Approach

The primary treatment modality for the hypoventilation syndromes is nocturnal ventilation. With most disorders, nocturnal noninvasive ventilation (NIV) has become an increasingly used treatment option that is both effective and well tolerated.[29] Guidelines recommend appropriate titration techniques and methods for NIV in patients with the hypoventilation syndromes.[52][53]​ With some disorders, especially with disease progression, invasive mechanical ventilation via tracheostomy may be indicated.

This topic focuses on obesity hypoventilation syndrome, restrictive thoracic disorders, Cheyne-Stokes respiration, and COPD.

See Central sleep apnea and Obstructive sleep apnea.

Obesity hypoventilation syndrome (OHS)

Continuous positive airway pressure (CPAP) may be used as an initial treatment of OHS, because most patients with OHS have associated obstructive sleep apnea.[40] There are reports of successful treatment of OHS with CPAP, usually requiring pressures of 12 to 14 cm H₂O.[13][54][55][56][57][58][59][60] However, there are reports of failure with CPAP therapy as well when used alone.[54][56][61][62][63]

Bilevel positive airway pressure (PAP), with individually adjusted inspiratory and expiratory pressures, is probably the most effective noninvasive treatment for reversing the hypercapnia associated with OHS.[13][64][65][66]​ With a pressure differential, bilevel PAP is more effective at ventilating than merely reversing upper airway obstruction as seen with CPAP. It should be considered during PAP titration when the oxygen saturation remains <90% despite the elimination of obstructive apneas and hypopneas.[52] Most studies have demonstrated that the differential between inspiratory PAP and expiratory PAP must be at least 8 to 10 cm H₂O to correct the hypercapnia and hypoxemia on a long-term basis with bilevel PAP therapy.[13][67][68][69][70]​ A retrospective study demonstrated good long-term outcome in patients treated with NIV after a mean follow-up of 4 years.[66] In addition, use of bilevel PAP results in better respiratory function improvement compared with CPAP.[70] In a prospective study, bilevel PAP was associated with greater PAP adherence when compared to CPAP therapy.[71] With either form of PAP therapy, patients who used their device for more than 6 hours had better improvement in arterial blood gases, improved quality of life scores, and a lower mortality compared to those that used their device for less than 6 hours.[71] It is now recommended that patients hospitalized with suspected OHS should be discharged on nocturnal NIV prior to having a formal outpatient titration study.[40]

Nocturnal invasive mechanical ventilation by tracheostomy can be used effectively in patients with severe OHS who have not been able to tolerate or have had unsuccessful treatment with noninvasive forms of PAP therapy.

Oxygen therapy should not be used alone in patients with OHS.[72][73] However, approximately half of patients with OHS require the addition of oxygen to some form of PAP therapy.[13][54][74][75] Oxygen therapy is added when bilevel has been titrated but there is residual oxygen desaturation in the absence of obstructive apneas and hypopneas.[52] Long-term use of PAP therapy often results in oxygen therapy no longer being required both nocturnally as well as during the day.[71]

Respiratory stimulants such as medroxyprogesterone have been used in reported cases of OHS, but they increase the risk of thromboembolic disease.[76][77]​​

Weight reduction, including diet or the use of gastric bypass surgery, has been shown to be effective.[39][40] Many of these patients with OHS require PAP therapy following surgery until they have lost a significant amount of weight. Even after significant weight loss, most gastric bypass surgery patients still have significant residual sleep-disordered breathing that requires continued use of NIV.[78]

Restrictive thoracic disorders

In patients with neuromuscular and chest wall diseases, the use of nocturnal ventilation has been associated with improved survival, sleep quality, daytime gas exchange, and daytime function and with decreased daytime sleepiness.[79][80][81][82] In addition, improvements in respiratory muscle function are noted, which may explain the improvements in daytime gas exchange.[80] Overall, nocturnal ventilation can slow the rate of decline in pulmonary function compared with nonventilated controls.

Amyotrophic lateral sclerosis has become the most common restrictive thoracic disorder to be prescribed NIV, which reportedly improves survival and quality of life, and reduces decline in forced vital capacity.[51][83][84]​​[85]​​​​ Predictors of a favorable response to nocturnal NIV include intact bulbar function, orthopnea, hypercapnia, and nocturnal oxygen desaturation.[17] However, studies suggest that starting nocturnal NIV before the development of hypercapnia may be of benefit in patients with restrictive thoracic disorders.[44][50]​​ For patients with preserved bulbar function using NIV, mouthpiece ventilation may be suitable for daytime ventilatory support.[45]

NIV using either bilevel PAP or a volume-cycled ventilator is preferred, with the latter able to generate larger tidal volumes than the standard bilevel PAPs that have a maximum inspiratory PAP of 30 cm H₂O. Settings should be titrated in a sleep center or in a controlled setting such as the hospital, or, at times, in the patient's home. With PAP therapy, both inspiratory PAP and expiratory PAP should be increased together until all apneas and hypopneas are resolved, followed by continued increases in inspiratory PAP to correct the hypoxemia related to alveolar hypoventilation.[52]

Patients with neuromuscular diseases and hypoventilation may benefit from lung volume recruitment (LVR) (e.g., glossopharyngeal breathing or breath stacking using a handheld resuscitation bag or mouthpiece) and airway clearance (e.g., manually assisted cough techniques).[45]

Nocturnal invasive mechanical ventilation by tracheostomy often becomes necessary in patients intolerant of NIV, including those with extended daytime use, worsening bulbar function, frequent aspiration, insufficient cough, episodes of chest infection despite adequate secretion management, and declining lung function.[45]​ It may be necessary to add regular mechanical insufflation-exsufflation (cough assist device) for continued reduced cough effectiveness or high-frequency chest wall oscillation, with or without cough assistance or LVR, for patients with continued difficulties clearing secretions.[45]

Oxygen therapy should not be used alone in patients with hypoventilation syndrome due to restrictive thoracic disorders.

Cheyne-Stokes respiration

CPAP therapy has been shown to decrease the central apnea-hypopnea index in patients with Cheyne-Stokes respiration (CSR) due to congestive heart failure (CHF), both after short-term use and after periods of 1 to 3 months.[8][86][87][88][89][90][91][92]​​​ By increasing intrathoracic pressure and decreasing the transmural pressure across the left ventricle, CPAP decreases left ventricular afterload, leading to an improvement in cardiac output.[13] It has been proposed that the increase in left ventricular ejection fraction with CPAP therapy reduces interstitial lung edema and decreases stimulation of the pulmonary vagal afferents, which are thought to cause the observed hyperventilation and hypocapnia in these patients.[92] While a previous multicenter study did not reveal an improved transplant-free survival with CPAP, a post-hoc analysis of the data revealed an improved outcome in those patients assigned to CPAP therapy who were able to correct their apnea-hypopnea index to <15 events/hour after 3 months of use.[93][94]

Bilevel PAP ventilation allows the individual adjustment of the inspiratory PAP and expiratory PAP and, when set with a backup rate, ensures ventilation during central apneic episodes. When compared with CPAP, both forms of therapy equally decreased the baseline apnea-hypopnea index and improved sleep quality and daytime fatigue.[87]

Adaptive servoventilation (ASV) is a form of noninvasive positive pressure ventilation that has been evaluated in the treatment of CSR. ASV provides a baseline degree of ventilatory support on top of an end-expiratory pressure of 5 cm H₂O and a default backup rate of 15 breaths/minute.[95] Inspiratory pressure increases from a low of 3 cm H₂O to a high of 10 cm H₂O to maintain ventilation at 90% of a running 3-minute reference period. When a decrease in ventilation is noted, such as during a central apnea, the inspiratory pressure increases to maintain ventilation, and then decreases again when spontaneous breathing resumes. Another device developed for ASV uses a flow-targeted approach to maintain ventilation. An end-expiratory pressure is adjusted to eliminate any obstructive events. The device then delivers an inspiratory PAP to maintain a target peak inspiratory airflow with a backup rate.[96] Comparing the one-night effects of CPAP, oxygen therapy, bilevel, and ASV, the apnea-hypopnea index decreased with all forms of therapy.[95] However, compared with baseline and the other treatments, ASV had the most significant improvement in the apnea-hypopnea index. The amount of slow-wave and REM sleep increased with ASV and was the preferred treatment modality. In a randomized study comparing ASV with CPAP, a more significant decrease in the apnea-hypopnea index was seen with ASV at both 3 and 6 months.[97] In addition, in a subset of patients who were evaluated, the left ventricular ejection fraction was noted to increase only in the ASV group at the end of 6 months. Overall, preliminary studies appeared to demonstrate that ASV was effective at normalizing the apnea-hypopnea index in patients with CSR. However, a large, end point-driven study demonstrated a higher all-cause mortality in patients receiving ASV compared with the control group. As a result, ASV is not recommended in patients with CHF and a LVEF ≤45% at this time until further analysis of the study is performed and the results from other ongoing trials are completed.[98] Using a flow-targeted ASV device, an ongoing trial has reported preliminary data showing increased hours of use each night and increased compliance at one year compared to those patients in the prior negative study.[99] In addition, there was no noted increase in mortality at one year in the patients treated with ASV. Final results and recommendations await the completion of this multicenter trial.

Nocturnal oxygen therapy has been shown to significantly decrease the apnea-hypopnea index, both acutely and after more prolonged therapy in patients with CSR due to CHF.[8]​​​​​[17][58][61][62][63][100][101][102][103]​​​​​ While oxygen therapy has been shown to decrease the apnea-hypopnea index, no study has demonstrated an improvement in left ventricular function in patients with CSR and CHF.[89][100]​​[103]

Theophylline has been used for the treatment of CSR in CHF. Proposed mechanisms include improvement in cardiac function and thus circulation time, as well as a possible enhanced central respiratory drive effect.[104][105] Acetazolamide induces a metabolic acidosis and thus increases minute ventilation. Studies have shown a decrease in the apnea-hypopnea index and number of arousals with acetazolamide.[106][107] Both theophylline and acetazolamide have been described as being effective in the treatment of CSR, but they are rarely used clinically. Practice parameters have been published to help guide physicians in regards to treatment options for CSR.[108]

COPD

The use of noninvasive positive pressure ventilation has been shown to be beneficial both during an acute exacerbation of COPD and in selected groups of patients with stable chronic emphysema.[109][110][111][112] Nocturnal NIV has been shown to acutely improve sleep quality without an associated improvement in nocturnal gas exchange in a group of stable hypercapnic patients with COPD, suggesting that factors other than improvement in gas exchange, such as unloading inspiratory muscles or effects on central drive, might play a role.[110] Other long-term trials have demonstrated improvements in sleep quality and gas exchange and a decrease in hospital admissions and office visits.[111][113] Nocturnal NIV combined with oxygen was shown to lower PaCO₂ and improve quality of life after two years in patients with hypercapnic COPD, when compared with oxygen therapy alone.[114] In addition, one trial noted improved survival in hypercapnic COPD patients who received NIV with oxygen therapy, compared with oxygen therapy alone.[112] One trial in patients with persistent hypercapnia following a recent COPD exacerbation, found that nocturnal NIV plus oxygen prolonged the time to readmission or death at 12 months when compared to just oxygen alone.[115] Guidelines have been developed for the use of noninvasive positive pressure ventilation in patients with stable COPD.[116]

The hypoxemia that develops in patients with alveolar hypoventilation most commonly is associated with hypercapnia. Thus, supplemental oxygen must be given with caution to these patients. In patients with COPD and hypoxemia, continuous low-flow oxygen has been shown to significantly affect mortality.[117] Yet, the use of nocturnal oxygen in COPD patients with REM-associated nocturnal oxygen desaturation has been shown to decrease pulmonary hypertension, but has no significant effect on mortality.[118]

Bilevel PAP can be initiated with most patients requiring an inspiratory PAP to expiratory PAP differential of at least 8 to 10 cm H₂O to have effective ventilation. Higher expiratory PAPs may be needed in those patients with the overlap syndrome where there is coexistent OSA. Otherwise, most patients may do well with an expiratory PAP of 5 cm H₂O, which is required to take up the dead space of the tubing and mask and allow effective sensing of an inspiratory effort. Excessive inspiratory PAPs are associated with increasing air leaks and less effective ventilation. However, pressure requirements vary greatly among patients.[119]

Use of this content is subject to our disclaimer