Efficacy and safety of maxillomandibular advancement in treatment of obstructive sleep apnoea syndrome.

To assess the effectiveness of maxillomandibular adavancement for treatment of adults with obstructive sleep apnoea, we report the results obtained after maxillomandibular advancement. A group of 16 patients were studied before surgery, at 6 months after surgery and at followup. The analysis included: upper airway endoscopy during Mueller's manoeuvre, lateral cephalometry, polysomnography and Epworth Sleepiness Scale. The results of surgical treatment were divided into "surgical success" and "surgical cure". The former was defined as an AHI < 20 events/hour and a > 50% reduction in AHI after surgical procedure, while the latter was defined as an AHI < 5 events/hour after surgical procedure. At follow-up, all patients had AHI < 20 events/hour with a surgical success rate of 100%. The surgical cure rate was 37.5%, with 6 patients having an AHI < 5 events/hour. Surgical success and long term stability of outcomes confirm the efficacy and safety of MMA for treatment of obstructive sleep apnoea syndrome. However, a continuous follow-up of these patients is necessary to control their lifestyle and to detect possible relapse.

Sleep disturbances in the critically ill patients: role of delirium and sedative agents.

BACKGROUND: Impairment of sleep quality and quantity has been described in critically ill patients. Delirium, an organ dysfunction that affects outcome of the critically ill patients, is characterized by an acute onset of impaired cognitive function, visual hallucinations, delusions, and illusions. These symptoms resemble the hypnagogic hallucinations and wakeful dreams seen in patients with neurological degenerative disorders and suffering of disorders of rapid eye movement (REM) sleep. We assessed the characteristics of sleep disruption in a cohort of surgical critically ill patients examining the hypothesis that severe impairments of rapid eyes movement (REM) sleep are associated to delirium. METHODS: Surgical patients admitted to the intensive care units of the San G. Battista Hospital (University of Turin) were enrolled. Once weaning was initiated, sleep was recorded for one night utilizing standard polysomnography. Clinical status, laboratory data on admission, co-morbidities and duration of mechanical ventilation were recorded. Patients were a priori classified as having a "severe REM reduction" or "REM reduction" if REM was higher or lower than 6% of the total sleep time (TST), respectively. Occurrence of delirium during intensive care unit (ICU) stay was identified by CAM-ICU twice a day. Multivariate forward stepwise logistic regression analysis was performed with sleep ("severe REM reduction" vs. "REM reduction") as the a priori dependent factor. RESULTS: REM sleep amounted to 44 (16-72) minutes [11 (8-55) % of the TST] in 14 patients ("REM reduction") and to 2.5 (0-36) minutes [1 (0-6) % of the TST] in the remaining 15 patients ("severe REM reduction") (P = 0.0004). SAPS II on admission was higher in " severely REM deprived" then in "REM deprived" patients. Delirium was present in 11 patients (73.3%) of the patients with "severe REM reduction" and lasted for a median of 3 (0-11) days before sleep assessment, while only one patient having "REM reduction" developed delirium that lasted for 1 day. The factors independently associated with a higher risk of developing "severe REM reduction" were delirium and daily dosage of lorazepam. CONCLUSION: The present study shows that while all critically ill patients present a profound fragmentation of sleep with a high frequency of arousals and awakenings and a reduction of REM sleep, a percentage of patients present an extremely severe reduction of REM sleep. Delirium and daily dosage of lorazepam are the factors independently associated to extremely severe REM sleep reduction.

Sleep-related breathing disorders in amyotrophic lateral sclerosis.

Sleep-related breathing events in patients with amyotrophic lateral sclerosis (ALS) have been reported in small case series, but the association with the clinical presentation--with (B) or without (nonB) bulbar symptoms--or the relevance for prognosis have not been investigated. We retrospectively analyzed sleep studies of 114 (46 nonB) ALS patients, aged 54 +/- 11 years. Respiratory function was better in nonB patients: forced vital capacity was 76 +/- 20% vs 55 +/- 23% in the bulbar group (p < 0.001); PaCO2 41 +/- 5 vs 44 +/- 6 mm Hg p < 0.05. The mean apnea/hypopnea index (AHI) was higher in nonB patients (22 +/- 12 vs 15 +/- 16 events per hour- p < 0.05); in this group 21 out of 46 patients (46%) had more than 20 events/hour versus 14 out of 68 (21%) in the nonB group (p < 0.005). On the contrary the oxygen desaturation index (ODI) was similar (10 +/- 11 vs 9 +/- 12 events per hour, p = NS). Most events had a central genesis and obstructive events were usually erratic, except in 7 patients (6 in group B) who had more than 10 obstructive events/hour. Data were stratified in three groups: with a disease duration below 1 year (< 1 yr), between 1 and 2 years (1-2 yr), and more than 2 years (> 2 yr). The occurrence of sleep-related respiratory disorders decreased with the increase of disease duration (23 +/- 15; 18 +/- 14; and 16 +/- 15 events per hour respectively), the decrease being significantly lower in the > 2 yr group than in the < 1 yr (p < 0.05). Again ODI was similar in the three groups. In conclusion the present study shows that sleep-related breathing events are more common than previously described in ALS patients, particularly in the first year following onset of the disease. Obstructive events occur rarely, although the prevalence of obstructive sleep apnea is higher than predicted, particularly when bulbar symptoms are present. Patients without bulbar signs show a higher prevalence of central events. The progressive decrease of events with the increase of disease duration could be due to a progressive weakness of respiratory muscles, but it could also suggest an independent role for nocturnal events which could be linked to a worse prognosis or to a more rapid decay of clinical status.

Blood pressure and heart rate during periodic breathing while asleep at high altitude.

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.

[Sleep disordered breathing: a new risk factor for accidents]. / I disturbi respiratori nel sonno: un nuovo fattore di rischio per gli infortuni.

An estimated 2%-4% of the working population could be affected by sleep disordered breathing, in particular by obstructive sleep apnea syndrome. The main symptom is excessive daytime sleepiness, caused by sleep interruptions induced by respiratory events. The level of sleepiness varies according to the severity and duration of the disease: from a slight decrease in vigilance to an almost total inability to keep alert for more than a few hours. In addition, there is an increase in cardiovascular risks and dysmetabolic disorders, which has a variable incidence in the affected population. Even less severe clinical conditions can lead to a reduction in the power of concentration, attention and working performance. The recent trend of research aims at verifying the association between risk factors and obstructive sleep apnea syndrome in order to identify those subjects at real risk, to determine the actual level of sleep-disordered breathing which should be treated and whether the less serious disturbances, so frequent in the general population, represent a real threat to health.

[The assessment of breathing during sleep: a curiosity or clinical necessity?]. / La valutazione del respiro durante il sonno: curiosità o necessità clinica?

The study of sleep, which initially focused on the neurophysiological mechanisms and cardiorespiratory function during the night, has shown the presence of sleep-related breathing disorders that epidemiological, pathophysiological and clinical data have indicated to be associated with increased cardiovascular morbidity and mortality: the obstructive sleep apnea syndrome (OSAS) and the central sleep apnea syndrome (CSAS). OSAS is a condition characterized by repetitive respiratory pauses due to the pharynx wall collapse, with a subsequent obstruction to the airflow. The hemodynamic consequences due to the markedly increased negative intrathoracic pressure (induced by the respiratory muscle effort towards the closed upper airways), the progressive hypercapnic hypoxemia and the arousal terminating the apneas, are the pathophysiological keys of the cardiovascular effects of OSAS and may explain the association between OSAS and the documented increase of cardiovascular morbidity and mortality. CSAS is a breathing disorder characterized by recurrent episodes of central hypopneas or apneas and hyperventilation which, is the classical form described by Cheyne and Stokes, show a crescendo-decrescendo pattern of respiration. Pathophysiological and epidemiological data clearly indicate the link between CSAS and heart failure, also showing a correlation between respiratory disorders and the severity of hemodynamic impairment. However, other mechanisms are involved in the genesis of CSAS in explaining the variable presence of CSAS independent of cardiac function and, more importantly, the impact of CSAS on poor prognosis in heart failure. In conclusion, the data available indicate the need to include screening for sleep-related breathing disorders in the evaluation of cardiac patients who are at risk for OSAS and, particularly, in patients with heart failure, who could really benefit from treatment of the respiratory disorder.

Periodic breathing during sleep in patients affected by fibromyalgia syndrome.

Seventeen patients affected by fibromyalgia syndrome (FMS) (16 females and one male) and 17 matched healthy subjects underwent formal polysomnography, a sleep questionnaire and lung function tests. FMS patients slept significantly less efficiently than the healthy controls (p<0.01), had a higher proportion of stage 1 sleep (mean+/-SD, 21+/-6% versus 11+/-4%; p<0.001), less slow wave sleep (p<0.01) and twice as many arousals per hour of sleep (p<0.001). The respiratory pattern of FMS patients showed a high occurrence of periodic breathing (PB) (15+/-8% of total sleep time) in 15/17 patients, versus 2/17 control subjects. The short length of apnoeas and hypopnoeas did not affect the apnoea/hypopnoea index (5.1+/-3.5 versus 3.2+/-1.6; NS), but FMS patients had a greater number of desaturations per hour of sleep (8+/-5 versus 3+/-3; p<0.01). Pulmonary volumes did not differ between the two groups, but FMS patients had a lower transfer factor of the lung for carbon monoxide (TL,CO (5.8+1 versus 7.7+1 mmol x min(-1) x kPa(-1); p=0.001). PB occurrence correlated with TL,CO (r=-0.62; p=0.01), number of desaturations (r=0.76, p=0.001) and carbon dioxide tension in arterial blood (Pa,CO2) (r=-0.50; p=0.05). Stepwise multiple linear regression analysis showed desaturation frequency (p=0.0001) and TL,CO (p=0.029) to be the best predictors of PB percentage (R2 0.73; p=0.0001). Patients complaining of daytime hypersomnolence had a higher number of tender points, about twice as many arousals per hour and a lower sleep efficiency than patients who did not report this symptom. TL,CO was more impaired and the occurrence of PB was higher. The occurrence of periodic breathing in fibromyalgia syndrome patients, which was previously unreported, and is shown to be linked to a reduction of transfer factor of the lung for carbon monoxide could play a major role in the symptoms of poor sleep of these patients.

Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.

BACKGROUND: Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in patients with chronic heart failure (CHF), and it may be associated with sympathetic activation. The aim of the present study was to evaluate whether CSR could affect prognosis in patients with CHF. METHODS AND RESULTS: Sixty-two CHF patients with left ventricular ejection fraction /=30/h and left atria >/=25 cm2. CONCLUSIONS: The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI >/=30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.

Effects of high-altitude periodic breathing on sleep and arterial oxyhaemoglobin saturation.

This study aimed to investigate the effect of periodic breathing (PB) at high altitude on sleep structure and arterial oxygen saturation (Sa,O2). Five healthy subjects underwent polysomnographic studies at sea level, and during the first and the fourth week of sojourn at 5,050 m. Their breathing pattern, sleep architecture and Sa,O2 were analysed. PB was detected in the high-altitude studies during nonrapid eye movement (NREM) sleep and tended to increase from the first to the fourth week. Stages 3-4 were absent in four subjects at the first week, but only in one at the fourth week, irrespective of the amount of PB. The arousal index was 11.6+/-3.8 at sea level, 30.1+/-15.5 at the first week at altitude and 33.0+/-18.2 at the fourth week. At altitude, arousal index in NREM sleep was higher during PB than during regular breathing. In NREM sleep, the mean highest Sa,O2 levels in NREM epochs with PB were higher than in those with regular breathing by 2.8+/-1.7% at the first week and 2.9+/-1.5% at the fourth week (p<0.025). From the first to the fourth week, mean Sa,O2 increased significantly during wakefulness (5.6%), NREM (5.2% with regular breathing and 5.3% with PB) and rapid eye movement sleep (7.6%). The data demonstrate a slight role of periodic breathing in altering sleep architecture at high altitude and also show that periodic breathing induces only a minor improvement in arterial oxygen saturation during nonrapid eye movement sleep.

Pulmonary failure as a cause of death in COPD.

Data on the outcome of patients with chronic obstructive pulmonary disease (COPD) are limited. We know that the prognosis is poor when respiratory insufficiency develops, but we have little information on the actual cause of death. Epidemiological studies are suitable for the assessment of the prevalence of the disease, but give no details on the actual cause of death. Age and forced expiratory volume in one second (FEV1) have been recognized as the best predictors of mortality in studies designed to quantify survival of COPD patients, particularly when the post-brochodilator value is used, as this provides a better estimate of airway and parenchymal damage. Data from Intensive Care Units on acute respiratory failure have several significant limitations. Firstly, it is probable that some patients elect not to undergo intensive treatment for a terminal bout of respiratory failure, particularly if it is not first episode. Secondly, the actual cause of death is often not described in adequate detail. Hypoxaemia and acidaemia are the main risk factors in acute exacerbation of the disease and the presence of pulmonary infiltrates on chest radiographs worsens the prognosis. A single bout of respiratory failure appears to have no effect on the prognosis of COPD patients after recovery, but there is a consistent increase in mortality after the second episode. It seems possible to manage the majority of episodes of acute respiratory failure with mechanical ventilation administered with noninvasive techniques. When endotracheal intubation is necessary, the prognosis is usually poor and the survival after 1 yr is usually lower than 40%. The role of long-term home mechanical ventilation is still unclear. Results from pivotal studies have been encouraging, although survival is far less impressive than in neuromuscular disorders. In patients with end-stage lung disease, lung transplantation can be considered the only possibility of increasing pulmonary functional capacity. However the technique is reserved only for a highly selected group of patients and data on the long-term outcome are awaited.

Causes of death in patients with COPD and chronic respiratory failure.

Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European centres participated in the study and data were collected from patients both during a period of clinical stability and at the time of death. Of the 215 patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major causes of death were: acute on chronic respiratory failure (38%); heart failure (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia (8%); and lung cancer (7%). Seventy five percent of patients died in hospital. There was no difference in the number of patients who died in the morning, afternoon and night hours. Twenty percent of the total died during sleep and in 26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those patients who died suddenly. Drug therapy was not related to unexpected death. The majority of patients with chronic obstructive pulmonary disease on long-term oxygen therapy died from chronic or acute on chronic respiratory failure. Prevention and treatment of respiratory failure in patients with chronic obstructive pulmonary disease is likely to have the greatest impact in reducing mortality.

Nocturnal asthma: mechanisms and therapy.

Nocturnal worsening of symptoms affects a large number of patients suffering from asthma. Recent studies show that airway inflammation underlies nocturnal awakenings and increased airway hyperreactivity. These studies, however, yield conflicting results concerning the pathogenesis of the disease, making it difficult to understand the mechanisms involved in sustaining nocturnal asthma. This article reviews the principal pathogenetic mechanisms of nocturnal asthma, showing that worsening of symptoms at night may be the result of a more severe disease as well as of increased inflammation at night and higher susceptibility. We also review the pharmacologic treatment of nocturnal asthma which is mainly based on antiinflammatory treatment with inhaled or oral steroids or combined therapies with theophylline and beta 2 agonists. The activity of antileukotrine compounds in asthma is also summarized.

Cardiovascular and ventilatory response to isocapnic hypoxia at sea level and at 5,050 m.

To assess the effect of chronic hypoxic conditions on ventilatory, heart rate (HR), and blood pressure (BP) responses to acute progressive isocapnic hypoxia, we studied five healthy Caucasian subjects (3 men and 2 women). Each subject performed one rebreathing test at sea level (SL) and two tests at the Pyramid laboratory at Lobuche, Nepal, at the altitude of 5,050 m, 1 day after arrival (HA1) and after 24 days of sojourn (HA2). The effects of progressive isocapnic hypoxia were tested by using a standard rebreathing technique. BP, electrocardiogram, arterial oxygen saturation, airflow and end-tidal CO2 and O2 were recorded. For each subject, the relationships between arterial oxygen saturation and HR, systolic BP and minute ventilation (VE), respectively, were evaluated. At HA1, the majority of subjects showed a significant increase in VE and BP response and a decrease in HR response to progressive isocapnic hypoxia as compared to SL. At HA2, VE and BP responses further increased, whereas the HR response remained similar to that observed at HA1. A significant relationship between hypoxic ventilatory responses and both systolic and diastolic BP responses to progressive hypoxia was found. No significant correlation was found between hypoxic ventilatory and HR responses.

When is liquid oxygen really needed?

Liquid oxygen is a synonym for portable oxygen, as it combines a big cylinder with an easy-to-fill portable unit, suitable for exercise and use out-doors. The main drawback is its high cost, inherent in a home delivery system, which discouraged many nations from its introduction. The best candidates are patients able to move, who are still active and do not have psychological reticence to its use in public. Transtracheal systems and the advantage of a round the clock treatment and a reduction of flow rate, crucial both to lengthen the autonomy of portable units and to avoid flows higher than 4 L.min-1, which cannot be maintained. Finally, patients on liquid oxygen usually have a better adherence to treatment, mainly compared to those using a concentrator, possibly improving its effectiveness, which is notoriously dependent on total usage per day.

The effects of doxofylline versus theophylline on sleep architecture in COPD patients.

Theophylline is known to alter sleep architecture because of its affinity to adenosine receptors. One of the consequences of disrupted sleep is impaired cognitive performance. A single-blind, randomized cross-over study of eight male chronic obstructive pulmonary disease (COPD) patients was undertaken to evaluate the effects of theophylline versus doxofylline on sleep architecture. The patients, who were all ex-smokers, had been treated with theophylline. Mean age was 53 +/- 12 yrs, forced expiratory volume in one second (FEV1) 50 +/- 22% predicted and forced vital capacity (FVC) 70 +/- 18% predicted. Following a wash-out period, four patients were given oral slow-release theophylline (T) (300 mg b.i.d.) for one week, followed by a cross-over to doxofylline (D) (400 mg t.i.d.) for a second week. The other four patients were given the drugs in the reverse order. All patients underwent polysomnography at baseline and at the end of each week of treatment. The number of arousals per hour was 5.5 +/- 2.9 at baseline, 9.4 +/- 5.2 during T treatment and 5.4 +/- 4.4 during D treatment. During T treatment, sleep efficiency was 60 +/- 19% vs 75 +/- 13% recorded at baseline trial and 68 +/- 25 recorded during D treatment. Sleep quality, during T treatment, was poorer than at baseline, with a greater increase in the percentage of wakefulness and more stage 2 sleep than at baseline. Slow wave sleep was reduced with both treatments, particularly D. Neither drug affected the arterial oxygen saturation (Sao2) or respiratory rate during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term oxygen therapy.

Controlled studies have demonstrated that the correction of tissue hypoxia increases survival and reduces pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD) receiving oxygen therapy 15 h/day or longer. Long-term oxygen therapy (LTOT) is recommended to any patient with COPD who has a PaO2 of < or = 7.3 kPa. In most countries, the PaO2 threshold is 8kPa in patients with chronic hypoxemia (PaO2 > or = 55 mm Hg) with associated hematocrit > or = 55%, pulmonary hypertension or cor pulmonale. Desaturations during sleep or exercise should be investigated, although a consensus as to whether and how these episodes should be treated has yet to be reached. The indications for LTOT in restrictive lung diseases, such as interstitial pulmonary fibrosis and pneumoconiosis, remain controversial. In many countries, oxygen is not prescribed if the patient is a current smoker. Breathlessness without hypoxemia should not be considered an indication for LTOT. The oxygen is usually administered through nasal cannula. Venturi type masks, nasopharyngeal and transtracheal catheters are associated with several drawbacks. Oxygen is usually supplied by the relatively cheap oxygen concentrator. Liquid oxygen is favored when a portable source is an important requirement. Many questions remain unanswered concerning the duration of added survival, the effect of LTOT on physiological parameters such as pulmonary artery pressure, respiratory failure in non-COPD patients, exercise and nocturnal desaturations.