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Contemporary Reviews in Sleep Medicine |

Clinical Applications of Adaptive Servoventilation DevicesAdaptive Servoventilation: Part 2: Part 2 FREE TO VIEW

Shahrokh Javaheri, MD, FCCP; Lee K. Brown, MD, FCCP; Winfried J. Randerath, MD, FCCP
Author and Funding Information

From the College of Medicine (Dr Javaheri), University of Cincinnati, Cincinnati, OH; Department of Internal Medicine (Dr Brown), School of Medicine, The University of New Mexico, Albuquerque, NM; and Zentrum für Schlaf- und Beatmungsmedizin Aufderhöher (Dr Randerath), Institut für Pneumologie an der Universität Witten/Herdecke, Klinik für Pneumologie und Allergologie, Krankenhaus Bethanien, Solingen, Germany.

CORRESPONDENCE TO: Shahrokh Javaheri, MD, FCCP; e-mail: shahrokhjavaheri@icloud.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(3):858-868. doi:10.1378/chest.13-1778
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Adaptive servoventilation (ASV) is an automated treatment modality used to treat many types of sleep-disordered breathing. Although default settings are available, clinician-specified settings determined in the sleep laboratory are preferred. Depending on the device, setting choices may include a fixed expiratory positive airway pressure (EPAP) level or a range for autotitrating EPAP; minimum and maximum inspiratory positive airway pressure or pressure support values; and type of backup rate algorithm or a selectable fixed backup rate. ASV was initially proposed for treatment of central sleep apnea and Hunter-Cheyne-Stokes breathing associated with congestive heart failure (CHF), and numerous observational studies have demonstrated value in this setting. Other studies have reported varying efficacy in patients with complex sleep apnea syndromes, including those with mixtures of obstructive and central sleep-disordered breathing associated with CHF, renal failure, or OSA with central apneas developing on conventional positive airway pressure therapy. Patients with opioid-induced sleep apnea, both obstructive and central, may also respond to ASV. The variability in response to ASV in a given patient along with the myriad choices of specific models and settings demand a high degree of expertise from the clinician. Finally, randomized controlled studies are needed to determine long-term clinical efficacy of these devices.

Figures in this Article

In part 1 of this two-part series, we discussed the operation of three adaptive servoventilation (ASV) devices.1 In the present article, we discuss some of the clinical applications for this technology. Potential applications include hybrid sleep-related breathing disorders (SRBDs) associated with conventional positive airway pressure (PAP) treatment of OSA and complex or central SRBDs in patients with congestive heart failure (CHF); cerebrovascular, neuromuscular, and neurologic disorders; and sojourn at high altitude. In most cases, however, prospective randomized controlled studies are needed to determine whether ASV devices will enhance the clinical outcomes of these disorders. We have successfully used these devices in three types of SRBDs, including CHF with predominant central sleep apnea (CSA)/Hunter-Cheyne-Stokes breathing (HCSB), sleep apnea induced by long-term opioid medication use, and persistent complex sleep apnea (CompSA) in which OSA coexists with one or more of the following: treatment-emergent CSA, CSA due to high-altitude periodic breathing (PB), CSA due to a medical disorder without HCSB, CSA with HCSB, or primary CSA2-6 (for reviews7-10).

We emphasize the absence in most cases of randomized controlled trials with ASV devices and that in some of the aforementioned SRBDs, conventional PAP devices with or without an oxygen bleed (and in particular, bilevel devices with a backup rate) may be effective and could be used. However, differences exist between conventional PAP and ASV devices that could be anticipated to improve long-term outcome. In contrast to ASV technology, bilevel devices generally use fixed pressure support values and backup rates. Thus, minute ventilation (MV) cannot fall below a fixed value and, hence, could be excessive, augmenting hypocapnia and promoting rather than suppressing CSA. Furthermore, during crescendo episodes of HCSB, the patient may perceive excess ventilation as uncomfortable and thereby curtail adherence. In addition to the lack of variation in MV, bilevel devices with fixed inspiratory and expiratory pressures may increase intrathoracic pressure, and the effect on cardiac hemodynamics can be unpredictable,11,12 particularly in patients with CHF. Depending on the existing operating point on the Starling curve, the reduction in preload and afterload could decrease cardiac output rather than augment it. As discussed in part 1, we suspect that ASV devices with algorithms designed to achieve the minimum effective inspiratory pressure support (IPS), backup rate, and expiratory PAP (EPAP) should, in the long run, prove most effective in terms of patient comfort and preservation of hemodynamics1; these advantages may, therefore, improve adherence and outcome. The results of the long-term randomized controlled trials currently in progress are awaited to clarify these issues.

Patients with CHF frequently suffer from CompSA, predominantly CSA/HCSB and components of OSA. Moreover, the proportion of CSA/HCSB vs OSA contributing to the overall apnea-hypopnea index (AHI) may vary with body position, time during the night, and sleep state. In a large number of these patients, CSA is not suppressed with CPAP use, and we recommend ASV therapy. CPAP, however, is the treatment of choice in patients with heart failure and exclusively (or perhaps predominantly) OSA, although CSA13,14 may emerge with the use of this therapeutic modality as we observed in an early study.13 In a study comprising 192 patients,14 the prevalence of CompSA was estimated at 15%. The patients demonstrating CompSA were found to exhibit heightened CO2 chemosensitivity, which has been shown to predispose to PB by increasing loop gain.15,16 In as many as 53% of patients with CHF and heart failure with reduced ejection fraction (HFrEF), CSA is not suppressed during the first night of CPAP titration,13 and this finding usually persists, with prevalence declining only slightly to 43% at 3 months.17 At present, it is not possible to accurately predict whether a given patient will exhibit CSA/HCSB on CPAP. One study found that a low Paco2 may be a surrogate for high loop gain and CPAP nonresponsiveness, but this was not an invariable relationship.13 Further prospective studies phenotyping patients with heart failure are needed to determine whether high loop gain and low Paco2 reliably predict CPAP nonresponse and obviate the need for a trial of CPAP titration. At present, we recommend continued use of CPAP only in patients in whom CSA is suppressed during the initial titration.13,17 We recommend ASV titration when CSA/HCSB persists during the initial CPAP titration because we believe that continued use could be detrimental.7-11,17 To emphasize, even though a small proportion of patients with CHF will exhibit resolution of CSA/HCSB over time when central events are not initially suppressed by CPAP therapy, the high failure rate (43% at 3 months)17 and the inability to predict long-term success suggest that it is not beneficial to recommend CPAP therapy if the AHI does not fall to < 15/h on the first night of titration.

There are many short- and long-term observational studies of ASV devices used to treat sleep apnea in HFrEF5,6,18-49 and heart failure with preserved ejection fraction.50,51 The following discussion concentrates on the studies that make specific points of greatest importance to the clinician.

Teschler et al19 were the first to report using an ASV device (the MV-targeted ResMed-AutoSet CS) to treat CSA/HCSB in patients with CHF. The patients underwent 5 nights of polysomnography (PSG): a baseline night without treatment followed by 4 nights titrated with (in random order) oxygen, CPAP, bilevel PAP-spontaneous/timed (S/T), and ASV. The most effective modality was ASV, with the mean ± SD AHI falling from 46 ± 13/h (n = 14) at baseline to 6 ± 3/h and the arousal index falling from 67 ± 14/h to 17 ± 17/h. Importantly, ASV normalized the central apnea index (CAI) in almost all patients.

Pepperell et al18 performed the only randomized sham-controlled double-blind study of ASV in HFrEF with CSA/HCSB, but the investigation examined outcomes over a limited time period. The authors examined sleep quality, indices of CHF severity, and daytime performance in 30 patients with CHF (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF], 33%-36%) randomized to receive 1 month of either therapeutic or subtherapeutic ASV. In an intention-to-treat analysis, patients treated with an MV-targeted ASV device demonstrated a significant decrease in mean AHI from 25 to 5/h, improved Oxford sleep resistance (Osler) test results, and decreased plasma brain natriuretic peptide (BNP) and urinary metnorepinephine levels compared with those receiving sham ASV. However, LVEF and subjective daytime sleepiness did not change significantly. Adherence to ASV use was lower in the sham group, with four patients not using the device at home at all. The surprising disparity between objective and subjective measures of sleepiness may be explained by previous reports that patients with heart failure and sleep apnea frequently do not complain of subjective daytime sleepiness. In three early studies of SRBD52-54 in patients with heart failure, the prevalence of subjective sleepiness was similar between those with and those without sleep apnea, despite some patients having severe SRBD. This lack of subjective daytime sleepiness is mysterious because patients with heart failure objectively studied for sleepiness with either the Multiple Sleep Latency Test55 or the Osler test18 demonstrate significant degrees of hypersomnia. Furthermore, a significant inverse linear correlation exists between AHI and mean sleep latency on the Multiple Sleep Latency Test,54 and with treatment of sleep apnea, objective sleepiness improves without a change in subjective daytime sleepiness.18,24 The lack of subjective daytime sleepiness in patients with CHF and SRBD may account for the underdiagnosis of sleep apnea in these individuals and poor CPAP compliance, even when the disorder is properly diagnosed and treated.

The aforementioned studies focused on patients with predominantly CSA/HCSB. However, because of the frequency of coexisting OSA and CSA/HCSB, identifying viable treatment options in these more complex patients is very important.5,6,47 An 8-week prospective observational study in 10 consecutive male patients with coexisting OSA and CSA/HCSB and with and without heart failure found that flow-targeted ASV with manual titration of EPAP achieved suppression of all types of SRBDs and improved sleep architecture and frequency of arousals regardless of whether the patients had coexisting cardiovascular disease.5 The more novel combination of MV-targeted ASV with automatically titrating EPAP was tested in a similar population during a short-term pilot study.6 Sixteen patients with an AHI comprising < 80% obstructive events were included. The device normalized AHI and effectively suppressed both central and obstructive events; arousals were significantly reduced as well. In a randomized prospective study comparing CPAP with ASV by Randerath et al,47 26 of 36 patients with heart failure and coexisting OSA and CSA demonstrated acceptable adherence to ASV at 12 months and exhibited a substantial improvement in both types of SRBDs, BNP level, and sleepiness and attention on a self-administered questionnaire. Patients randomized to CPAP exhibited a similar dropout rate but experienced lesser degrees of SRBD control and higher BNP levels at 12 months. In addition to the study by Randerath et al,47 several long-term observational studies of ASV devices in patients with HFrEF and sleep apnea had significant rates of PAP device nonadherence. This may not only reflect a behavior of nonadherence to other medical therapies as well but also may be characteristic of patient resistance to PAP. In a study of Japanese patients with an average age of 72 years and LVEF of 41%, Takama and Kurabayashi42 reported significantly improved 1-year survival in those who successfully adhered to MV-targeted ASV using default settings and no titration. Patients using ASV for > 4 h/night (n = 57) were compared with patients who were not considered adherent (n = 27). All patients had severe sleep apnea comprising both obstructive and central sleep-disordered breathing (mean AHI, 43/h [CAI, 10/h] vs 36/h [CAI, 7/h] in the adherent group vs the nonadherent group, respectively). However, 42% of the patients were on a β-blocker in the adherent group compared with 29% in the nonadherent group, a potential confounder. In a second study, Jilek et al43 (Fig 1) reported significantly improved survival in 91 patients who used flow-targeted ASV compared with 85 untreated patients. The patients had severe sleep apnea, predominantly central sleep-disordered breathing, with a mean AHI of about 44/h. More than 85% of these patients were taking β-blocker medication consistent with current standards of care. The adjusted hazard ratio was 0.3 (95% CI, 0.2-0.6; P = .001) in favor of ASV.

Figure Jump LinkFigure 1  Effect of PAP therapy on survival of patients with heart failure with reduced ejection fraction and sleep apnea. AHI = apnea-hypopnea index; HR = hazard ratio; PAP = positive airway pressure. (Adapted from Jilek et al.43)Grahic Jump Location

Heart failure may commonly be associated with a number of comorbidities in addition to sleep apnea. One such important comorbidity is chronic renal failure, which has been associated with hybrid forms of SRBD.56 In addition, chronic renal failure is frequently accompanied by fluid overload and heart failure. Because kidney function, fluid status, and cardiovascular function vary over time and with treatment, the severity and phenotype of sleep apnea may change. In an observational study, Owada et al48 followed 36 patients with chronic kidney disease, heart failure, and sleep apnea who accepted therapy with ASV at home compared with 44 matched patients who refused ASV treatment. The estimated glomerular filtration rate for the entire group averaged 48 mL/min/1.73 cm2 (all chronic kidney disease grades were 3 or 4), and all patients had OSA and CSA, with a mean AHI of 34.6 ± 15.8/h on full-night PSG. Patients underwent titration with MV-targeted ASV, resulting in the mean AHI declining to < 10/h. After 6 months of ASV therapy, BNP, C-reactive protein, and noradrenaline levels decreased, whereas estimated glomerular filtration rate and LVEF increased significantly. These variables did not change significantly in the control group. Importantly, the event-free rate defined as death due to cardiac disease or hospitalization significantly improved in the ASV group. In a Cox proportional hazard model using cardiac events as the outcome, four variables were found to be independent predictors: diabetes, hemoglobin concentration, BNP level, and ASV therapy. The hazard ratio associated with ASV therapy was 0.42 (95% CI, 0.019-0.097; P = .04).

To date, only one small randomized controlled clinical trial of ASV treatment in patients with CHF exists in the literature.51 Interestingly, this study was in patients with heart failure with preserved ejection fraction rather than overt systolic failure. Eighteen patients were randomized to ASV, and 18 served as control subjects; all were well matched at baseline with an LVEF of > 50% and NYHA class above II. All patients had at least moderately severe SRBD (mean AHI, 36.5 ± 14.7/h). The ASV group showed significant improvement in the two coprimary end points of cardiac death and worsening heart failure at 6 months. In a Cox proportional hazard analysis, use of ASV was the only variable predictive of the end points (hazard ratio, 0.58; 95% CI, 0.18-0.8; P = .016).

Another important group to consider is patients with heart failure and predominant OSA in whom CSA either increases13 or emerges14 with the commencement of CPAP titration. In a study of 192 patients with HFrEF and OSA, treatment-emergent CSA (defined as ≥ 15 episodes of central apnea or PB per hour during CPAP titration) developed in 34 patients (18%), whereas < 10% of the residual disordered breathing events were obstructive in nature. Twenty-seven patients with OSA and treatment-emergent CSA underwent ASV titration, and the mean follow-up was 14 months. A combination of CPAP, autotitrating CPAP, respiratory polygraphy, and nocturnal PSG were used for diagnosis and treatment, a potential methodologic weakness. CAI decreased from 17/h to < 1/h, and the minimum saturation increased from about 82% to 87%. Important and significant improvement occurred in NYHA class, LVEF (increasing from 31% to 35%), maximum oxygen consumption, and N-terminal proBNP level. Furthermore, the slope of the hypercapnic ventilatory response decreased significantly from 4.8 to 3.1 L/min/mm Hg, indicating an improvement (reduction) in the overall loop gain, which is considered to be a major mechanism underlying the occurrence of PB in patients with heart failure.15,16

Two meta-analyses reviewed studies that used various types of ASV devices available in the United States. The first examined the application of ASV to patients with CSA and computed an effect size characterized as moderate, with the AHI decreasing by a mean of 31/h (95% CI, 25-36/h).57 In the second meta-analysis, which involved only patients with heart failure comorbid with sleep apnea, Sharma et al58 performed a systematic search of the PubMed database up through March 2012 and included studies that were of ≥ 1 weeks duration and that compared ASV to a control condition (which included subtherapeutic ASV, CPAP, bilevel PAP, oxygen therapy, and no treatment). Fourteen studies in a total of 538 subjects were identified. The weighted mean difference in AHI was −15/h (95% CI, −21.03 to −8.25/h) and in LVEF, 0.40% (95% CI, 0.08%-0.71%), both significantly favoring ASV. Importantly, when crossover studies were compared, AHI decreased from a baseline of about 50 to 6/h with ASV compared with 21/h for control subjects. ASV also improved 6-min walk distance but not peak % predicted oxygen consumption, MV/CO2 production, expired volume per unit time/CO2 production slope, or quality of life compared with the control treatments. It was concluded that in patients with CHF and SRBD, ASV is more efficacious than the other therapeutic modalities in reducing AHI and improving cardiac function and exercise capacity. These data provide a compelling rationale for large-scale randomized controlled trials to assess the clinical impact of ASV on hard outcomes, such as mortality or transplant-free survival, in these patients.

One important issue not previously emphasized is that treatment of SRBDs may decrease the rate of hospital readmissions for patients with CHF. In the United States, Medicare began financially penalizing hospitals with excess readmissions in 2012, and starting in October 2013, readmission penalties doubled to 2% of reimbursement. In a study of Medicare beneficiaries with CHF, readmission costs for those treated for sleep apnea (mostly with CPAP) were much lower than for those suspected of having sleep apnea but who were not referred for sleep studies and, consequently, remained untreated59 (Table 1).

Table Graphic Jump Location
TABLE 1  ] Two-Year Hospitalizations, Health-care Costs, and All-Cause Mortality in Patients From the Medicare Database With Newly Diagnosed Heart Failure

Data are presented as No. (%) unless otherwise indicated. The average additional health-care cost for each patient not tested and treated was $20,888. Data from Javaheri et al.59

Overall, it seems reasonable to hypothesize that systematic long-term studies of ASV devices will demonstrate that effective treatment of CSA/HCSB or mixed CSA/OSA translates into improved survival of patients with heart failure. Currently, two randomized clinical trials are expected to provide the level of evidence needed. In the meantime, the fact that ASV devices have proven efficacy in controlling all varieties of SRBDs in heart failure supports their use in patients who do not respond to CPAP or bilevel PAP. However, a number of challenges remain regarding the proper choice of the various operator-dependent settings (particularly EPAP and inspiratory PAP ranges) (Table 2) for each individual patient. In particular, injudicious choice of pressure settings can increase intrathoracic pressure to the extent that left- and right-side heart preload and afterload are altered in directions that adversely affect hemodynamic stability in patients with CHF. Conversely, inappropriately low EPAP in a patient with CHF and OSA may fail to decrease left ventricular afterload, a postulated mechanism by which PAP benefits these patients. It is believed that large negative swings in intrathoracic (and thus juxtacardiac) pressure associated with upper airway occlusion increases transmural pressure gradients of the atria and ventricles as well as that of the intrathoracic aorta. In addition to increasing left ventricular afterload and adversely affecting contractility and stroke volume, this may predispose to arrhythmias, further disturbing cardiac output as well as increasing the likelihood of sudden death. A carefully chosen value of EPAP, adequate to eliminate these obstructive events, should result in improved cardiac function and augmented stroke volume. In contrast, patients with predominant CSA will not experience such large negative swings in intrathoracic pressure and should require a different choice of EPAP settings. Regardless of the phenotype of sleep apnea, increased intrathoracic pressure will decrease right ventricular preload to some extent.

Table Graphic Jump Location
TABLE 2  ] Choices of ASV Parameters Available for Initial Setting by Clinician

ASV = adaptive servoventilation; EPAP = expiratory positive airway pressure; IPAP = inspiratory positive airway pressure; IPS = inspiratory pressure support; PAP = positive airway pressure; Ti = inspiratory time.

a 

All may be adjusted during the course of a titration.

b 

May differ depending on make/model of flow generator (see Javaheri et al1).

Summary of Our Approach to Sleep Apnea in Heart Failure

  1. Predominantly OSA. In the absence of randomized controlled trials, we consider CPAP to remain as the therapy of choice for patients with heart failure and predominantly OSA. This should be effective in most patients. However, if during the titration study, CSA increases or emerges, and persists with continued use of CPAP (with an overall CAI ≥ 5/h or AHI ≥ 15), we recommend a trial of ASV.

  2. Predominantly CSA. We also recommend a trial of CPAP for patients with heart failure and predominantly CSA. If AHI decreases to < 15/h of sleep on the night of titration, we recommend continued use of CPAP. However, based on our review of the literature, in almost 50% of patients with predominantly CSA with or without OSA, central apneas are not suppressed by CPAP and an overall AHI < 15/h is unattainable. For these patients, ASV trial is recommended because continued use of CPAP may not achieve the improved outcomes (including reduced mortality) that would be anticipated.

  3. Autotitrating devices other than ASV. We do not recommend autotitrating CPAP or bilevel devices for heart failure comorbid with sleep apnea because of the unpredictable level of control and adverse effects on hemodynamics that may occur.

  4. Patients intolerant of CPAP. We recommend a trial of an ASV device equipped with autotitrating EPAP because ASV devices with variable inspiratory PAP and EPAP may be more patient friendly and result in improved adherence, although only low-grade evidence exists. For ASV pressure settings, see Javaheri et al.1

Patients using long-term opioids are at risk for complex and even fatal SRBDs, including central and obstructive apneas and hypopneas, hypoventilation, and hypoxemia. Several studies60-65 (for reviews66,67) show that long-term opioids provoke a high prevalence of SRBDs. Obstructive and central sleep apneas and hypopneas are observed, and frequently, a unique respiratory pattern referred to as Biot (or ataxic) breathing is observed. Biot breathing is different from CSA/HCSB and OSA in that it is aperiodic and disorganized, with pauses in respiratory effort that are seemingly random in length and timing, tidal volumes of great variability.

Animal studies indicate that opioids can decrease upper airway tone,68,69 particularly that of the genioglossus muscle, thus contributing to or causing OSA. Opioids also inhibit activity in the pre-Bötzinger complex, the brainstem pacemaker involved in generating rhythmic breathing accounting for the occurrence of CSA or Biot breathing.68,70

In one human study, Webster et al64 routinely recommended PSG to 392 consecutive patients in their pain clinic. Of the 140 patients who underwent PSG, 75% had an AHI ≥ 5/h, 50% had an AHI ≥ 15/h, and 36% had severe sleep apnea with an AHI ≥ 30/h. Opioid use was associated with a mixed pattern of disordered breathing events, although central apneas commonly predominated.

Buprenorphine, a partial μ-opioid agonist, is currently used for the treatment of opioid dependency and posited to have limited respiratory toxicity. However, in a comprehensive and systematic study, Farney et al71 performed overnight PSG in 70 consecutive patients admitted for therapy with buprenorphine/naloxone. The sample comprised young adults (mean age, 32 years) who were relatively thin (mean BMI, 25 kg/m2) and included both sexes (60% women). Mild (AHI ≥ 5/h), moderate (AHI ≥ 15-30/h), and severe sleep apnea (AHI ≥ 30/h) was observed in 63%, 16%, and 17% of the patients, respectively. Many of these patients had large numbers of central apneas despite the putative protective ceiling effect of ventilatory suppression observed with this drug during wakefulness. The authors concluded that buprenorphine, like other opioids, commonly produces clinically significant sleep apnea.

CPAP treatment of sleep apnea due to opioid use has proven difficult because of the simultaneous presence of OSA and CSA, with the latter being resistant to therapy.2,72-76 Furthermore, even in those with predominant OSA on presentation, CSA may emerge during treatment with CPAP.74 A preliminary study demonstrated that MV-targeted ASV with autotitration of EPAP (VPAP Adapt SV Enhanced; ResMed) was effective in the treatment of both OSA and CSA associated with the use of opioids,2 an observation similar to the reports of treatment with ASV in heart failure discussed previously. It has subsequently become clear, however, that titration with appropriate adjustment of both EPAP and IPS is critical2,75; otherwise, residual disordered breathing events remain.72

A recent study76 examined acute (overnight) and short-term (up to 8 weeks) efficacy of CPAP and ASV in 20 patients receiving long-term opioid therapy. These patients were referred with symptoms consistent with OSA, but based on full-night attended PSG, they were found have severe sleep apnea (average AHI, 61/h) in which CSA predominated (CAI = 32/h). Acute and short-term use of CPAP, despite documented adherence, proved ineffective. After several weeks of CPAP use, AHI stayed elevated (mean, 33/h) as did CAI (mean, 19/h). However, on optimal ASV settings, mean CAI and hypopnea index were 0 and 11/h, respectively. Minimum oxyhemoglobin saturation increased (mean, 83% and 90% at baseline vs on ASV, respectively) and arousal index decreased (29/h of sleep to 12/h). Seventeen patients were followed for a minimum of 9 months and as long as 6 years and exhibited a mean long-term adherence to ASV therapy of 5.1 h/night.

Summary of Our Approach to Sleep Apnea in Association With Opioid Use

  1. OSA. CPAP titration is the initial treatment of choice. If CSA emerges, ASV titration is recommended, although bilevel PAP-S/T could be tried first.71

  2. CSA. Because CPAP has proven ineffective despite several weeks of use, we do not recommend therapy with CPAP and directly proceed with ASV or an intermediate step of bilevel PAP-S/T titration.

  3. Persistent hypoventilation or desaturation while awake or with ASV. If there is significant hypoventilation while awake as measured by Paco2 or persistent sustained desaturation while awake or being treated with an ASV device despite elimination of sleep apneas and hypopneas, we recommend titration with bilevel PAP-S/T as a more reliable ventilatory support mode. Theoretically, volume-assured pressure support devices could also be used as in patients with ventilatory failure from neuromuscular disease. A discussion of volume-assured pressure support devices is beyond the scope of this review.

CompSA has been defined as the development of CSA during initiation of CPAP therapy in patients with OSA or as the presence of both OSA and CSA in the same patient under various conditions (eg, changes in treatment settings, body position, sleep stage).77,78 The presence of CSA (CAI ≥ 5/h) on CPAP often represents an emergent phenomenon (ie, CSA not present on the diagnostic PSG) but may also be presaged by central or mixed apneas observed during a diagnostic recording. Studies have indicated that the prevalence of CPAP-induced CSA varies from 5% to 20%.79-83

In one study that examined a robust sample of 1,286 patients referred for evaluation of OSA, we found that the monthly incidence of CPAP-emergent CSA during an initial titration varied between 3% and 10% during the 1-year study period, averaging 6.5% (84 patients).79 In this study, we sought to determine the natural history of CSA during long-term CPAP treatment. In 42 of the 84 patients with CSA during the initial CPAP titration, the CSA resolved in most with long-term use of CPAP (average adherence, 5.6 h/night). However, nine of the 42 patients (about 1.5% of the total sample) had persistent CSA despite long-term CPAP use. We emphasize in a subsequent report76 that this study may have underestimated the prevalence of CompSA because 42 of the 84 patients did not return for follow-up studies. The incidence of CPAP-emergent CSA appears to be far greater with residence at altitude,84 and other authors have estimated a higher likelihood (8%-22%) that CSA will persist despite continued use of CPAP.85

Summary of Our Approach to the Presence of CSA (CAI ≥ 5/h) on the First Night of CPAP Titration

  1. Patient reassurance. Given the likelihood that CSA will resolve over time, we reassure the patient and prescribe CPAP at the optimal pressure, or we may lower the pressure at least temporarily if overtitration is suspected.

  2. Persistent CSA (AHI ≥ 15/h). Retitration with bilevel PAP-S/T, or especially ASV, will almost always resolve persistent CSA. Another approach we occasionally use is combining CPAP with sleep position training. Enforcing a nonsupine sleeping posture sometimes allows for a lower CPAP setting that does not prompt the emergence of significant CSA. These strategies are also useful if the patient is nonadherent to CPAP or continues to be symptomatic (eg, complains of persistent excessive daytime sleepiness).

There are two manufacturers of ASV devices currently available in the United States who use different treatment algorithms and incorporate different arrays of features. They represent the most advanced type of PAP devices for the treatment of SRBDs, have thus far proven extremely effective in the treatment of CSA/HCSB when CPAP or other modalities fail, and appear effective in treating more-complex types of SRBDs. Differences between these devices (even within the models offered by a single vendor), translate into the need to be familiar with approaches for programming initial settings as well as with strategies for successful titration in a given patient. Therefore, it is very important that technologists and physicians be aware of these differences and confirm the efficacy of any proposed treatment by careful monitoring in a controlled setting, such as the sleep laboratory.

Table 2 shows some operator choices regarding three important variables: EPAP, minimum and maximum IPS, and backup rate. Default algorithms have been used in some studies; however, one size does not fit all, and settings should be individualized for each patient. For example, if the minimum EPAP is set to eliminate obstructive apneas as well as hypopneas (using information based on a previous CPAP study), the patient may experience difficulty with exhalation; thus, choosing a device with expiratory pressure relief could enhance patient adherence. Other approaches include choosing a fixed EPAP that eliminates only frank obstructive apneas on the previous CPAP titration, depending on the autotitration of IPS to eliminate obstructive hypopneas and lesser degrees of inspiratory flow limitation, or setting a minimum and maximum EPAP and allowing the device to autotitrate this setting. Decisions can be made regarding the minimum IPS, which could be as low as 0 cm H2O or start at 3 or 5 cm H2O. In the face of poor respiratory system compliance (as in morbid obesity), a high IPS may well be preferred. Proper choices of all ASV variables are critically important in order to achieve maximum suppression of SRBD, to assure patient comfort and long-term adherence, and to minimize possible adverse hemodynamic effects for those patients subject to compromised hemodynamics.

Given the concerns universally expressed by stakeholders with respect to the rising costs of medical care, it is important to stress that future studies must identify the most cost-effective strategies for deploying ASV devices. The current retail price for the Respironics autoSV Advanced—System One is $3,700,86 and the ResMed VPAP Adapt with heated humidifier and tubing is $3,800.87 Bilevel PAP-S/T devices may be purchased at retail for as little as one-half of these prices, and standard, fixed-pressure CPAP machines can be purchased for about 20% to 25% of the cost of an ASV flow generator. Factoring in the cost and professional time involved in performing laboratory titrations for each device (which we advocate) raises the ante considerably. Consequently, at present, we strongly recommend a sequential approach to using these devices, starting with the least costly flow generator that efficacy studies support and escalating to the more expensive technology if laboratory results and other outcomes do not favor its use in a given patient.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Javaheri has received research grants from Philips Respironics, Inc (Koninklijke Philips N.V.) and honoraria for lectures from ResMed and Philips Respironics, Inc (Koninklijke Philips N.V.). Dr Brown has chaired, co-chaired, and continues as a member of the Polysomnography Practice Advisory Committee of the New Mexico Medical Board and serves on the New Mexico Respiratory Care Advisory Board. He currently receives no grant or commercial funding pertinent to the subject of this article. Dr Randerath has received fees for speaking and research funds from companies producing positive airway pressure devices including Weinmann Medical Technology (Weinmann Geräte für Medizin GmbH + Co. KG), Philips Respironics, Inc (Koninklijke Philips N.V.), and ResMed companies.

AHI

apnea-hypopnea index

ASV

adaptive servoventilation

BNP

brain natriuretic peptide

CAI

central apnea index

CHF

congestive heart failure

CompSA

complex sleep apnea

CSA

central sleep apnea

EPAP

expiratory positive airway pressure

HCSB

Hunter-Cheyne-Stokes breathing

HFrEF

heart failure with reduced ejection fraction

IPS

inspiratory pressure support

LVEF

left ventricular ejection fraction

MV

minute ventilation

NYHA

New York Heart Association

PAP

positive airway pressure

PB

periodic breathing

PSG

polysomnography

SRBD

sleep-related breathing disorder

S/T

spontaneous/timed

Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514-523. [CrossRef] [PubMed]
 
Javaheri S, Malik A, Smith J, Chung E. Adaptive pressure support servoventilation: a novel treatment for sleep apnea associated with use of opioids. J Clin Sleep Med. 2008;4(4):305-310. [PubMed]
 
Brown LK. Adaptive servo-ventilation for sleep apnea: technology, titration protocols, and treatment efficacy. Sleep Med Clin. 2010;5(3):419-437. [CrossRef]
 
Javaheri S, Goetting MG, Khayat R, Wylie PE, Goodwin JL, Parthasarathy S. The performance of two automatic servo-ventilation devices in the treatment of central sleep apnea. Sleep. 2011;34(12):1693-1698. [PubMed]
 
Randerath WJ, Galetke W, Stieglitz S, Laumanns C, Schäfer T. Adaptive servo-ventilation in patients with coexisting obstructive sleep apnoea/hypopnoea and Cheyne-Stokes respiration. Sleep Med. 2008;9(8):823-830. [CrossRef] [PubMed]
 
Randerath WJ, Galetke W, Kenter M, Richter K, Schäfer T. Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing. Sleep Med. 2009;10(8):898-903. [CrossRef] [PubMed]
 
Javaheri S. Heart failure.. In:Kryger MH, Roth T, Dement WC, Saunders WB., eds. Principles and Practices of Sleep Medicine.5th ed. Philadelphia, PA: Elsevier Saunders; 2011:1400-1415.
 
Javaheri S. Heart failure.. In:Kushida CA., ed. The Encyclopedia of Sleep. Waltham, MA: Academic Press; 2013;:374-386.
 
Javaheri S. Heart failure as a consequence of sleep-disordered breathing.. In:Mann DL., ed. Heart Failure: A Companion to Braunwald’s Heart Disease.2nd ed. Philadelphia, PA: Elsevier Saunders; 2010:477-494.
 
Javaheri S. Positive airway pressure treatment of central sleep apnea with emphasis on heart failure, opioids, and complex sleep apnea. Sleep Med Clin. 2010;5(3):407-417. [CrossRef]
 
Javaheri S. CPAP should not be used for central sleep apnea in congestive heart failure patients. J Clin Sleep Med. 2006;2(4):399-402. [PubMed]
 
Oldenburg O, Bartsch S, Bitter T, et al. Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing. Sleep Breath. 2012;16(3):753-757. [CrossRef] [PubMed]
 
Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation. 2000;101(4):392-397. [CrossRef] [PubMed]
 
Bitter T, Westerheide N, Hossain MS, et al. Complex sleep apnoea in congestive heart failure. Thorax. 2011;66(5):402-407. [CrossRef] [PubMed]
 
Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med. 1999;341(13):949-954. [CrossRef] [PubMed]
 
Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Am J Respir Crit Care Med. 2000;162(6):2194-2200. [CrossRef] [PubMed]
 
Arzt M, Floras JS, Logan AG, et al; CANPAP Investigators. Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP). Circulation. 2007;115(25):3173-3180. [CrossRef] [PubMed]
 
Pepperell JC, Maskell NA, Jones DR, et al. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med. 2003;168(9):1109-1114. [CrossRef] [PubMed]
 
Teschler H, Döhring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164(4):614-619. [CrossRef] [PubMed]
 
Fietze I, Blau A, Glos M, Theres H, Baumann G, Penzel T. Bi-level positive pressure ventilation and adaptive servo ventilation in patients with heart failure and Cheyne-Stokes respiration. Sleep Med. 2008;9(6):652-659. [CrossRef] [PubMed]
 
Arzt M, Wensel R, Montalvan S, et al. Effects of dynamic bilevel positive airway pressure support on central sleep apnea in men with heart failure. Chest. 2008;134(1):61-66. [CrossRef] [PubMed]
 
Zhang XL, Yin KS, Li XL, Jia EZ, Su M. Efficacy of adaptive servoventilation in patients with congestive heart failure and Cheyne-Stokes respiration. Chin Med J (Engl). 2006;119(8):622-627. [PubMed]
 
Kasai T, Usui Y, Yoshioka T, et al; JASV Investigators. Effect of flow-triggered adaptive servo-ventilation compared with continuous positive airway pressure in patients with chronic heart failure with coexisting obstructive sleep apnea and Cheyne-Stokes respiration. Circ Heart Fail. 2010;3(1):140-148. [CrossRef] [PubMed]
 
Philippe C, Stoïca-Herman M, Drouot X, et al. Compliance with and effectiveness of adaptive servoventilation versus continuous positive airway pressure in the treatment of Cheyne-Stokes respiration in heart failure over a six month period. Heart. 2006;92(3):337-342. [CrossRef] [PubMed]
 
Töpfer V, El-Sebai M, Wessendorf TE, Moraidis I, Teschler H. Adaptive servoventilation: effect on Cheyne-Stokes-Respiration and on quality of life [in German]. Pneumologie. 2004;58(1):28-32. [CrossRef] [PubMed]
 
Schädlich S, Königs I, Kalbitz F, Blankenburg T, Busse HJ, Schütte W. Cardiac function in patients with congestive heart failure and Cheyne-Stokes respiration in long-term treatment with adaptive servo ventilation (AutoSet CS) [in German]. Z Kardiol. 2004;93(6):454-462. [PubMed]
 
Szollosi I, O’Driscoll DM, Dayer MJ, Coats AJ, Morrell MJ, Simonds AK. Adaptive servo-ventilation and deadspace: effects on central sleep apnoea. J Sleep Res. 2006;15(2):199-205. [CrossRef] [PubMed]
 
Morrell MJ, Meadows GE, Hastings P, et al. The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing. Sleep. 2007;30(5):648-653. [PubMed]
 
Hastings PC, Vazir A, Meadows GE, et al. Adaptive servo-ventilation in heart failure patients with sleep apnea: a real world study. Int J Cardiol. 2010;139(1):17-24. [CrossRef] [PubMed]
 
Ono H, Fujimoto H, Kobayashi Y, Kudoh S, Gemma A. Sleep apnea syndrome: central sleep apnea and pulmonary hypertension worsened during treatment with auto-CPAP, but improved by adaptive servo-ventilation. Intern Med. 2010;49(5):415-421. [CrossRef] [PubMed]
 
Westhoff M, Arzt M, Litterst P. Influence of adaptive servoventilation on B-type natriuretic peptide in patients with Cheyne-Stokes respiration and mild to moderate systolic and diastolic heart failure [in German]. Pneumologie. 2010;64(8):467-473. [CrossRef] [PubMed]
 
Harada D, Joho S, Oda Y, Hirai T, Asanoi H, Inoue H. Short term effect of adaptive servo-ventilation on muscle sympathetic nerve activity in patients with heart failure. Auton Neurosci. 2011;161(1-2):95-102. [CrossRef] [PubMed]
 
Carnevale C, Georges M, Rabec C, Tamisier R, Levy P, Pépin J-L. Effectiveness of adaptive servo ventilation in the treatment of hypocapnic central sleep apnea of various etiologies. Sleep Med. 2011;12(10):952-958. [CrossRef] [PubMed]
 
Oldenburg O, Bitter T, Lehmann R, et al. Adaptive servoventilation improves cardiac function and respiratory stability. Clin Res Cardiol. 2011;100(2):107-115. [CrossRef] [PubMed]
 
Koyama T, Watanabe H, Terada S, et al. Adaptive servo-ventilation improves renal function in patients with heart failure. Respir Med. 2011;105(12):1946-1953. [CrossRef] [PubMed]
 
Haruki N, Takeuchi M, Kaku K, et al. Comparison of acute and chronic impact of adaptive servo-ventilation on left chamber geometry and function in patients with chronic heart failure. Eur J Heart Fail. 2011;13(10):1140-1146. [CrossRef] [PubMed]
 
Campbell AJ, Ferrier K, Neill AM. Effect of oxygen versus adaptive pressure support servo-ventilation in patients with central sleep apnoea-Cheyne Stokes respiration and congestive heart failure. Intern Med J. 2012;42(10):1130-1136. [CrossRef] [PubMed]
 
Yagi S, Akaike M, Iwase T, et al. Acute hemodynamic effects of adaptive servo ventilation in patients with pulmonary hypertension. Int J Cardiol. 2011;148(1):125-127. [CrossRef] [PubMed]
 
Koyama T, Watanabe H, Igarashi G, Terada S, Makabe S, Ito H. Short-term prognosis of adaptive servo-ventilation therapy in patients with heart failure. Circ J. 2011;75(3):710-712. [CrossRef] [PubMed]
 
Kazimierczak A, Krzyżanowski K, Wierzbowski R, et al. Resolution of exercise oscillatory ventilation with adaptive servoventilation in patients with chronic heart failure and Cheyne-Stokes respiration: preliminary study. Kardiol Pol. 2011;69(12):1266-1271. [PubMed]
 
Oldenburg O, Schmidt A, Lamp B, et al. Adaptive servoventilation improves cardiac function in patients with chronic heart failure and Cheyne-Stokes respiration. Eur J Heart Fail. 2008;10(6):581-586. [CrossRef] [PubMed]
 
Takama N, Kurabayashi M. Effect of adaptive servo-ventilation on 1-year prognosis in heart failure patients. Circ J. 2012;76(3):661-667. [CrossRef] [PubMed]
 
Jilek C, Krenn M, Sebah D, et al. Prognostic impact of sleep disordered breathing and its treatment in heart failure: an observational study. Eur J Heart Fail. 2011;13(1):68-75. [CrossRef] [PubMed]
 
Ramar K, Ramar P, Morgenthaler TI. Adaptive servoventilation in patients with central or complex sleep apnea related to chronic opioid use and congestive heart failure. J Clin Sleep Med. 2012;8(5):569-576. [PubMed]
 
Brown SE, Mosko SS, Davis JA, Pierce RA, Godfrey-Pixton TV. A retrospective case series of adaptive servoventilation for complex sleep apnea. J Clin Sleep Med. 2011;7(2):187-195. [PubMed]
 
Damy T, Margarit L, Noroc A, et al. Prognostic impact of sleep-disordered breathing and its treatment with nocturnal ventilation for chronic heart failure. Eur J Heart Fail. 2012;14(9):1009-1019. [CrossRef] [PubMed]
 
Randerath WJ, Nothofer G, Priegnitz C, et al. Long-term auto-servoventilation or constant positive pressure in heart failure and coexisting central with obstructive sleep apnea. Chest. 2012;142(2):440-447. [PubMed]
 
Owada T, Yoshihisa A, Yamauchi H, et al. Adaptive servoventilation improves cardiorenal function and prognosis in heart failure patients with chronic kidney disease and sleep-disordered breathing. J Card Fail. 2013;19(4):225-232. [CrossRef] [PubMed]
 
Oldenburg O, Bitter T, Wellmann B, et al. Trilevel adaptive servoventilation for the treatment of central and mixed sleep apnea in chronic heart failure patients. Sleep Med. 2013;14(5):422-427. [CrossRef] [PubMed]
 
Bitter T, Westerheide N, Faber L, et al. Adaptive servoventilation in diastolic heart failure and Cheyne-Stokes respiration. Eur Respir J. 2010;36(2):385-392. [CrossRef] [PubMed]
 
Yoshihisa A, Suzuki S, Yamaki T, et al. Impact of adaptive servo-ventilation on cardiovascular function and prognosis in heart failure patients with preserved left ventricular ejection fraction and sleep-disordered breathing. Eur J Heart Fail. 2013;15(5):543-550. [CrossRef] [PubMed]
 
Javaheri S, Parker TJ, Wexler L, et al. Occult sleep-disordered breathing in stable congestive heart failure. Ann Intern Med. 1995;122(7):487-492. [CrossRef] [PubMed]
 
Javaheri S, Parker TJ, Liming JD, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation. 1998;97(21):2154-2159. [CrossRef] [PubMed]
 
Javaheri S. Sleep disorders in systolic heart failure: a prospective study of 100 male patients. The final report. Int J Cardiol. 2006;106(1):21-28. [CrossRef] [PubMed]
 
Hanly P, Zuberi-Khokhar N. Daytime sleepiness in patients with congestive heart failure and Cheyne-Stokes respiration. Chest. 1995;107(4):952-958. [CrossRef] [PubMed]
 
Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344(2):102-107. [CrossRef] [PubMed]
 
Aurora RN, Chowdhuri S, Ramar K, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012;35(1):17-40. [PubMed]
 
Sharma BK, Bakker JP, McSharry DG, Desai AS, Javaheri S, Malhotra A. Adaptive servoventilation for treatment of sleep-disordered breathing in heart failure: a systematic review and meta-analysis. Chest. 2012;142(5):1211-1221. [CrossRef] [PubMed]
 
Javaheri S, Caref EB, Chen E, Tong KB, Abraham WT. Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure. Am J Respir Crit Care Med. 2011;183(4):539-546. [CrossRef] [PubMed]
 
Teichtahl H, Prodromidis A, Miller B, Cherry G, Kronborg I. Sleep-disordered breathing in stable methadone programme patients: a pilot study. Addiction. 2001;96(3):395-403. [CrossRef] [PubMed]
 
Farney RJ, Walker JM, Cloward TV, Rhondeau S. Sleep-disordered breathing associated with long-term opioid therapy. Chest. 2003;123(2):632-639. [CrossRef] [PubMed]
 
Walker JM, Farney RJ, Rhondeau SM, et al. Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. J Clin Sleep Med. 2007;3(5):455-461. [PubMed]
 
Mogri M, Khan MIA, Grant BJB, Mador MJ. Central sleep apnea induced by acute ingestion of opioids. Chest. 2008;133(6):1484-1488. [CrossRef] [PubMed]
 
Webster LR, Choi Y, Desai H, Webster L, Grant BJ. Sleep-disordered breathing and chronic opioid therapy. Pain Med. 2008;9(4):425-432. [CrossRef] [PubMed]
 
Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints. Drug Alcohol Depend. 2010;108(1-2):77-83. [CrossRef] [PubMed]
 
Cao M, Javaheri S. Chronic opioid use: effects on respiration and sleep.. In:Tvildiani D, Gegechkori K., eds. Opioids Pharmacology, Clinical Uses and Adverse Effects. New York, NY: Nova Science Publishers; 2012:1-13.
 
Javaheri S, Cao M. Opioid induced central sleep apnea.. InFabiani M., ed. Proceedings of the X World Congress on Sleep Apnea. Section: Respiratory Disorders and Snoring. Turin, Italy: Edizioni Minerva Medica; 2012:133-137.
 
Feldman JL, Del Negro CA. Looking for inspiration: new perspectives on respiratory rhythm. Nat Rev Neurosci. 2006;7(3):232-242. [CrossRef] [PubMed]
 
Hajiha M, DuBord MA, Liu H, Horner RL. Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue muscle activity in vivo. J Physiol. 2009;587(pt 11):2677-2692. [CrossRef] [PubMed]
 
Montandon G, Qin W, Liu H, Ren J, Greer JJ, Horner RL. PreBotzinger complex neurokinin-1 receptor-expressing neurons mediate opioid-induced respiratory depression. J Neurosci. 2011;31(4):1292-1301. [CrossRef] [PubMed]
 
Farney RJ, McDonald AM, Boyle KM, et al. Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone. Eur Respir J. 2013;42(2):394-403. [CrossRef] [PubMed]
 
Farney RJ, Walker JM, Boyle KM, Cloward TV, Shilling KC. Adaptive servoventilation (ASV) in patients with sleep disordered breathing associated with chronic opioid medications for non-malignant pain. J Clin Sleep Med. 2008;4(4):311-319. [PubMed]
 
Morgenthaler TI, Gay PC, Gordon N, Brown LK. Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes. Sleep. 2007;30(4):468-475. [PubMed]
 
Guilleminault C, Cao M, Yue HJ, Chawla P. Obstructive sleep apnea and chronic opioid use. Lung. 2010;188(6):459-468. [CrossRef] [PubMed]
 
Morganthaler T. The quest for stability in an unstable world: adaptive servoventilation in opioid induced complex sleep apnea syndrome. J Clin Sleep Med. 2008;4(4):321-323. [PubMed]
 
Javaheri S, Harris N, Howard J, Chung E. Adaptive servoventilation for treatment of opioid-associated central sleep apnea. J Clin Sleep Med. 2014;10(6):637-643. [PubMed]
 
Gilmartin GS, Daly RW, Thomas RJ. Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med. 2005;11(6):485-493. [CrossRef] [PubMed]
 
Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep. 2006;29(9):1203-1209. [PubMed]
 
Javaheri S, Smith J, Chung E. The prevalence and natural history of complex sleep apnea. J Clin Sleep Med. 2009;5(3):205-211. [PubMed]
 
Lehman S, Antic NA, Thompson C, Catcheside PG, Mercer J, McEvoy RD. Central sleep apnea on commencement of continuous positive airway pressure in patients with a primary diagnosis of obstructive sleep apnea-hypopnea. J Clin Sleep Med. 2007;3(5):462-466. [PubMed]
 
Dernaika T, Tawk M, Nazir S, Younis W, Kinasewitz GT. The significance and outcome of continuous positive airway pressure-related central sleep apnea during split-night sleep studies. Chest. 2007;132(1):81-87. [CrossRef] [PubMed]
 
Endo Y, Suzuki M, Inoue Y, et al. Prevalence of complex sleep apnea among Japanese patients with sleep apnea syndrome. Tohoku J Exp Med. 2008;215(4):349-354. [CrossRef] [PubMed]
 
Yaegashi H, Fujimoto K, Abe H, Orii K, Eda S, Kubo K. Characteristics of Japanese patients with complex sleep apnea syndrome: a retrospective comparison with obstructive sleep apnea syndrome. Intern Med. 2009;48(6):427-432. [CrossRef] [PubMed]
 
Pagel JF, Kwiatkowski C, Parnes B. The effects of altitude associated central apnea on the diagnosis and treatment of obstructive sleep apnea: comparative data from three different altitude locations in the mountain west. J Clin Sleep Med. 2011;7(6):610-5A. [PubMed]
 
Hoffman M, Schulman DA. The appearance of central sleep apnea after treatment of obstructive sleep apnea. Chest. 2012;142(2):517-522. [PubMed]
 
Respironics BiPAP autoSV Advanced-System One. The CPAP Shop website. http://www.thecpapshop.com/respironics-bipap-autosv-advanced-system-one?gclid=COni2faJk74CFYlhfgodAkQAEA. Accessed May 4, 2014.
 
ResMed VPAPTMAdapt with H5iTMHumidifier and ClimateLineTM1800CPAP.comwebsite.http://1800cpap.com/resmed-vpap-adapt-with-h5i-humidifier-and-climateline.aspx?gclid=CPqt3OKIk74CFU5lfgodhZ4AVA. Accessed May 4, 2014.
 

Figures

Figure Jump LinkFigure 1  Effect of PAP therapy on survival of patients with heart failure with reduced ejection fraction and sleep apnea. AHI = apnea-hypopnea index; HR = hazard ratio; PAP = positive airway pressure. (Adapted from Jilek et al.43)Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1  ] Two-Year Hospitalizations, Health-care Costs, and All-Cause Mortality in Patients From the Medicare Database With Newly Diagnosed Heart Failure

Data are presented as No. (%) unless otherwise indicated. The average additional health-care cost for each patient not tested and treated was $20,888. Data from Javaheri et al.59

Table Graphic Jump Location
TABLE 2  ] Choices of ASV Parameters Available for Initial Setting by Clinician

ASV = adaptive servoventilation; EPAP = expiratory positive airway pressure; IPAP = inspiratory positive airway pressure; IPS = inspiratory pressure support; PAP = positive airway pressure; Ti = inspiratory time.

a 

All may be adjusted during the course of a titration.

b 

May differ depending on make/model of flow generator (see Javaheri et al1).

References

Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514-523. [CrossRef] [PubMed]
 
Javaheri S, Malik A, Smith J, Chung E. Adaptive pressure support servoventilation: a novel treatment for sleep apnea associated with use of opioids. J Clin Sleep Med. 2008;4(4):305-310. [PubMed]
 
Brown LK. Adaptive servo-ventilation for sleep apnea: technology, titration protocols, and treatment efficacy. Sleep Med Clin. 2010;5(3):419-437. [CrossRef]
 
Javaheri S, Goetting MG, Khayat R, Wylie PE, Goodwin JL, Parthasarathy S. The performance of two automatic servo-ventilation devices in the treatment of central sleep apnea. Sleep. 2011;34(12):1693-1698. [PubMed]
 
Randerath WJ, Galetke W, Stieglitz S, Laumanns C, Schäfer T. Adaptive servo-ventilation in patients with coexisting obstructive sleep apnoea/hypopnoea and Cheyne-Stokes respiration. Sleep Med. 2008;9(8):823-830. [CrossRef] [PubMed]
 
Randerath WJ, Galetke W, Kenter M, Richter K, Schäfer T. Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing. Sleep Med. 2009;10(8):898-903. [CrossRef] [PubMed]
 
Javaheri S. Heart failure.. In:Kryger MH, Roth T, Dement WC, Saunders WB., eds. Principles and Practices of Sleep Medicine.5th ed. Philadelphia, PA: Elsevier Saunders; 2011:1400-1415.
 
Javaheri S. Heart failure.. In:Kushida CA., ed. The Encyclopedia of Sleep. Waltham, MA: Academic Press; 2013;:374-386.
 
Javaheri S. Heart failure as a consequence of sleep-disordered breathing.. In:Mann DL., ed. Heart Failure: A Companion to Braunwald’s Heart Disease.2nd ed. Philadelphia, PA: Elsevier Saunders; 2010:477-494.
 
Javaheri S. Positive airway pressure treatment of central sleep apnea with emphasis on heart failure, opioids, and complex sleep apnea. Sleep Med Clin. 2010;5(3):407-417. [CrossRef]
 
Javaheri S. CPAP should not be used for central sleep apnea in congestive heart failure patients. J Clin Sleep Med. 2006;2(4):399-402. [PubMed]
 
Oldenburg O, Bartsch S, Bitter T, et al. Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing. Sleep Breath. 2012;16(3):753-757. [CrossRef] [PubMed]
 
Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation. 2000;101(4):392-397. [CrossRef] [PubMed]
 
Bitter T, Westerheide N, Hossain MS, et al. Complex sleep apnoea in congestive heart failure. Thorax. 2011;66(5):402-407. [CrossRef] [PubMed]
 
Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med. 1999;341(13):949-954. [CrossRef] [PubMed]
 
Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Am J Respir Crit Care Med. 2000;162(6):2194-2200. [CrossRef] [PubMed]
 
Arzt M, Floras JS, Logan AG, et al; CANPAP Investigators. Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP). Circulation. 2007;115(25):3173-3180. [CrossRef] [PubMed]
 
Pepperell JC, Maskell NA, Jones DR, et al. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med. 2003;168(9):1109-1114. [CrossRef] [PubMed]
 
Teschler H, Döhring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164(4):614-619. [CrossRef] [PubMed]
 
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