Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes

RATIONALE: Although continuous positive airway pressure (CPAP) is most often effective in patients with obstructive sleep apnea, optimal treatment of patients with predominantly mixed apneas, central sleep apnea syndrome/Cheyne-Stokes respiration (CSA/CSR), or complex sleep apnea (CompSAS) is less straightforward, and may require alternative ventilatory assist modalities. OBJECTIVES: To compare the efficacy of noninvasive positive pressure ventilation (NPPV) with adaptive servoventilation (ASV) in treating patients with centrally mediated breathing abnormalities. We hypothesized that NPPV and ASV would be equivalently efficacious in improving the apnea/hypopnea index (AHI) and respiratory arousal index (RAI). METHODS: Prospective randomized crossover clinical trial comparing NPPV with ASV in patients with CSA/CSR, predominantly mixed apneas, and CompSAS in an acute setting. MEASUREMENTS AND MAIN RESULTS: 21 patients (6 with CSA/CSR, 6 with predominantly mixed apneas, and 9 with CompSAS) with initial diagnostic AHI +/- standard deviation 51.9 +/- 22.8/hr and RAI 45.5 < or = 26.5/hr completed the study. Following optimal titration with CPAP (N = 15), disturbed breathing and disturbed sleep remained high with mean AHI = 34.3 +/- 25.7 and RAI = 32.1 +/- 29.7. AHI and RAI were markedly reduced with both NPPV (6.2 +/- 7.6 and 6.4 +/- 8.2) and ASV (0.8 +/- 2.4 and 2.4 +/- 4.5). Treatment AHI and RAI were both significantly lower using ASV (P < 0.01). CONCLUSION: These data confirm that in patients with CSA/CSR, mixed apneas, and CompSAS, both NPPV and ASV are effective in normalizing breathing and sleep parameters, and that ASV does so more effectively than NPPV in these types of patients.     

Sleep apnea and body position during sleep

In patients with obstructive sleep apnea, it is believed that body position influences apnea frequency. Sleeping in the lateral decubitus position often results in significantly fewer apneas, and some have recommended sleeping on the side as the major treatment intervention. Previous studies, although calculating apnea-hypopnea index (AHI) for supine and lateral decubitus positions, have not taken sleep stage into account. To examine the effect of both sleep stage and body position on apnea duration (AD) and frequency, we determined AHI and AD in all spontaneous body positions during rapid eye movement (REM) and non-REM (NREM) sleep by reviewing videotapes and polysomnograms from 11 overnight studies of 7 obese patients with severe sleep apnea. Consistent with previous work, AD was significantly longer in REM then in NREM (32.5 +/- 2.3 s versus 23.5 +/- 1.9 s; p less than 0.05). This difference persisted when adjusting for body position. AHI was greater on the back than on the sides (84.4 +/- 4.9/h versus 73.6 +/- 7.5/h, p less than 0.05), but after accounting for sleep stage, this difference remained only for NREM (103 +/- 4.8/h versus 80.3 +/- 9.2/h, p less than 0.05) and not for REM (83.6 +/- 5.3/h versus 71.1 +/- 4.2/h, p NS). Although reduced, AHI on the sides still remained clinically very high. Body position changed frequently throughout the night, but some patients spent little or no time on their back. We conclude that AD is longer in REM than NREM, regardless of position, and AHI is higher on the back only in NREM. As AHI remains very high on the sides, favoring the lateral decubitus position may not be as beneficial as previously thought in very obese patients. Less obese patients are more likely to benefit by position changes.     

Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure

OBJECTIVE: The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. INTERVENTIONS: Oxygen. MEASUREMENTS AND RESULTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). CONCLUSION: In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.     

Correlation between the severity of obstructive sleep apnea and heart rate variability indices

The risk of cardiovascular disease is known to be increased in obstructive sleep apnea syndrome (OSAS). Its mechanism can be explained by the observation that the sympathetic tone increases due to repetitive apneas accompanied by hypoxias and arousals during sleep. Heart rate variability (HRV) representing cardiac autonomic function is mediated by respiratory sinus arrhythmia, baroreflex-related fluctuation, and thermoregulation-related fluctuation. We evaluated the heart rate variability of OSAS patients during night to assess their relationship with the severity of the symptoms. We studied overnight polysomnographies of 59 male untreated OSAS patients with moderate to severe symptoms (mean age 45.4+/- 11.7 yr, apnea-hypopnea index [AHI]=43.2+/-23.4 events per hour, and AHI >15). Moderate (mean age 47.1+/-9.4 yr, AHI=15-30, n=22) and severe (mean age 44.5 +/-12.9 yr, AHI >30, n=37) OSAS patients were compared for the indices derived from time and frequency domain analysis of HRV, AHI, oxygen desaturation event index (ODI), arousal index (ArI), and sleep parameters. As a result, the severe OSAS group showed higher mean powers of total frequency (TF) (p=0.012), very low frequency (VLF) (p= 0.038), and low frequency (LF) (p=0.002) than the moderate OSAS group. The LF/HF ratio (p=0.005) was higher in the severe group compared to that of the moderate group. On the time domain analysis, the HRV triangular index (p=0.026) of severe OSAS group was significantly higher. AHI was correlated best with the LF/HF ratio (r(p))=0.610, p<0.001) of all the HRV indices. According to the results, the frequency domain indices tended to reveal the difference between the groups better than time domain indices. Especially the LF/HF ratio was thought to be the most useful parameter to estimate the degree of AHI in OSAS patients.     

Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial

STUDY OBJECTIVE: To investigate the short-term effect (4 weeks) of oral appliance therapy for obstructive sleep apnea on blood pressure. DESIGN: Randomized, controlled, crossover trial. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Sixty-one patients diagnosed with obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per hour and at least 2 of the following symptoms--daytime sleepiness, snoring, witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular protrusion of 3 mm). INTERVENTION: A mandibular advancement splint (MAS) and control oral appliance for 4 weeks each. MEASUREMENTS AND RESULTS: Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out at baseline and following each 4-week intervention period. Patients showed a 50% reduction in mean apnea hypopnea index with MAS compared with the control and a significant improvement in both minimum oxygen saturation and arousal index. There was a significant reduction with the MAS in mean (+/- SEM) 24-hour diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001) but not in 24-hour systolic blood pressure. Awake blood-pressure variables were reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood pressure (P < .0001). There was no significant difference in blood pressure measured asleep. CONCLUSION: Oral appliance therapy for obstructive sleep apnea over 4 weeks results in a reduction in blood pressure, similar to that reported with continuous positive airway pressure therapy.     

Nocturnal overdrive pacing for the treatment of sleep apnea syndrome

STUDY OBJECTIVES: We investigated the effect of 1 week of nocturnal overdrive pacing (NOP) on the apnea-hypopnea index (AHI) in patients with a chronically implanted pacemaker and diagnosed during a screening phase with sleep apnea. DESIGN: Randomized, single-blind, crossover study. SETTING: University medical centers in Zürich, Switzerland, and Berlin, Germany. PATIENTS: Nineteen patients with mild to severe sleep apnea/hypopnea (16 men, mean age = 68.8 +/- 11.4 years) participated. The individuals did not suffer from permanent atrial arrhythmia, did not use continuous positive airway pressure, and had been implanted with atrial or dual-chamber pacemakers. INTERVENTIONS: Nocturnal lower rates were 45 and 75 beats per minute (bpm) at night for the control and NOP arms, respectively, and daytime lower rates were 60 bpm. Subjects were in each arm for 1 week. MEASUREMENTS AND RESULTS: Heart-rate increase from control (61 +/- 9 bpm) to NOP (78 +/- 4 bpm) followed by significant reduction in circulation time (24.6 seconds control, 20.7 seconds NOP; p = .04) resulted in no significant change in AHI (26.8 +/- 17.1/h control, 23.0 +/- 16.7/h NOP; p = .49). Seven subjects characterized by a higher hypopnea index, less stage 1 and 2 sleep, and less slow-wave sleep improved at least 1 AHI severity level with NOP, mainly attributable to reduction of hypopneas. CONCLUSION: NOP over a period of 1 week followed by a reduction in circulation time did not improve AHI in patients with SA. Whether an improvement by 1 AHI severity level in a specific subset of patients reflects a true response remains to be elucidated by further studies.     

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/? periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), ? obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, ? obstructive sleep apnea/? periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.     

Sleep apnea in acute cerebrovascular diseases: final report on 128 patients

Although obstructive sleep apnea (OSA) appears to be a cardiovascular risk factor, its frequency in patients with transient ischemic attack (TIA) and stroke remains poorly known. We prospectively studied 128 patients (mean +/- SD age = 59 +/- 15 years) with stroke (n = 75) or TIA (n = 53). Assessment included body mass index (BMI); history of snoring and daytime sleepiness; cardiovascular risk factors and diseases; and severity of stroke (Scandinavian Stroke Scale = SSS). Polysomnography (PSG) was obtained in 80 subjects (group 1), a mean of 9 days (range, 1-71 days) after TIA or stroke. In 48 subjects (group 2), PSG was not available, refused, or inadequate. Groups 1 and 2 were similar with the exception of gender distribution. Clinical and PSG data were compared to those of 25 healthy controls matched for age, gender, and BMI. An apnea-hypopnea index (AHI) > 10 was found in 62.5% of subjects and 12.5% of controls. Between patients and controls there was a significant difference in AHI (mean [range]: 28 (0-140) vs 5 (0-24), p < 0.001), maximal apnea duration (mean + SD: 37 +/- 23 vs 23 +/- 13 seconds, p = 0.009), and minimal oxygen saturation (mean + SD: 82 +/- 10% vs 90 +/- 5%, p < 0.001). Conversely, frequency and severity of OSA were similar in stroke and TIA subjects. Multiple regression analysis identified age, BMI, diabetes, and SSS as independent predictors of AHI. Sleep apnea has a high frequency in patients with TIA and stroke, particularly in older patients with high BMI, diabetes, and severe stroke. These results may have implications for prevention, acute treatment, and rehabilitation of patients with acute cerebrovascular diseases.     

Sleep apnea, proteinuria, and nephrotic syndrome

Renal abnormalities in patients with obstructive sleep apnea syndrome (OSAS) have not been previously described. Medical records of patients who had been evaluated for possible sleep apnea syndrome and had had complete polysomnograms and urinalyses were reviewed to determine the frequency of proteinuria. High-grade proteinuria (greater than or equal to 3+ on urinalysis) was found in 6 of the 34 patients with obstructive sleep apnea, but in none of 34 patients in a control group matched for sex, age, and weight. In three patients, proteinuria was in the nephrotic range (3.5 g/24 h). The weight (mean +/- SD) of the patients with obstructive sleep apnea (112.7 +/- 35.3 kg) was not significantly different from the control group (109.2 +/- 30.3 kg). Microscopic examination of renal tissue in one patient with OSAS showed minimal changes. In four patients who were followed for 3 years, proteinuria improved after therapy for sleep apnea syndrome. We suggest that proteinuria may not be uncommon in patients with severe obstructive sleep apnea syndrome and may be reversible with correction of the sleep apnea syndrome.     

Maintenance of wakefulness test as a predictor of driving performance in patients with untreated obstructive sleep apnea

STUDY OBJECTIVE: To determine the ability of Maintenance of Wakefulness Test (MWT) to predict simulated driving performance in patients suffering from sleep apnea syndrome. DESIGN: Study involving one hour of simulated driving, one night of polysomnography (PSG), and a 4 x 40-minute MWT. SETTING: Sleep laboratory. PATIENTS: Thirty male patients with untreated obstructive sleep apnea syndrome (OSAS) (mean age [+/- SD] = 51 +/- 8 years, range 34-62; mean body mass index (BMI) [+/- SD] = 29 +/- 3, range 24-37; mean apnea/hypopnea index (AHI) [+/- SD] = 43 +/- 24, range 14-96). As defined by MWT mean sleep latency, 23.3% of the patients were sleepy (0-19 min), 33.3% were alert (20-33 min), and 43.4% were fully alert (34-40 min). MEASUREMENTS: Nocturnal PSG, mean sleep latency at 4 x 40-minute MWT trials, Epworth Sleepiness Scale (ESS), and standard deviation from the center of the road (SDS) on driving simulator. RESULTS: Mean MWT scores inversely correlated with SDS during the simulated driving session (Pearson's r = -0.513, P < 0.01). We found a significant effect of MWT groups (sleepy, alert, or fully alert) on SDS (ANOVA, F(2, 29) = 5.861, P < 0.01). Post hoc tests revealed that the sleepy group had a higher SDS than the fully alert group (P = 0.006). ESS, AHI, microarousal index, and total sleep time did not predict simulated driving performance. CONCLUSIONS: A pathological MWT mean sleep latency (0-19 min) is associated with simulated driving impairment. Before MWT can be used to predict the driving ability of untreated patients with OSAS, further studies are needed to confirm that pathological MWT scores are associated with real driving impairment.     

A novel adaptive wrist actigraphy algorithm for sleep-wake assessment in sleep apnea patients

STUDY OBJECTIVES: Current actigraphic algorithms are relatively less accurate in detecting sleep and wake in sleep apnea patients than in people without sleep apnea. In the current study, we attempted to validate a novel automatic algorithm, which was developed for actigraphic studies in normal subjects and patients with obstructive sleep apnea by comparing it on an epoch-by-epoch basis to standard polysomnography. DESIGN: Prospective cohort study. SETTING: Multicenter, university hospital, sleep laboratories. PARTICIPANTS: A total of 228 subjects from 3 different sleep centers (Skara, Boston, Haifa) participated. INTERVENTION AND MEASUREMENTS: Simultaneous recording of polysomnography and Watch_PAT100, an ambulatory device that contains a built-in actigraph. The automatic sleep/wake algorithm is based on both the quantification of motion (magnitude and duration) and the various periodic movement patterns, such as those occurring in patients with moderate to severe obstructive sleep apnea. RESULTS: The overall sensitivity and specificity to identify sleep was 89% and 69%, respectively. The agreement ranged from 86% in the normal subjects to 86%, 84%, and 80% in the patients with mild, moderate, and severe obstructive sleep apnea, respectively. There was a tight agreement between actigraphy and polysomnography in determining sleep efficiency (78.4 +/- 9.9 vs 78.8 +/- 13.4%), total sleep time (690 +/- 152 vs 690 +/- 154 epochs), and sleep latency (56.8 +/- 31.4 vs 43.3 +/- 45.4 epochs). While for most individuals the difference between the polysomnography and actigraphy was relatively small, for some there was a substantial disagreement. CONCLUSIONS: We conclude that this actigraphy algorithm provides a reasonably accurate estimation of sleep and wakefulness in normal subjects and patients with obstructive sleep apnea on an epoch-by-epoch basis. This simple method for assessment of total sleep time may provide a useful tool for the accurate quantification of obstructive sleep apnea in the home environment.     

Oxidative stress and quality of life in elderly patients with obstructive sleep apnea syndrome: are there differences after six months of Continuous Positive Airway Pressure treatment?

OBJECTIVES:

This study evaluated the effect of Continuous Positive Airway Pressure treatment on oxidative stress parameters and the quality of life of elderly patients with obstructive sleep apnea syndrome.

METHODS:

In total, 30 obstructive sleep apnea syndrome patients and 27 subjects without obstructive sleep apnea syndrome were included in this study. Both groups underwent quality of life and oxidative stress evaluations at baseline and after six months. Polysomnography was performed in both groups at baseline and a second time in the obstructive sleep apnea syndrome group after six months of Continuous Positive Airway Pressure treatment. All of the variables were compared between the control and obstructive sleep apnea syndrome groups in this prospective case-control study.

RESULTS:

The baseline concentrations of the antioxidant enzyme catalase were higher in the obstructive sleep apnea syndrome group than the control group. After Continuous Positive Airway Pressure treatment, the obstructive sleep apnea syndrome group exhibited a reduction in the level of oxidative stress, as indicated by a decrease in the level of lipid peroxidation measured by the malondialdehyde (MDA) concentration [pre: 2.7 nmol malondialdehyde/mL (95% 1.6-3.7) vs. post: 1.3 nmol MDA/mL (0.7-1.9), p<0.01]. Additionally, improvements were observed in two domains covered by the SF-36 questionnaire: functional capacity [pre: 77.4 (69.2-85.5) vs. post: 83.4 (76.9-89.9), p = 0.002] and pain [pre: 65.4 (52.8-78.1) vs. post: 77.8 (67.2-88.3), p = 0.004].

CONCLUSION:

Our study demonstrated that the use of Continuous Positive Airway Pressure to treat obstructive sleep apnea syndrome in elderly patients reduced oxidative stress and improved the quality of life.     

Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea

STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study. SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy for at least 6 months. INTERVENTION: Three sleep studies were performed over three consecutive weeks. On night one the pressure level required to prevent apnea, hypopnea, and snoring was determined. On the second and third study nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and subjects slept on the CPAP level determined on the first night. MEASUREMENTS: Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS: The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P < 0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights. The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour), oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29 desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%). CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea.     

Oropharyngeal collapse predicts treatment response with oral appliance therapy in obstructive sleep apnea

STUDY OBJECTIVES: To examine whether primary oropharyngeal collapse of the upper airway during sleep predicts treatment success with oral appliance therapy in patients with obstructive sleep apnea. DESIGN: Prospective physiologic study. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Twelve treatment-na?ve adult patients with obstructive sleep apnea (apnea-hypopnea index > or = 10/h and at least 2 of the following symptoms: snoring, fragmented sleep, witnessed apneas, or daytime sleepiness). INTERVENTION: Custom-made mandibular advancement splint (MAS). MEASUREMENTS AND RESULTS: A baseline diagnostic polysomnogram confirmed AHI > or = 10 per hour. During the following acclimatization period, a custom-made adjustable MAS was incrementally advanced until maximum comfortable mandibular protrusion was reached. A second polysomnogram with MAS in situ determined efficacy. Following a 1-week washout period, a final sleep study was performed using multisensor catheters (with and without MAS, in random order during the same night) to determine upper-airway closing pressures and the site or sites of upper-airway collapse. MAS resulted in significant improvements, mean +/- SEM, in AHI (22.0 +/- 2.6 vs 9.2 +/- 1.9/h, p < .01) and upper-airway closing pressures during stage 2 non-rapid eye movement sleep (-1.1 +/- 0.3 vs -2.8 +/- 0.5 cm H2O, p < .01). All 4 patients with primary oropharyngeal collapse achieved an AHI < 5 per hour. Only 1 of the 8 patients with primary velopharyngeal collapse achieved an AHI < 5 per hour. Oropharyngeal collapse, compared with velopharyngeal collapse, predicted treatment success with MAS (p < .02). CONCLUSIONS: These preliminary data suggest that primary oropharyngeal collapse of the upper airway during sleep is an important predictor of treatment outcome with MAS therapy.     

Protriptyline in obstructive sleep apnea: a double-blind trial

We evaluated protriptyline, a nonsedating tricyclic antidepressant, as a treatment for obstructive sleep apnea in a double-blind crossover study of five men. After two weeks of treatment, with no change in body weight, daytime somnolence was markedly reduced and nocturnal oxygenation was improved, although apnea duration and frequency were not significantly decreased. Rapid-eye-movement (REM) stage time as a fraction of the total sleep time was reduced during treatment from 0.231 +/- 0.031 to 0.107 +/- 0.013 (mean +/- S.E.M.) (P less than 0.05). REM apnea time as a fraction of total sleep time was reduced from 0.145 +/- 0.022 to 0.054 +/- 0.006 (P less than 0.05). REM reduction during treatment with protriptyline can account for decreased REM apnea time. Similar decreases in REM stage time and REM apnea duration and similar improvement in oxygenation continued after six months of treatment. In addition, body weight, apnea, and arousal frequency were decreased at this time. Although the obstructive sleep apnea was not resolved, it was reduced. Protriptyline can be effective in patients with sleep apnea when the disorder is not life-threatening.     

Sleep apnea syndrome: a possible contributing factor to resistant

STUDY OBJECTIVES: There is evidence supporting an association between sleep apnea and hypertension. However, it is not clear if sleep apnea interteres with the pharmacotherapy of hypertension. To investigate this question, we studied the relationship between the effectiveness of anti-hypertensive treatment in reducing blood pressure, and severity of sleep apnea in a large group of apneic patients referred to a sleep disorders centre at St. Michael's Hospital at the University of Toronto. DESIGN: N/A SETTING: N/A PARTICIPANTS: 1,485 adult patients with sleep apnea, as defined by the apnea/hypopnea index (AHI) >10 events/hr, were analyzed. There were 393 who reported using anti-hypertensive medications on a regular basis for more than 6 months. One hundred and eighty-three patients were treated "effectively" (i.e. blood pressure lower than 140/90 mm Hg in the morning and in the evening). Seventy-four patients were treated "ineffectively," defined as blood pressure >140/90 mm Hg in the morning or in the evening. Both groups were compared with respect to clinical and demographic data using analysis of covariance with gender, age, body mass index (BMI), and neck circumference (NC) as covariates. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Ineffectively and effectively treated patients were similar in age (57 +/- 9) vs. 57 +/- 10 years, respectively), and had similar body mass index (33.8 +/- 7.4 vs. 33.4 +/- 7.3 kg/m2, respectively). However, ineffectively treated patients had significantly higher apnea/hypopnea index (44 +/- 29 vs. 33 +/- 25 events/hr, p<.0005), despite having similar nocturnal oxygenation (percent of total sleep time spent with oxygen desaturation lower than 90% was 36 +/- 34 vs. 29 +/- 30% in the ineffective and effective groups, respectively). The difference in AHI persisted even after adjusting for age, gender, and body mass index. CONCLUSIONS: Our results demonstrate that hypertensive patients with sleep apnea whose blood pressure responds beneficially to treatment have less severe sleep apnea than those patients whose blood pressure remains elevated despite anti-hypertensive therapy. Since neither obesity nor nocturnal hypoxemia appear to be important determinants of ineffective treatment, we suggest that resistant hypertension may be caused by frequent intermittent sympathetic stimulation.     

Obstructive sleep apnea in Costello syndrome

Costello syndrome (CS) was initially described by Costello in 1971; it is caused by a germline mutation in HRAS proto-oncogene. The aim of the present study was to evaluate the respiratory activity during sleep in a group of subjects with CS. We studied 10 consecutive patients, 4 males and 6 females, aged 3-29 years, affected by CS. All patients underwent clinical, neurological, otholaryngologic and radiologic evaluation, and a full-night polysomnography in the sleep laboratory. Polysomnography showed that seven patients presented a relevant number of respiratory events of obstructive type during sleep. The apnea-hypopnea index (AHI) ranged from 0 to 19.2 events per hour (mean index = 7.5 +/- 6.9 events/hr). In one patient AHI was not evaluable because of tracheostomy. Apnea induced mild or moderate hemoglobin desaturations (mean of lowest SpO2 values = 85.4 +/- 5.5%). Only sporadic respiratory pauses of central type were observed (mean number of central apnea per study: 7.2 +/- 6.8 events/hr). Sleep structure was fragmented, with a high number of awakenings (mean number of awakenings was 13.2 +/- 8.1; of these, 4.8 +/- 2.5 lasted longer than 2 min). In all patients, otolaryngologic and radiologic observations revealed one or more sites of narrowing in the upper airways. Our results suggest that Costello patients have a high prevalence of obstructive sleep-related respiratory disorders, which need to be assessed by means of polysomnography.     

Arterial stiffness increases during obstructive sleep apneas

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) appears to be an independent risk factor for diurnal systemic hypertension, but the specific biologic markers for this association have not been well established. Increased arterial stiffness is an important measure of increased left ventricular load and a predictor of cardiovascular morbidity and may precede the onset of systemic hypertension in humans. However, arterial stiffness has not been measured in association with obstructive apneas in patients with OSA, nor related to systemic blood pressure (BP) activity in this setting. Our objective was to test the hypothesis that arterial stiffness may be utilized as a sensitive measure of arterial vasomotor perturbation during obstructive events in patients with OSA, by demonstrating that (1) arterial stiffness increases acutely in association with obstructive apnea and hypopnea, and that (2) such increased stiffness may occur in the absence of acute BP increase. DESIGN: Prospective, cross-sectional. SETTING: A tertiary-care university-based sleep and ventilatory disorders center. PATIENTS: Forty-four normo- and hypertensive adult patients (11 women, 33 men) with polysomnographically diagnosed moderate to severe OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Beat-to-beat BP was recorded from the radial artery by applanation tonometry during nocturnal polysomnography. Arterial augmentation index (AAI), a measure of arterial stiffness, was calculated as the ratio of augmented systolic BP (SBP) to pulse pressure and expressed as a percentage for the following conditions: awake, the first 10 ("early apnea") and last 10 ("late apnea") cardiac cycles of obstructive events, and the first 15 cardiac cycles following apnea termination ("post apnea"). Mean AAI (+/-SD) for the group was significantly increased during NREM sleep from early apnea to late apnea (12.02 +/- 2.70% vs 13.35 +/- 3.54%, p<0.05, ANOVA). During REM (analyzed in 20 patients), MI again significantly increased from early apnea to late apnea (11.75 +/- 2.81% vs 13.43 +/- 4.97%). Conversely, neither mean SBP nor mean arterial BP was significantly changed from early apnea to late apnea in NREM (SBP 130 +/- 14 mmHg vs 129 +/- 14 mmHg) or REM (SBP 128 +/- 22 mmHg vs 127 +/- 21 mmHg). CONCLUSIONS: Arterial stiffness increases acutely during obstructive apneas in both NREM and REM sleep, in the absence of measurable BP change. These data suggest that arterial stiffness may be a sensitive measure of acute arterial vasomotor perturbation in this setting and may have implications concerning cardiovascular sequelae in patients with OSA.     

Effect of expiratory positive airway pressure on sleep disordered breathing

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.     

Relationship between smoking and sleep apnea in clinic population

STUDY OBJECTIVE: To examine the relationship between smoking and sleep apnea. DESIGN: Cross-sectional case study SETTING: University hospital sleep clinic PATIENTS: We studied 3,509 patients. INTERVENTIONS: None MEASUREMENTS AND RESULTS: Smoking history (past, present, never-smoker, pack-years of smoking) and nocturnal polysomnography was obtained in all patients. Data analysis was performed as follows: Patients were divided into groups based on apnea seventy (to compare smoking), and on smoking seventy (to compare apnea hypopnea index - AHI). The relationship between smoking and apnea was examined using univariate, multivariate, and logistic regression analysis. We found that patients with AHI greater than 50 were heavier smokers than nonapneic controls (14+/-17 vs. 10+/-17 pack-years, respectively). Conversely, heavy smokers had higher AHI than non-smokers (26.3+/-28.3 vs. 19.7+/-23.9, respectively). There was no significant relationship between AHI and smoking in multiple regression analysis. Although logistic regression revealed that heavy smokers (>30 pack-yrs) had almost twice the risk of having AHI greater than 50 compared to nonsmokers, the odds ratio fell below one after adjusting for age, BMI, and gender. CONCLUSIONS: In our patient population, smoking is not an independent risk factor for sleep apnea after adjusting for other confounding variables.