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Abstract & Commentary
Although noninvasive positive-pressure ventilation (NPPV) has become a standard of care for acute-on-chronic ventilatory failure in patients with chronic obstructive pulmonary disease (COPD), the numerous reported studies have left uncertain how the clinician should select patients who should receive this therapy. Keenan and associates include eminent authorities in the fields of NPPV and evidence-based medicine and conducted a very thorough examination of available randomized, controlled trials (RCTs) of NPPV vs standard therapy in the management of acute exacerbations of COPD. They included only RCTs, only studies of COPD patients admitted to hospital with acute exacerbations, and only investigations that used endotracheal intubation, length of hospital stay and/or in-hospital mortality as outcomes.
The search produced 704 candidate trials, of which 608 were uncontrolled or otherwise inapplicable, 23 were not on COPD patients, 12 were on at least some patients with stable COPD, 22 applied NPPV or continuous positive airway pressure (CPAP) in both study arms, and 39 were unacceptable for other reasons. This left 13 trials for meta-analysis, from which 2 were excluded for a priori reasons, and 4 additional trials reported only in abstract form were added, making 15 studies altogether. These studies involved COPD patients in 10 different countries.
In 11 trials (629 patients) reporting in-hospital mortality, the use of NPPV was associated with a 10% risk reduction of death (95% CI, 5-15%). The 13 trials reporting intubation rates had an overall risk reduction for this outcome of 28% (95% CI, 15-40%). Duration of hospital stay was reduced by a mean of 4.57 days (95% CI, 2.30-6.83 days) in patients randomized to receive NPPV, as reported in the 9 studies that reported this outcome. All 3 of these outcomes were statistically different in patients with severe COPD exacerbations (as defined either by an initial arterial pH < 7.30 or an in-hospital mortality rate > 10% in the control group): mean risk reduction with NPPV, as compared with standard therapy, was 12% for mortality, 34% for endotracheal intubation, and 5.59 days for hospital length of stay in patients with severe vs those with less severe exacerbations, respectively. Two studies of NPPV in patients admitted with mild exacerbations (n = 72) showed no benefit in any of these 3 outcomes (Keenan SP, et al. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? Ann Intern Med. 2003;138:861-870).
Comment by David J. Pierson, MD
There is no longer any doubt that adding NPPV to standard therapy (such as aerosolized bronchodilators, systemic corticosteroids, antibiotics, and controlled oxygen therapy) can reduce mortality and hospital length of stay and decrease the need for endotracheal intubation in many patients with acute exacerbations of COPD. But which patients? The most widely used system for classifying the severity of acute exacerbations is that of Anthonisen and colleagues,1 which identifies a severe acute exacerbation as one with increased dyspnea, increased sputum quantity, and increased sputum purulence. According to this scheme, moderate and mild exacerbations have only 2 and 1 of these components, respectively. However, the Anthonisen grading system has not been applied to the selection of patients for NPPV. In the present study, Keenan et al demonstrated the benefits of NPPV for patients with initial arterial pH < 7.30, but not for less acidemic patients. The finding that NPPV was efficacious in studies whose control patients had a mortality of more than 10%, but not when the standard therapy group had less than a 10% mortality, is not directly helpful.
Other possible selection criteria for individual patients have not been validated by this meta-analysis or other studies of which I am aware. However, in their discussion, Keenan et al make the following points, which seem reasonable and reflect the best available evidence:
1) NPPV should be used, in addition to standard therapy, in patients with acute exacerbations of COPD and initial arterial pH values < 7.30;
2) Such patients should be managed in a high-dependency unit (ie, ICU or special respiratory ward) in which adequate, experienced personnel can monitor the success of treatment and proceed with intubation in a timely fashion if NPPV fails;
3) Patients with less severe exacerbations should be monitored so that NPPV can be initiated if respiratory distress or respiratory acidosis worsen with standard therapy; and
4) Hemodynamically unstable patients and those with impending respiratory arrest are not candidates for NPPV and should be intubated without delay.
This study did not find evidence in support of any one approach to NPPV over any other. That is, whether nasal or oronasal masks work better cannot be answered from the available literature. Neither can it be said for certain whether portable ventilators like the BiPAP machine or standard ICU-type ventilators should be used, nor whether pressure-targeted or volume-targeted modes are preferable. In addition, as has been pointed out previously in these pages,2 experience and technical expertise, although less tangible than the other variables mentioned, are very important determinants of the success of a trial of NPPV in any given patient.
1. Anthonisen NR, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106:196-204.
2. Kacmarek RM. Noninvasive ventilation in acute respiratory failure: Practical tips for success. Critical Care Alert. 1999;7(5):37-40.
Dr. Pierson is Professor of Medicine University of Washington Medical Director Respiratory Care Harborview Medical Center, Seattle.