treatment of the patients with CPAP in subjective sleep quality (p=0.05) and disturbance to sleep (p=0.03). The reported change in partners' sleep quality between pre-study and following CPAP treatment correlated positively with CPAP use (r=0.5, p=0.01). CONCLUSIONS: Partners of patients with SAHS have poor sleep quality and self-reported health status but only subjective sleep quality benefits from treatment of the patient with CPAP.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome.

Some patients with the sleep apnea/hypopnea syndrome (SAHS) remain subjectively and objectively sleepy despite using effective continuous positive airway pressure (CPAP) therapy. The aim of this single center study was to determine the efficacy and safety of the novel wake-promoting medication modafinil in the treatment of CPAP-resistant daytime sleepiness. Thirty sleep apneics receiving effective CPAP therapy (objective use, 6.5 +/- 1.1 h/night) received daily single doses of 400 mg modafinil or placebo for 2 wk in a double-blind randomized crossover design. Outcome measures were assessed at baseline and at the end of both 2-wk treatment periods. Treatment periods were separated by a 1-wk washout. Modafinil had no effect on sleepiness as measured by the Epworth Sleepiness Scale or the Multiple Sleep Latency Test (p > 0.1); however, significant improvements in alertness were found with the Maintenance of Wakefulness Test (modafinil 18.3 +/- 3.9 min; placebo, 16.6 +/- 5.0 min; p < 0.02). No significant treatment-related improvements in cognitive performance or quality of life were found with modafinil (all p > 0.05). There was a significant reduction in CPAP use on modafinil compared to placebo (6.3 +/- 1 h/ night; 6.5 +/- 1, p = 0.03). This study suggests that modafinil may improve some aspects of alertness in patients with SAHS who remain sleepy during CPAP therapy, but further studies are required to assess the significance of the reduction in CPAP use.

Controlled, prospective trial of psychosocial function before and after continuous positive airway pressure therapy.

The aim of the study was to investigate psychosocial function before and after continuous positive airway pressure (CPAP) therapy, and establish the determinants and consequences of objective CPAP use. In a prospective, parallel-group study, changes in psychosocial scores were compared with conservative management or CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS). Patient/partner couples from the top (CPAP treated, n=44) or bottom (conservatively treated, n=25) of a CPAP waiting list rated marital satisfaction (evaluation and nurturing relationship issues, communication and happiness (ENRICH), behavioural questionnaire), health/functional status (Short-Form-36 Health Survey, functional outcomes of sleep questionnaire) and sleepiness (Epworth sleepiness scale). Both groups' ratings at baseline were completed while on conservative therapy. Baseline variables did not differ between groups. At follow-up, all seven summary psychosocial scores were statistically better in CPAP-treated patients, effect sizes (ES) ranging from moderate (0.5 SD: marital satisfaction) to very large (>1.0 SD: patients health, functional status and sleepiness scores). Scores in conservatively-treated patients deteriorated to a small or moderate degree (ES -0.2- -0.7 SD), while those in the CPAP-treated group improved to a larger degree (0.3-1.3 SD). Baseline polysomnographical and psychosocial scores, including marital satisfaction, did not predict objective CPAP use (r<0.3). CPAP use was modestly correlated (r=0.3-0.6) with improvement in all psychosocial areas. Continuous positive airway pressure produced statistically and clinically significant psychosocial improvements, some of large magnitude, in psychosocial function. Determinants of usage were not identified, but benefits and usage were positively correlated.

Cognitive function in the sleep apnea/hypopnea syndrome (SAHS).

The magnitude, determinants and reversibility of cognitive deficits associated with the sleep apnea/hypopnea syndrome (SAHS) are of clinical and research interest. A quantitative overview of impairment effect sizes (ESs) from case-control studies of cognitive performance in SAHS suggests that deficits broadly worsen with disease severity, with large average values for attentional (ES approximately 1.0 SD units) and executive (ES approximately 0.9 SD units) cognitive scores, and moderate values for memory-related (ES approximately 0.6 SD units) performance scores. A study of determinants of cognitive outcomes conducted in 150 patients with SAHS (AHI 5+ and > or =2 symptoms) showed significant but weak associations between a cognitive 'intellectual ability' component score (CS) and both AHI (r=-0.14) and minimum oxygen saturation (r = 0.15), linking increasing disease severity with poorer performance. A somewhat stronger correlation between a cognitive 'response slowing' CS and a 'wakefulness' CS was observed (r=-0.34). That sleepiness as well as hypoxemia might contribute to cognitive deficit has also been suggested by experimental sleep fragmentation in normals, producing small to moderate impairments (average ES approximately 0.3 SD units) in attention-biased scores. The reversibility of attentional cognitive deficits has been investigated through a meta-analysis of randomized placebo-controlled crossover studies of CPAP treatment, involving 98 SAHS patients (AHI 5+ and > or =2 symptoms). While cognitive outcomes showed at least trends towards better performance on CPAP than on placebo (p< or =0.1), the ESs of cognitive enhancements following CPAP were small (average ES approximately 0.2 SD units). This may be due either to the relatively mild study population, suboptimal CPAP use or to an irreversible component in cognitive impairment in SAHS.

Effects of CPAP on vigilance and related functions in patients with the sleep apnea/hypopnea syndrome.

There have been relatively few robust studies of the effects of CPAP therapy on vigilance and daytime function. This article will use all known published and unpublished randomized clinical trials on this area. There is good evidence that CPAP helps subjective sleepiness, objective sleepiness, quality of life, mood and driving performance. However, CPAP does not appear to normalize objective sleepiness. Many of the improvements are directly related to the nightly use of CPAP. Recent data suggest that increasing CPAP usage improves outcomes.

Predictors of improvements in daytime function outcomes with CPAP therapy.

Continuous positive airway pressure (CPAP) therapy improves daytime function in the sleep apnea/ hypopnea syndrome (SAHS) but it is unclear which patients benefit and what factors predict this improvement. To test the hypothesis that brief arousals from sleep predict improvements in daytime functioning with CPAP therapy, we prospectively studied 62 patients with polysomnography-defined SAHS. Each underwent daytime function assessments at baseline and after 6 mo of CPAP therapy to measure objective sleepiness, psychological well-being, quality of life, and cognitive performance. The microarousal frequency and AHI were poor predictors of improvements in daytime function with CPAP. Measures of hypoxemia predicted improvements in the mean sleep latency on the maintenance of wakefulness test, SAHS symptoms, quality of life, and reaction time, but such correlations were weak or moderate only explaining between 7% and 22% of variance. Significant relationships were found between CPAP use and improvements in self-ratings of daytime function. Results suggest that standard polysomnographic baseline variables are poor predictors of the response to CPAP therapy.

Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome?

Continuous positive airway pressure (CPAP) therapy is widely prescribed for patients with the sleep apnea/hypopnea syndrome (SAHS), but the use of CPAP for such patients is disappointingly low. We postulated that providing intensive educational programs and nursing support to SAHS patients might improve CPAP use and outcomes. We also examined the hypothesis that CPAP use would be greater among patients who had initiated their own referral than among those asked to seek help by a partner. We randomized 80 consecutive, new patients with SAHS to receive either usual support or additional nursing input including CPAP education at home and involving their partners, a 3-night trial of CPAP in our institution's sleep center, and additional home visits once they had begun CPAP. The primary outcome variable was objective CPAP use; symptoms, mood, and cognitive function were also assessed after 6 mo. CPAP use over 6 mo was greater (p = 0.003) among patients receiving intensive than among those receiving standard support (5.4 +/- 0.3 versus 3.9 +/- 0. 4 h/night [mean +/- SEM]), with greater improvements (p < 0.05) in SAHS symptoms, mood, and reaction time in the intensively supported group. CPAP use was greater (p = 0.002) among patients who initiated their own referrals. CPAP use and outcomes of therapy can be improved by provision of a nurse-led intensive CPAP education and support program. CPAP use is lower among patients whose partners ask them to seek treatment.

Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome.

Patients with the sleep apnea/hypopnea syndrome (SAHS) treated by nasal continuous positive airway pressure (CPAP) need to use CPAP long-term to prevent recurrence of symptoms. It is thus important to clarify the level of long-term CPAP use and the factors influencing long-term use. We examined determinants of objective CPAP use in 1, 211 consecutive patients with SAHS who were prescribed a CPAP trial between 1986 and 1997. Prospective CPAP use data were available in 1, 155 (95.4%), with a median follow-up of 22 mo (interquartile range [IQR], 12 to 36 mo). Fifty-two (4.5%) patients refused CPAP treatment (these were more often female and current smokers); 1,103 patients took CPAP home, and during follow-up 20% stopped treatment, primarily because of a lack of benefit. Methods of survival analysis showed that 68% of patients continued treatment at 5 yr. Independent predictors of long-term CPAP use were snoring history, apnea/hypopnea index (AHI), and Epworth score; 86% of patients with Epworth > 10 and an AHI >/= 30 were still using CPAP at 3 yr. Average nightly CPAP use within the first 3 mo was strongly predictive of long-term use. We conclude that long-term CPAP use is related to disease severity and subjective sleepiness and can be predicted within 3 mo.

Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome.

The minimal disease severity at which patients with the sleep apnea/hypopnea syndrome (SAHS) gain benefit from treatment is not well characterized, although a pilot study of continuous positive airway pressure (CPAP) therapy showed daytime improvements in patients with 5 to 15 apneas + hypopneas per hour slept (AHI). We have thus performed a second, larger, randomized, placebo- controlled study in a prospective series of 34 patients (13 female) with mild SAHS (AHI 5 to 15) and daytime sleepiness. Patients spent 4 wk on CPAP treatment and 4 wk on an oral placebo, with randomization of treatment order, and daytime assessments on the last day of each treatment. Effective CPAP use averaged 2.8 +/- 2.1 h (mean +/- SD) per night. Compared with placebo, CPAP improved symptom score (p < 0.01), subjective (Epworth; p < 0.01) but not objective (maintenance of wakefulness test; p > 0.2) sleepiness, performances on 2 of 7 cognitive tasks (p < 0.02), depression score (p < 0.01), and five subscales of the SF-36 health/functional status questionnaire (p

Randomised placebo controlled trial of daytime function after continuous positive airway pressure (CPAP) therapy for the sleep apnoea/hypopnoea syndrome.

BACKGROUND: Patients with the sleep apnoea/hypopnoea syndrome (SAHS) report improved sleepiness, cognitive function, and psychological well being after continuous positive airway pressure (CPAP) therapy, and it is for these daytime features that CPAP is usually given. However, few randomised or controlled studies exist on the effects of CPAP on daytime function. METHODS: A prospective, randomised, single blind, placebo controlled, crossover trial of daytime function after CPAP was conducted in 23 patients with SAHS, all with > or = 15 apnoeas + hypopnoeas/hour and > or = 2 symptoms of SAHS. All patients spent four weeks on CPAP therapy and four weeks on oral placebo treatment, following randomisation to treatment order. With ethics committee approval, patients were told the placebo tablet might improve upper airway function. Average effective CPAP use was monitored using hidden time clocks. Assessments of objective and subjective sleepiness, symptoms, cognitive performance, and psychological well being were performed on the last day of each treatment and compared. RESULTS: Objective sleepiness measured by sleep onset latency on the multiple sleep latency test improved with CPAP (mean difference from placebo +2.4 min, 95% CI 0.8 to 4.0; p < 0.001) as did subjective sleepiness on the Epworth scale (mean difference -6, 95% CI -3 to -9; p = 0.001). Symptom total score also fell with CPAP (mean difference -1.6, 95% CI -2.2 to -1.0; p < 0.001). No determinants of these changes with active treatment were identified, and no significant enhancements to cognitive function or psychosocial well being were found in this small sample. CONCLUSIONS: These findings provide further evidence for clinically significant benefits to daytime function from CPAP.

Does arousal frequency predict daytime function?

Patients with the sleep apnoea/hypopnoea syndrome (SAHS) have impaired daytime function with demonstrable sleepiness and impaired cognition. The hypothesis that brief arousals from sleep cause these daytime impairments was tested. One hundred and fifty patients with sleep disordered breathing were studied prospectively, comparing overnight polysomnography with daytime measures of objective sleepiness, psychological well-being and cognitive performance. Significant, but weak (r2<0.1), relationships were seen between several nocturnal measures (apnoea/hypopnoea index, arousals and desaturation variables) and daytime measures of quality of life, well-being, subjective sleepiness, symptoms and cognitive performance. The only significant relationship between nocturnal variables and objective sleepiness was a very weak correlation (r2<0.05) between the lowest oxygen saturation and mean maintenance of wakefulness test (MWT) result. The MWT was better correlated with daytime function than the multiple sleep latency test. This study shows a lack of strong relationships between conventional nocturnal measures and daytime function in patients with sleep disordered breathing.

Effect of CPAP therapy on daytime function in patients with mild sleep apnoea/hypopnoea syndrome.

BACKGROUND: Continuous positive airway pressure (CPAP) is an effective treatment in patients with moderate and severe sleep apnoea/hypopnoea syndrome (SAHS), but the minimum illness severity at which patients obtain benefit from CPAP is unclear. A study was therefore undertaken to investigate whether CPAP improves symptoms and daytime function in patients with mild SAHS. METHODS: Sixteen consecutively recruited patients with mild SAHS (5.0-14.9 apnoeas + hypopnoeas per hour slept and two or more symptoms of SAHS) participated in a prospective placebo controlled randomised crossover trial to assess the effects of CPAP on symptoms and daytime function. Patients spent four weeks on placebo and four weeks on CPAP, undergoing assessments of sleepiness, symptoms, cognitive performance, and well being on the last day of each treatment. Data from the placebo and CPAP assessments were compared. RESULTS: The mean (SE) objective effective use of CPAP was 2.8 (0.7) hours per night. Significant improvements in symptom score (-1.7 (0.5), p < 0.01), mental flexibility (-14 (5) seconds, p = 0.02), and depression rating (-1.6 (0.8), p = 0.03) on CPAP were observed. However, no significant differences in subjective or objective sleepiness were found. Ten of the 16 patients preferred CPAP and opted to continue with this treatment, although this proportion was non-significant (p > 0.4). The eight patients with best CPAP use showed an additional CPAP related improvement in quality of life (-4.4 (1.8), p = 0.03). Those who complied better with CPAP therapy also had a higher average microarousal frequency (p < 0.01) and apnoea+hypopnoea index (p = 0.02) than the poorer compliers. CONCLUSIONS: The results of this study provide evidence for improvements in symptoms and daytime function for patients with mild SAHS treated with CPAP.

Inhaled salmeterol or oral theophylline in nocturnal asthma?

Nocturnal cough and wheeze are common in asthma and often treated with beta2 agonists or theophyllines. As nocturnal asthma and these therapies may affect sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with individually dose-titrated sustained-release oral theophylline on sleep quality and cognitive performance in 15 patients with stable nocturnal asthma (overnight peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic awakening/week) using a double-blind, double-dummy, crossover design with 14-d therapy limbs. Cognitive testing and polysomnography were performed on Nights 13 and 14. Trough plasma theophylline concentration after Night 14 on theophylline was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4] but on salmeterol there were more nights without awakenings [median difference 1 (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p < 0.05] and improved quality of life (p = 0.05). Sleep architecture did not otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but otherwise daytime cognition was unaffected. There was no patient preference for either therapy. Hence in patients with nocturnal asthma, we demonstrate no major clinical advantage, but a small benefit in sleep quality, quality of life, and daytime cognitive function with salmeterol.

Under reporting of sleepiness and driving impairment in patients with sleep apnoea/hypopnoea syndrome.

Under reporting of symptoms by patients with sleep apnoea/hypopnoea syndrome (SAHS) has been reported anecdotally, but investigation of the prevalence or determinants of this is limited. To assess this, repeated ratings in 99 patients with sleep apnoea/hypopnoea syndrome of pre-treatment Epworth sleepiness score, unintended napping, driving impairment and mood were obtained, first at presentation and then after treatment with continuous positive airway pressure (CPAP) therapy of median 22 (range 2-70) weeks duration. Median Epworth score for pre-treatment sleepiness rose from 12 (range 0-24) initially to 14 (range 5-24) retrospectively (P<0.0001). More patients initially under-rated Epworth score (67%) than over-rated (29%; P<0.001). 'False negative' cases with an initially 'normal' (< or = 10) and retrospectively 'sleepy' (> or = 11) Epworth score comprised 24% of all patients and 62% of initially 'normal' scorers. Unintended napping behaviour also was rated as significantly more severe on retrospective assessment (P<0.001). Driving impairment due to sleepiness was initially reported by 23% of all drivers and retrospectively by 37% (P=0.01), with 25% of initial deniers retrospectively admitting compromised driving ability before continuous positive airway pressure. No polysomnographic predictors of symptom under reporting were found (P>0.1). These results suggest a high prevalence of symptom minimization before treatment in patients with sleep apnoea/hypopnoea syndrome.