Treatment Of Central Sleep Apnea Research Articles

Adaptive servoventilation for treatment of opioid-associated central sleep apnea.

Opioids have become part of contemporary treatment in the management of chronic pain. Although severe daytime ventilatory depression is uncommon, chronic use of opioids could be associated with severe central and obstructive sleep apnea. To determine the acute efficacy, and prolonged use of adaptive servoventilation (ASV) to treat central sleep apnea in patients on chronic opioids. Twenty patients on opioid therapy referred for evaluation of obstructive sleep apnea (OSA) were found to have central sleep apnea (CSA). The first 16 patients underwent continuous positive airway pressure (CPAP) titration, which showed persistent CSA. With the notion that CSA will be eliminated with continued use of CPAP, 4 weeks later, 9 of the 16 patients underwent a second CPAP titration which proved equally ineffective. Therefore, therapy with CPAP was abandoned. All patients underwent ASV titration. Diagnostic polysomnography showed an average apnea-hypopnea index (AHI) of 61/h and a central-apnea index (CAI) of 32/h. On CPAP 1, AHI was 34/h and CAI was 20/h. Respective indices on CPAP 2 were AHI 33/h and CAI 19/h. During titration with ASV, CAI was 0/h and the average HI was 11/h on final pressures. With a reduction in AHI, oxyhemoglobin saturation nadir increased from 83% to 90%, and arousal index decreased from 29/h of sleep to 12/h on final ASV pressures. Seventeen patients were followed for a minimum of 9 months and up to 6 years. The mean long-term adherence was 5.1 ± 2.5 hours. Chronic use of opioids could be associated with severe CSA which remains resistant to CPAP therapy. ASV device is effective in the treatment of CSA and over the long run, most patients remain compliant with the device. Randomized long-term studies are necessary to determine if treatment of sleep apnea with ASV improves quality of life and the known mortality associated with opioids.

A novel therapeutic approach for the treatment of central sleep apnea: The remedē® system.

Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē® System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA.

Opioid-Induced Central Sleep Apnea

Patients on chronic opioids have significant central sleep apnea (CSA) and complex sleep apnea. The mechanism of opioid-induced CSA most probably has to do with suppression of inspiration generated by the pre-Botzinger complex. The best approach for treatment of opioid-induced CSA is a programmed withdrawal of opioids. Another option is treatment with bilevel devices with backup rate, or the new adaptive servoventilation devices, which are effective in eliminating sleep-related breathing disorders. However, randomized clinical trials are needed to determine if treatment with positive airway pressure devices has any effect on quality of life or excess mortality.

Treatment of opioid-related central sleep apnea with positive airway pressure: A systematic review

To systematically review the various modalities of positive airway pressure (PAP) in the treatment of opioid-related central sleep apnea (CSA). Systematic review. MEDLINE, the Cochrane Library, and EMBASE were screened through March 2013 to identify articles which investigated treatment of opioid related CSA with PAP. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Five articles met the inclusion criteria for a total of 127 patients. All patients had been on opioids for at least 6 months. The dose ranged from 10 mg to 450 mg daily of morphine equivalent dose. Continuous positive airway pressure (CPAP) was proven mostly ineffective in reducing central apneic events. Bi-level positive airway pressure (BiPAP) with and without supplemental oxygen achieved elimination of central apneas in 62 percent of patients. Adaptive servo ventilation (ASV) yielded conflicting results with 58 percent of participants attaining a central apnea index <10 per hour. The presence of ataxic breathing predicted poor response to PAP. The available evidence on the efficacy of PAP in opioid-related CSA is inconclusive. With the increasing use of opioids, further studies are needed to assess optimal PAP therapy and predictors of success in this group of patients.

Alternative approaches to treatment of Central Sleep Apnea.

Divergent approaches to treatment of hypocapnic central sleep apnea syndromes reflect the difficulties in taming a hyperactive respiratory chemoreflex. As both sleep fragmentation and a narrow CO2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable non-rapid eye movement (NREM) sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO2-based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient dyssynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO2 manipulation directly stabilize respiratory control by moving CO2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent and Winx may be less likely to trigger central apneas or periodic breathing in those with a narrow CO2 reserve. An oral appliance can meaningfully reduce positive pressure requirements and thus enable treatment of complex apnea. Novel pharmacological approaches may target mediators of carotid body glomus cell excitation, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is not always successful, and multi-modality therapy might need to be considered. Phenotyping of sleep apnea beyond conventional scoring approaches is the key to optimal management.

TCT-134 Transvenous Phrenic Nerve Stimulation in the Treatment of Central Sleep Apnea in Patients with Reduced Ejection Fraction: A Report from the remede(r) System Pilot Study

Central sleep apnea (CSA), usually presenting as Hunter-Cheyne-Stokes Breathing, occurs in approximately 35% of patients with heart failure. Current treatment options for CSA have been limited and focus on mask based therapies and therefore are highly dependent on tolerability and adherence. A novel

Treatment of Central Sleep Apnea in US Veterans

There are no standard therapies for the management of central sleep apnea (CSA). Either positive pressure therapy (PAP) or supplemental oxygen (O(2)) may stabilize respiration in CSA by reducing ventilatory chemoresponsiveness. Additionally, increasing opioid use and the presence of comorbid conditions in US veterans necessitates investigations into alternative titration protocols to treat CSA. The goal was to report on the effectiveness of titration with PAP, used alone or in conjunction with O(2), for the management of CSA associated with varying comorbidities and opioid use. This was a retrospective chart review over 3 years, performed at a VA sleep disorders center. The effects of CPAP, CPAP+O(2), and BPAP+O(2), used in a step-wise titration protocol, on consecutive patients diagnosed with CSA were studied. CSA was diagnosed in 162 patients. The protocol was effective in eliminating CSA (CAI ≤ 5/h) in 84% of patients. CPAP was effective in 48%, while CPAP+O(2) combination was effective in an additional 25%, and BPAP+O(2) in 11%. The remaining 16% were non-responders. Forty-seven patients (29%) were on prescribed opioid therapy for chronic pain, in whom CPAP, CPAP+O(2), or BPAP+O(2) eliminated CSA in 54%, 28%, and 10% cases, respectively. CPAP, CPAP+O(2), and BPAP+O(2) each produced significant declines in the AHI, CAI, and arousal index, and an increase in the SpO(2). The data demonstrate that using a titration protocol with CPAP and then PAP with O(2) effectively eliminates CSA in individuals with underlying comorbid conditions and prescription opioid use. Comparative studies with other therapeutic modalities are required.

Adaptive servoventilation in patients with central or complex sleep apnea related to chronic opioid use and congestive heart failure.

Adaptive servoventilation (ASV) is often used to treat central sleep apnea (CSA) and complex sleep apnea syndrome (CompSAS). Both CompSAS and CSA may occur in the setting of CHF and with the use of chronic opioids. We hypothesized that ASV would be less successful in treatment of CSA and CompSAS secondary to opioid use than in CHF patients. Consecutive patients were studied between January and December 2009 who underwent ASV titration for CSA or CompSAS due to CHF (defined as EF < 45%, or > 50% with evidence for diastolic dysfunction on echocardiogram) and chronic opioid users (defined by the use of opioids > 6 months). Study included one hundred and eight patients with 77 males (71.3%) and 31 females (28.7%). Subjects had severe sleep apnea at baseline (AHI 45.6 ± 27.4) and inadequate control of sleep disordered breathing on CPAP (AHI 50.0 ± 32.2, CAI 36.6 ± 32). No significant differences were found between the groups in overall ASV success, defined as AHI < 10/h (p = 0.236). ASV was successful in 28 (59.6%) of those in the opioid group, compared to 43 (70.5%) of those in the CHF group. When ASV success was defined as AHI < 5/h at optimum EEP, there was again no significant difference between the groups (p-value = 0.812). Logistic regression showed unit increases in BMI, unit increases in HCO(3), and presence of CSR were each associated with decreased likelihood of ASV success. We did not find a statistically significant difference in the effectiveness of ASV between CHF patients and chronic opioid users, with the overall success rate approaching 70%, as defined by an AHI < 10/h. A commentary on this article appears in this issue on page 577.

Diagnosis and treatment of central sleep apnea

中枢性睡眠呼吸暂停(CSA)是由于呼吸中枢驱动消失所引起的呼吸停顿,在常规睡眠多导图上表现为口鼻气流停止和无胸腹运动,持续时间＞10 s.当呼吸气流幅度较基础水平降低≥30％持续10 s以上,同时伴有血氧饱和度下降≥4％或微觉醒时,则这一事件定义为低通气[1].低通气由呼吸中枢驱动下降所致者为中枢性,由上气道部分阻塞所致者为阻塞性.呼吸暂停和低通气事件常同时存在,二者对机体的损害及导致的病理生理变化相似,临床上常通称为呼吸暂停低通气,并把平均每小时发生的呼吸暂停和低通气次数称为呼吸暂停低通气指数(AHI).许多情况下,阻塞性睡眠呼吸暂停(OSA)低通气与CSA低通气事件同时存在,如果50％以上事件是中枢性的,则诊断为CSA低通气综合征。

Pearls &amp; Oy-sters: Treatment of central sleep apnea with topiramate

A 67-year-old man with a history of epilepsy, cardiac failure, alcohol dependence, and hypercholesterolemia underwent a polysomnogram (PSG) study because of snoring and observed apnea during sleep. Body mass index was recorded at 25.9 kg/m2. Medications included metoprolol, valsartan, simvastatin, phenytoin, valproate, and levetiracetam. Prior echocardiogram had shown an ejection fraction of 35%. PSG showed an overall Central Apnea Index (CAI) of 18, with 18 central apneas/hour, 7 hypopneas/hour, 0 mixed apneas/hour, and 0 obstructive apneas/hour (figure 1). Central apneas displayed a crescendo-decrescendo pattern, consistent with CSB. Because of recurrent seizures, topiramate was added to the medication regimen, with a titration schedule to 100 mg twice per day. After 5 months, a second PSG for titration with adaptive servo-ventilation was obtained. Baseline portion of the study (about 90 minutes) showed a significant decrease in number of central apneas, with an overall CAI of 0, with 0 central apneas/hour, 12 hypopneas/hour, 0 mixed apneas/hour, 0 obstructive apneas per hour of sleep, and …

Central sleep apnea treatment in heart failure: are we counting chickens before they are hatched?

Central sleep apnea treatment in heart failure: are we counting chickens before they are hatched?

A novel approach to the treatment of central sleep apnea in patients with heart failure

Central sleep apnea (CSA) is a common, though often unrecognized, finding in congestive heart failure (HF) patients that is associated with poor quality of life and increased morbidity and mortality. While various treatment strategies, including continuous positive airway pressure (CPAP) therapy, have been devised and tested to treat CSA in HF, none thus far have been proven effective over the long term or been shown to improve survival. Adaptive pressure support servo-ventilation (ASV) is a promising potential new therapy for CSA, but like its predecessor, CPAP, it is often not well tolerated by patients, and results from clinical trials evaluating its long-term effectiveness in reducing morbidity and mortality are still a number of years off. Recently, a new therapy utilizing unilateral transvenous phrenic nerve stimulation has been introduced to treat CSA in HF. As a totally implantable, device-based therapy, it may be better tolerated than CPAP or ASV in HF patients and, thus, improve patient compliance with treatment. Early studies using this therapy have been encouraging, with patients demonstrating significant improvement in major indices of CSA severity.

The Performance of Two Automatic Servo-Ventilation Devices in the Treatment of Central Sleep Apnea

This study was conducted to evaluate the therapeutic performance of a new auto Servo Ventilation device (Philips Respironics autoSV Advanced) for the treatment of complex central sleep apnea (CompSA). The features of autoSV Advanced include an automatic expiratory pressure (EPAP) adjustment, an advanced algorithm for distinguishing open versus obstructed airway apnea, a modified auto backup rate which is proportional to subject's baseline breathing rate, and a variable inspiratory support. Our primary aim was to compare the performance of the advanced servo-ventilator (BiPAP autoSV Advanced) with conventional servo-ventilator (BiPAP autoSV) in treating central sleep apnea (CSA). A prospective, multicenter, randomized, controlled trial. Five sleep laboratories in the United States. Thirty-seven participants were included. All subjects had full night polysomnography (PSG) followed by a second night continuous positive airway pressure (CPAP) titration. All had a central apnea index ≥ 5 per hour of sleep on CPAP. Subjects were randomly assigned to 2 full-night PSGs while treated with either the previously marketed autoSV, or the new autoSV Advanced device. The 2 randomized sleep studies were blindly scored centrally. Across the 4 nights (PSG, CPAP, autoSV, and autoSV Advanced), the mean ± 1 SD apnea hypopnea indices were 53 ± 23, 35 ± 20, 10 ± 10, and 6 ± 6, respectively; indices for CSA were 16 ± 19, 19 ± 18, 3 ± 4, and 0.6 ± 1. AutoSV Advanced was more effective than other modes in correcting sleep related breathing disorders. BiPAP autoSV Advanced was more effective than conventional BiPAP autoSV in the treatment of sleep disordered breathing in patients with CSA.

Effectiveness of Adaptive Servo Ventilation in the treatment of hypocapnic central sleep apnea of various etiologies

Central sleep apnea (CSA) occurs in clinical situations that induce hypocapnia and respiratory instability during sleep. This is true, not only in heart failure patients, but also in patients suffering from neurological diseases and idiopathic CSA. Adaptive Servo Ventilation (ASV) is frequently prescribed in France for the treatment of CSA, but only a few studies have evaluated ASV treatment with regards to long term effectiveness and compliance. Retrospective chart review in two French centers of the outcome of 74 CSA patients treated by ASV with a mean follow up on ASV of 36±18 months. Thirty-three of the 74 patients suffered from CSA related to heart failure (HF), whereas the 41 others exhibited CSA mainly associated with neurological disorders or idiopathic CSA. Mean ASV compliance was 5.2±2.6 and 5.9±2.9h per night in cardiac failure and non-cardiac failure patients, respectively. All patients significantly improved their apnea+hypopnea index (from 47.4±19.8 to 6.9±9.3/h [p<0.001]) and mean nocturnal SaO(2) (from 92.1±2.6% to 93.6±3.2% [p<0.001]). The Epworth sleepiness scale score was reduced from 10.2±5.2 to 6.5±3.9 (p<0.01) in compliant patients but not in non-compliant patients (less than 3h per night). Moreover, compliant cardiac failure patients demonstrated a significant improvement in their NYHA score [p<0.05]. Lastly, ASV significantly reduced chronic hyperventilation as assessed by blood gases. Our findings suggest that ASV is well tolerated and effective for most patients with hypocapnic central sleep apnea and chronic hyperventilation.

Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure

Periodic breathing with central sleep apnoea (CSA) is common in heart failure patients and is associated with poor quality of life and increased risk of morbidity and mortality. We conducted a prospective, non-randomized, acute study to determine the feasibility of using unilateral transvenous phrenic nerve stimulation for the treatment of CSA in heart failure patients. Thirty-one patients from six centres underwent attempted transvenous lead placement. Of these, 16 qualified to undergo two successive nights of polysomnography-one night with and one night without phrenic nerve stimulation. Comparisons were made between the two nights using the following indices: apnoea-hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%). Patients underwent phrenic nerve stimulation from either the right brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic vein (n = 8). Therapy period was (mean ± SD) 251 ± 71 min. Stimulation resulted in significant improvement in the AHI [median (inter-quartile range); 45 (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5) events/h, P≤ 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P = 0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead thrombus and episode of ventricular tachycardia), though neither was directly related to phrenic nerve stimulation therapy. Unilateral transvenous phrenic nerve stimulation significantly reduces episodes of CSA and restores a more natural breathing pattern in patients with heart failure. This approach may represent a novel therapy for CSA and warrants further study.

27. What is the likelihood of sleep disordered breathing in your heart failure patient?

Sleep disordered breathing (SDB) occurs in approximately 75% of patients with heart failure, and most often presents in the forms of central sleep apnea (CSA) or obstructive sleep apnea (OSA). While OSA is common in both the normal population and in heart failure, CSA occurs almost exclusively in the heart failure population. Both are easily diagnosed with a sleep study, but few patients with heart failure have undergone this testing. As the benefit of the treatment of CSA and OSA becomes better established, identification of patients at highest risk for SDB will help with screening the large number of heart failure patients.

Prevalence and treatment of central sleep apnoea emerging after initiation of continuous positive airway pressure in patients with obstructive sleep apnoea without evidence of heart failure

This study aimed to assess the prevalence of complex sleep apnoea (CompSA), defined as central sleep apnoea (CSA) emerging after the initiation of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA), in patients with normal brain natriuretic peptide (BNP) levels, along with assessing the prevalence of CSA persisting in such patients after the onset of CPAP therapy. We hypothesised that the prevalence of CompSA and persistent CSA after CPAP initiation would be low in patients with OSA and normal BNP levels. Between April 2004 and July 2007, CPAP was initiated for all patients with OSA for two nights using a standardised protocol. The prevalence of CompSA syndrome (CompSAS) and persisting CSA [central apnoea index (CAI) >5/h and apnoea-hypopnoea index (AHI) >15/h with >50% central events during CPAP therapy] was prospectively assessed in patients with normal BNP levels. Patients with CompSAS or persisting CSA upon CPAP treatment received adaptive servoventilation (ASV). Of 1,776 patients with OSA receiving CPAP, 28 patients (1.57%) had CSA at the time of CPAP therapy and normal BNP levels. Additionally, 10 patients had CompSAS (0.56%) and 18 patients (1.01%) had persisting CSA. In patients with CompSA or persisting CSA, the AHI was significantly lower with CPAP therapy than at the time of diagnosis (34 ± 15/h vs. 47 ± 20/h, p = 0.005). The CAI increased from 10 ± 10/h to 18/h ± 13/h (p = 0.009) upon initiation of CPAP therapy. ASV reduced the AHI to 6 ± 12/h (p < 0.001) during the first night of use. The prevalence of CompSA or persisting CSA in patients with OSA and normal BNP levels who are receiving CPAP therapy is low (1.57%). ASV is an effective treatment for these patients.

Sleep Apnea and Cardiovascular Disease

Cardiovascular disease is still the leading cause of death in North America. To improve outcomes, it will likely be necessary to identify new potentially treatable conditions. Sleep apnea affects approximately 50% of patients with cardiovascular disease and is associated with increased cardiovascular risk. Continuous positive airway pressure is currently the treatment of choice and has many short-term favorable effects. The long-term benefits, however, remain elusive. Further, it may not be the ideal treatment for central sleep apnea, and the benefits of alternatives such adaptive servo-ventilation are currently being tested. Randomized controlled trials are now needed to determine whether treating sleep apnea will improve survival and reduce cardiovascular disease risk. Until better evidence becomes available, testing for sleep apnea cannot be recommended as part of the routine cardiovascular disease risk assessment, nor can its treatment be recommended for the prevention or management of cardiovascular disease in asymptomatic patients.

Prevalence and management of central sleep apnea in heart failure patients

There is increasing awareness of sleep-disordered breathing, which may manifest as obstructive sleep apnea, central sleep apnea (CSA), or a mixture of the two. Obstructive sleep apnea and CSA are strongly associated with heart failure (HF) and risk factors for developing HF. CSA may be considered a manifestation of the pathophysiology of HF; hence, approaches to optimize pharmacologic and nonpharmacologic treatment of HF should help to ameliorate CSA. However, if CSA also contributes to HF progression, CSA may represent a potential therapeutic target. There was hope that CSA prevalence would decline with better HF therapies. However, contemporary studies of HF patients on optimal medical therapy have shown that CSA prevalence remains 30% to 40%. Treating CSA poses significant challenges. Presently, the role of routine continuous positive airway pressure remains unclear, although newer ventilatory strategies may prove effective. Currently, CSA treatment involves standard optimal HF therapies, although growing evidence indicates that newer ventilation modes and cardiac resynchronization therapy may prove to be useful.

Opioid-associated central sleep apnea: a case series

Subjects on methadone maintenance for drug addiction have been reported to have central sleep apnea (CSA). However, there are few reports of disordered breathing in patients receiving opioids for chronic pain. We report on six patients (ages 41-68, two females, body mass index 27-34, morphine equivalent doses 120-420 mg/day, Epworth Scales 7-21) referred to our sleep center receiving sustained release opioids for more than 6 months with excessive daytime sleepiness. CSA was defined as apnea-hypopnea index (AHI) more than 5 per hour with > or =50% central events. Bilevel (BLV) titration was done to determine settings and all patients were followed for at least 6 months on nocturnal BLV. AHI ranged 28.4-106 per hour. Time less than 90% O(2) saturation ranged 1.8 min to 6.4 h. Four of the patients were treated with chronic BLV ventilation with settings ranging 12-16 cm H(2)O (inspiratory positive airway pressure)/4-8 cm H(2)O (expiratory positive airway pressure) with backup rate of 12-16. Among the four patients who used BLV treatment for at least 6 months, Epworth scores improved (by 4, 12, 5, and 9, respectively). Treatment of opioid-associated CSA with BLV corrected nocturnal hypoxemia and reduced sleep fragmentation. Randomized controlled trials, with objective measures of daytime function, are recommended in opioid-induced CSA patients.