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.

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 This article will use all known published and unpublished randomized clinical trials on this area.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.

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.

Ambulatory blood pressure on and off continuous positive airway pressure therapy for the sleep apnea/hypopnea syndrome: effects in "non-dippers".

Ambulatory blood pressure (BP) monitoring was performed in 13 patients with the sleep apnea/ hypopnea syndrome (SAHS) during a randomized, placebo controlled crossover trial of the effects of continuous positive airway pressure (CPAP) therapy. BP was monitored at half-hourly intervals for a 24-hour period both on CPAP and on an oral placebo, each given for a minimum of 3 weeks. Objective effective CPAP use averaged 4.3 hours per night. Weight and anti-hypertensive medications remained stable over the study period. Systolic, diastolic and mean arterial BP for 24-hour, daytime and nighttime periods were not significantly different on placebo compared to CPAP. Those patients with no significant overnight fall in BP on placebo ("non-dippers") showed a significant improvement in daytime mean arterial BP on CPAP (98 +/- 4 mm Hg) compared to placebo (102 +/- 4 mm Hg; p = 0.01). These findings, in a well-controlled trial, suggest that BP is not reduced by CPAP in a heterogeneous group of SAHS patients, but it may be selectively improved in those patients most at risk for cardiovascular morbidity and mortality.

Self-reported use of CPAP and benefits of CPAP therapy: a patient survey.

The benefits of continuous positive airway pressure (CPAP) therapy in patients with the sleep apnea/hypopnea syndrome (SAHS) are poorly documented and patients use CPAP less than physicians recommend. To establish patients' perceptions of benefit from CPAP and to identify determinants of CPAP use, 204 CPAP users completed a questionnaire relating to use of CPAP therapy, sleepiness, and road traffic incident rate before and after CPAP, perceived change in daytime function and nocturnal symptoms with treatment, and problems with CPAP. Variables from these domains of interest were examined, reduced through principal components analysis and correlated to assess associations between these and polysomnographic measures of illness severity. Self-reported CPAP use averaged 5.8 +/- SD 2 h a night. Subjective sleepiness rated by the Epworth sleepiness scale and road traffic incident rate were significantly reduced by CPAP (p<0.0001). A broad range of function and symptom items were highly significantly improved with CPAP (p<0.0001), corroborating the cost to community and industry from SAHS and the preventive value of CPAP. Road traffic incident rate before treatment was correlated with pre-CPAP sleepiness and SAHS severity. Subjective CPAP use correlated with sleepiness before treatment but not with SAHS severity. CPAP mask problems and side effects were not associated with reduced CPAP use, but "nuisance" complaints of awakenings, noise, and sore eyes from CPAP correlated negatively with reported use. Greater reported CPAP use was associated with better resolution of sleepiness and greater improvement in daytime function and nocturnal symptoms.

Brain hydration during alcohol withdrawal in alcoholics measured by magnetic resonance imaging.

Twenty-seven patients had a first Magnetic Resonance Imaging (MRI) scan 1-3 days after stopping drinking and a second approximately 2 weeks later with no change in whole brain T1 or T1 in selected brain areas. Six patients whose first scan was over 36 h after the last drink underwent an increase in whole brain T1 in the interval to the second scan. The later the first scan was performed the greater was the increase in T1. These results are compatible with a very early fall in brain water immediately on cessation of drinking (perhaps due to a rebound increase of vasopressin activity) with a return to 'baseline' after two weeks. A third scan after discharge from hospital in 23 individuals who had abstained from alcohol or drank very little did not reveal any further significant change in brain T1.

The use of CSF pressure recordings in acute purulent meningitis.

Non-fluid displacing pressure transducers can be applied to a spinal needle at LP and direct CSF pressure recordings obtained routinely. The method is particularly applicable to children with suspected meningitis and is both a safer and a more accurate estimate of CSF pressure. Children with acute purulent meningitis frequently have raised intracranial pressure on presentation and Mannitol infusion during the LP recording is useful in returning the pressure to normal.

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.

CSF production rate: "real time" estimation.

CSF production rate has been measured by a drip detector method in 5 cases of childhood hydrocephalus undergoing closed ventricular drainage. The rate of production of CSF with this "real time" estimation is shown not to be constant but to be discontinuous and may vary by a factor of 10 over a one hour period, although the average rate of CSF production remains within previously established normal limits.

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.

Cerebrospinal fluid pressure in pyogenic meningitis.

The pressure of cerebrospinal fluid taken at lumbar puncture was recorded objectively by strain gauge pressure measurement in 35 infants and children with pyogenic meningitis. Raised pressures were found in 33 children. The median pressure was 15 mm Hg (range 4-70 mm Hg) in all age groups. The pressure level varied throughout the infection, but a higher median pressure (19 mm Hg) was found when this was measured on the day of admission. The clinical features of the meningitis in these patients suggest that many of the presenting symptoms and signs are those of pressure. These results show that high pressure is frequently present in childhood meningitis, not just in those who die from cones or who have radiological evidence of hydrocephalus. We conclude that raised cerebrospinal fluid pressure is a frequent accompaniment of childhood meningitis and may need treatment in its own right and is therefore one further important factor influencing the course and outcome of childhood meningitis.

Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is the treatment of choice for the sleep apnoea/hypopnoea syndrome. Compliance with this relatively obtrusive therapy has not been well studied. METHODS: Usage of CPAP was investigated in 54 patients with sleep apnoea/hypopnoea syndrome (median 36 (range 7-129) apnoeas + hypopnoeas/hour slept) over the first 1-3 months after starting CPAP therapy. In all cases CPAP usage was monitored by hidden time clocks that indicated for how long the machines were switched on--that is, the CPAP run time. In 32 patients the time at which the CPAP mask pressure was at the therapeutic level of CPAP pressure set for that patient--that is, the mask time--was also monitored. In all patients objective daytime sleepiness was assessed by multiple sleep latency before and after CPAP therapy. RESULTS: The mean (SE) nightly CPAP run time was 4.7 (0.4) hours. There was no correlation between run time and severity of the sleep apnoea/hypopnoea syndrome as assessed by apnoea + hypopnoea frequency or multiple sleep latency, and no correlation between CPAP usage and improvement in multiple sleep latency. Thirty two patients in whom mask time was recorded had therapeutic CPAP pressures for 89% (3%) of their CPAP run times. Patients who experienced side effects from CPAP used their CPAP machines significantly less than those who did not. CONCLUSIONS: Patients with sleep apnoea/hypopnoea syndrome used CPAP for less than five hours/night on average with no correlation between severity of sleep apnoea/hypopnoea syndrome and CPAP usage. Patients who complained of side effects used their CPAP therapy less. It is recommended that, as a minimum, CPAP run time should be regularly recorded in all patients receiving CPAP therapy.

Microarousals in patients with sleep apnoea/hypopnoea syndrome.

Upper airway obstructions during sleep cause recurrent brief awakenings or microarousals. Standard criteria exist for sleep and respiratory event scoring, however, there are different definitions currently used to score microarousals. We therefore compared three definitions of microarousal (ranging from 1.5-3 s in duration) and one of awakening (>15 s). We examined their occurrence at the termination of apnoeas and hypopnoeas and their correlation with daytime sleepiness in patients with sleep apnoea/hypopnoea syndrome (SAHS). Sixty-three patients (aged 49, SD 10) had overnight polysomnography, multiple sleep latency tests (MSLT) and Epworth Sleepiness Scales (ESS). There were significantly more microarousals by any definition than there were awakenings (P<0.001) and there were more 1.5 s than 3 s microarousals (P<0.001). Significantly more apnoeas and hypopnoeas were terminated by 1.5 s microarousals (83% and 81%) than by 3 s microarousals (75%) (all P<0.001). Apnoea/ hypopnoea index (AHI) correlated significantly with objective daytime sleepiness (rho=-0.30, P<0.01). There were weakly significant relationships between all three microarousal definitions (-0.24

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.

Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hypopnoea syndrome.

BACKGROUND: Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking. METHODS: A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period. RESULTS: Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function. CONCLUSION: This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.

The effect of sleep fragmentation on daytime function.

Patients with the sleep apnea/hypopnea syndrome suffer from impaired daytime function. This has been attributed to both sleep fragmentation and hypoxemia. To help understand which is casual, we studied the effects of sleep fragmentation alone on daytime function. Sixteen normal subjects were studied on two pairs of two nights. The first night of each pair was for acclimatization, and on the second the subject either slept undisturbed or had sleep fragmented with sound pulses every 2 min. Sound volume and duration was titrated to cause a return to theta or alpha rhythm on the EEG for at least 3 s. Study nights were followed by daytime testing of psychometric function and mood and by a multiple sleep latency test (MSLT) and a maintenance of wakefulness test (MWT). Total sleep time did not differ between study nights (400 +/- 20 SD min undisturbed, 396 +/- 24 min fragmented; p = 0.6). Fragmentation decreased sleep latency on both the MSLT (11 +/- 3, 7 +/- 2 min; p = 0.001) and the MWT (34 +/- 8, 24 +/- 10 min; p<0.001). Energetic arousal (22 +/- 4, 19 +/- 4; p = 0.005) and hedonic tone (29 +/- 4, 27 +/- 4; p = 0.05) decreased after fragmentation. Fragmentation impaired daytime function adjudged by the Trailmaking B (p = 0.05) and PASAT 4-s tests (p<0.03). One night of sleep fragmentation makes normal subjects sleepier during the day, impairs their subjective assessment of mood, and decreases mental flexibility and sustained attention.