UARS is defined as daytime sleepiness associated to a sleep disordered breathing and arousals related to respiratory effort (RERA) but without sufficient apneas/hypopneas for OSAS. The diagnosis is based on the association of clinical symptoms and polysomnographic findings.
Nocturnal polysomnography, which is the gold standard for diagnosing SAHS, sometimes demonstrates the presence of apneic events and non apneic breathing (hypopneas), but does not definitively diagnose UARS. Nevertheless, an increased number of RERA may lead to suspicion of UARS. Simplified polygraphic studies are not useful in this disease because they do not provide arousal information. Some laboratories have used the split-night technique followed by CPAP titration successfully. These situations require an index of over 20 RERA during the first three hours of sleep (Kristo 2009).
The continuous recording of esophageal pressure throughout the night is the gold standard for the diagnosis of UARS (Kushida 2002; Iber 2007). Esophageal manometry is a complex technique which may be affected by the placement of the probe and the position of the catheter. Moreover, it is time-comsuming, may affect patient's sleep, and is not widely available (Johnson 2008). The correct positioning of the esophageal catheter requires a lot of experience and clinical practice. The use of a small catheter has improved tolerance of the procedure. The analysis of esophageal pressure can be quantitative or qualitative, though the latter approach is more common in clinical practice (Watanabae 2000). Gold et als used the critical pressure criteria to differentiate between SAHS and UARS patients [Gold 2002].
The esophageal pressure reading may present three different patterns: a crescendo pattern that ends in arousal without achieving 3% desaturation, continuous sustained effort for at least four breaths, and finally an abrupt drop in respiratory effort indicated by a less negative peak inspiratory pressure after a sequence of increased respiratory efforts independent of the EEG patterns (Pes reversal).
Although esophageal manometry is indicated mainly for the diagnosis of UARS has also demonstrated its usefulness in studying the Cheyne-Stokes syndrome as it allows to differentiate obstructive from central apneas. However, it is a laborious technique, disruptive for patients and normal values remain to be established. The utility in the clinic is unclear and have been confined its use to research.
Indeed, the presence of RERA in the absence of apneas and hypopneas is the key polysomnography finding for diagnosing UARS (Bonnet 2007). However, the difficulty of registering respiratory effort has prompted the search for other non-invasive methods that can provide similar information (Hosselet 1998; Loube 1999; Badia 2001; Mosler 2002; Kenach 2005; Popovic 2009)(Table 1). Most systems try to develop a reliable non-invasive tecnique for respiratory effort and upper airway resistance that could represent a noninvasive alternative to esophageal pressure measurement. Of these, the most widely used and accepted by the American Academy of Sleep Medicine are nasal pressure cannulas, inductance plethysmography or diaphragmatic/ intercostal EMG. The nasal cannula is the tool of choice for monitoring respiratory airflow during sleep in both clinical and research sleep studies. Nasal cannula is more sensitive than thermistor for detecting RERA The use of new technologies such as pressure probes have made it possible to identify signs of UARS in patients with high levels of arousal and airflow limitation (Krakow 2001). The diagnostic criteria for UARS have not been established. At present, the diagnostic polysomnography of UARS is based on careful analysis of the esophageal pressure reading and nasal cannula (Guilleminault 1995, 2001; Black 2000), together with an AHI under 5 and the presence of desaturation of no more than 92%. Visual identification of intermitent flow limitation is cumbersome, subjective and trought with variability and potential error. Some authors recommend determining the length of airflow limitation episodes as well as the total percentage of airflow limitation with respect to total sleep time. Termination of flow limitation was indicated either by respiratory events related to arousal or with essofageal pressure reversal (Guilleminault 1995; 2001) without alpha EEG arousal (Guilleminault 2005b). In UARS patients these episodes of airflow limitation that is not accompanied by desaturation, are of varying lengths, and are not always associated with an increase in esophageal pressure. The coincidence of EEG arousals and Pes events is well documented. A percentage of Pes events terminate without coincident EEG activity. However, Guilleminault describes that, in patients with UARS, apnoeas accompanied by arousals have a greater tachycardic effect, even if there is only a small reduction in blood oxygen saturation (Guilleminault 2005). The shape of the inspiratory flow contour has been proposed as a noninvasive predictor of increased upper airway obstruction, increasing the potential for erroneous classification of respiratorye events (Hosselet 1998; Rees 2000; Ayyapa & Rapoport 2003). Various definitions of airflow limitation exist (Norman 2007; Mansour 2004; Kaplan 2000;Aittokallio 2001)(Table 2).
RERA is the most important event in UARS patients. In early studies, the definition of UARS included the presence of frequent arousals, indicating an RERA index >10/h as a diagnostic criteria. Owing to their relation, treating RERA tends to improve excessive daytime sleepiness. This index was established as a treatment criterion. UARS has not found its way into the International Classification of Sleep Disorders Diagnostic and Coding Manual, which is one of the main problems for the acceptance of UARS as a specific entity (AASM 1999; Iber 2007). RERA has been accepted by the American Academy of Sleep Medicine Task Force (AASM, 1999) but it has yet to be standardized. According to the AASM and a number of authors (Cracowski 2001), RERA episodes are rare and their encoding need not be mandatory. However, others consider it to be a key element, with an identifiable pathophysiology. RERAs have been incorporated into normal clinical practice, and the respiratory disturbance index used to quantify OSAS severity takes them into account together with apneas, and hypopneas.
• Nasal cannula pressure
• Resistive Inductance Plethismography
• Pulse Transit Time
• Neural network
• Forced oscillation technique
• Suprasternal pressure transducer
• Presence ofalteringcyclicpattern(EEG)
• Forehead venous pressure signal
• Snore signals
Table 1. Techniques to assess respiratory effort.
Periods of high esophageal pressure swings with associated inspiratory flow limitation
Lack of increase in airflow despite increasing respiratory effort.
Flattening of the normal bell-shaped curve of normal breath with a drop in the amplitude of the curve by 2-29% compared to the normal breaths immediately preceding
Abnormal inspiratory air flow shape during partialupper airway obstruction
Abnormal contour in the nasal/presure transducer signal waveform
Presence of an inspiratory plateau or reduction in inspiratory flow independent of any increase in inspiratory efforts.
Pressure waveflattening<30% is associated with a physiological event (arousal, CAP complex, variabilidad RR, etc)
Two or more breaths (10 sec) without sinusoidal appearance and without hypopnea criteria, end abruptly, taking on the sinuidal flow aspect
At least four successive breaths reduction in amplitude simultaneously with the development of an inspiratory plateau (loss of a sinusoidal inspiratory waveform)
Table 2. Inspiratory flow limitation: Definitions.
From the standpoint of polysomnography in recent years has gained great interest to consider these patients have instability in their sleep nonREM. OSAS and UARS patients have different brain activity during sleep. Thus, in patients with UARS have described alterations in sleep architecture, such as sleep fragmentation, consequent to the presence of respiratory arousals, the presence of an alpha-delta pattern, characteristic modifications in the EEG spectral analysis and the existence of an increase of cyclic alternating pattern. Alpha-delta sleep is characterized by an intrusion of alpha EEG waves into slow delta waves during deep sleep, which also occurs in insomnia and non-refreshing sleep. It appears that cyclic alternating pattern could be a valid indicator for the persistence of some degree of sleep disturbance and instability of NREM sleep. With respect to the EEG spectral analysis in patients with UARS have less activity in slow wave sleep (delta) and a higher prevalence in the range of 7-9 Hz consequent to a different cortical activity. The development of slow wave sleep is also abnormal, with persistence of a large number of "power delta" at the end of sleep cycles. Both abnormalities may explain the symptoms of daytime sleepiness, insomnia and fatigue in patients with UARS (Guilleminault 2001a).Black et als found that visually undetectable EEG alterations may occur during breathing disturbances in the absence of arousal (Black 2000).
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