Noninvasive positive pressure ventilation for stable outpatients: CPAP and beyond
ABSTRACTNoninvasive positive pressure ventilation (NIPPV) has been used in outpatients with sleep apnea, sleep disorders associated with heart failure, restrictive pulmonary diseases (subsuming neuromuscular diseases and thoracic cage deformities), severe stable chronic obstructive pulmonary disease, and the obesity-hypoventilation syndrome. NIPPV in these settings has resulted in significant physiologic benefits, improved quality of life, and in some cases longer survival. We discuss the modes of NIPPV, current indications, and potential benefits.
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.
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.
