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Noninvasive positive pressure ventilation for stable outpatients: CPAP and beyond
Author(s)
Theerakorn Theerakittikul, MD
Basma Ricaurte, MD
Loutfi S. Aboussouan, MD

Noninvasive positive pressure ventilation (NIPPV) is any form of positive ventilatory support applied without an endotracheal tube, including continuous positive airway pressure (CPAP).1 The role of NIPPV in acute care has been discussed in an earlier review in the Cleveland Clinic Journal of Medicine.2

NIPPV is also used at night in outpatients with stable chronic conditions, first used in the 1980s in the treatment of obstructive sleep apnea3 and neuromuscular diseases,4 and since then in several other conditions including sleep disorders associated with congestive heart failure (including sleep apnea and the Cheyne-Stokes respiration-central sleep apnea syndrome), chronic obstructive pulmonary disease (COPD), and the obesity-hypoventilation syndrome.

In this review, we discuss the different types of NIPPV, the specific conditions in which they can be used, and the indications, recommendations, and evidence supporting the efficacy of NIPPV in outpatients.

THE TYPES OF NIPPV AND THEIR USES

Although the conditions for which different types of NIPPV can be used overlap significantly, each type has general indications and different goals of treatment. This section begins with types of NIPPV that are predominantly used to treat sleep-disordered breathing, and then proceeds to those predominantly used for conditions associated with hypoventilation and hypercapnia.

Continuous positive airway pressure

CPAP, currently the most widely used form of NIPPV, applies a constant level of positive pressure at the airway opening during spontaneous breathing.

CPAP is commonly used to treat obstructive sleep-disordered breathing, with the goals of improving daytime sleepiness and reducing cardiovascular risk. It has also been used to treat sleep-disordered breathing associated with congestive heart failure.

CPAP’s role in the support of ventilation is limited and indirect. For instance, it has been used in the obesity-hypoventilation syndrome and in the “overlap” syndrome (in which both sleep apnea and COPD coexist). However, its benefits in those conditions are probably derived in large part from correction of underlying obstructive sleep apnea.

The mechanisms of action of CPAP include:

  • Preventing intermittent narrowing and collapse of the airway in patients with obstructive sleep apnea-hypopnea syndrome by acting as a pneumatic splint during sleep3,5,6
  • Counteracting auto-positive end-expiratory pressure, thereby reducing respiratory muscle load, reducing the work of breathing, and lowering daytime Paco2 in patients with coexistent COPD and obstructive sleep apnea-hypopnea syndrome (the overlap syndrome)7–9
  • Improving lung function (particularly the functional residual capacity) and daytime gas exchange in obstructive sleep apnea-hypopnea syndrome 10
  • Improving left ventricular systolic function in patients with heart failure coexisting with obstructive sleep apnea-hypopnea syndrome.11,12

Auto-CPAP is delivered via a self-titrating CPAP device, which uses algorithms to detect variations in the degree of obstruction and consequently adjusts the pressure level to restore normal breathing. Auto-CPAP therefore compensates for factors that modify the upper airway collapsibility, such as body posture during sleep, stage of sleep, use of alcohol, and drugs that affect upper airway muscle tone.13

Although one of the premises of using auto-CPAP is that it improves the patient’s satisfaction and compliance, several studies found it to be no more effective than fixed CPAP for treating obstructive sleep apnea-hypopnea syndrome.14–16 Current guidelines of the American Academy of Sleep Medicine do not recommend self-titrating CPAP devices to diagnose obstructive sleep apnea or to treat patients with cardiopulmonary disorders or other conditions in which nocturnal desaturation may be unrelated to obstructive events.17

Adaptive servo-ventilation

Adaptive servo-ventilation was developed for Cheyne-Stokes respiration-central sleep apnea syndrome in patients with congestive heart failure, who may have periods of crescendo-decrescendo change in tidal volume (Cheyne-Stokes respiration) with possible intercalated episodes of central apnea or hypopnea. It is also applied in patients with the complex sleep apnea syndrome.

Adaptive servo-ventilation devices are usually set at an expiratory positive airway pressure (EPAP) level sufficient to control obstructive sleep apnea. The device then automatically adjusts the pressure support for each inspiration, within a prespecified range, to maintain a moving-target ventilation set at 90% of the patient’s recent average ventilation. The aim is to stabilize breathing and reduce respiratory alkalosis, which can trigger apnea reentry cycles.18

Bilevel positive airway pressure

Bilevel positive airway pressure (bilevel PAP) can be of use in sleep-disordered breathing (including cases associated with congestive heart failure), but it is predominantly applied in conditions associated with hypoventilation.

Bilevel PAP devices deliver a higher pressure during inspiration (inspiratory positive airway pressure, or IPAP) and a lower pressure during expiration (EPAP). The gradient between IPAP and EPAP is of key importance in maintaining alveolar ventilation and reducing Paco2. The IPAP acts as pressure support to augment the patient’s effort, maintain adequate alveolar ventilation, unload respiratory muscles, decrease the work of breathing, and control obstructive hypopnea, whereas EPAP is set to maintain upper airway patency, control obstructive apnea, improve functional residual capacity, and prevent microatelectasis.

Although there is no evidence that bilevel PAP is better adhered to or more effective than CPAP, current guidelines propose it as an option for patients who require high pressures to control obstructive sleep apnea-hypopnea syndrome or for those who cannot tolerate exhaling against a high fixed CPAP pressure.19

Other, more-common uses of bilevel PAP are to treat coexisting central sleep apnea or hypoventilation,19 the obesity-hypoventilation syndrome with residual alveolar hypoventilation despite CPAP and control of concomitant obstructive sleep apnea-hypopnea syndrome,5,20 severe stable COPD with significant nocturnal hypoventilation and daytime hypercarbia,21 and restrictive pulmonary diseases.21

Although the patient should be able to maintain spontaneous breathing on bilevel PAP, a backup rate option can be set for those whose ventilation during sleep may be significantly impaired (eg, those with neuromuscular diseases, complex sleep apnea, central apnea in congestive heart failure, or obesity-hypoventilation syndrome) (Table 1, Table 2).22,23 However, one important paradoxical consideration is that both CPAP and bilevel PAP (with or without a backup rate) promote ventilation and have the potential of dropping the carbon dioxide level below a hypocapnic apneic threshold during sleep, thereby triggering central apnea and the complex sleep apnea syndrome.24

Average volume-assured pressure support

Average volume-assured pressure support is directed mainly at patients with chronic hypoventilation such as those with obesity-hypoventilation syndrome, neuromuscular diseases, and COPD. In this mode, a target tidal volume is set, and the device adjusts the pressure support to reach that set tidal volume. The advantage is that it guarantees a delivered tidal volume despite variability in patient effort, airway resistance, and lung or chest wall compliance. A particular potential benefit is that it may adapt to disease progression, as may occur in patients with progressive neuromuscular disorders.

 

 

CONDITIONS IN WHICH NOCTURNAL NIPPV IS USED IN OUT PATIENTS

Obstructive sleep apnea-hypopnea syndrome

Obstructive sleep apnea-hypopnea syndrome is estimated to affect 2% of women and 4% of men.25 It is characterized by recurrent episodes of partial (hypopnea) or complete (apnea) upper airway obstruction during sleep despite ongoing inspiratory efforts, with associated episodes of arousal or desaturation or both. Corresponding symptoms include excessive daytime sleepiness, choking and gasping during sleep, recurrent awakenings from sleep, unrefreshing sleep, daytime fatigue, and impaired concentration that is not explained by other factors.26

Current understanding of the pathophysiology of obstructive sleep apnea implicates an impairment in the balance between factors that promote collapsibility of the airway (including obesity and anatomic issues such as the volume of the soft-tissue structures surrounding the upper airway) and the compensatory neuromuscular response.27,28

Long-standing obstructive sleep apnea-hypopnea syndrome has been linked in prospective studies to the development of hypertension,29–31 coronary artery disease,32,33 increased coagulation,34,35 and stroke or death from any cause.36,37 It is also associated with a greater rate and severity of motor vehicular accidents,38 greater health care utilization, impaired work performance, and occupational injuries.39

Strong evidence exists that NIPPV (most commonly CPAP) is beneficial in obstructive sleep apnea-hypopnea syndrome, improving sleep quality, sleepiness, cognitive impairment, and quality of life,40,41 decreasing motor vehicle accidents,42 lowering blood pressure, 43,44 and decreasing the rates of myocardial infarction,32 stroke,32 and death.45

The American Academy of Sleep Medicine recommends CPAP as an optional adjunctive therapy to lower blood pressure in patients with obstructive sleep apnea-hypopnea syndrome with concomitant hypertension.19 This is supported by a recent study that suggested that CPAP may have additional benefits on blood pressure in a subgroup of patients with uncontrolled hypertension while on antihypertensive medications.46 Indications with Medicare guidelines for reimbursement of CPAP devices are summarized in Table 2.

Complex sleep apnea syndrome

The complex sleep apnea syndrome is characterized by the emergence of significant central sleep apnea or Cheyne-Stokes respiration after obstructive events have been brought under control with NIPPV in patients who initially appear to have obstructive sleep apnea-hypopnea syndrome. A retrospective study of patients with the complex sleep apnea syndrome who continued their NIPPV use until a subsequent polysomnographic study and NIPPV titration showed that the syndrome may resolve spontaneously, but that 46% of patients had a persistently elevated apnea-hypopnea index with central apnea activity.47

Restoration of upper airway patency by CPAP and dysregulation or delayed adaptation of chemosensitive ventilatory control to a changing Paco2 level may be a key pathophysiologic mechanism of the complex sleep apnea syndrome.48 In this mechanism, increased ventilation from restored airway patency and from an increase in the slope of the ventilatory response may intermittently draw the Paco2 to below the hypocapnic apneic threshold and trigger episodes of central apnea.48

The ideal NIPPV device for use in the complex sleep apnea syndrome should be able to provide enough pressure to resolve the obstructive sleep apnea-hypopnea syndrome while maintaining proper ventilatory support during central apnea episodes without fluctuations of Paco2, which could further worsen the dysregulated ventilatory control. Currently, adaptive servo-ventilation appears to be superior to bilevel PAP and CPAP in the management of the complex sleep apnea syndrome.49,50

Sleep disturbances associated with cardiac dysfunction

There are specific indications for NIPPV modes in the setting of respiratory sleep disturbances associated with heart failure.

Obstructive sleep apnea in congestive heart failure. The prevalence of obstructive sleep apnea in patients with impaired left ventricular ejection fraction is 11% to 53%.51 Obstructive sleep apnea-hypopnea syndrome can worsen congestive heart failure by causing a periodic increase in negative intrathoracic pressure from breathing against an occluded airway, by raising arterial blood pressure, and causing tachycardia from sympathetic nervous system stimulation from hypoxia, hypercarbia, and arousals.52,53 Both heart failure and sleep apnea contribute in an additive manner to the increased sympathetic nervous activity.54

Fortunately, treatment with CPAP has been found to reduce systolic blood pressure and improve left ventricular systolic function in medically treated patients with heart failure and coexisting obstructive sleep apnea.11,12 Furthermore, in a randomized trial in patients with stable congestive heart failure and newly diagnosed obstructive sleep apnea-hypopnea syndrome, a greater improvement in cardiac function was observed in patients on bilevel PAP than in those on CPAP.55 The authors speculated that bilevel PAP might provide more unloading of the respiratory muscles, reduce the work of breathing more, and result in less positive intrathoracic pressure than with CPAP, and that the higher intrathoracic pressure with CPAP could reduce the left ventricular ejection fraction in patients with low filling pressures (pulmonary capillary wedge pressure < 12 mm Hg) and low baseline left ventricular ejection fractions (< 30%).55

Whether these interventions reduce the mortality rate is uncertain. In a prospective nonrandomized study, 9 (24%) of 37 patients who had heart failure with untreated obstructive sleep apnea died, compared with no deaths in 14 treated patients (P = .07).56

Cheyne-Stokes respiration with central sleep apnea in congestive heart failure. A related but different situation is central apnea associated with congestive heart failure.

There are several pathophysiologic mechanisms of Cheyne-Stokes respiration with central sleep apnea. Specifically, the elevation of left ventricular filling pressures, end-diastolic volumes, and pulmonary congestion generate hyperventilation, chronic hypocapnia, and increased chemoreceptor responsiveness, which contribute to the development of central apnea by promoting a decrease in the Paco2 during sleep to below the hypocapnic apneic threshold.57,58 Additionally, an increase in circulation time may result in periodicity of breathing and hyperpnea.59 Obstructive events can then occur at the end of the central events corresponding with the nadir of the inspiratory drive.60,61

The Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure (CANPAP) trial, a randomized trial of CPAP in this clinical setting, showed that compared with optimal medical therapy alone, CPAP plus optimal medical therapy improved the ejection fraction, reduced central sleep apnea, improved nocturnal oxygenation, and improved the 6-minute walking distance, but without a survival benefit.62 The disappointing survival results from CANPAP have to be interpreted in the context that CPAP may have failed to control the central apnea in some patients, such that the mean apnea-hypopnea index in treated patients (19 events/hour) remained above the entry criterion for recruitment (15 events/hour). In a post hoc analysis of this study, the heart-transplantation-free survival rate was significantly greater in the subgroup of patients in whom CPAP effectively suppressed central sleep apnea (< 15 events/hour).63

Other NIPPV modes such as bilevel PAP with backup rate and adaptive servo-ventilation have been shown in some studies to be superior to CPAP in controlling respiratory events, with adaptive servo-ventilation being the most effective in controlling central, mixed, and complex sleep apnea in this setting. 49,50 Whether more effective resolution of obstructive and central events with these treatment modes translates into improved mortality rates and transplantation-free survival rates remains to be determined.

 

 

Obesity-hypoventilation syndrome

Obesity-hypoventilation syndrome refers to daytime hypercapnia (Paco2 > 45 mm Hg) in obese people when no other cause of hypoventilation is present.

The prevalence of obesity-hypoventilation syndrome among patients with obstructive sleep apnea-hypopnea syndrome is 20% to 30% and is greater in extremely obese patients (body mass index > 40 kg/m2).64 However, about 10% of patients with obesity-hypoventilation syndrome do not have obstructive sleep apnea-hypopnea syndrome.64 Additionally, nocturnal hypoxemia and diurnal hypercapnia persist in about 40% of patients with obesity-hypoventilation syndrome after CPAP eliminates their sleep apnea.65 Therefore, factors other than sleep apnea contribute to the development of obesity-hypoventilation syndrome, and in a meta-analysis, factors associated with daytime hypercapnia included, in addition to body mass index and the apnea-hypopnea index, mean overnight oxygen saturation and severity of restrictive pulmonary function.66 Predictors of success with CPAP include better spirometric findings, a higher apnea-hypopnea index, and adequate oxygenation.67,68

Bilevel PAP therapy can be tried in patients in whom CPAP by itself fails. In a study of patients with obesity-hypoventilation syndrome in whom initial CPAP treatment failed, average volume-assured pressure support lowered Paco2 compared to bilevel PAP alone, but did not further improve oxygenation, sleep quality, or quality of life.69

Restrictive pulmonary diseases

Neuromuscular diseases and thoracic cage abnormalities. Noninvasive ventilation has been used in patients with progressive neuromuscular disorders or severe thoracic cage abnormalities, with recognized benefits including an improved survival rate and improved quality of life.70,71 However, NIPPV is used in only 9% of patients with amyotrophic lateral sclerosis when clearly indicated.72 The indications and Medicare guidelines for reimbursement of NIPPV (with or without a backup rate) in this setting are shown in Table 2.

Potential contraindications to starting NIPPV in this population include upper airway obstruction, failure to clear secretions despite optimal noninvasive support, inability to achieve a mask fit, and intolerance of the intervention.73,74

The mechanisms of benefit of NIPPV in these settings include improvements in daytime blood gas levels (including hypercapnia75), a reduction in the oxygen cost of breathing,76 an increase in the ventilatory response to carbon dioxide,75 and improved lung compliance.77

Chronic hypercapnic failure due to severe COPD

The use of NIPPV in chronic COPD is less well established than in patients with exacerbations of COPD,78 and limitations in its use are reflected in the more stringent Medicare indications for NIPPV in this setting (Table 2).

A particular subset of patients with stable COPD who may benefit from NIPPV includes those with daytime hypercapnia and super-imposed nocturnal hypoventilation.78 The potential benefits of NIPPV in these patients include improved daytime and nocturnal gas exchange, increased sleep duration, and improved quality of life.78 Additionally, a recent randomized controlled trial of NIPPV plus long-term oxygen therapy compared with oxygen therapy alone in patients with severe COPD and a Paco2 greater than 46 mm Hg demonstrated a survival benefit in favor of adding NIPPV (hazard ratio 0.6).79

However, that study also found no reduction in hospitalization rates, an apparent worsening in general and mental health (as reflected on the 36-Item Short Form Health Survey or SF-36, a quality-of-life questionnaire), as well as increased confusion and bewilderment (reflected on the Profile of Mood States scale).79 These potentially deleterious effects may explain why adherence to NIPPV is low in patients with stable COPD: only 37% to 57% of patients continued to use it in several reported studies.79–81

A level of inspiratory pressure support that is insufficient to reduce hypercapnia may account for the low adherence rate and worsened quality of life in such patients. For instance, in a randomized trial,82 compared with low-intensity NIPPV (mean IPAP 14 cm H2O, backup rate 8 per minute), settings that aimed to maximally reduce Paco2 (mean IPAP 29 cm H2O with a backup rate of 17.5 per minute) increased the daily use of NIPPV by 3.6 hours/day and improved exercise-related dyspnea, daytime Paco2, forced expiratory volume in 1 second (FEV1), vital capacity, and health-related quality of life.

The overlap syndrome was first described by Flenley in 1985 as a combination of chronic respiratory disease (more generally limited to COPD) and obstructive sleep apnea-hypopnea syndrome.83 Epidemiologic studies do not consistently show a higher incidence of obstructive sleep apnea-hypopnea syndrome in patients with COPD, but the exaggerated oxygen desaturation during sleep in patients with this combination increases the risk of hypoxemia, hypercapnia, and pulmonary hypertension. 84 In addition, there was evidence of higher risks of death and of hospitalization for COPD in patients with the overlap syndrome. 85 NIPPV is the main treatment for obstructive sleep apnea-hypopnea syndrome with or without COPD.

A recent study by Marin et al85 showed that CPAP was associated with improved survival and decreased hospitalization in patients with the overlap syndrome. However, polysomnography or nocturnal oximetry while on NIPPV alone must be done, as additional nocturnal oxygen therapy may be warranted when significant chronic respiratory illness coexists with sleep apnea.
 

Acknowledgment: The authors gratefully acknowledge the contribution of Scott Marlow, RRT, to Table 2 of this review.

References
  1. Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001; 163:283–291.
  2. Aboussouan LS, Ricaurte B. Noninvasive positive pressure ventilation: increasing use in acute care. Cleve Clin J Med 2010; 77:307–316.
  3. Sullivan CE, Berthon-Jones M, Issa FG. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure. Am Rev Respir Dis 1983; 128:177–181.
  4. Ellis ER, Bye PT, Bruderer JW, Sullivan CE. Treatment of respiratory failure during sleep in patients with neuromuscular disease. Positive-pressure ventilation through a nose mask. Am Rev Respir Dis 1987; 135:148–152.
  5. Berger KI, Ayappa I, Chatr-Amontri B, et al. Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest 2001; 120:1231–1238.
  6. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948–956.
  7. de Miguel J, Cabello J, Sánchez-Alarcos JM, Alvarez-Sala R, Espinós D, Alvarez-Sala JL. Long-term effects of treatment with nasal continuous positive airway pressure on lung function in patients with overlap syndrome. Sleep Breath 2002; 6:3–10.
  8. Mezzanotte WS, Tangel DJ, Fox AM, Ballard RD, White DP. Nocturnal nasal continuous positive airway pressure in patients with chronic obstructive pulmonary disease. Influence on waking respiratory muscle function. Chest 1994; 106:1100–1108.
  9. Petrof BJ, Legaré M, Goldberg P, Milic-Emili J, Gottfried SB. Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1990; 141:281–289.
  10. Verbraecken J, Willemen M, De Cock W, Van de Heyning P, De Backer WA. Continuous positive airway pressure and lung inflation in sleep apnea patients. Respiration 2001; 68:357–364.
  11. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348:1233–1241.
  12. Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med 2004; 169:361–366.
  13. Malhotra A, Trinder J, Fogel R, et al. Postural effects on pharyngeal protective reflex mechanisms. Sleep 2004; 27:1105–1112.
  14. Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep 2004; 27:249–253.
  15. Nolan GM, Ryan S, O’Connor TM, McNicholas WT. Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea. Eur Respir J 2006; 28:159–164.
  16. Meurice JC, Cornette A, Philip-Joet F, et al; ANTADIR “PPC” Working Group. Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome. Sleep Med 2007; 8:695–703.
  17. Morgenthaler TI, Aurora RN, Brown T, et al; Standards of Practice Committee of the AASM; American Academy of Sleep Medicine. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep 2008; 31:141–147.
  18. 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; 164:614–619.
  19. Kushida CA, Littner MR, Hirshkowitz M, et al; American Academy of Sleep Medicine. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006; 29:375–380.
  20. Schäfer H, Ewig S, Hasper E, Lüderitz B. Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure. Respir Med 1998; 92:208–215.
  21. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation—a consensus conference report. Chest 1999; 116:521–534.
  22. Aboussouan LS, Khan SU, Meeker DP, Stelmach K, Mitsumoto H. Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis. Ann Intern Med 1997; 127:450–453.
  23. Köhnlein T, Welte T, Tan LB, Elliott MW. Assisted ventilation for heart failure patients with Cheyne-Stokes respiration. Eur Respir J 2002; 20:934–941.
  24. Johnson KG, Johnson DC. Bilevel positive airway pressure worsens central apneas during sleep. Chest 2005; 128:2141–2150.
  25. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328:1230–1235.
  26. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22:667–689.
  27. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007; 132:325–337.
  28. Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003; 168:522–530.
  29. Hedner J, Bengtsson-Boström K, Peker Y, Grote L, Råstam L, Lindblad U. Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study. Eur Respir J 2006; 27:564–570.
  30. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283:1829–1836.
  31. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342:1378–1384.
  32. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365:1046–1053.
  33. Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006; 28:596–602.
  34. Guardiola JJ, Matheson PJ, Clavijo LC, Wilson MA, Fletcher EC. Hypercoagulability in patients with obstructive sleep apnea. Sleep Med 2001; 2:517–523.
  35. von Känel R, Loredo JS, Ancoli-Israel S, Mills PJ, Natarajan L, Dimsdale JE. Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 2007; 131:733–739.
  36. Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2010; Epub ahead of print.
  37. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034–2041.
  38. Mulgrew AT, Nasvadi G, Butt A, et al. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax 2008; 63:536–541.
  39. AlGhanim N, Comondore VR, Fleetham J, Marra CA, Ayas NT. The economic impact of obstructive sleep apnea. Lung 2008; 186:7–12.
  40. Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2006; 3:CD001106.
  41. Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 2003; 163:565–571.
  42. George CF. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax 2001; 56:508–512.
  43. Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107:68–73.
  44. Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 163:344–348.
  45. Campos-Rodriguez F, Peña-Griñan N, Reyes-Nuñez N, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest 2005; 128:624–633.
  46. Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive sleep apnea patients. Am J Respir Crit Care Med 2010; Epub ahead of print.
  47. Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea—a retrospective study. Sleep Breath 2008; 12:135–139.
  48. Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep 2006; 29:1203–1209.
  49. Allam JS, Olson EJ, Gay PC, Morgenthaler TI. Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest 2007; 132:1839–1846.
  50. 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; 30:468–475.
  51. Bordier P. Sleep apnoea in patients with heart failure. Part I: diagnosis, definitions, prevalence, pathophysiology and haemodynamic consequences. Arch Cardiovasc Dis 2009; 102:651–661.
  52. Romero-Corral A, Somers VK, Pellikka PA, et al. Decreased right and left ventricular myocardial performance in obstructive sleep apnea. Chest 2007; 132:1863–1870.
  53. Solin P, Kaye DM, Little PJ, Bergin P, Richardson M, Naughton MT. Impact of sleep apnea on sympathetic nervous system activity in heart failure. Chest 2003; 123:1119–1126.
  54. Floras JS. Should sleep apnoea be a specific target of therapy in chronic heart failure? Heart 2009; 95:1041–1046.
  55. Khayat RN, Abraham WT, Patt B, Roy M, Hua K, Jarjoura D. Cardiac effects of continuous and bilevel positive airway pressure for patients with heart failure and obstructive sleep apnea: a pilot study. Chest 2008; 134:1162–1168.
  56. Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 2007; 49:1625–1631.
  57. Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med 1999; 341:949–954.
  58. Tkacova R, Hall MJ, Liu PP, Fitzgerald FS, Bradley TD. Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep. Am J Respir Crit Care Med 1997; 156:1549–1555.
  59. Lorenzi-Filho G, Rankin F, Bies I, Douglas Bradley T. Effects of inhaled carbon dioxide and oxygen on Cheyne-Stokes respiration in patients with heart failure. Am J Respir Crit Care Med 1999; 159:1490–1498.
  60. Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol 1995; 78:1806–1815.
  61. Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol 1986; 61:1438–1443.
  62. Bradley TD, Logan AG, Kimoff RJ, et al; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005; 353:2025–2033.
  63. 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; 115:3173–3180.
  64. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath 2007; 11:117–124.
  65. Banerjee D, Yee BJ, Piper AJ, Zwillich CW, Grunstein RR. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678–1684.
  66. Kaw R, Hernandez AV, Walker E, Aboussouan L, Mokhlesi B. Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Chest 2009; 136:787–796.
  67. Pérez de Llano LA, Golpe R, Piquer MO, et al. Clinical heterogeneity among patients with obesity hypoventilation syndrome: therapeutic implications. Respiration 2008; 75:34–39.
  68. Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63:395–401.
  69. Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial. Chest 2006; 130:815–821.
  70. Aboussouan LS, Khan SU, Banerjee M, Arroliga AC, Mitsumoto H. Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis. Muscle Nerve 2001; 24:403–409.
  71. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 5:140–147.
  72. Miller RG, Anderson F, Brooks BR, Mitsumoto H, Bradley WG, Ringel SP; ALS CARE Study Group. Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database. Ann Neurol 2009; 65(suppl 1):S24–S28.
  73. Bach JR. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory AIDS. Chest 2002; 122:92–98.
  74. Perrin C, Unterborn JN, Ambrosio CD, Hill NS. Pulmonary complications of chronic neuromuscular diseases and their management. Muscle Nerve 2004; 29:5–27.
  75. Nickol AH, Hart N, Hopkinson NS, Moxham J, Simonds A, Polkey MI. Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation. Thorax 2005; 60:754–760.
  76. Barle H, Söderberg P, Haegerstrand C, Markström A. Bi-level positive airway pressure ventilation reduces the oxygen cost of breathing in long-standing post-polio patients on invasive home mechanical ventilation. Acta Anaesthesiol Scand 2005; 49:197–202.
  77. Lechtzin N, Shade D, Clawson L, Wiener CM. Supramaximal inflation improves lung compliance in subjects with amyotrophic lateral sclerosis. Chest 2006; 129:1322–1329.
  78. Hill NS. Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care 2004; 49:72–87;
  79. McEvoy RD, Pierce RJ, Hillman D, et al; Australian trial of noninvasive Ventilation in Chronic Airflow Limitation (AVCAL) Study Group. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Thorax 2009; 64:561–566.
  80. Criner GJ, Brennan K, Travaline JM, Kreimer D. Efficacy and compliance with noninvasive positive pressure ventilation in patients with chronic respiratory failure. Chest 1999; 116:667–675.
  81. Strumpf DA, Millman RP, Carlisle CC, et al. Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 144:1234–1239.
  82. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax 2010; 65:303–308.
  83. Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med 1985; 6:651–661.
  84. Weitzenblum E, Chaouat A, Kessler R, Canuet M. Overlap syndrome: obstructive sleep apnea in patients with chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008; 5:237–241.
  85. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea. The overlap syndrome. Am J Respir Crit Care Med 2010; Epub ahead of print.
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Theerakorn Theerakittikul, MD
Sleep Disorders Center, Neurological Institute, Cleveland Clinic

Basma Ricaurte, MD
Pulmonary and Critical Care, Fairview Hospital, a Cleveland Clinic Hospital

Loutfi S. Aboussouan, MD
Sleep Disorders Center, Neurological Institute, and Respiratory Institute, Cleveland Clinic

Address: Loutfi S. Aboussouan, MD, Respiratory Institute, Cleveland Clinic Beachwood, 26900 Cedar Road, Suite 325-S, Beachwood, OH 44122; e-mail aboussl@ccf.org

Issue
Cleveland Clinic Journal of Medicine - 77(10)
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Cleveland Clinic Journal of Medicine
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Pulmonology
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Cardiology
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Author(s)
Theerakorn Theerakittikul, MD
Basma Ricaurte, MD
Loutfi S. Aboussouan, MD
Author(s)
Theerakorn Theerakittikul, MD
Basma Ricaurte, MD
Loutfi S. Aboussouan, MD
Author and Disclosure Information

Theerakorn Theerakittikul, MD
Sleep Disorders Center, Neurological Institute, Cleveland Clinic

Basma Ricaurte, MD
Pulmonary and Critical Care, Fairview Hospital, a Cleveland Clinic Hospital

Loutfi S. Aboussouan, MD
Sleep Disorders Center, Neurological Institute, and Respiratory Institute, Cleveland Clinic

Address: Loutfi S. Aboussouan, MD, Respiratory Institute, Cleveland Clinic Beachwood, 26900 Cedar Road, Suite 325-S, Beachwood, OH 44122; e-mail aboussl@ccf.org

Author and Disclosure Information

Theerakorn Theerakittikul, MD
Sleep Disorders Center, Neurological Institute, Cleveland Clinic

Basma Ricaurte, MD
Pulmonary and Critical Care, Fairview Hospital, a Cleveland Clinic Hospital

Loutfi S. Aboussouan, MD
Sleep Disorders Center, Neurological Institute, and Respiratory Institute, Cleveland Clinic

Address: Loutfi S. Aboussouan, MD, Respiratory Institute, Cleveland Clinic Beachwood, 26900 Cedar Road, Suite 325-S, Beachwood, OH 44122; e-mail aboussl@ccf.org

Article PDF
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Noninvasive positive pressure ventilation (NIPPV) is any form of positive ventilatory support applied without an endotracheal tube, including continuous positive airway pressure (CPAP).1 The role of NIPPV in acute care has been discussed in an earlier review in the Cleveland Clinic Journal of Medicine.2

NIPPV is also used at night in outpatients with stable chronic conditions, first used in the 1980s in the treatment of obstructive sleep apnea3 and neuromuscular diseases,4 and since then in several other conditions including sleep disorders associated with congestive heart failure (including sleep apnea and the Cheyne-Stokes respiration-central sleep apnea syndrome), chronic obstructive pulmonary disease (COPD), and the obesity-hypoventilation syndrome.

In this review, we discuss the different types of NIPPV, the specific conditions in which they can be used, and the indications, recommendations, and evidence supporting the efficacy of NIPPV in outpatients.

THE TYPES OF NIPPV AND THEIR USES

Although the conditions for which different types of NIPPV can be used overlap significantly, each type has general indications and different goals of treatment. This section begins with types of NIPPV that are predominantly used to treat sleep-disordered breathing, and then proceeds to those predominantly used for conditions associated with hypoventilation and hypercapnia.

Continuous positive airway pressure

CPAP, currently the most widely used form of NIPPV, applies a constant level of positive pressure at the airway opening during spontaneous breathing.

CPAP is commonly used to treat obstructive sleep-disordered breathing, with the goals of improving daytime sleepiness and reducing cardiovascular risk. It has also been used to treat sleep-disordered breathing associated with congestive heart failure.

CPAP’s role in the support of ventilation is limited and indirect. For instance, it has been used in the obesity-hypoventilation syndrome and in the “overlap” syndrome (in which both sleep apnea and COPD coexist). However, its benefits in those conditions are probably derived in large part from correction of underlying obstructive sleep apnea.

The mechanisms of action of CPAP include:

  • Preventing intermittent narrowing and collapse of the airway in patients with obstructive sleep apnea-hypopnea syndrome by acting as a pneumatic splint during sleep3,5,6
  • Counteracting auto-positive end-expiratory pressure, thereby reducing respiratory muscle load, reducing the work of breathing, and lowering daytime Paco2 in patients with coexistent COPD and obstructive sleep apnea-hypopnea syndrome (the overlap syndrome)7–9
  • Improving lung function (particularly the functional residual capacity) and daytime gas exchange in obstructive sleep apnea-hypopnea syndrome 10
  • Improving left ventricular systolic function in patients with heart failure coexisting with obstructive sleep apnea-hypopnea syndrome.11,12

Auto-CPAP is delivered via a self-titrating CPAP device, which uses algorithms to detect variations in the degree of obstruction and consequently adjusts the pressure level to restore normal breathing. Auto-CPAP therefore compensates for factors that modify the upper airway collapsibility, such as body posture during sleep, stage of sleep, use of alcohol, and drugs that affect upper airway muscle tone.13

Although one of the premises of using auto-CPAP is that it improves the patient’s satisfaction and compliance, several studies found it to be no more effective than fixed CPAP for treating obstructive sleep apnea-hypopnea syndrome.14–16 Current guidelines of the American Academy of Sleep Medicine do not recommend self-titrating CPAP devices to diagnose obstructive sleep apnea or to treat patients with cardiopulmonary disorders or other conditions in which nocturnal desaturation may be unrelated to obstructive events.17

Adaptive servo-ventilation

Adaptive servo-ventilation was developed for Cheyne-Stokes respiration-central sleep apnea syndrome in patients with congestive heart failure, who may have periods of crescendo-decrescendo change in tidal volume (Cheyne-Stokes respiration) with possible intercalated episodes of central apnea or hypopnea. It is also applied in patients with the complex sleep apnea syndrome.

Adaptive servo-ventilation devices are usually set at an expiratory positive airway pressure (EPAP) level sufficient to control obstructive sleep apnea. The device then automatically adjusts the pressure support for each inspiration, within a prespecified range, to maintain a moving-target ventilation set at 90% of the patient’s recent average ventilation. The aim is to stabilize breathing and reduce respiratory alkalosis, which can trigger apnea reentry cycles.18

Bilevel positive airway pressure

Bilevel positive airway pressure (bilevel PAP) can be of use in sleep-disordered breathing (including cases associated with congestive heart failure), but it is predominantly applied in conditions associated with hypoventilation.

Bilevel PAP devices deliver a higher pressure during inspiration (inspiratory positive airway pressure, or IPAP) and a lower pressure during expiration (EPAP). The gradient between IPAP and EPAP is of key importance in maintaining alveolar ventilation and reducing Paco2. The IPAP acts as pressure support to augment the patient’s effort, maintain adequate alveolar ventilation, unload respiratory muscles, decrease the work of breathing, and control obstructive hypopnea, whereas EPAP is set to maintain upper airway patency, control obstructive apnea, improve functional residual capacity, and prevent microatelectasis.

Although there is no evidence that bilevel PAP is better adhered to or more effective than CPAP, current guidelines propose it as an option for patients who require high pressures to control obstructive sleep apnea-hypopnea syndrome or for those who cannot tolerate exhaling against a high fixed CPAP pressure.19

Other, more-common uses of bilevel PAP are to treat coexisting central sleep apnea or hypoventilation,19 the obesity-hypoventilation syndrome with residual alveolar hypoventilation despite CPAP and control of concomitant obstructive sleep apnea-hypopnea syndrome,5,20 severe stable COPD with significant nocturnal hypoventilation and daytime hypercarbia,21 and restrictive pulmonary diseases.21

Although the patient should be able to maintain spontaneous breathing on bilevel PAP, a backup rate option can be set for those whose ventilation during sleep may be significantly impaired (eg, those with neuromuscular diseases, complex sleep apnea, central apnea in congestive heart failure, or obesity-hypoventilation syndrome) (Table 1, Table 2).22,23 However, one important paradoxical consideration is that both CPAP and bilevel PAP (with or without a backup rate) promote ventilation and have the potential of dropping the carbon dioxide level below a hypocapnic apneic threshold during sleep, thereby triggering central apnea and the complex sleep apnea syndrome.24

Average volume-assured pressure support

Average volume-assured pressure support is directed mainly at patients with chronic hypoventilation such as those with obesity-hypoventilation syndrome, neuromuscular diseases, and COPD. In this mode, a target tidal volume is set, and the device adjusts the pressure support to reach that set tidal volume. The advantage is that it guarantees a delivered tidal volume despite variability in patient effort, airway resistance, and lung or chest wall compliance. A particular potential benefit is that it may adapt to disease progression, as may occur in patients with progressive neuromuscular disorders.

 

 

CONDITIONS IN WHICH NOCTURNAL NIPPV IS USED IN OUT PATIENTS

Obstructive sleep apnea-hypopnea syndrome

Obstructive sleep apnea-hypopnea syndrome is estimated to affect 2% of women and 4% of men.25 It is characterized by recurrent episodes of partial (hypopnea) or complete (apnea) upper airway obstruction during sleep despite ongoing inspiratory efforts, with associated episodes of arousal or desaturation or both. Corresponding symptoms include excessive daytime sleepiness, choking and gasping during sleep, recurrent awakenings from sleep, unrefreshing sleep, daytime fatigue, and impaired concentration that is not explained by other factors.26

Current understanding of the pathophysiology of obstructive sleep apnea implicates an impairment in the balance between factors that promote collapsibility of the airway (including obesity and anatomic issues such as the volume of the soft-tissue structures surrounding the upper airway) and the compensatory neuromuscular response.27,28

Long-standing obstructive sleep apnea-hypopnea syndrome has been linked in prospective studies to the development of hypertension,29–31 coronary artery disease,32,33 increased coagulation,34,35 and stroke or death from any cause.36,37 It is also associated with a greater rate and severity of motor vehicular accidents,38 greater health care utilization, impaired work performance, and occupational injuries.39

Strong evidence exists that NIPPV (most commonly CPAP) is beneficial in obstructive sleep apnea-hypopnea syndrome, improving sleep quality, sleepiness, cognitive impairment, and quality of life,40,41 decreasing motor vehicle accidents,42 lowering blood pressure, 43,44 and decreasing the rates of myocardial infarction,32 stroke,32 and death.45

The American Academy of Sleep Medicine recommends CPAP as an optional adjunctive therapy to lower blood pressure in patients with obstructive sleep apnea-hypopnea syndrome with concomitant hypertension.19 This is supported by a recent study that suggested that CPAP may have additional benefits on blood pressure in a subgroup of patients with uncontrolled hypertension while on antihypertensive medications.46 Indications with Medicare guidelines for reimbursement of CPAP devices are summarized in Table 2.

Complex sleep apnea syndrome

The complex sleep apnea syndrome is characterized by the emergence of significant central sleep apnea or Cheyne-Stokes respiration after obstructive events have been brought under control with NIPPV in patients who initially appear to have obstructive sleep apnea-hypopnea syndrome. A retrospective study of patients with the complex sleep apnea syndrome who continued their NIPPV use until a subsequent polysomnographic study and NIPPV titration showed that the syndrome may resolve spontaneously, but that 46% of patients had a persistently elevated apnea-hypopnea index with central apnea activity.47

Restoration of upper airway patency by CPAP and dysregulation or delayed adaptation of chemosensitive ventilatory control to a changing Paco2 level may be a key pathophysiologic mechanism of the complex sleep apnea syndrome.48 In this mechanism, increased ventilation from restored airway patency and from an increase in the slope of the ventilatory response may intermittently draw the Paco2 to below the hypocapnic apneic threshold and trigger episodes of central apnea.48

The ideal NIPPV device for use in the complex sleep apnea syndrome should be able to provide enough pressure to resolve the obstructive sleep apnea-hypopnea syndrome while maintaining proper ventilatory support during central apnea episodes without fluctuations of Paco2, which could further worsen the dysregulated ventilatory control. Currently, adaptive servo-ventilation appears to be superior to bilevel PAP and CPAP in the management of the complex sleep apnea syndrome.49,50

Sleep disturbances associated with cardiac dysfunction

There are specific indications for NIPPV modes in the setting of respiratory sleep disturbances associated with heart failure.

Obstructive sleep apnea in congestive heart failure. The prevalence of obstructive sleep apnea in patients with impaired left ventricular ejection fraction is 11% to 53%.51 Obstructive sleep apnea-hypopnea syndrome can worsen congestive heart failure by causing a periodic increase in negative intrathoracic pressure from breathing against an occluded airway, by raising arterial blood pressure, and causing tachycardia from sympathetic nervous system stimulation from hypoxia, hypercarbia, and arousals.52,53 Both heart failure and sleep apnea contribute in an additive manner to the increased sympathetic nervous activity.54

Fortunately, treatment with CPAP has been found to reduce systolic blood pressure and improve left ventricular systolic function in medically treated patients with heart failure and coexisting obstructive sleep apnea.11,12 Furthermore, in a randomized trial in patients with stable congestive heart failure and newly diagnosed obstructive sleep apnea-hypopnea syndrome, a greater improvement in cardiac function was observed in patients on bilevel PAP than in those on CPAP.55 The authors speculated that bilevel PAP might provide more unloading of the respiratory muscles, reduce the work of breathing more, and result in less positive intrathoracic pressure than with CPAP, and that the higher intrathoracic pressure with CPAP could reduce the left ventricular ejection fraction in patients with low filling pressures (pulmonary capillary wedge pressure < 12 mm Hg) and low baseline left ventricular ejection fractions (< 30%).55

Whether these interventions reduce the mortality rate is uncertain. In a prospective nonrandomized study, 9 (24%) of 37 patients who had heart failure with untreated obstructive sleep apnea died, compared with no deaths in 14 treated patients (P = .07).56

Cheyne-Stokes respiration with central sleep apnea in congestive heart failure. A related but different situation is central apnea associated with congestive heart failure.

There are several pathophysiologic mechanisms of Cheyne-Stokes respiration with central sleep apnea. Specifically, the elevation of left ventricular filling pressures, end-diastolic volumes, and pulmonary congestion generate hyperventilation, chronic hypocapnia, and increased chemoreceptor responsiveness, which contribute to the development of central apnea by promoting a decrease in the Paco2 during sleep to below the hypocapnic apneic threshold.57,58 Additionally, an increase in circulation time may result in periodicity of breathing and hyperpnea.59 Obstructive events can then occur at the end of the central events corresponding with the nadir of the inspiratory drive.60,61

The Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure (CANPAP) trial, a randomized trial of CPAP in this clinical setting, showed that compared with optimal medical therapy alone, CPAP plus optimal medical therapy improved the ejection fraction, reduced central sleep apnea, improved nocturnal oxygenation, and improved the 6-minute walking distance, but without a survival benefit.62 The disappointing survival results from CANPAP have to be interpreted in the context that CPAP may have failed to control the central apnea in some patients, such that the mean apnea-hypopnea index in treated patients (19 events/hour) remained above the entry criterion for recruitment (15 events/hour). In a post hoc analysis of this study, the heart-transplantation-free survival rate was significantly greater in the subgroup of patients in whom CPAP effectively suppressed central sleep apnea (< 15 events/hour).63

Other NIPPV modes such as bilevel PAP with backup rate and adaptive servo-ventilation have been shown in some studies to be superior to CPAP in controlling respiratory events, with adaptive servo-ventilation being the most effective in controlling central, mixed, and complex sleep apnea in this setting. 49,50 Whether more effective resolution of obstructive and central events with these treatment modes translates into improved mortality rates and transplantation-free survival rates remains to be determined.

 

 

Obesity-hypoventilation syndrome

Obesity-hypoventilation syndrome refers to daytime hypercapnia (Paco2 > 45 mm Hg) in obese people when no other cause of hypoventilation is present.

The prevalence of obesity-hypoventilation syndrome among patients with obstructive sleep apnea-hypopnea syndrome is 20% to 30% and is greater in extremely obese patients (body mass index > 40 kg/m2).64 However, about 10% of patients with obesity-hypoventilation syndrome do not have obstructive sleep apnea-hypopnea syndrome.64 Additionally, nocturnal hypoxemia and diurnal hypercapnia persist in about 40% of patients with obesity-hypoventilation syndrome after CPAP eliminates their sleep apnea.65 Therefore, factors other than sleep apnea contribute to the development of obesity-hypoventilation syndrome, and in a meta-analysis, factors associated with daytime hypercapnia included, in addition to body mass index and the apnea-hypopnea index, mean overnight oxygen saturation and severity of restrictive pulmonary function.66 Predictors of success with CPAP include better spirometric findings, a higher apnea-hypopnea index, and adequate oxygenation.67,68

Bilevel PAP therapy can be tried in patients in whom CPAP by itself fails. In a study of patients with obesity-hypoventilation syndrome in whom initial CPAP treatment failed, average volume-assured pressure support lowered Paco2 compared to bilevel PAP alone, but did not further improve oxygenation, sleep quality, or quality of life.69

Restrictive pulmonary diseases

Neuromuscular diseases and thoracic cage abnormalities. Noninvasive ventilation has been used in patients with progressive neuromuscular disorders or severe thoracic cage abnormalities, with recognized benefits including an improved survival rate and improved quality of life.70,71 However, NIPPV is used in only 9% of patients with amyotrophic lateral sclerosis when clearly indicated.72 The indications and Medicare guidelines for reimbursement of NIPPV (with or without a backup rate) in this setting are shown in Table 2.

Potential contraindications to starting NIPPV in this population include upper airway obstruction, failure to clear secretions despite optimal noninvasive support, inability to achieve a mask fit, and intolerance of the intervention.73,74

The mechanisms of benefit of NIPPV in these settings include improvements in daytime blood gas levels (including hypercapnia75), a reduction in the oxygen cost of breathing,76 an increase in the ventilatory response to carbon dioxide,75 and improved lung compliance.77

Chronic hypercapnic failure due to severe COPD

The use of NIPPV in chronic COPD is less well established than in patients with exacerbations of COPD,78 and limitations in its use are reflected in the more stringent Medicare indications for NIPPV in this setting (Table 2).

A particular subset of patients with stable COPD who may benefit from NIPPV includes those with daytime hypercapnia and super-imposed nocturnal hypoventilation.78 The potential benefits of NIPPV in these patients include improved daytime and nocturnal gas exchange, increased sleep duration, and improved quality of life.78 Additionally, a recent randomized controlled trial of NIPPV plus long-term oxygen therapy compared with oxygen therapy alone in patients with severe COPD and a Paco2 greater than 46 mm Hg demonstrated a survival benefit in favor of adding NIPPV (hazard ratio 0.6).79

However, that study also found no reduction in hospitalization rates, an apparent worsening in general and mental health (as reflected on the 36-Item Short Form Health Survey or SF-36, a quality-of-life questionnaire), as well as increased confusion and bewilderment (reflected on the Profile of Mood States scale).79 These potentially deleterious effects may explain why adherence to NIPPV is low in patients with stable COPD: only 37% to 57% of patients continued to use it in several reported studies.79–81

A level of inspiratory pressure support that is insufficient to reduce hypercapnia may account for the low adherence rate and worsened quality of life in such patients. For instance, in a randomized trial,82 compared with low-intensity NIPPV (mean IPAP 14 cm H2O, backup rate 8 per minute), settings that aimed to maximally reduce Paco2 (mean IPAP 29 cm H2O with a backup rate of 17.5 per minute) increased the daily use of NIPPV by 3.6 hours/day and improved exercise-related dyspnea, daytime Paco2, forced expiratory volume in 1 second (FEV1), vital capacity, and health-related quality of life.

The overlap syndrome was first described by Flenley in 1985 as a combination of chronic respiratory disease (more generally limited to COPD) and obstructive sleep apnea-hypopnea syndrome.83 Epidemiologic studies do not consistently show a higher incidence of obstructive sleep apnea-hypopnea syndrome in patients with COPD, but the exaggerated oxygen desaturation during sleep in patients with this combination increases the risk of hypoxemia, hypercapnia, and pulmonary hypertension. 84 In addition, there was evidence of higher risks of death and of hospitalization for COPD in patients with the overlap syndrome. 85 NIPPV is the main treatment for obstructive sleep apnea-hypopnea syndrome with or without COPD.

A recent study by Marin et al85 showed that CPAP was associated with improved survival and decreased hospitalization in patients with the overlap syndrome. However, polysomnography or nocturnal oximetry while on NIPPV alone must be done, as additional nocturnal oxygen therapy may be warranted when significant chronic respiratory illness coexists with sleep apnea.
 

Acknowledgment: The authors gratefully acknowledge the contribution of Scott Marlow, RRT, to Table 2 of this review.

Noninvasive positive pressure ventilation (NIPPV) is any form of positive ventilatory support applied without an endotracheal tube, including continuous positive airway pressure (CPAP).1 The role of NIPPV in acute care has been discussed in an earlier review in the Cleveland Clinic Journal of Medicine.2

NIPPV is also used at night in outpatients with stable chronic conditions, first used in the 1980s in the treatment of obstructive sleep apnea3 and neuromuscular diseases,4 and since then in several other conditions including sleep disorders associated with congestive heart failure (including sleep apnea and the Cheyne-Stokes respiration-central sleep apnea syndrome), chronic obstructive pulmonary disease (COPD), and the obesity-hypoventilation syndrome.

In this review, we discuss the different types of NIPPV, the specific conditions in which they can be used, and the indications, recommendations, and evidence supporting the efficacy of NIPPV in outpatients.

THE TYPES OF NIPPV AND THEIR USES

Although the conditions for which different types of NIPPV can be used overlap significantly, each type has general indications and different goals of treatment. This section begins with types of NIPPV that are predominantly used to treat sleep-disordered breathing, and then proceeds to those predominantly used for conditions associated with hypoventilation and hypercapnia.

Continuous positive airway pressure

CPAP, currently the most widely used form of NIPPV, applies a constant level of positive pressure at the airway opening during spontaneous breathing.

CPAP is commonly used to treat obstructive sleep-disordered breathing, with the goals of improving daytime sleepiness and reducing cardiovascular risk. It has also been used to treat sleep-disordered breathing associated with congestive heart failure.

CPAP’s role in the support of ventilation is limited and indirect. For instance, it has been used in the obesity-hypoventilation syndrome and in the “overlap” syndrome (in which both sleep apnea and COPD coexist). However, its benefits in those conditions are probably derived in large part from correction of underlying obstructive sleep apnea.

The mechanisms of action of CPAP include:

  • Preventing intermittent narrowing and collapse of the airway in patients with obstructive sleep apnea-hypopnea syndrome by acting as a pneumatic splint during sleep3,5,6
  • Counteracting auto-positive end-expiratory pressure, thereby reducing respiratory muscle load, reducing the work of breathing, and lowering daytime Paco2 in patients with coexistent COPD and obstructive sleep apnea-hypopnea syndrome (the overlap syndrome)7–9
  • Improving lung function (particularly the functional residual capacity) and daytime gas exchange in obstructive sleep apnea-hypopnea syndrome 10
  • Improving left ventricular systolic function in patients with heart failure coexisting with obstructive sleep apnea-hypopnea syndrome.11,12

Auto-CPAP is delivered via a self-titrating CPAP device, which uses algorithms to detect variations in the degree of obstruction and consequently adjusts the pressure level to restore normal breathing. Auto-CPAP therefore compensates for factors that modify the upper airway collapsibility, such as body posture during sleep, stage of sleep, use of alcohol, and drugs that affect upper airway muscle tone.13

Although one of the premises of using auto-CPAP is that it improves the patient’s satisfaction and compliance, several studies found it to be no more effective than fixed CPAP for treating obstructive sleep apnea-hypopnea syndrome.14–16 Current guidelines of the American Academy of Sleep Medicine do not recommend self-titrating CPAP devices to diagnose obstructive sleep apnea or to treat patients with cardiopulmonary disorders or other conditions in which nocturnal desaturation may be unrelated to obstructive events.17

Adaptive servo-ventilation

Adaptive servo-ventilation was developed for Cheyne-Stokes respiration-central sleep apnea syndrome in patients with congestive heart failure, who may have periods of crescendo-decrescendo change in tidal volume (Cheyne-Stokes respiration) with possible intercalated episodes of central apnea or hypopnea. It is also applied in patients with the complex sleep apnea syndrome.

Adaptive servo-ventilation devices are usually set at an expiratory positive airway pressure (EPAP) level sufficient to control obstructive sleep apnea. The device then automatically adjusts the pressure support for each inspiration, within a prespecified range, to maintain a moving-target ventilation set at 90% of the patient’s recent average ventilation. The aim is to stabilize breathing and reduce respiratory alkalosis, which can trigger apnea reentry cycles.18

Bilevel positive airway pressure

Bilevel positive airway pressure (bilevel PAP) can be of use in sleep-disordered breathing (including cases associated with congestive heart failure), but it is predominantly applied in conditions associated with hypoventilation.

Bilevel PAP devices deliver a higher pressure during inspiration (inspiratory positive airway pressure, or IPAP) and a lower pressure during expiration (EPAP). The gradient between IPAP and EPAP is of key importance in maintaining alveolar ventilation and reducing Paco2. The IPAP acts as pressure support to augment the patient’s effort, maintain adequate alveolar ventilation, unload respiratory muscles, decrease the work of breathing, and control obstructive hypopnea, whereas EPAP is set to maintain upper airway patency, control obstructive apnea, improve functional residual capacity, and prevent microatelectasis.

Although there is no evidence that bilevel PAP is better adhered to or more effective than CPAP, current guidelines propose it as an option for patients who require high pressures to control obstructive sleep apnea-hypopnea syndrome or for those who cannot tolerate exhaling against a high fixed CPAP pressure.19

Other, more-common uses of bilevel PAP are to treat coexisting central sleep apnea or hypoventilation,19 the obesity-hypoventilation syndrome with residual alveolar hypoventilation despite CPAP and control of concomitant obstructive sleep apnea-hypopnea syndrome,5,20 severe stable COPD with significant nocturnal hypoventilation and daytime hypercarbia,21 and restrictive pulmonary diseases.21

Although the patient should be able to maintain spontaneous breathing on bilevel PAP, a backup rate option can be set for those whose ventilation during sleep may be significantly impaired (eg, those with neuromuscular diseases, complex sleep apnea, central apnea in congestive heart failure, or obesity-hypoventilation syndrome) (Table 1, Table 2).22,23 However, one important paradoxical consideration is that both CPAP and bilevel PAP (with or without a backup rate) promote ventilation and have the potential of dropping the carbon dioxide level below a hypocapnic apneic threshold during sleep, thereby triggering central apnea and the complex sleep apnea syndrome.24

Average volume-assured pressure support

Average volume-assured pressure support is directed mainly at patients with chronic hypoventilation such as those with obesity-hypoventilation syndrome, neuromuscular diseases, and COPD. In this mode, a target tidal volume is set, and the device adjusts the pressure support to reach that set tidal volume. The advantage is that it guarantees a delivered tidal volume despite variability in patient effort, airway resistance, and lung or chest wall compliance. A particular potential benefit is that it may adapt to disease progression, as may occur in patients with progressive neuromuscular disorders.

 

 

CONDITIONS IN WHICH NOCTURNAL NIPPV IS USED IN OUT PATIENTS

Obstructive sleep apnea-hypopnea syndrome

Obstructive sleep apnea-hypopnea syndrome is estimated to affect 2% of women and 4% of men.25 It is characterized by recurrent episodes of partial (hypopnea) or complete (apnea) upper airway obstruction during sleep despite ongoing inspiratory efforts, with associated episodes of arousal or desaturation or both. Corresponding symptoms include excessive daytime sleepiness, choking and gasping during sleep, recurrent awakenings from sleep, unrefreshing sleep, daytime fatigue, and impaired concentration that is not explained by other factors.26

Current understanding of the pathophysiology of obstructive sleep apnea implicates an impairment in the balance between factors that promote collapsibility of the airway (including obesity and anatomic issues such as the volume of the soft-tissue structures surrounding the upper airway) and the compensatory neuromuscular response.27,28

Long-standing obstructive sleep apnea-hypopnea syndrome has been linked in prospective studies to the development of hypertension,29–31 coronary artery disease,32,33 increased coagulation,34,35 and stroke or death from any cause.36,37 It is also associated with a greater rate and severity of motor vehicular accidents,38 greater health care utilization, impaired work performance, and occupational injuries.39

Strong evidence exists that NIPPV (most commonly CPAP) is beneficial in obstructive sleep apnea-hypopnea syndrome, improving sleep quality, sleepiness, cognitive impairment, and quality of life,40,41 decreasing motor vehicle accidents,42 lowering blood pressure, 43,44 and decreasing the rates of myocardial infarction,32 stroke,32 and death.45

The American Academy of Sleep Medicine recommends CPAP as an optional adjunctive therapy to lower blood pressure in patients with obstructive sleep apnea-hypopnea syndrome with concomitant hypertension.19 This is supported by a recent study that suggested that CPAP may have additional benefits on blood pressure in a subgroup of patients with uncontrolled hypertension while on antihypertensive medications.46 Indications with Medicare guidelines for reimbursement of CPAP devices are summarized in Table 2.

Complex sleep apnea syndrome

The complex sleep apnea syndrome is characterized by the emergence of significant central sleep apnea or Cheyne-Stokes respiration after obstructive events have been brought under control with NIPPV in patients who initially appear to have obstructive sleep apnea-hypopnea syndrome. A retrospective study of patients with the complex sleep apnea syndrome who continued their NIPPV use until a subsequent polysomnographic study and NIPPV titration showed that the syndrome may resolve spontaneously, but that 46% of patients had a persistently elevated apnea-hypopnea index with central apnea activity.47

Restoration of upper airway patency by CPAP and dysregulation or delayed adaptation of chemosensitive ventilatory control to a changing Paco2 level may be a key pathophysiologic mechanism of the complex sleep apnea syndrome.48 In this mechanism, increased ventilation from restored airway patency and from an increase in the slope of the ventilatory response may intermittently draw the Paco2 to below the hypocapnic apneic threshold and trigger episodes of central apnea.48

The ideal NIPPV device for use in the complex sleep apnea syndrome should be able to provide enough pressure to resolve the obstructive sleep apnea-hypopnea syndrome while maintaining proper ventilatory support during central apnea episodes without fluctuations of Paco2, which could further worsen the dysregulated ventilatory control. Currently, adaptive servo-ventilation appears to be superior to bilevel PAP and CPAP in the management of the complex sleep apnea syndrome.49,50

Sleep disturbances associated with cardiac dysfunction

There are specific indications for NIPPV modes in the setting of respiratory sleep disturbances associated with heart failure.

Obstructive sleep apnea in congestive heart failure. The prevalence of obstructive sleep apnea in patients with impaired left ventricular ejection fraction is 11% to 53%.51 Obstructive sleep apnea-hypopnea syndrome can worsen congestive heart failure by causing a periodic increase in negative intrathoracic pressure from breathing against an occluded airway, by raising arterial blood pressure, and causing tachycardia from sympathetic nervous system stimulation from hypoxia, hypercarbia, and arousals.52,53 Both heart failure and sleep apnea contribute in an additive manner to the increased sympathetic nervous activity.54

Fortunately, treatment with CPAP has been found to reduce systolic blood pressure and improve left ventricular systolic function in medically treated patients with heart failure and coexisting obstructive sleep apnea.11,12 Furthermore, in a randomized trial in patients with stable congestive heart failure and newly diagnosed obstructive sleep apnea-hypopnea syndrome, a greater improvement in cardiac function was observed in patients on bilevel PAP than in those on CPAP.55 The authors speculated that bilevel PAP might provide more unloading of the respiratory muscles, reduce the work of breathing more, and result in less positive intrathoracic pressure than with CPAP, and that the higher intrathoracic pressure with CPAP could reduce the left ventricular ejection fraction in patients with low filling pressures (pulmonary capillary wedge pressure < 12 mm Hg) and low baseline left ventricular ejection fractions (< 30%).55

Whether these interventions reduce the mortality rate is uncertain. In a prospective nonrandomized study, 9 (24%) of 37 patients who had heart failure with untreated obstructive sleep apnea died, compared with no deaths in 14 treated patients (P = .07).56

Cheyne-Stokes respiration with central sleep apnea in congestive heart failure. A related but different situation is central apnea associated with congestive heart failure.

There are several pathophysiologic mechanisms of Cheyne-Stokes respiration with central sleep apnea. Specifically, the elevation of left ventricular filling pressures, end-diastolic volumes, and pulmonary congestion generate hyperventilation, chronic hypocapnia, and increased chemoreceptor responsiveness, which contribute to the development of central apnea by promoting a decrease in the Paco2 during sleep to below the hypocapnic apneic threshold.57,58 Additionally, an increase in circulation time may result in periodicity of breathing and hyperpnea.59 Obstructive events can then occur at the end of the central events corresponding with the nadir of the inspiratory drive.60,61

The Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure (CANPAP) trial, a randomized trial of CPAP in this clinical setting, showed that compared with optimal medical therapy alone, CPAP plus optimal medical therapy improved the ejection fraction, reduced central sleep apnea, improved nocturnal oxygenation, and improved the 6-minute walking distance, but without a survival benefit.62 The disappointing survival results from CANPAP have to be interpreted in the context that CPAP may have failed to control the central apnea in some patients, such that the mean apnea-hypopnea index in treated patients (19 events/hour) remained above the entry criterion for recruitment (15 events/hour). In a post hoc analysis of this study, the heart-transplantation-free survival rate was significantly greater in the subgroup of patients in whom CPAP effectively suppressed central sleep apnea (< 15 events/hour).63

Other NIPPV modes such as bilevel PAP with backup rate and adaptive servo-ventilation have been shown in some studies to be superior to CPAP in controlling respiratory events, with adaptive servo-ventilation being the most effective in controlling central, mixed, and complex sleep apnea in this setting. 49,50 Whether more effective resolution of obstructive and central events with these treatment modes translates into improved mortality rates and transplantation-free survival rates remains to be determined.

 

 

Obesity-hypoventilation syndrome

Obesity-hypoventilation syndrome refers to daytime hypercapnia (Paco2 > 45 mm Hg) in obese people when no other cause of hypoventilation is present.

The prevalence of obesity-hypoventilation syndrome among patients with obstructive sleep apnea-hypopnea syndrome is 20% to 30% and is greater in extremely obese patients (body mass index > 40 kg/m2).64 However, about 10% of patients with obesity-hypoventilation syndrome do not have obstructive sleep apnea-hypopnea syndrome.64 Additionally, nocturnal hypoxemia and diurnal hypercapnia persist in about 40% of patients with obesity-hypoventilation syndrome after CPAP eliminates their sleep apnea.65 Therefore, factors other than sleep apnea contribute to the development of obesity-hypoventilation syndrome, and in a meta-analysis, factors associated with daytime hypercapnia included, in addition to body mass index and the apnea-hypopnea index, mean overnight oxygen saturation and severity of restrictive pulmonary function.66 Predictors of success with CPAP include better spirometric findings, a higher apnea-hypopnea index, and adequate oxygenation.67,68

Bilevel PAP therapy can be tried in patients in whom CPAP by itself fails. In a study of patients with obesity-hypoventilation syndrome in whom initial CPAP treatment failed, average volume-assured pressure support lowered Paco2 compared to bilevel PAP alone, but did not further improve oxygenation, sleep quality, or quality of life.69

Restrictive pulmonary diseases

Neuromuscular diseases and thoracic cage abnormalities. Noninvasive ventilation has been used in patients with progressive neuromuscular disorders or severe thoracic cage abnormalities, with recognized benefits including an improved survival rate and improved quality of life.70,71 However, NIPPV is used in only 9% of patients with amyotrophic lateral sclerosis when clearly indicated.72 The indications and Medicare guidelines for reimbursement of NIPPV (with or without a backup rate) in this setting are shown in Table 2.

Potential contraindications to starting NIPPV in this population include upper airway obstruction, failure to clear secretions despite optimal noninvasive support, inability to achieve a mask fit, and intolerance of the intervention.73,74

The mechanisms of benefit of NIPPV in these settings include improvements in daytime blood gas levels (including hypercapnia75), a reduction in the oxygen cost of breathing,76 an increase in the ventilatory response to carbon dioxide,75 and improved lung compliance.77

Chronic hypercapnic failure due to severe COPD

The use of NIPPV in chronic COPD is less well established than in patients with exacerbations of COPD,78 and limitations in its use are reflected in the more stringent Medicare indications for NIPPV in this setting (Table 2).

A particular subset of patients with stable COPD who may benefit from NIPPV includes those with daytime hypercapnia and super-imposed nocturnal hypoventilation.78 The potential benefits of NIPPV in these patients include improved daytime and nocturnal gas exchange, increased sleep duration, and improved quality of life.78 Additionally, a recent randomized controlled trial of NIPPV plus long-term oxygen therapy compared with oxygen therapy alone in patients with severe COPD and a Paco2 greater than 46 mm Hg demonstrated a survival benefit in favor of adding NIPPV (hazard ratio 0.6).79

However, that study also found no reduction in hospitalization rates, an apparent worsening in general and mental health (as reflected on the 36-Item Short Form Health Survey or SF-36, a quality-of-life questionnaire), as well as increased confusion and bewilderment (reflected on the Profile of Mood States scale).79 These potentially deleterious effects may explain why adherence to NIPPV is low in patients with stable COPD: only 37% to 57% of patients continued to use it in several reported studies.79–81

A level of inspiratory pressure support that is insufficient to reduce hypercapnia may account for the low adherence rate and worsened quality of life in such patients. For instance, in a randomized trial,82 compared with low-intensity NIPPV (mean IPAP 14 cm H2O, backup rate 8 per minute), settings that aimed to maximally reduce Paco2 (mean IPAP 29 cm H2O with a backup rate of 17.5 per minute) increased the daily use of NIPPV by 3.6 hours/day and improved exercise-related dyspnea, daytime Paco2, forced expiratory volume in 1 second (FEV1), vital capacity, and health-related quality of life.

The overlap syndrome was first described by Flenley in 1985 as a combination of chronic respiratory disease (more generally limited to COPD) and obstructive sleep apnea-hypopnea syndrome.83 Epidemiologic studies do not consistently show a higher incidence of obstructive sleep apnea-hypopnea syndrome in patients with COPD, but the exaggerated oxygen desaturation during sleep in patients with this combination increases the risk of hypoxemia, hypercapnia, and pulmonary hypertension. 84 In addition, there was evidence of higher risks of death and of hospitalization for COPD in patients with the overlap syndrome. 85 NIPPV is the main treatment for obstructive sleep apnea-hypopnea syndrome with or without COPD.

A recent study by Marin et al85 showed that CPAP was associated with improved survival and decreased hospitalization in patients with the overlap syndrome. However, polysomnography or nocturnal oximetry while on NIPPV alone must be done, as additional nocturnal oxygen therapy may be warranted when significant chronic respiratory illness coexists with sleep apnea.
 

Acknowledgment: The authors gratefully acknowledge the contribution of Scott Marlow, RRT, to Table 2 of this review.

References
  1. Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001; 163:283–291.
  2. Aboussouan LS, Ricaurte B. Noninvasive positive pressure ventilation: increasing use in acute care. Cleve Clin J Med 2010; 77:307–316.
  3. Sullivan CE, Berthon-Jones M, Issa FG. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure. Am Rev Respir Dis 1983; 128:177–181.
  4. Ellis ER, Bye PT, Bruderer JW, Sullivan CE. Treatment of respiratory failure during sleep in patients with neuromuscular disease. Positive-pressure ventilation through a nose mask. Am Rev Respir Dis 1987; 135:148–152.
  5. Berger KI, Ayappa I, Chatr-Amontri B, et al. Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest 2001; 120:1231–1238.
  6. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948–956.
  7. de Miguel J, Cabello J, Sánchez-Alarcos JM, Alvarez-Sala R, Espinós D, Alvarez-Sala JL. Long-term effects of treatment with nasal continuous positive airway pressure on lung function in patients with overlap syndrome. Sleep Breath 2002; 6:3–10.
  8. Mezzanotte WS, Tangel DJ, Fox AM, Ballard RD, White DP. Nocturnal nasal continuous positive airway pressure in patients with chronic obstructive pulmonary disease. Influence on waking respiratory muscle function. Chest 1994; 106:1100–1108.
  9. Petrof BJ, Legaré M, Goldberg P, Milic-Emili J, Gottfried SB. Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1990; 141:281–289.
  10. Verbraecken J, Willemen M, De Cock W, Van de Heyning P, De Backer WA. Continuous positive airway pressure and lung inflation in sleep apnea patients. Respiration 2001; 68:357–364.
  11. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348:1233–1241.
  12. Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med 2004; 169:361–366.
  13. Malhotra A, Trinder J, Fogel R, et al. Postural effects on pharyngeal protective reflex mechanisms. Sleep 2004; 27:1105–1112.
  14. Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep 2004; 27:249–253.
  15. Nolan GM, Ryan S, O’Connor TM, McNicholas WT. Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea. Eur Respir J 2006; 28:159–164.
  16. Meurice JC, Cornette A, Philip-Joet F, et al; ANTADIR “PPC” Working Group. Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome. Sleep Med 2007; 8:695–703.
  17. Morgenthaler TI, Aurora RN, Brown T, et al; Standards of Practice Committee of the AASM; American Academy of Sleep Medicine. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep 2008; 31:141–147.
  18. 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; 164:614–619.
  19. Kushida CA, Littner MR, Hirshkowitz M, et al; American Academy of Sleep Medicine. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006; 29:375–380.
  20. Schäfer H, Ewig S, Hasper E, Lüderitz B. Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure. Respir Med 1998; 92:208–215.
  21. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation—a consensus conference report. Chest 1999; 116:521–534.
  22. Aboussouan LS, Khan SU, Meeker DP, Stelmach K, Mitsumoto H. Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis. Ann Intern Med 1997; 127:450–453.
  23. Köhnlein T, Welte T, Tan LB, Elliott MW. Assisted ventilation for heart failure patients with Cheyne-Stokes respiration. Eur Respir J 2002; 20:934–941.
  24. Johnson KG, Johnson DC. Bilevel positive airway pressure worsens central apneas during sleep. Chest 2005; 128:2141–2150.
  25. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328:1230–1235.
  26. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22:667–689.
  27. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007; 132:325–337.
  28. Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003; 168:522–530.
  29. Hedner J, Bengtsson-Boström K, Peker Y, Grote L, Råstam L, Lindblad U. Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study. Eur Respir J 2006; 27:564–570.
  30. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283:1829–1836.
  31. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342:1378–1384.
  32. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365:1046–1053.
  33. Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006; 28:596–602.
  34. Guardiola JJ, Matheson PJ, Clavijo LC, Wilson MA, Fletcher EC. Hypercoagulability in patients with obstructive sleep apnea. Sleep Med 2001; 2:517–523.
  35. von Känel R, Loredo JS, Ancoli-Israel S, Mills PJ, Natarajan L, Dimsdale JE. Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 2007; 131:733–739.
  36. Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2010; Epub ahead of print.
  37. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034–2041.
  38. Mulgrew AT, Nasvadi G, Butt A, et al. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax 2008; 63:536–541.
  39. AlGhanim N, Comondore VR, Fleetham J, Marra CA, Ayas NT. The economic impact of obstructive sleep apnea. Lung 2008; 186:7–12.
  40. Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2006; 3:CD001106.
  41. Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 2003; 163:565–571.
  42. George CF. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax 2001; 56:508–512.
  43. Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107:68–73.
  44. Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 163:344–348.
  45. Campos-Rodriguez F, Peña-Griñan N, Reyes-Nuñez N, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest 2005; 128:624–633.
  46. Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive sleep apnea patients. Am J Respir Crit Care Med 2010; Epub ahead of print.
  47. Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea—a retrospective study. Sleep Breath 2008; 12:135–139.
  48. Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep 2006; 29:1203–1209.
  49. Allam JS, Olson EJ, Gay PC, Morgenthaler TI. Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest 2007; 132:1839–1846.
  50. 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; 30:468–475.
  51. Bordier P. Sleep apnoea in patients with heart failure. Part I: diagnosis, definitions, prevalence, pathophysiology and haemodynamic consequences. Arch Cardiovasc Dis 2009; 102:651–661.
  52. Romero-Corral A, Somers VK, Pellikka PA, et al. Decreased right and left ventricular myocardial performance in obstructive sleep apnea. Chest 2007; 132:1863–1870.
  53. Solin P, Kaye DM, Little PJ, Bergin P, Richardson M, Naughton MT. Impact of sleep apnea on sympathetic nervous system activity in heart failure. Chest 2003; 123:1119–1126.
  54. Floras JS. Should sleep apnoea be a specific target of therapy in chronic heart failure? Heart 2009; 95:1041–1046.
  55. Khayat RN, Abraham WT, Patt B, Roy M, Hua K, Jarjoura D. Cardiac effects of continuous and bilevel positive airway pressure for patients with heart failure and obstructive sleep apnea: a pilot study. Chest 2008; 134:1162–1168.
  56. Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 2007; 49:1625–1631.
  57. Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med 1999; 341:949–954.
  58. Tkacova R, Hall MJ, Liu PP, Fitzgerald FS, Bradley TD. Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep. Am J Respir Crit Care Med 1997; 156:1549–1555.
  59. Lorenzi-Filho G, Rankin F, Bies I, Douglas Bradley T. Effects of inhaled carbon dioxide and oxygen on Cheyne-Stokes respiration in patients with heart failure. Am J Respir Crit Care Med 1999; 159:1490–1498.
  60. Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol 1995; 78:1806–1815.
  61. Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol 1986; 61:1438–1443.
  62. Bradley TD, Logan AG, Kimoff RJ, et al; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005; 353:2025–2033.
  63. 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; 115:3173–3180.
  64. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath 2007; 11:117–124.
  65. Banerjee D, Yee BJ, Piper AJ, Zwillich CW, Grunstein RR. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678–1684.
  66. Kaw R, Hernandez AV, Walker E, Aboussouan L, Mokhlesi B. Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Chest 2009; 136:787–796.
  67. Pérez de Llano LA, Golpe R, Piquer MO, et al. Clinical heterogeneity among patients with obesity hypoventilation syndrome: therapeutic implications. Respiration 2008; 75:34–39.
  68. Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63:395–401.
  69. Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial. Chest 2006; 130:815–821.
  70. Aboussouan LS, Khan SU, Banerjee M, Arroliga AC, Mitsumoto H. Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis. Muscle Nerve 2001; 24:403–409.
  71. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 5:140–147.
  72. Miller RG, Anderson F, Brooks BR, Mitsumoto H, Bradley WG, Ringel SP; ALS CARE Study Group. Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database. Ann Neurol 2009; 65(suppl 1):S24–S28.
  73. Bach JR. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory AIDS. Chest 2002; 122:92–98.
  74. Perrin C, Unterborn JN, Ambrosio CD, Hill NS. Pulmonary complications of chronic neuromuscular diseases and their management. Muscle Nerve 2004; 29:5–27.
  75. Nickol AH, Hart N, Hopkinson NS, Moxham J, Simonds A, Polkey MI. Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation. Thorax 2005; 60:754–760.
  76. Barle H, Söderberg P, Haegerstrand C, Markström A. Bi-level positive airway pressure ventilation reduces the oxygen cost of breathing in long-standing post-polio patients on invasive home mechanical ventilation. Acta Anaesthesiol Scand 2005; 49:197–202.
  77. Lechtzin N, Shade D, Clawson L, Wiener CM. Supramaximal inflation improves lung compliance in subjects with amyotrophic lateral sclerosis. Chest 2006; 129:1322–1329.
  78. Hill NS. Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care 2004; 49:72–87;
  79. McEvoy RD, Pierce RJ, Hillman D, et al; Australian trial of noninvasive Ventilation in Chronic Airflow Limitation (AVCAL) Study Group. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Thorax 2009; 64:561–566.
  80. Criner GJ, Brennan K, Travaline JM, Kreimer D. Efficacy and compliance with noninvasive positive pressure ventilation in patients with chronic respiratory failure. Chest 1999; 116:667–675.
  81. Strumpf DA, Millman RP, Carlisle CC, et al. Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 144:1234–1239.
  82. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax 2010; 65:303–308.
  83. Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med 1985; 6:651–661.
  84. Weitzenblum E, Chaouat A, Kessler R, Canuet M. Overlap syndrome: obstructive sleep apnea in patients with chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008; 5:237–241.
  85. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea. The overlap syndrome. Am J Respir Crit Care Med 2010; Epub ahead of print.
References
  1. Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001; 163:283–291.
  2. Aboussouan LS, Ricaurte B. Noninvasive positive pressure ventilation: increasing use in acute care. Cleve Clin J Med 2010; 77:307–316.
  3. Sullivan CE, Berthon-Jones M, Issa FG. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure. Am Rev Respir Dis 1983; 128:177–181.
  4. Ellis ER, Bye PT, Bruderer JW, Sullivan CE. Treatment of respiratory failure during sleep in patients with neuromuscular disease. Positive-pressure ventilation through a nose mask. Am Rev Respir Dis 1987; 135:148–152.
  5. Berger KI, Ayappa I, Chatr-Amontri B, et al. Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest 2001; 120:1231–1238.
  6. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948–956.
  7. de Miguel J, Cabello J, Sánchez-Alarcos JM, Alvarez-Sala R, Espinós D, Alvarez-Sala JL. Long-term effects of treatment with nasal continuous positive airway pressure on lung function in patients with overlap syndrome. Sleep Breath 2002; 6:3–10.
  8. Mezzanotte WS, Tangel DJ, Fox AM, Ballard RD, White DP. Nocturnal nasal continuous positive airway pressure in patients with chronic obstructive pulmonary disease. Influence on waking respiratory muscle function. Chest 1994; 106:1100–1108.
  9. Petrof BJ, Legaré M, Goldberg P, Milic-Emili J, Gottfried SB. Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1990; 141:281–289.
  10. Verbraecken J, Willemen M, De Cock W, Van de Heyning P, De Backer WA. Continuous positive airway pressure and lung inflation in sleep apnea patients. Respiration 2001; 68:357–364.
  11. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003; 348:1233–1241.
  12. Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med 2004; 169:361–366.
  13. Malhotra A, Trinder J, Fogel R, et al. Postural effects on pharyngeal protective reflex mechanisms. Sleep 2004; 27:1105–1112.
  14. Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis. Sleep 2004; 27:249–253.
  15. Nolan GM, Ryan S, O’Connor TM, McNicholas WT. Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea. Eur Respir J 2006; 28:159–164.
  16. Meurice JC, Cornette A, Philip-Joet F, et al; ANTADIR “PPC” Working Group. Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome. Sleep Med 2007; 8:695–703.
  17. Morgenthaler TI, Aurora RN, Brown T, et al; Standards of Practice Committee of the AASM; American Academy of Sleep Medicine. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep 2008; 31:141–147.
  18. 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; 164:614–619.
  19. Kushida CA, Littner MR, Hirshkowitz M, et al; American Academy of Sleep Medicine. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006; 29:375–380.
  20. Schäfer H, Ewig S, Hasper E, Lüderitz B. Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure. Respir Med 1998; 92:208–215.
  21. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation—a consensus conference report. Chest 1999; 116:521–534.
  22. Aboussouan LS, Khan SU, Meeker DP, Stelmach K, Mitsumoto H. Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis. Ann Intern Med 1997; 127:450–453.
  23. Köhnlein T, Welte T, Tan LB, Elliott MW. Assisted ventilation for heart failure patients with Cheyne-Stokes respiration. Eur Respir J 2002; 20:934–941.
  24. Johnson KG, Johnson DC. Bilevel positive airway pressure worsens central apneas during sleep. Chest 2005; 128:2141–2150.
  25. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328:1230–1235.
  26. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22:667–689.
  27. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007; 132:325–337.
  28. Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003; 168:522–530.
  29. Hedner J, Bengtsson-Boström K, Peker Y, Grote L, Råstam L, Lindblad U. Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study. Eur Respir J 2006; 27:564–570.
  30. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283:1829–1836.
  31. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342:1378–1384.
  32. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365:1046–1053.
  33. Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006; 28:596–602.
  34. Guardiola JJ, Matheson PJ, Clavijo LC, Wilson MA, Fletcher EC. Hypercoagulability in patients with obstructive sleep apnea. Sleep Med 2001; 2:517–523.
  35. von Känel R, Loredo JS, Ancoli-Israel S, Mills PJ, Natarajan L, Dimsdale JE. Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 2007; 131:733–739.
  36. Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2010; Epub ahead of print.
  37. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034–2041.
  38. Mulgrew AT, Nasvadi G, Butt A, et al. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax 2008; 63:536–541.
  39. AlGhanim N, Comondore VR, Fleetham J, Marra CA, Ayas NT. The economic impact of obstructive sleep apnea. Lung 2008; 186:7–12.
  40. Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2006; 3:CD001106.
  41. Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 2003; 163:565–571.
  42. George CF. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax 2001; 56:508–512.
  43. Becker HF, Jerrentrup A, Ploch T, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107:68–73.
  44. Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 163:344–348.
  45. Campos-Rodriguez F, Peña-Griñan N, Reyes-Nuñez N, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest 2005; 128:624–633.
  46. Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive sleep apnea patients. Am J Respir Crit Care Med 2010; Epub ahead of print.
  47. Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea—a retrospective study. Sleep Breath 2008; 12:135–139.
  48. Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep 2006; 29:1203–1209.
  49. Allam JS, Olson EJ, Gay PC, Morgenthaler TI. Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest 2007; 132:1839–1846.
  50. 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; 30:468–475.
  51. Bordier P. Sleep apnoea in patients with heart failure. Part I: diagnosis, definitions, prevalence, pathophysiology and haemodynamic consequences. Arch Cardiovasc Dis 2009; 102:651–661.
  52. Romero-Corral A, Somers VK, Pellikka PA, et al. Decreased right and left ventricular myocardial performance in obstructive sleep apnea. Chest 2007; 132:1863–1870.
  53. Solin P, Kaye DM, Little PJ, Bergin P, Richardson M, Naughton MT. Impact of sleep apnea on sympathetic nervous system activity in heart failure. Chest 2003; 123:1119–1126.
  54. Floras JS. Should sleep apnoea be a specific target of therapy in chronic heart failure? Heart 2009; 95:1041–1046.
  55. Khayat RN, Abraham WT, Patt B, Roy M, Hua K, Jarjoura D. Cardiac effects of continuous and bilevel positive airway pressure for patients with heart failure and obstructive sleep apnea: a pilot study. Chest 2008; 134:1162–1168.
  56. Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 2007; 49:1625–1631.
  57. Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med 1999; 341:949–954.
  58. Tkacova R, Hall MJ, Liu PP, Fitzgerald FS, Bradley TD. Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep. Am J Respir Crit Care Med 1997; 156:1549–1555.
  59. Lorenzi-Filho G, Rankin F, Bies I, Douglas Bradley T. Effects of inhaled carbon dioxide and oxygen on Cheyne-Stokes respiration in patients with heart failure. Am J Respir Crit Care Med 1999; 159:1490–1498.
  60. Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol 1995; 78:1806–1815.
  61. Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol 1986; 61:1438–1443.
  62. Bradley TD, Logan AG, Kimoff RJ, et al; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005; 353:2025–2033.
  63. 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; 115:3173–3180.
  64. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath 2007; 11:117–124.
  65. Banerjee D, Yee BJ, Piper AJ, Zwillich CW, Grunstein RR. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678–1684.
  66. Kaw R, Hernandez AV, Walker E, Aboussouan L, Mokhlesi B. Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Chest 2009; 136:787–796.
  67. Pérez de Llano LA, Golpe R, Piquer MO, et al. Clinical heterogeneity among patients with obesity hypoventilation syndrome: therapeutic implications. Respiration 2008; 75:34–39.
  68. Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63:395–401.
  69. Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial. Chest 2006; 130:815–821.
  70. Aboussouan LS, Khan SU, Banerjee M, Arroliga AC, Mitsumoto H. Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis. Muscle Nerve 2001; 24:403–409.
  71. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 5:140–147.
  72. Miller RG, Anderson F, Brooks BR, Mitsumoto H, Bradley WG, Ringel SP; ALS CARE Study Group. Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database. Ann Neurol 2009; 65(suppl 1):S24–S28.
  73. Bach JR. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory AIDS. Chest 2002; 122:92–98.
  74. Perrin C, Unterborn JN, Ambrosio CD, Hill NS. Pulmonary complications of chronic neuromuscular diseases and their management. Muscle Nerve 2004; 29:5–27.
  75. Nickol AH, Hart N, Hopkinson NS, Moxham J, Simonds A, Polkey MI. Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation. Thorax 2005; 60:754–760.
  76. Barle H, Söderberg P, Haegerstrand C, Markström A. Bi-level positive airway pressure ventilation reduces the oxygen cost of breathing in long-standing post-polio patients on invasive home mechanical ventilation. Acta Anaesthesiol Scand 2005; 49:197–202.
  77. Lechtzin N, Shade D, Clawson L, Wiener CM. Supramaximal inflation improves lung compliance in subjects with amyotrophic lateral sclerosis. Chest 2006; 129:1322–1329.
  78. Hill NS. Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care 2004; 49:72–87;
  79. McEvoy RD, Pierce RJ, Hillman D, et al; Australian trial of noninvasive Ventilation in Chronic Airflow Limitation (AVCAL) Study Group. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Thorax 2009; 64:561–566.
  80. Criner GJ, Brennan K, Travaline JM, Kreimer D. Efficacy and compliance with noninvasive positive pressure ventilation in patients with chronic respiratory failure. Chest 1999; 116:667–675.
  81. Strumpf DA, Millman RP, Carlisle CC, et al. Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 144:1234–1239.
  82. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax 2010; 65:303–308.
  83. Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med 1985; 6:651–661.
  84. Weitzenblum E, Chaouat A, Kessler R, Canuet M. Overlap syndrome: obstructive sleep apnea in patients with chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008; 5:237–241.
  85. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea. The overlap syndrome. Am J Respir Crit Care Med 2010; Epub ahead of print.
Issue
Cleveland Clinic Journal of Medicine - 77(10)
Issue
Cleveland Clinic Journal of Medicine - 77(10)
Page Number
705-714
Page Number
705-714
Publications
Cleveland Clinic Journal of Medicine
Publications
Cleveland Clinic Journal of Medicine
Topics
Pulmonology
Sleep Medicine
Cardiology
Article Type
Article
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Noninvasive positive pressure ventilation for stable outpatients: CPAP and beyond
Display Headline
Noninvasive positive pressure ventilation for stable outpatients: CPAP and beyond
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KEY POINTS

  • In sleep apnea, NIPPV has both short-term benefits such as improved daytime alertness and reduced fatigue, and long-term benefits such as a reduced cardiovascular risk.
  • The potential development of complex sleep apnea with NIPPV may be managed by using lower pressures, by continued treatment (more than half of cases improve over time), and by advanced options such as adaptive servo-ventilation.
  • In patients with concomitant obstructive sleep apnea and congestive heart failure, NIPPV, particularly bilevel positive airway pressure, improves blood pressure and left ventricular function, though it is not clear whether it has a survival benefit.
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