Noninvasive Ventilation for COPD: Volume Assurance not very Reassuring

Noninvasive ventilation (NIV) to treat severe COPD was first proposed over 50 years ago as a way of stabilizing PaCO₂ in hypercapnic patients using either positive pressure (1), negative pressure (2) or both techniques (3). In 1984, Braun and Marino used a negative pressure “jacket ventilator” for 5 hours daily for 5 months in a small cohort of COPD patients (4). Not only was daytime PaCO2 reduced, but they also observed improvements in maximum inspiratory and expiratory pressures and a reduction in hospitalization rate.

These findings suggested that NIV rests the respiratory muscles in patients with severe COPD, enabling them to function better, and stimulated a number of subsequent studies that yielded conflicting findings regarding the efficacy of NIV in COPD (5–8). A 2003 meta-analysis concluded that there was no convincing evidence that NIV works to help COPD patients, although the authors allowed that the quality of the evidence was limited (9).

Subsequent randomized controlled trials (RCT)s have shown minor benefits, with an Italian trial showing that 2 years of NIV stabilized PaCO2 and improved dyspnea and quality of life compared to controls (10) An Australian RCT observed an improved adjusted but not unadjusted survival, no change in PaCO2 and a worsened quality of life after a year of NIV therapy (11).

A promising approach, termed “high intensity” NIV, uses much higher inspiratory pressures than in previous studies (mean inspiratory pressure approaching 30 cm H2O). (12). In a recent small RCT, this approach was associated with better tolerance than a low intensity approach (mean inspiratory pressure 14.6 cm H2O) and, compared to baseline, significant improvements in exercise-related dyspnea, daytime PaCO2, FEV1, vital capacity and the Severe Respiratory Insufficiency Questionnaire Summary Score (13).

In the current issue of COPD, Oscroft et al (14) sought to test the “safety and efficacy” in COPD patients of volume assured pressure support, a newer mode for NIV that automatically adjusts inspiratory pressure within pre-set limits to achieve a targeted minute volume. The authors compared this to the more traditional pressure pre-set “bilevel” mode in a group of stable, well experienced NIV users with severe COPD, hypothesizing that the newer mode would afford more effective ventilation. Using two eight-week periods in a crossover design in 23 patients, the authors found no clinically significant differences between the two modes, including lung function, gas exchange, exercise capacity as assessed by the shuttle walk test, quality of life and ventilator adherence and tolerance.

A number of methodologic issues should be considered in interpreting these findings. First, it is not surprising that the two modes performed similarly, considering that the settings were adjusted to deliver similar minute volumes. In a previous study comparing a volume assured mode vs a pressure preset mode in patients with obesity-hypoventilation (14), the volume-assured mode was set to maximize the decrease in nocturnal transcutaneous PCO₂ within the patient's limits of tolerance. When the volume assured mode was set in this way, daytime PaCO2 was significantly lower than with the standard pressure preset mode.

Second, the authors did not monitor breathing pattern, air leaks, or responses of the ventilator mode to air leaks during use. If the volume assured mode fails to compensate for leaks more effectively than the pressure preset mode or adopts a pattern of breathing that is less favorable in response to leaks, this might prevent the mode from consistently delivering the targeted tidal volume and negate benefits that might otherwise accrue. In this context, it is important to point out that the mode selected for comparison was that of a single manufacturer and other commercially available modes might have performed differently.

Third, the study enrolled a highly selected population of experienced NIV users already adapted to “high intensity” NIV with average baseline inspiratory positive airway pressures of 30 cm H2O. The results might have been different had the study compared a population of naïve users starting out on NIV. The volume-assured mode could conceivably have effected more rapid improvements in gas exchange in naive patients than the standard pressure preset mode because of its ability to deliver a targeted tidal volume.

Despite these limitations, the volume-assured mode actually achieved a statistically significant reduction in daytime PaCO2 and increase in oxygen saturation (0.4 kPa and 1.5%, respectively) compared to values during pressure preset ventilation, differences that the authors dismiss as clinically insignificant. Although differences in this range have been considered clinically important in previous studies (15), the absence of correlative differences in nocturnal transcutaneous PCO₂ or other clinical variables makes it difficult to argue that the gas exchange differences in the Oscroft study are clinically meaningful. On the other hand, they could have attained clinical significance in a longer-term study.

It must also be acknowledged that although the improvements over pre-ventilation values in the long-term NIV users in the Oscroft study were impressive, there was no untreated control group, so it is conceivable that both modes were equally ineffective rather than equally effective. Along these lines, one could argue that the Oscroft study is premature in that the efficacy of NIV for COPD has not been established and rather than compare modes, studies should assess the efficacy of NIV in COPD patients by including an oxygen therapy or sham NIV control group.

Not only does the efficacy of NIV in patients with severe stable COPD remain to be convincingly shown, but the ideal mode for achieving optimal efficacy also awaits clarification. The Oscroft study suggests that volume assured pressure support offers no substantial advantage over the more traditional pressure preset mode under the specific conditions of the study, but further investigation is certainly needed. Future studies should establish definitively, using a variety of ventilators at different pressures in different patient populations, whether the “high intensity” approach is truly more effective than a lower intensity approach and whether, under different conditions, more sophisticated “hybrid modes” like the volume assured mode tested herein offer clinically meaningful advantages.

Declaration of interest

The author has received research grants from Respironics, Inc., and Breathe Technologies, Inc., manufacturers of noninvasive ventilators. The author alone is responsible for the content and writing of the paper.