Polysomnographic characteristics of severe obstructive sleep apnea vary significantly between hypertensive and normotensive patients of both genders.

PURPOSE: Hypertension is a common finding in patients with obstructive sleep apnea (OSA), but it has remained unclear whether or not the amount of disturbed breathing and characteristics of individual respiratory events differ between hypertensive and normotensive patients with severe OSA. METHODS: Full polysomnographic recordings of 323 men and 89 women with severe OSA were analyzed. Differences in the duration of individual respiratory events, total apnea and hypopnea times, and the percentage of disturbed breathing from total sleep time (AHT%) were compared between normotensive and hypertensive patients separately by genders. Furthermore, differences in the respiratory event characteristics were assessed between three AHT% groups (AHT% ≤ 30%, 30% < AHT% ≤ 45%, and AHT% > 45%). RESULTS: Hypertensive women had lower percentage apnea time (15.2% vs. 18.2%, p = 0.003) and AHT% (33.5% vs. 36.5%, p = 0.021) when compared with normotensive women. However, these differences were not observed between hypertensive and normotensive men. Percentage hypopnea time was higher in hypertensive men (13.5% vs. 11.2%, p = 0.043) but not in women (15.2% vs. 12.2%, p = 0.130) compared with their normotensive counterparts. The variation in AHI explained 60.5% (ρ = 0.778) and 65.0% (ρ = 0.806) of the variation in AHT% in normotensive and hypertensive patients, respectively. However, when AHT% increased, the capability of AHI to explain the variation in AHT% declined. CONCLUSIONS: There is a major inter- and intra-gender variation in percentage apnea and hypopnea times between hypertensive and normotensive patients with severe OSA. OSA is an important risk factor for hypertension and thus, early detection and phenotyping of OSA would allow timely treatment of patients with the highest risk of hypertension.

Comparison of Bispectral Index and Entropy values with electroencephalogram during surgical anaesthesia with sevoflurane.

BACKGROUND: Concomitantly recorded Bispectral Index® (BIS) and Entropy™ values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. METHODS: In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed ≥10-unit disagreement for ≥60 s, the raw EEG signal was analysed both in time and frequency domain. RESULTS: A ≥10-unit disagreement ≥60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). CONCLUSIONS: Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. CLINICAL TRIAL REGISTRATIONCLINICALTRIALSGOVIDENTIFIER: NCT01077674.

Adjustment of apnea-hypopnea index with severity of obstruction events enhances detection of sleep apnea patients with the highest risk of severe health consequences.

INTRODUCTION: Presently, the severity of obstructive sleep apnea (OSA) is estimated based on the apnea-hypopnea index (AHI). Unfortunately, AHI does not provide information on the severity of individual obstruction events. Previously, the severity of individual obstruction events has been suggested to be related to the outcome of the disease. In this study, we incorporate this information into AHI and test whether this novel approach would aid in discriminating patients with the highest risk. We hypothesize that the introduced adjusted AHI parameter provides a valuable supplement to AHI in the diagnosis of the severity of OSA. METHODS: This hypothesis was tested by means of retrospective follow-up (mean ± sd follow-up time 198.2 ± 24.7 months) of 1,068 men originally referred to night polygraphy due to suspected OSA. After exclusion of the 264 patients using CPAP, the remaining 804 patients were divided into normal (AHI < 5) and OSA (AHI ≥ 5) categories based on conventional AHI and adjusted AHI. For a more detailed analysis, the patients were divided into normal, mild, moderate, and severe OSA categories based on conventional AHI and adjusted AHI. Subsequently, the mortality and cardiovascular morbidity in these groups were determined. RESULTS: Use of the severity of individual obstruction events for adjustment of AHI led to a significant rearrangement of patients between severity categories. Due to this rearrangement, the number of deceased patients diagnosed to have OSA was increased when adjusted AHI was used as the diagnostic index. Importantly, risk ratios of all-cause mortality and cardiovascular morbidity were higher in moderate and severe OSA groups formed based on the adjusted AHI parameter than in those formed based on conventional AHI. CONCLUSIONS: The adjusted AHI parameter was found to give valuable supplementary information to AHI and to potentially improve the recognition of OSA patients with the highest risk of mortality or cardiovascular morbidity.

Elevated BIS and Entropy values after sugammadex or neostigmine: an electroencephalographic or electromyographic phenomenon?

BACKGROUND: Sugammadex is designed to antagonize neuromuscular blockade (NMB) induced by rocuronium or vecuronium. In clinical practice, we have noticed a rise in the numerical values of bispectral index (BIS) and Entropy, two electroencephalogram (EEG) - based depth of anesthesia monitors, during the reversal of the NMB with sugammadex. The aim of this prospective, randomized, double-blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB. METHODS: Thirty patients undergoing gynecological operations were studied. Patients were anesthetized with target-controlled infusions of propofol and remifentanil, and rocuronium was used to induce NMB. After operation, during light propofol-remifentanil anesthesia, NMB was antagonized with sugammadex or neostigmine. During the following 5 min, the numerical values of BIS, BIS electromyographic (BIS EMG) and Entropy were recorded on a laptop computer, as well as the biosignal recorded by the Entropy strip. The Entropy biosignal was studied off-line both in time and frequency domain to see if NMB reversal causes changes in EEG. RESULTS: In some patients, administration of sugammadex or neostigmine caused a significant rise in the numerical values of BIS, BIS EMG and Entropy. This phenomenon was most likely caused by increased electromyographic (EMG) activity. The administration of sugammadex or neostigmine appeared to have only minimal effect on EEG. CONCLUSION: The EMG contamination of EEG causes BIS and Entropy values to rise during reversal of rocuronium-induced NMB in light propofol-remifentanil anesthesia.

High frequency components of tracheal sound are emphasized during prolonged flow limitation.

A nasal pressure transducer, which is used to study nocturnal airflow, also provides information about the inspiratory flow waveform. A round flow shape is presented during normal breathing. A flattened, non-round shape is found during hypopneas and it can also appear in prolonged episodes. The significance of this prolonged flow limitation is still not established. A tracheal sound spectrum has been analyzed further in order to achieve additional information about breathing during sleep. Increased sound frequencies over 500 Hz have been connected to obstruction of the upper airway. The aim of the present study was to examine the tracheal sound signal content of prolonged flow limitation and to find out whether prolonged flow limitation would consist of abundant high frequency activity. Sleep recordings of 36 consecutive patients were examined. The tracheal sound spectral analysis was performed on 10 min episodes of prolonged flow limitation, normal breathing and periodic apnea-hypopnea breathing. The highest total spectral amplitude, implicating loudest sounds, occurred during flow-limited breathing which also presented loudest sounds in all frequency bands above 100 Hz. In addition, the tracheal sound signal during flow-limited breathing constituted proportionally more high frequency activities compared to normal breathing and even periodic apnea-hypopnea breathing.

Diffuse sleep spindles show similar frequency in central and frontopolar positions.

The objective of the present work was to examine fronto-central spindle frequency. A previously validated spindle detector, providing an electroencephalographic (EEG) amplitude independent spindle detection, was used to detect bilateral sleep spindles from sleep EEG recordings of ten healthy subjects with a time resolution of 0.33-s. A bilateral spindle detected centrally and frontopolarly simultaneously is called here a diffuse spindle. A bilateral spindle detected only frontopolarly or centrally at a given time is called a pure frontopolar and a pure central spindle, respectively. Spindle frequency was obtained with zero-padded discrete Fourier transform (DFT). Waveform phase angle of diffuse spindles was also examined. A total of 1230 diffuse spindles and 5316 pure central and 2595 pure frontopolar spindles were detected. The difference of median spindle frequency between central and frontopolar brain positions was clearly smaller in diffuse spindles than in pure spindles. Moreover, 34% of the diffuse spindles showed a similar frequency in central and frontopolar locations. This figure was up to 50.9% when including the 700 diffuse spindles fulfilling a strict anteroposterior (AP) timing criteria. The timing criteria selection in diffuse spindle analysis is a new functionality, enabled by the present spindle analysis method. Diffuse spindles showed coherent spindle oscillation in a large fronto-central area. Pure frontopolar spindles might be special cases of diffuse spindles, both of them seem to be generated in the nucleus medialis dorsalis (NMD) of the thalamus.

Detection of compressed tracheal sound patterns with large amplitude variation during sleep.

The objective of the present work was to develop automated methods for the compressed tracheal breathing sound analysis. Overnight tracheal breathing sound was recorded from ten apnoea patients. From each patient, three different types of tracheal sound deflection pattern, each of 10 min duration, were visually scored, viewing the compressed tracheal sound curve. Among them, high deflection patterns are of special interest due to the possible correlation with apnoea-hypopnoea sequences. Three methods were developed to detect patterns with high deflection, utilizing nonlinear filtering in local characterization of tracheal sounds. Method one comprises of local signal maximum, the second method of its local range, and the third of its relative range. The three methods provided 80% sensitivity with 57, 91 and 93% specificity, respectively. Method three provided an amplitude-independent approach. The nonlinear filtering based methods developed here offer effective means for analysing tracheal sounds of sleep-disordered breathing.

Amount of weight loss or gain influences the severity of respiratory events in sleep apnea.

Severity of obstructive sleep apnea (OSA) is estimated based on respiratory events per hour [i.e., apnea-hypopnea index (AHI)]. The aim of this study was to investigate effects of weight change on the severity of respiratory events. Respiratory event severity, including duration and morphology, was estimated by determining parameters quantifying obstruction and desaturation event lengths and areas, respectively. Respiratory events of 54 OSA patients treated with dietary intervention were evaluated at baseline and after 5-year follow-up in subgroups with different levels of weight change. AHI, oxygen desaturation index (ODI) and obstruction event severities decreased during weight loss. In lower level weight loss, the decrease was milder in obstruction severity than in AHI and ODI, indicating that the decrease in the number of events is more focused on less severe events. In weight gain groups, parameters incorporating obstruction event severity, AHI and ODI increased, although increase was greater in parameters incorporating obstruction event severity. The number and severity of respiratory events were modulated differently by the level of weight change. AHI misses this change in the severity of respiratory events. Therefore, parameters incorporating information on the respiratory event severities may bring additional information on the health effects obtained with dietary treatment of OSA.

Weight loss alters severity of individual nocturnal respiratory events depending on sleeping position.

Weight loss is an effective treatment for obstructive sleep apnea (OSA). The mechanisms of how weight loss affects nocturnal breathing are not fully understood. The severity of OSA is currently estimated by the number of respiratory events per hour of sleep (i.e. apnea-hypopnea-index, AHI). AHI neglects duration and morphology of individual respiratory events, which describe the severity of individual events. In the current paper, we investigate the novel Adjusted-AHI parameter (incorporating individual event severity) and AHI after weight loss in relation to sleeping position. It was hypothesised that there are positional differences in individual event severity changes during weight loss. Altogether, 32 successful (> 5% of weight) and 34 unsuccessful weight loss patients at baseline and after 1 year follow-up were analysed. The results revealed that individual respiratory event severity was reduced differently in supine and non-supine positions during weight loss. During weight loss, AHI was reduced by 54% (p = 0.004) and 74% (p < 0.001), while Adjusted-AHI was reduced by 14% (p = 0.454) and 48% (p = 0.003) in supine and non-supine positions, respectively. In conclusion, the severity of individual respiratory events decreased more in the non-supine position. The novel Adjusted-AHI parameter takes these changes into account and might therefore contribute additional information to the planning of treatment of OSA patients.

Novel parameters for evaluating severity of sleep disordered breathing and for supporting diagnosis of sleep apnea-hypopnea syndrome.

Sleep apnea-hypopnea syndrome (SAHS) is a complex public health problem causing increased risk of cardiovascular diseases. Traditionally, evaluation of the severity of the disease is based on Apnea-Hypopnea Index (AHI). It is defined as the average number of apnea and hypopnea events per hour during sleep. However, e.g. the total duration and the morphology of the recorded events are not considered when evaluating the severity of the disease. This is surprising, as increasing the length of apnea and hypopnea events will most likely lead to longer and deeper oxygen desaturation events. Obviously, this is physiologically more stressful and may have more severe health consequences than shorter and shallower desaturation events. Paradoxically, the lengthening of apnea and hypopnea events may even lead to a decrease in AHI and oxygen desaturation index (ODI). This raises the question of whether additional information is needed besides AHI and ODI for the evaluation of the severity of SAHS and its potential cardiovascular consequences. In the present paper, several novel parameters are introduced to bring additional information for evaluation of the severity of SAHS. Besides the number of events per hour, that AHI and ODI takes into account, the duration of the breathing cessations and the morphology of the oxygen desaturation events are considered as important factors that may influence the daytime fatigue and also the related cardiovascular problems. In this study diagnostic ambulatory polygraphy recordings of 19 male patients were retrospectively analysed. Importantly, the novel parameters showed significant variation amongst patients with similar AHI. For example, the correlation between AHI and the Obstruction severity-parameter was only moderate (r(2)=0.604, p<0.001). This suggests that patients with similar AHI may exhibit significantly different cardiovascular stress related to the disease. It is suggested that the present novel parameters might provide additional information over the currently used parameters and support the evaluation of the severity of SAHS.

Novel parameters reflect changes in morphology of respiratory events during weight loss.

Apnea-hypopnea-index (AHI), disregarding the respiratory event morphology, is currently used in estimation of severity of obstructive sleep apnea (OSA). The purpose of the current study was to evaluate the potential of novel parameters in estimation of changes in severity of OSA during weight loss. Polygraphic data of 67 patients, 37 in the control (no weight loss) and 30 in the weight loss (>5%) groups was evaluated at baseline and after two year follow-up. Changes in the values of novel parameters, incorporating detailed information of respiratory event characteristics, were evaluated and compared with changes in AHI. The median AHI in the weight loss group decreased significantly during the follow-up. The number of shorter respiratory events decreased in the weight loss group, while the longer ones remained, increasing the median durations of the respiratory events by 20-62%. For this reason the decrease of the values of the novel parameters were smaller compared to AHI in the weight loss group. This suggests that the severity of OSA might not fall as linearly during weight loss as AHI suggests. Moreover, the novel parameters containing more detailed information on the morphology characteristics may provide valuable supplementary information for the assessment of the severity of OSA.

Tracheal sound parameters of respiratory cycle phases show differences between flow-limited and normal breathing during sleep.

The objective of the present work was to develop new computational parameters to examine the characteristics of respiratory cycle phases from the tracheal breathing sound signal during sleep. Tracheal sound data from 14 patients (10 males and 4 females) were examined. From each patient, a 10 min long section of normal and a 10 min section of flow-limited breathing during sleep were analysed. The computationally determined proportional durations of the respiratory phases were first investigated. Moreover, the phase durations and breathing sound amplitude levels were used to calculate the area under the breathing sound envelope signal during inspiration and expiration phases. An inspiratory sound index was then developed to provide the percentage of this type of area during the inspiratory phase with respect to the combined area of inspiratory and expiratory phases. The proportional duration of the inspiratory phase showed statistically significantly higher values during flow-limited breathing than during normal breathing and inspiratory pause displayed an opposite difference. The inspiratory sound index showed statistically significantly higher values during flow-limited breathing than during normal breathing. The presented novel computational parameters could contribute to the examination of sleep-disordered breathing or as a screening tool.

Improved computational fronto-central sleep depth parameters show differences between apnea patients and control subjects.

All-night EEG recordings from 12 male apnea patients and 12 age-matched healthy control subjects were studied in the present work. The spectral mean frequency was used to provide computational sleep depth curves from two frontopolar and two central EEG channels. Our previously presented computational parameters quantifying the properties of the sleep depth curves were improved. The resulting light sleep percentage (LS%) values were higher in apnea patients than in control subjects in the right central brain position (P = 0.028), in concordance to our previous work. Moreover, apnea patients showed higher LS% values in the right frontopolar position (P = 0.008). Also, apnea patients showed a smaller anteroposterior sleep depth difference than control subjects on the right hemisphere (P = 0.002). These are interesting new findings, achieved by the present methodology. Thus, the developed computational parameters were able to quantify, at least to some degree, the disruption of sleep process caused by the recurrent apneic events.

New tracheal sound feature for apnoea analysis.

Sleep apnoea syndrome is common in the general population and is currently underdiagnosed. The aim of the present work was to develop a new tracheal sound feature for separation of apnoea events from non-apnoea time. Ten overnight recordings from apnoea patients containing 1,107 visually scored apnoea events totalling 7 h in duration and 72 h of non-apnoea time were included in the study. The feature was designed to describe the local spectral content of the sound signal. The median, maximum and mean smoothing of different time scales were compared in the feature extraction. The feature was designed to range from 0 to 1 irrespective of tracheal sound amplitudes. This constant range could offer application of the feature without patient-specific adjustments. The overall separation of feature values during apnoea events from non-apnoea time across all patients was good, reaching 80.8%. Due to the individual differences in tracheal sound signal amplitudes, developing amplitude-independent means for screening apnoea events is beneficial.

Intelligent methods for identifying respiratory cycle phases from tracheal sound signal during sleep.

We present two methods for identifying respiratory cycle phases from tracheal sound signal during sleep. The methods utilize the Hilbert transform in envelope extraction. They determine automatically a patient-specific amplitude threshold to be used in the detection. The core of one method is designed to be amplitude-independent whereas the other method uses solely the amplitude information. The methods provided average sensitivities of 98% and 99%, respectively, and positive prediction values of 100% on the total of 1434 respiratory cycles analysed from six different patients. The developed methods seem promising as such or as tools for analysing sleep disordered breathing.