Noninvasive Ventilation Has Been Shown to be Ineffective in Stable COPD

Nicholas S. Hill

Pulmonary Division,Rhode Island Hospital,Providence, Rhode Island

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The possibility that noninvasive ventilation (NIV) might aid patients with severe stable COPD has intrigued clinicians for decades. Early investigators thought that intermittent use of NIV might rest the mechanically disadvantaged respiratory muscles, relieving chronic fatigue, and enhancing ventilatory and overall function (1). More recently, attention has focused on reversal of sleep disturbances and chronic hypoventilation by using NIV, with the hope that sleep quality, hypoventilation, and overall health status would improve. These are laudatory goals for these incapacitated patients who have few other substantially effective therapies available to them. Unfortunately, the results of studies evaluating the effectiveness of NIV in severe stable COPD have been, for the most part, disappointing.

Early investigations into the therapeutic role of NIV in resting chronically fatigued respiratory muscles produced mixed results. Uncontrolled series demonstrated improvements in maximal inspiratory and expiratory pressures and daytime Pa_CO2 after several months of intermittent negative pressure ventilation (2, 3), as did short-term controlled trials that lasted only a few days to a week, mainly in markedly hypercapnic patients (4). However, the longer controlled trials came up empty-handed (7). Not only did these trials show no improvement in respiratory muscle strength, blood gases, functional status, or symptoms, but they also found that negative pressure ventilators were poorly tolerated. In a study that randomized 184 subjects to receive negative pressure or sham ventilation daily for 12 wk (10), no improvements were detectable in respiratory muscle strength, dyspnea scores, daytime blood gases, or in the primary outcome variable, the 6-minute-walk test. Higher Pa_CO2 or more hours of ventilator use failed to correlate with greater benefit. Further, over one-third of ventilated patients failed to complete the trial and actual ventilator use averaged less than 3 h/d. These findings suggest that with the exception of short-term applications in markedly hypercapnic patients, negative pressure ventilation is ineffective in improving respiratory muscle strength, daytime blood gases, or functional status in severe stable COPD, partly because of poor tolerance of the therapy.

The unfavorable experience with negative pressure ventilation and technological advances in noninvasive positive pressure ventilation (NPPV) have shifted attention to the use of NPPV in severe stable COPD. Here, the rationale is based on the observation that sleep quality in severe COPD patients is poor, with reductions in total sleep time and frequent oxygen desaturations and arousals compared to normals (10). The hypothesis is that if NPPV prevents the episodic hypoventilation and desaturations, arousals may be suppressed, total duration of sleep enhanced, and sleep quality improved. Elimination of the nocturnal hypoventilation might also lead to improved daytime gas exchange as well as enhanced overall function. Uncontrolled studies demonstrating improvements in gas exchange as well as increases in total sleep time (11) and quality of life (11, 12) suggest that this might well be the case. Unfortunately, uncontrolled trials only help to identify possible therapeutic interventions; they can be used neither to prove nor disprove effectiveness.

Very few controlled trials have examined the efficacy of NPPV in severe stable COPD. One randomized short-term study found that total sleep time was significantly increased by NPPV compared to CPAP (5 cm H₂O), but there were no differences in blood gases or sleep efficiency (13). The only favorable long-term controlled trial of NPPV in severe stable COPD (mean baseline Pa_CO2 56 mm Hg) was a 3-mo crossover trial by Meecham-Jones and colleagues (14). This showed improvements in total sleep time, daytime and nocturnal gas exchange, and quality of life scores during NPPV use compared to O₂ supplementation alone. However, a major concern regarding this study is that the average number of hypopneas per hour at baseline was 10, indicating that many enrolled patients would have been considered to have some sleep-disordered breathing and qualified for nocturnal positive pressure therapy. The authors did not perform a subgroup analysis of patients with less than 10 hypopneas per hour compared to those with more than 10 per hour, but the responders in this study may have been mainly those with an "overlap" syndrome; the combination of severe COPD and sleep-disordered breathing.

Three randomized controlled trials evaluating NPPV for severe stable COPD have reported unfavorable findings (15). These studies had flaws; all were underpowered, two had low compliance rates (15, 17) and two used low inspiratory pressures (15, 16) or insufficient periods (2 wk) to allow for adequate adaptation (16). The third (17) was a 3-mo crossover trial similar in design to the Meecham-Jones study, but enrolled patients had milder hypercapnia (46 mm Hg) despite having worse airway obstruction (541 versus 860 ml). Also, patients with apnea-hypopnia indexes (AHI) > 5 were excluded. These differences, combined with the findings from the negative pressure ventilator studies, suggest that NPPV is ineffective in stable COPD patients, even those with very severe airway obstruction unless they have severe hypercapnia and evidence of nocturnal hypoventilation or an "overlap" syndrome.

No controlled trial has yet shown any significant favorable effect of NPPV on other outcomes such as functional status or survival. Two long-term observational studies (18, 19) from Europe demonstrated that continuation rates for NPPV among COPD patients are much lower than for patients with restrictive thoracic disease. In one of these studies (19), the continuation curve for NPPV was virtually superimposable over the survival curve for patients treated with continuous oxygen in the nocturnal oxygen therapy trial (20), suggesting that NPPV offered no survival benefit over that for O₂ supplementation alone. One of the studies (18) also suggested that days of hospitalization were less after initiation of NPPV, but this awaits confirmation in a controlled trial.

Has NPPV been shown to be effective or ineffective for severe stable COPD? The data are admittedly flimsy either way. However, the weight of the evidence favors the view that, with the possible exception of a small subgroup of COPD patients who have severe hypercapnia and sleep-disordered breathing/ hypoventilation, NIV is ineffective and should not be used as routine therapy in most of these unfortunate patients. This goes with the usual disclaimer that more studies are clearly needed. To view the data otherwise would require excessive reliance on anecdotal data and the one controlled trial with favorable results, along with unbridled optimism.

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