- Email: [email protected]
Adaptive Servoventilation
10. Shum AK, Alimohammadi M, Tan CL, et al. BPIFBI is a lungspecific autoantigen associated with interstitial lung disease. Sci Transl Med. 2013;5(206):206ra139. 11. Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364(16): 1503-1512. 12. Peljto AL, Steele MP, Fingerlin TE, et al. The pulmonary fibrosisassociated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis. Chest. 2012;142(6):1584-1588.
Adaptive Servoventilation Answer to a Sleep Physician’s Dream? Lee K. Brown, MD, FCCP Albuquerque, NM
Detective Tom Polhaus: [picks up the falcon] “Heavy. What is it?” Sam Spade: “The, uh, stuff that dreams are made of.” –The Maltese Falcon based on the novel by Dashiell Hammett1
When sleep physicians dream, do they sometimes have nightmares about the difficult management of complex sleep apnea syndromes? Do their dreams now end happily with the application of adaptive servoventilation (ASV), whose magical properties promptly resolve all forms of sleep-disordered breathing (SDB)? To be sure, accumulating literature has proven that ASV may be a major advance in the treatment of central sleep apnea (CSA) with or without OSA. However, the question remains: To what extent has the ASV dream become reality? Originally, ASV was conceived to treat hypocapnic CSA (with or without the pattern of Hunter-Cheyne-Stokes breathing [HCSB]) by providing artificial ventilatory support out of phase with the patient’s own waxing AFFILIATIONS: From the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, School of Medicine, and the Department of Electrical and Computer Engineering, School of Engineering, University of New Mexico. CONFLICT OF INTEREST: L. K. B. serves on the Polysomnography Practice Advisory Committee of the New Mexico Medical Board and chairs the New Mexico Respiratory Care Advisory Board. He currently receives no grant or commercial funding pertinent to the subject of this article. CORRESPONDENCE TO: Lee K. Brown, MD, FCCP, Department of Internal Medicine, School of Medicine, and Department of Electrical and Computer Engineering, University of New Mexico, 1101 Medical Arts Ave NE, Bldg #2, Albuquerque, NM 87102; e-mail: lkbrown@ alum.mit.edu © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.15-1540
journal.publications.chestnet.org
and waning ventilatory drive.2-5 The two ASV devices available in the United States differ significantly in terms of the variable used as the target of the operational algorithm: ResMed devices (ResMed Inc) target minute ventilation (MV), while Respironics technology (Koninklijke Philips NV) targets peak inspiratory flow (PIF).6,7 (Henceforth in this article, these manufacturers’ flow generators will be referred to as the MV-targeted device and the PIF-targeted device, respectively.) Since such devices can detect obstructive as well as central events, and since their output (bilevel positive airway pressure [PAP]) is plainly capable of suppressing OSA, it is not surprising that ASV has found uses in treating the cooccurrence of obstructive and central SDB, including situations where CSA emerges from more conventional modes of PAP treatment of OSA. Moreover, ASV has also been applied to treat hypercapnic forms of CSA, particularly that associated with chronic opioid use.5 Both devices initially titrated only pressure support (PS), but before long, manufacturers incorporated optional autotitration of expiratory PAP (EPAP).6,7 Both devices also compute apnea-hypopnea index (AHI) and other respiratory metrics, which are available when compliance is downloaded. Given these capabilities, it might be concluded that laboratory titration for any and all varieties of SDB is a thing of the past, although, to my knowledge, no device manufacturer has made this claim. However, it seems inevitable that some practitioners may adopt the practice of prescribing ASV with a standard array of settings without laboratory titration, with the expectation that the patient (and presumably the prescriber) will rest peacefully at night. In this issue of CHEST (see page 1454), Javaheri et al8 report on a prospective multicenter trial evidently meant to test this hypothesis. Their subjects had significant CSA with central apnea index (CAI) ⱖ 5 assessed by polysomnography (PSG); 24 subjects had CSA only and three had OSA with PAP-emergent CSA. All had an AHI ⱖ 15/h at baseline. Of the patients with pure CSA, 13 exhibited ataxic breathing presumably associated with opioid use, six demonstrated HCSB, two had atrial fibrillation without congestive heart failure, two had multiple sclerosis, and one had a previous cerebrovascular accident. All subjects underwent a second PSG with CPAP titration and a third PSG with the PIF-targeted ASV device, programmed for autotitration of EPAP and with fixed standardized settings. Subjects were prescribed the same ASV device at home for 3 months, but, paradoxically, some alterations of settings were allowed when the devices were in the home. At the end
1369
of 3 months, the accumulated adherence and estimated AHI data were downloaded for the 26 subjects who remained. Overall, AHI declined significantly during both the ASV PSG night and at 3 months, compared with the diagnostic night and the CPAP night. Subjective sleep quality (Likert scale) after the ASV PSG night improved compared with the previous treatment night, and Epworth Sleepiness Scale (ESS) score declined significantly at 3 months. The authors concluded that the ASV device, configured to automatically titrate EPAP and inspiratory PAP (IPAP) using standardized, minimally customized settings, effectively suppressed SDB of all types both acutely and with long-term use in patients with all of the phenotypes studied. Prescribing ASV using standardized or factory default settings, without laboratory titration, is not without precedent in published randomized controlled trials (RCTs) encompassing a variety of SDB phenotypes, although most studies used fixed EPAP.9-17 Several RCTs incorporating autotitration of EPAP as well as PS have appeared that do seem to use default settings, although that is not always explicitly stated. Galetke et al18 reported an RCT examining the use of an ASV device not available in the United States, the SOMNOventCR (Weinmann Geräte für Medizin GmbH 1 Co. KG).18 Thirty-nine patients with heart disease and coexisting OSA and HCSB participated in a crossover trial in which they received either CPAP or ASV for 4 weeks.18 An initial PSG with CPAP titration was used to determine the minimum EPAP setting and maximum IPAP was set to 20 cm H2O (it was set lower in four patients because of intolerance). Successive PSGs found that ASV prescribed in this way was superior to CPAP in terms of AHI as well as obstructive AHI and central AHI, although ESS improved only with CPAP. Javaheri et al previously reported a crossover RCT in patients with OSA with CPAP-emergent CSA that compared PIF-targeted ASV with fixed EPAP (values obtained from a previous CPAP titration) and a later generation of the same PIF-targeted ASV device that added autotitrating EPAP.17 The minimum EPAP was set to 2 cm H2O below the CPAP-determined fixed EPAP, and maximum IPAP was 30 cm H2O, implying that this study qualifies as one largely using default settings. Efficacy assessed during PSGs with both devices demonstrated clinically significant improvements in AHI, CAI, obstructive apnea index, and hypopnea index in comparison with the diagnostic and CPAP nights. Moreover, the autotitrating EPAP device was superior to the fixed EPAP device in terms of obstructive and 17
1370 Editorials
central apnea indexes, although the differences do not appear to be of clinical significance. Two RCTs have been published evaluating ASV for opioid-induced complex sleep apnea syndromes.19,20 Cao et al19 compared bilevel PAP in spontaneous/timed mode (all of the subjects were current users) with the MV-targeted autotitrating EPAP device in 18 subjects, using a blinded, random-order crossover design. Respiratory indexes assessed by PSG (AHI and CAI) were superior with ASV, but it is not clearly stated whether ASV settings were actively manipulated during the PSG or whether default settings were maintained. More to the point, Shapiro et al20 explicitly tested ASV with the manufacturer’s default settings (EPAP range, 4-15 cm H2O; PS range, 0-21 cm H2O, automatic backup rate) in a random-order crossover design vs CPAP and manual titration of the same ASV modified to provide a minimum MV of 5 L/min. Thirty-one patients (13 men) completed PSGs with each device, and 20 completed a 3-month trial with ASV (all but four with the unmodified device). The two ASV modalities provided similar degrees of SDB control acutely with significant reductions in AHI, CAI, and obstructive apnea index compared with the diagnostic and CPAP nights. The downloaded AHI at 3 months also demonstrated sustained efficacy, although adherence was suboptimal. One RCT in patients with congestive heart failure with “pure” CSA/HCSB investigated the use of autotitrating EPAP, PIF-targeted ASV, with default settings (EPAP range, 4-15 cm H2O) in comparison with fixed EPAP.21 This prospective, crossover, noninferiority trial in 21 patients demonstrated that SDB indexes during PSG improved and were not significantly different between the two treatment modalities. These RCTs do provide a measure of support for prescribing ASV with autotitrating EPAP without PSG titration using standardized settings. However, all involve relatively small numbers of subjects, and the current study by Javaheri et al8 suffers from this and other weaknesses as well. The total number of subjects enrolled is quite small, with even smaller numbers exhibiting each SDB phenotype despite the relatively high prevalence of these disorders.22-25 The clinical characteristics of the study group, a fundamental requirement for judging an article about therapy before the results are put into practice, are only sketchily described.26,27 Investigators permitted the clinicians involved to change ASV settings during the 90-day home trial, seemingly a violation of the treatment paradigm; maximum pressure was altered in all 28 patients, with changes in maximum
[
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]
PS averaging 3 cm H2O in 16 patients. The acute effect of the device was assessed during PSG, but 90-day data were from the device downloads, are based solely on airflow, and can differ from PSG values.28 Finally, the results apply only to the PIF-targeted ASV device of the generation used in their study. There is only one head-to-head comparison between the MV-targeted and the PIF-targeted devices: a nonrandomized parallel study using laboratory titrations in patients with CPAP-emergent CSA, which demonstrated satisfactory control of SDB and adherence for both devices, although ESS responded significantly better in patients using the PIF-targeted device.29 There exists another line of evidence that further muddles this issue. Zhu et al30 bench-tested the BiPAP autoSV Advanced System One (Koninklijke Philips NV) and the SOMNOvent CR, both with autotitrating EPAP engaged, and the S9 VPAP Adapt (ResMed Inc) without autotitrating EPAP, all with factory default settings. Pitted against a piston-driven Starling resistor that simulated various types of SDB, the two auto-titrating EPAP devices were less effective at suppressing SDB events overall, particularly central hypopneas, compared with the fixed EPAP device. All three devices also underestimated the actual AHI programmed into the breathing simulator. The study by Javaheri et al8 is a provocative attempt at presenting a treatment paradigm that could be the “stuff that dreams are made of ” in both the figurative and literal senses. However, the many uncertainties and gaps in our knowledge should discourage widespread adoption of this paradigm. For the time being, titration and validation of ASV device type, mode, and settings during laboratory PSG remain the only means by which control of SDB can be assured in any given patient.
References 1. The Maltese Falcon. Dir. John Huston. Warner Bros, 1941. Film. 2. Teschler H, Döhring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for CheyneStokes respiration in heart failure. Am J Respir Crit Care Med. 2001; 164(4):614-619. 3. Dempsey JA. Crossing the apnoeic threshold: causes and consequences. Exp Physiol. 2005;90(1):13-24. 4. Plataki M, Sands SA, Malhotra A. Clinical consequences of altered chemoreflex control. Respir Physiol Neurobiol. 2013;189(2):354-363. 5. Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central sleep apnea: pathophysiology and treatment. Chest. 2007;131(2):595-607. 6. Brown LK. Adaptive servo-ventilation for sleep apnea: technology, titration protocols, and treatment efficacy. Sleep Med Clin. 2010; 5(3):419-437. 7. Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514-523. 8. Javaheri S, Winslow D, McCullough P, Wylie P, Kryger MH. The use of a fully automated automatic adaptive servoventilation algorithm
journal.publications.chestnet.org
in the acute and long-term treatment of central sleep apnea. Chest. 2015;148(6):1454-1461. 9. Arzt M, Schroll S, Series F, et al. Auto-servoventilation in heart failure with sleep apnoea: a randomised controlled trial. Eur Respir J. 2013; 42(5):1244-1254. 10. Birner C, Series F, Lewis K, et al. Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial. Respiration. 2014;87(1):54-62. 11. 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. 12. Hetland A, Haugaa KH, Olseng M, et al. Three-month treatment with adaptive servoventilation improves cardiac function and physical activity in patients with chronic heart failure and CheyneStokes respiration: a prospective randomized controlled trial. Cardiology. 2013;126(2):81-90. 13. Ushijima R, Joho S, Akabane T, Oda Y, Inoue H. Differing effects of adaptive servoventilation and continuous positive airway pressure on muscle sympathetic nerve activity in patients with heart failure. Circ J. 2014;78(6):1387-1395. 14. Seino Y, Momomura S, Kihara Y, Adachi H, Yasumura Y, Yokoyama H; SAVIOR-C investigators. Effects of adaptive servo-ventilation therapy on cardiac function and remodeling in patients with chronic heart failure (SAVIOR-C): study protocol for a randomized controlled trial. Trials. 2015;16:14-21. 15. Momomura S, Seino Y, Kihara Y, et al; SAVIOR-C investigators. Adaptive servo-ventilation therapy for patients with chronic heart failure in a confirmatory, multicenter, randomized, controlled study. Circ J. 2015;79(5):981-990. 16. Morgenthaler TI, Kuzniar TJ, Wolfe LF, Willes L, McLain WC III, Goldberg R. The complex sleep apnea resolution study: a prospective randomized controlled trial of continuous positive airway pressure versus adaptive servoventilation therapy. Sleep. 2014;37(5):927-934. 17. 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. 18. Galetke W, Ghassemi BM, Priegnitz C, et al. Anticyclic modulated ventilation versus continuous positive airway pressure in patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration: a randomized crossover trial. Sleep Med. 2014;15(8):874-879. 19. Cao M, Cardell C-Y, Willes L, Mendoza J, Benjafield A, Kushida C. A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. J Clin Sleep Med. 2014;10(8):855-861. 20. Shapiro CM, Chung SA, Wylie PE, et al. Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up [published online ahead of print March 27, 2015]. Sleep Breath. doi:10.1007/s11325-015-1161-7. 21. Oldenburg O, Spießhöfer J, Fox H, Horstkotte D. Performance of conventional and enhanced adaptive servoventilation (ASV) in heart failure patients with central sleep apnea who have adapted to conventional ASV. Sleep Breath. 2015;19(3):795-800. 22. Javaheri S, Smith J, Chung E. The prevalence and natural history of complex sleep apnea. J Clin Sleep Med. 2009;5(3):205-211. 23. Herrscher TE, Akre H, Øverland B, Sandvik L, Westheim AS. High prevalence of sleep apnea in heart failure outpatients: even in patients with preserved systolic function. J Card Fail. 2011;17(5):420-425. 24. Paulino A, Damy T, Margarit L, et al. Prevalence of sleep-disordered breathing in a 316-patient French cohort of stable congestive heart failure. Arch Cardiovasc Dis. 2009;102(3):169-175. 25. Correa D, Farney RJ, Chung F, Prasad A, Lam D, Wong J. Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg. 2015; 120(6):1273-1285. 26. Guyatt GH, Sackett DL, Cook DJ. Users’ guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA. 1993;270(21):2598-2601.
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27. Guyatt GH, Sackett DL, Cook DJ. Users’ guides to the medical literature. II. How to use an article about therapy or prevention. B. What were the results and will they help me in caring for my patients? Evidence-Based Medicine Working Group. JAMA. 1994; 271(1):59-63.
29. Kuzniar TJ, Patel S, Nierodzik CL, Smith LC. Comparison of two servo ventilator devices in the treatment of complex sleep apnea. Sleep Med. 2011;12(6):538-541.
28. Schwab RJ, Badr SM, Epstein LJ, et al; ATS Subcommittee on CPAP Adherence Tracking Systems. An official American Thoracic Society statement: continuous positive airway pressure adherence tracking
30. Zhu K, Kharboutly H, Ma J, Bouzit M, Escourrou P. Bench test evaluation of adaptive servoventilation devices for sleep apnea treatment. J Clin Sleep Med. 2013;9(9):861-871.
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systems. The optimal monitoring strategies and outcome measures in adults. Am J Respir Crit Care Med. 2013;188(5):613-620.
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Adaptive Servoventilation Answer to a Sleep Physician’s Dream? Lee K. Brown, MD, FCCP Albuquerque, NM
Detective Tom Polhaus: [picks up the falcon] “Heavy. What is it?” Sam Spade: “The, uh, stuff that dreams are made of.” –The Maltese Falcon based on the novel by Dashiell Hammett1
When sleep physicians dream, do they sometimes have nightmares about the difficult management of complex sleep apnea syndromes? Do their dreams now end happily with the application of adaptive servoventilation (ASV), whose magical properties promptly resolve all forms of sleep-disordered breathing (SDB)? To be sure, accumulating literature has proven that ASV may be a major advance in the treatment of central sleep apnea (CSA) with or without OSA. However, the question remains: To what extent has the ASV dream become reality? Originally, ASV was conceived to treat hypocapnic CSA (with or without the pattern of Hunter-Cheyne-Stokes breathing [HCSB]) by providing artificial ventilatory support out of phase with the patient’s own waxing AFFILIATIONS: From the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, School of Medicine, and the Department of Electrical and Computer Engineering, School of Engineering, University of New Mexico. CONFLICT OF INTEREST: L. K. B. serves on the Polysomnography Practice Advisory Committee of the New Mexico Medical Board and chairs the New Mexico Respiratory Care Advisory Board. He currently receives no grant or commercial funding pertinent to the subject of this article. CORRESPONDENCE TO: Lee K. Brown, MD, FCCP, Department of Internal Medicine, School of Medicine, and Department of Electrical and Computer Engineering, University of New Mexico, 1101 Medical Arts Ave NE, Bldg #2, Albuquerque, NM 87102; e-mail: lkbrown@ alum.mit.edu © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.15-1540
journal.publications.chestnet.org
and waning ventilatory drive.2-5 The two ASV devices available in the United States differ significantly in terms of the variable used as the target of the operational algorithm: ResMed devices (ResMed Inc) target minute ventilation (MV), while Respironics technology (Koninklijke Philips NV) targets peak inspiratory flow (PIF).6,7 (Henceforth in this article, these manufacturers’ flow generators will be referred to as the MV-targeted device and the PIF-targeted device, respectively.) Since such devices can detect obstructive as well as central events, and since their output (bilevel positive airway pressure [PAP]) is plainly capable of suppressing OSA, it is not surprising that ASV has found uses in treating the cooccurrence of obstructive and central SDB, including situations where CSA emerges from more conventional modes of PAP treatment of OSA. Moreover, ASV has also been applied to treat hypercapnic forms of CSA, particularly that associated with chronic opioid use.5 Both devices initially titrated only pressure support (PS), but before long, manufacturers incorporated optional autotitration of expiratory PAP (EPAP).6,7 Both devices also compute apnea-hypopnea index (AHI) and other respiratory metrics, which are available when compliance is downloaded. Given these capabilities, it might be concluded that laboratory titration for any and all varieties of SDB is a thing of the past, although, to my knowledge, no device manufacturer has made this claim. However, it seems inevitable that some practitioners may adopt the practice of prescribing ASV with a standard array of settings without laboratory titration, with the expectation that the patient (and presumably the prescriber) will rest peacefully at night. In this issue of CHEST (see page 1454), Javaheri et al8 report on a prospective multicenter trial evidently meant to test this hypothesis. Their subjects had significant CSA with central apnea index (CAI) ⱖ 5 assessed by polysomnography (PSG); 24 subjects had CSA only and three had OSA with PAP-emergent CSA. All had an AHI ⱖ 15/h at baseline. Of the patients with pure CSA, 13 exhibited ataxic breathing presumably associated with opioid use, six demonstrated HCSB, two had atrial fibrillation without congestive heart failure, two had multiple sclerosis, and one had a previous cerebrovascular accident. All subjects underwent a second PSG with CPAP titration and a third PSG with the PIF-targeted ASV device, programmed for autotitration of EPAP and with fixed standardized settings. Subjects were prescribed the same ASV device at home for 3 months, but, paradoxically, some alterations of settings were allowed when the devices were in the home. At the end
1369
of 3 months, the accumulated adherence and estimated AHI data were downloaded for the 26 subjects who remained. Overall, AHI declined significantly during both the ASV PSG night and at 3 months, compared with the diagnostic night and the CPAP night. Subjective sleep quality (Likert scale) after the ASV PSG night improved compared with the previous treatment night, and Epworth Sleepiness Scale (ESS) score declined significantly at 3 months. The authors concluded that the ASV device, configured to automatically titrate EPAP and inspiratory PAP (IPAP) using standardized, minimally customized settings, effectively suppressed SDB of all types both acutely and with long-term use in patients with all of the phenotypes studied. Prescribing ASV using standardized or factory default settings, without laboratory titration, is not without precedent in published randomized controlled trials (RCTs) encompassing a variety of SDB phenotypes, although most studies used fixed EPAP.9-17 Several RCTs incorporating autotitration of EPAP as well as PS have appeared that do seem to use default settings, although that is not always explicitly stated. Galetke et al18 reported an RCT examining the use of an ASV device not available in the United States, the SOMNOventCR (Weinmann Geräte für Medizin GmbH 1 Co. KG).18 Thirty-nine patients with heart disease and coexisting OSA and HCSB participated in a crossover trial in which they received either CPAP or ASV for 4 weeks.18 An initial PSG with CPAP titration was used to determine the minimum EPAP setting and maximum IPAP was set to 20 cm H2O (it was set lower in four patients because of intolerance). Successive PSGs found that ASV prescribed in this way was superior to CPAP in terms of AHI as well as obstructive AHI and central AHI, although ESS improved only with CPAP. Javaheri et al previously reported a crossover RCT in patients with OSA with CPAP-emergent CSA that compared PIF-targeted ASV with fixed EPAP (values obtained from a previous CPAP titration) and a later generation of the same PIF-targeted ASV device that added autotitrating EPAP.17 The minimum EPAP was set to 2 cm H2O below the CPAP-determined fixed EPAP, and maximum IPAP was 30 cm H2O, implying that this study qualifies as one largely using default settings. Efficacy assessed during PSGs with both devices demonstrated clinically significant improvements in AHI, CAI, obstructive apnea index, and hypopnea index in comparison with the diagnostic and CPAP nights. Moreover, the autotitrating EPAP device was superior to the fixed EPAP device in terms of obstructive and 17
1370 Editorials
central apnea indexes, although the differences do not appear to be of clinical significance. Two RCTs have been published evaluating ASV for opioid-induced complex sleep apnea syndromes.19,20 Cao et al19 compared bilevel PAP in spontaneous/timed mode (all of the subjects were current users) with the MV-targeted autotitrating EPAP device in 18 subjects, using a blinded, random-order crossover design. Respiratory indexes assessed by PSG (AHI and CAI) were superior with ASV, but it is not clearly stated whether ASV settings were actively manipulated during the PSG or whether default settings were maintained. More to the point, Shapiro et al20 explicitly tested ASV with the manufacturer’s default settings (EPAP range, 4-15 cm H2O; PS range, 0-21 cm H2O, automatic backup rate) in a random-order crossover design vs CPAP and manual titration of the same ASV modified to provide a minimum MV of 5 L/min. Thirty-one patients (13 men) completed PSGs with each device, and 20 completed a 3-month trial with ASV (all but four with the unmodified device). The two ASV modalities provided similar degrees of SDB control acutely with significant reductions in AHI, CAI, and obstructive apnea index compared with the diagnostic and CPAP nights. The downloaded AHI at 3 months also demonstrated sustained efficacy, although adherence was suboptimal. One RCT in patients with congestive heart failure with “pure” CSA/HCSB investigated the use of autotitrating EPAP, PIF-targeted ASV, with default settings (EPAP range, 4-15 cm H2O) in comparison with fixed EPAP.21 This prospective, crossover, noninferiority trial in 21 patients demonstrated that SDB indexes during PSG improved and were not significantly different between the two treatment modalities. These RCTs do provide a measure of support for prescribing ASV with autotitrating EPAP without PSG titration using standardized settings. However, all involve relatively small numbers of subjects, and the current study by Javaheri et al8 suffers from this and other weaknesses as well. The total number of subjects enrolled is quite small, with even smaller numbers exhibiting each SDB phenotype despite the relatively high prevalence of these disorders.22-25 The clinical characteristics of the study group, a fundamental requirement for judging an article about therapy before the results are put into practice, are only sketchily described.26,27 Investigators permitted the clinicians involved to change ASV settings during the 90-day home trial, seemingly a violation of the treatment paradigm; maximum pressure was altered in all 28 patients, with changes in maximum
[
148#6 CHEST DECEMBER 2015
]
PS averaging 3 cm H2O in 16 patients. The acute effect of the device was assessed during PSG, but 90-day data were from the device downloads, are based solely on airflow, and can differ from PSG values.28 Finally, the results apply only to the PIF-targeted ASV device of the generation used in their study. There is only one head-to-head comparison between the MV-targeted and the PIF-targeted devices: a nonrandomized parallel study using laboratory titrations in patients with CPAP-emergent CSA, which demonstrated satisfactory control of SDB and adherence for both devices, although ESS responded significantly better in patients using the PIF-targeted device.29 There exists another line of evidence that further muddles this issue. Zhu et al30 bench-tested the BiPAP autoSV Advanced System One (Koninklijke Philips NV) and the SOMNOvent CR, both with autotitrating EPAP engaged, and the S9 VPAP Adapt (ResMed Inc) without autotitrating EPAP, all with factory default settings. Pitted against a piston-driven Starling resistor that simulated various types of SDB, the two auto-titrating EPAP devices were less effective at suppressing SDB events overall, particularly central hypopneas, compared with the fixed EPAP device. All three devices also underestimated the actual AHI programmed into the breathing simulator. The study by Javaheri et al8 is a provocative attempt at presenting a treatment paradigm that could be the “stuff that dreams are made of ” in both the figurative and literal senses. However, the many uncertainties and gaps in our knowledge should discourage widespread adoption of this paradigm. For the time being, titration and validation of ASV device type, mode, and settings during laboratory PSG remain the only means by which control of SDB can be assured in any given patient.
References 1. The Maltese Falcon. Dir. John Huston. Warner Bros, 1941. Film. 2. Teschler H, Döhring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for CheyneStokes respiration in heart failure. Am J Respir Crit Care Med. 2001; 164(4):614-619. 3. Dempsey JA. Crossing the apnoeic threshold: causes and consequences. Exp Physiol. 2005;90(1):13-24. 4. Plataki M, Sands SA, Malhotra A. Clinical consequences of altered chemoreflex control. Respir Physiol Neurobiol. 2013;189(2):354-363. 5. Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central sleep apnea: pathophysiology and treatment. Chest. 2007;131(2):595-607. 6. Brown LK. Adaptive servo-ventilation for sleep apnea: technology, titration protocols, and treatment efficacy. Sleep Med Clin. 2010; 5(3):419-437. 7. Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514-523. 8. Javaheri S, Winslow D, McCullough P, Wylie P, Kryger MH. The use of a fully automated automatic adaptive servoventilation algorithm
journal.publications.chestnet.org
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