Complex sleep apnea syndrome: is it a unique clinical syndrome?

STUDY OBJECTIVES: Some patients with apparent obstructive sleep apnea hypopnea syndrome (OSAHS) have elimination of obstructive events but emergence of problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this sleep-disordered breathing problem, which for the sake of study we call the "complex sleep apnea syndrome," are not well characterized. We sought to determine the prevalence of complex sleep apnea syndrome and hypothesized that the clinical characteristics of patients with complex sleep apnea syndrome would more nearly resemble those of patients with central sleep apnea syndrome (CSA) than with those of patients with OSAHS. DESIGN: Retrospective review SETTING: Sleep disorders center. PATIENTS OR PARTICIPANTS: Two hundred twenty-three adults consecutively referred over 1 month plus 20 consecutive patients diagnosed with CSA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Prevalence of complex sleep apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%, respectively. Patients with complex sleep apnea syndrome differed in gender from patients with OSAHS (81% vs 60% men, p < .05) but were otherwise similar in sleep and cardiovascular history. Patients with complex sleep apnea syndrome had fewer maintenance-insomnia complaints (32% vs 79%; p < .05) than patients with CSA but were otherwise not significantly different clinically. Diagnostic apnea-hypopnea index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/- 26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous positive airway pressure suppressed obstructive breathing, but residual apnea-hypopnea index, mostly from central apneas, remained high in patients with complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p < .001). CONCLUSIONS: Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS until one applies continuous positive airway pressure. They are left with very disrupted breathing and sleep on continuous positive airway pressure. Clinical risk factors don't predict the emergence of complex sleep apnea syndrome, and best treatment is not known.     

Herzinsuffizienz

Sleep-disordered breathing is highly prevalent in heart failure patients. This accounts for patients with heart failure due to reduced ejection fraction (HF-REF) or with preserved ejection fraction (HF-PEF). Independent of HF-REF or HF-PEF, prevalence of central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) increases with deterioration in cardiac function. While obstructive sleep apnea (OSA) represents a cardiovascular risk factor per se, CSA with CSR might reflect impairment in cardiac function. However, both entities seem to further impair cardiac function and patients’ prognosis. Continuous positive airway pressure (CPAP) therapy is recommended to treat OSA, while adaptive servoventilation (ASV) therapy seems to be the therapy of choice in heart failure patients with CSA. With these therapies, small studies show an improvement in symptoms quality of life, and cardiac performance. Thus, large randomized controlled trials investigating morbidity and mortality are underway, but first results will be expected not before end of 2015.     

Effect of Continuous Positive Airway Pressure on Sleep Structure in Heart Failure Patients with Central Sleep Apnea

Study Objectives:

At termination of obstructive apneas, arousal is a protective mechanism that facilitates restoration of upper airway patency and airflow. Treating obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) reduces arousal frequency indicating that such arousals are caused by OSA. In heart failure (HF) patients with central sleep apnea (CSA), however, arousals frequently occur several breaths after apnea termination, and there is uncertainty as to whether arousals from sleep are a consequence of CSA. If so, they should diminish in frequency when CSA is attenuated. We therefore sought to determine whether attenuation of CSA by CPAP reduces arousal frequency.

Design:

Randomized controlled clinical trial.

Patients and Setting:

We examined data from 205 HF patients with CSA (apnea-hypopnea index [AHI] ≥ 15, > 50% were central) randomized to CPAP or control who had polysomnograms performed at baseline and 3 months later.

Measurements and Results:

In the control group, there was no change in AHI or frequency of arousals. In the CPAP-treated group, the AHI decreased significantly (from [mean ± SD] 38.9 ± 15.0 to 17.6 ± 16.3, P < 0.001) but neither the frequency of arousals nor sleep structure changed significantly.

Conclusion:

These data suggest that attenuation of CSA by CPAP does not reduce arousal frequency in HF patients. We conclude that arousals were not mainly a consequence of CSA, and may not have been acting as a defense mechanism to terminate apneas in the same way they do in OSA.

Citation:

Ruttanaumpawan P; Logan AG; Floras JS; Bradley TD. Effect of Continuous Positive Airway Pressure on Sleep Structure in Heart Failure Patients with Central Sleep Apnea. SLEEP 2009;32(1):91-98.     

Night-to-night alterations in sleep apnea type in patients with heart failure

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.     

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.     

A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea

STUDY OBJECTIVES: To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces. DESIGN: A randomized single-blind crossover study. SETTING: Hospital-based sleep laboratory. PATIENTS OR PARTICIPANTS: 21 CPAP-na?ve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) Interventions: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05). CONCLUSIONS: This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated.     

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.     

The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing

STUDY OBJECTIVE: Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR. DESIGN: Interventional, cross-over clinical study. SETTING: Research sleep laboratory. PATIENTS: Ten CHF patients with SDB, predominantly obstructive sleep apnea. INTERVENTIONS: The HCVR was measured from the change in middle cerebral artery velocity, using pulsed Doppler ultrasound. HCVR was determined during the evening (before) and morning (after) 1 night of sleep on ASV and 1 night of spontaneous sleep (control). MEASUREMENTS AND RESULTS: Compared with the control situation, ASV decreased the apnea-hypopnea index (group mean +/- SEM, control: 48 +/- 12, ASV: 4 +/- 1 events per hour). HCVR was 23% lower in the morning, compared with the evening, on the control night (evening: 1.3 +/- 0.2, morning: 1.0 +/- 0.2 cm/sec per mm Hg, P < 0.05) and 27% lower following the ASV night (evening: 1.5 +/- 0.2, morning: 1.1 +/- 0.2 cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning reduction in HCVR was not significant, compared with the control night (0.02 cm/sec per mm Hg, 95% confidence interval: -0.28, 0.32 P = 0.89). CONCLUSIONS: In CHF patients with SDB, HCVR was reduced in the morning compared with the evening. However, removal of SDB for 1 night did not reverse the reduced HCVR. The relatively low morning HCVR could be linked with an increased risk of stroke.     

Adaptive servo-ventilation and deadspace: effects on central sleep apnoea

Central Sleep Apnoea (CSA) occurs commonly in heart failure. Adaptive servo-ventilation (ASV) and deadspace (DS) have been shown in research settings to reverse CSA. The likely mechanism for this is the increase of PaCO(2) above the apnoeic threshold. However the role of increasing FiCO(2) on arousability remains unclear. To compare the effects of ASV and DS on sleep and breathing, in particular effects on Arousal Index (ArI), ten male patients with heart failure and CSA were studied during three nights with polysomnography plus measurements of PetCO(2). The order of the interventions control (C), ASV and DS was randomized. ASV and DS caused similar reductions in apnoea-hypopnoea index [(C) 30.0 +/- 6.6, (ASV) 14.0 +/- 3.8, (DS) 15.9 +/- 4.7 e h(-1); both P < 0.05]. However, DS was associated with decreased total sleep time compared with C (P < 0.02) and increased spontaneous ArI compared to C and ASV (both P < 0.01). Only DS was associated with increased DeltaPetCO(2) from resting wakefulness to eupnic sleep [(C) 2.1 +/- 0.9, (ASV) 1.3 +/- 1.0, (DS) 5.6 +/- 0.5 mmHg; P = 0.01]. ASV and DS both stabilized ventilation however DS application also increased sleep fragmentation with negative impacts on sleep architecture. We speculate that this effect is likely to be mediated by increased PetCO(2) and respiratory effort associated with DS application.     

Portable monitoring and autotitration versus polysomnography for the diagnosis and treatment of sleep apnea

STUDY OBJECTIVES: To compare a clinical pathway using portable monitoring (PM) for diagnosis and unattended autotitrating positive airway pressure (APAP) for selecting an effective continuous positive airway pressure (CPAP) with another pathway using polysomnography (PSG) for diagnosis and treatment of obstructive sleep apnea (OSA). DESIGN: Randomized parallel group SETTING: Veterans Administration Medical Center PATIENTS: 106 patients with daytime sleepiness and a high likelihood of having OSA MEASUREMENTS AND RESULTS: The AHI in the PM-APAP group was 29.2 +/- 2.3/h and in the PSG group was 36.8 +/- 4.8/h (P= NS). Patients with an AHI > or = 5 were offered CPAP treatment. Those accepting treatment (PM-APAP 45, PSG 43) were begun on CPAP using identical devices at similar mean pressures (11.2 +/- 0.4 versus 10.9 +/- 0.5 cm H2O). At a clinic visit 6 weeks after starting CPAP, 40 patients in the PM-APAP group (78.4% of those with OSA and 88.8% started on CPAP) and 39 in the PSG arm (81.2% of those with OSA and 90.6% of those started on CPAP) were using CPAP treatment (P = NS). The mean nightly adherence (PM-APAP: 5.20 +/- 0.28 versus PSG: 5.25 +/- 0.38 h/night), decrease in Epworth Sleepiness Scale score (-6.50 +/- 0.71 versus -6.97 +/- 0.73), improvement in the global Functional Outcome of Sleep Questionnaire score (3.10 +/- 0.05 versus 3.31 +/- 0.52), and CPAP satisfaction did not differ between the groups. CONCLUSIONS: A clinical pathway utilizing PM and APAP titration resulted in CPAP adherence and clinical outcomes similar to one using PSG.     

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.     

Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment

Periodic limb movements during sleep (PLMS) and obstructive sleep apnea syndrome (OSAS) are two common sleep disorders. The similarity in periodicity of periodic limb movements (PLMs) and obstructive sleep apneas (OSAs) led us to hypothesize the existence of a common central generator responsible for the periodicity of both OSAs and PLMs. In order to test this hypothesis, we compared apnea periodicity before continuous positive airway pressure (CPAP) treatment with PLMs periodicity during CPAP treatment in 26 OSA patients, consecutively recorded and treated in our sleep laboratory. The investigation on CPAP was performed twice, once during the initial evaluation and once during a follow-up evaluation after 3 months of home treatment with CPAP. Our results showed that, in this sample, 16 patients out of 26 had an association of OSAS and PLMS, defined as the occurrence of at least 5 PLMs per hour of sleep. The mean apnea interval - measured as the time between the beginning of two successive apneas - was 43.1 s (+/-15.2, SD) and the mean PLM interval - calculated in the same way - was 29.6 s (+/-15.2) during the baseline night, 28.5 s (+/-15.7) during the first CPAP night, and 29.8 s (+/-14.8) during the second CPAP night. Thus, the periodicity of the two phenomena (apneas and PLMs) was different, both before and after CPAP treatment (P< 0.05). When considering the interval between the end of an event (apnea or PLM) and the beginning of the next one the mean apnea interval was 19.5 s (+/-11. 6), and the mean PLM interval was 28.1 s (+/-15.3) during the untreated night, 26.6 s (+/-16) during the first CPAP night and 27.9 s (+/-15) during the second CPAP night. The shortening of apnea intervals with this method of measuring intervals reflects the longer duration of apneas as compared to PLMs. Again the intervals between PLMs were not different between each other but the intervals between apneas were different from the intervals between PLMs (P< 0. 05) These results show that the periodicity of PLMs is different from that of OSAs, suggesting that sleep apneas and PLMs are not generated by a common central generator.     

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.     

Sleep apnea in heart failure increases heart rate variability and sympathetic dominance

AIMS: Sleep disordered breathing (SDB) is common in heart failure and ventilation is known to influence heart rate. Our aims were to assess the influence of SDB on heart rate variability (HRV) and to determine whether central sleep apnea (CSA) and obstructive sleep apnea (OSA) produced different patterns of HRV. METHODS AND RESULTS: Overnight polysomnography was performed in 21 patients with heart failure and SDB. Two 10-minute segments each of SDB and stable breathing from each patient were visually identified and ECG signal exported for HRV analysis. SDB increased total power (TP) with very low frequency (VLF) power accounting for the greatest increase (1.89+/-0.54 vs 2.96+/-0.46 ms2, P <0.001); LF/HF ratio increased during SDB (1.2+/-1.0 vs 2.7+/-2.1, P <0.001). Compared to OSA, CSA was associated with lower absolute LF (2.10+/-0.47 vs 2.52+/-0.55 ms2, P = 0.049) and HF power (1.69+/-0.41 vs 2.34+/-0.58 ms2, P = 0.004), increased VLF% (78.9%+/-13.4% vs 60.9%+/-19.2%, P = 0.008), decreased HF% (6.9%+/-7.8% vs 16.0%+/-11.7%, P = 0.046) with a trend to higher LF/HF ratio. CONCLUSIONS: SDB increases HRV in the setting of increased sympathetic dominance. HRV in CSA and OSA have unique HRV patterns which are likely to reflect the different pathophysiological mechanisms involved.     

Sleep-disordered breathing and cardiovascular risk

Sleep-disordered breathing, broadly characterized by obstructive sleep apnea (OSA) and central sleep apnea (CSA), is an increasingly recognized public health burden. OSA, consisting of apneas or hypopneas associated with respiratory efforts in the face of upper airway narrowing or collapse, is a common disorder that can be effectively treated with continuous positive airway pressure (CPAP). OSA not only results in daytime sleepiness and impaired executive function, but also has been implicated as a possible cause of systemic disease, particularly of the cardiovascular system. CSA, which may coexist with OSA, has gained attention because of the association of Cheyne-Stokes respiration with an ever-increasing prevalence of heart failure in an aging population. This article reviews some of the extensive literature on pathophysiologic mechanisms as they may relate to the development of cardiac and vascular disease and examine the evidence suggesting OSA as a specific cause of certain cardiovascular conditions. Available evidence regarding the implications of CSA in the context of heart failure is discussed.     

The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses

The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) .     

Schlafbezogene Atmungsstörungen und zerebrovaskuläre Erkrankungen

Sleep-related breathing disorders comprise obstructive sleep apnea (OSA), central sleep apnea (CSA), Cheyne–Stokes respiration (CSR), and central alveolar hypoventilation. OSA is significantly associated with known cardiovascular risk factors, e.g., arterial hypertension, atrial fibrillation, and carotid atheromatosis. In addition, OSA has been shown to independently increase stroke risk. Thus, OSA is a direct and indirect risk factor of ischemic stroke, and early diagnosis and treatment of OSA may be crucial for stroke prevention. Acute ischemic stroke may cause any type of sleep-related breathing disorder in an affected patient. Nocturnal breathing abnormalities may be present transiently or persist for a longer period of time, affecting both neurological outcome and the risk of recurrent stroke. Sleep-disordered breathing is highly prevalent in patients with large supratentorial or bihemispheric infarctions, brainstem and cerebellar infarctions. It is associated with worse prognosis, increased disability, and higher mortality. Recently, several interventional studies showed that early implementation of continuous positive airway pressure (CPAP) treatment overnight is feasible and significantly improves neurological outcome in patients with ischemic stroke even if overall mortality may not be significantly reduced.     

Prevalence of persistent sleep apnea in patients treated with continuous positive airway pressure

STUDY OBJECTIVE: There are limited data on the prevalence of persistent obstructive sleep apnea (OSA) in patients who are clinically asymptomatic with continuous positive airway pressure (CPAP). Our objectives were to estimate the prevalence of persistent OSA and to explore the parameters that may be capable of discriminating these patients. DESIGN: Prospective survey. SETTING: A tertiary-care sleep-disorders clinic. PARTICIPANTS: Consecutive patients treated with single-pressure CPAP for at least 3 months were studied. All had undergone CPAP titrations and were compliant with treatment. They denied snoring or persistent excessive daytime somnolence. Of 114 who qualified, 101 were studied. INTERVENTIONS: Subjects underwent 16-channel polysomnography with electroencephalogram and pneumotachometer while using their CPAP. MEASUREMENTS AND RESULTS: Seventeen of 101 subjects (17%) had an apnea-hypopnea index of over 10. Fifty-one had only split-night protocols for CPAP titration. There was no significant difference between participants with persistent OSA and those with an apnea-hypopnea index < 5 with regard to age, sex, time since diagnosis, reported snoring, change in weight, or quality of life (all p > .10). Mean current CPAP level was higher, with a mean +/- SD 10.6 +/- 2.8 versus 8.6 +/- 2.3 cm H2O (p = .002). Unresolved air leak related to CPAP was more frequent in the patients with persistent OSA. Morning headaches, nonrestorative sleep, and frequent central apneas on the CPAP titration were all associated with persistent OSA. CONCLUSIONS: Persistent OSA is frequent in patients treated with CPAP. This is more frequent in patients with high body mass index, higher prescribed pressures, and unresolved mask leak.     

Obstructive sleep apnea can be provocative for right-to-left shunting through a patent foramen ovale

STUDY OBJECTIVES: Under particular conditions, a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxical embolization, due to right-to-left shunt. Our study aimed to evaluate the presence of right-to-left shunt in patients with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO during sleep. DESIGN AND SETTING: Assessment of provocative-only PFO and concomitant OSAS. Evaluation of right-to-left shunting during sleep by means of transcranial doppler with contrast medium injected in the cubital vein. PARTICIPANTS: 10 consecutive patients affected by PFO detectable only under Valsalva maneuver during wakefulness and affected by OSAS (mean age 52.8 +/- 10.7 years). INTERVENTIONS: Patients underwent transcranial doppler with injection of agitated saline solution mixed with air during normal breathing and during periods of apnea/hypopnea in nocturnal sleep. MEASUREMENTS AND RESULTS: Right-to-left shunt was present in 9 patients out of 10 and appeared during obstructive apneas longer than 17 seconds. In 1 out of 10 patients, only hypopneas occurred and no right-to-left shunt could be shown. The number of microembolic signals detected during periods of nocturnal apnea was positively correlated with the number detected during Valsalva maneuver in wakefulness (p<0.0001). CONCLUSIONS: In the nocturnal sleep period, right-to-left shunt can occur during single obstructive apneas in patients with OSAS and concomitant presence of PFO. This can be a risk factor for cerebrovascular diseases. This risk could probably increase proportionally to the respiratory disturbance index of these patients.     

Complex sleep apnea and obesity hypoventilation syndrome. Opposite ends of the spectrum of obstructive sleep apnea?

In most cases, the application of continuous positive airway pressure (CPAP) during sleep in patients affected by obstructive sleep apnea (OSA) eliminates upper airway obstruction and makes breathing stable and regular. However, some OSA patients develop periodic breathing and central apneas during CPAP administration, a finding that has been labelled as “complex sleep apnea” (complex SA). Such breathing disorder may occur only acutely after CPAP treatment initiation or sometimes persist with chronic CPAP treatment. We hypothesize that complex SA may be the consequence of mechanisms analogous to those leading to obesity hypoventilation syndrome (OHS), but operating in an opposite direction.Periodic breathing is one of the factors predisposing to OSA and is an essential factor for the recurrence of central apneas in normo or hypocapnic patients. A high ventilatory responsiveness to chemical stimuli enhances breathing periodicity. In subjects with periodic central apneas chemoresponsiveness is high, while in subjects with OSA it spans throughout a wide range, and is correlated to diurnal blood gas levels. In fact, sleep respiratory disorders may be responsible for either an augmentation in ventilatory responses to chemical stimuli consequent to chronic exposure to intermittent hypoxia, or for a decrease in ventilatory responses when prolonged exposure to hypercapnia is experienced. Among OSA subjects, those with OHS show very depressed hypercapnic responses. After chronic OSA treatment, ventilatory responses to chemical stimuli may either decrease, in previously hyperresponsive subjects, or increase, in previously hyporesponsive subjects. Most patients with OHS decrease daytime PCO₂ levels and increase their ventilatory responses after chronic CPAP treatment.Complex SA could appear in those OSA subjects in whom chronic exposure to nocturnal respiratory disorders leads to the highest responsiveness to chemical stimuli, and could disappear after blunting of ventilatory responses following chronic CPAP treatment. Complex SA may be one extreme of evolutionary spectrum of OSA, the opposite end being represented by OHS.