Also reduces need for intubation, Cochrane reviewers find
by Salynn Boyles, Contributing Writer, MedPage Today July 17, 2017

Action Points
• Non-invasive ventilation is an effective treatment strategy for chronic obstructive pulmonary disease (COPD) patients hospitalized for acute exacerbation and hypercapnic respiratory failure.
• Note that noninvasive positive pressure ventilation (NPPV) has been standard therapy for use in patients with COPD exacerbations who do not have a contraindication to its use, and the Cochrane findings support this.

Non-invasive ventilation is an effective treatment strategy for chronic obstructive pulmonary disease (COPD) patients hospitalized for acute exacerbation and hypercapnic respiratory failure, findings from a newly published Cochrane Review confirm.
The review of 17 clinical trials involving 1,264 patients found non-invasive ventilation to be associated with a 46% reduction in death risk and a 65% reduction in the risk of needing intubation.
The reviewers rated the quality of the evidence for both of these findings as “moderate,” according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations) criteria.
Patients in the studies treated with non-invasive ventilation were hospitalized, on average, 3½ days less than COPD patients with respiratory failure due to exacerbation who did not receive the treatment, wrote Christian Osadnik, PhD, of Monash University in Melbourne, Australia, and colleagues.
Their analysis is now online in the Cochrane Database of Systematic Reviews 2017.
Asked for his opinion, Ray S. Peebles, MD, of Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the review, said that noninvasive positive pressure ventilation (NPPV) has been standard therapy for use in patients with COPD exacerbations who do not have a contraindication to its use, and the Cochrane findings support this.
Contraindications to NPPV include respiratory arrest, cardiovascular instability, impaired mental status, high aspiration risk, extreme obesity, and recent facial or gastrointestinal surgery, he said. “In patients who do not have these contraindications, it is clear that NPPV reduces the rate of endotracheal intubation, hospital mortality, ventilator associated pneumonia, and other nosocomial infections. This confirmation is important to help spread the word of the efficacy of NPPV in this patient population.”
The Cochrane review included randomized, controlled trials comparing usual care plus non-invasive ventilation with usual care alone in an acute hospital setting in patients with acute exacerbations of COPD due to acute hypercapnic respiratory failure (AHRF).
AHRF was defined by a mean admission pH of <7.35 and mean partial pressure of carbon dioxide (PaCO2) of >45 mmHg (6kPa).
Primary outcomes included death during hospital admission and the need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in atrial blood gases.
The mean age of the patients included in the analysis was 66.8 (range of 57.7 to 70.5), and 65% of the participants were male.
In 12 of the 17 studies, the reviewers found a risk of performance bias, and the risk of detection was found to be uncertain in 14 studies.
“These risks may have affected subjective patient-reported outcome measures (e.g., dyspnea) and secondary review outcomes, respectively,” Osadnik and colleagues wrote.
Use of non-invasive ventilation was found to decrease the risk of death by 46% — risk ratio, 0.54, 95% CI, 0.38-0.76; N= 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9-23.
The treatment also decreased the need for endotracheal intubation by 65% (RR 0.36, 95% CI, 0.28-0.46; N=17 studies; NNTB 5, 95% CI, 5-6).
The authors graded both outcomes as being of “moderate” quality — “owing to uncertainty regarding risk of bias for several studies.”
“Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome,” the review team wrote.
Use of non-invasive ventilation was also associated with:
• Reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI, -5.93 to -0.85; N = 10 studies)
• Reduced incidence of complications (unrelated to non-invasive ventilation (RR 0.26, 95% CI, 0.13-0.53; N = 2 studies)
• Improvement in pH (MD 0.05, 95% CI, 0.02-0.07; N = 8 studies) and in partial pressure of oxygen (PaCO2) (MD 7.47 mmHg, 95% CI, 0.78-14.16 mmHg; N = 8 studies) at 1 hour
A trend toward improvement in PaCO2 was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI ,-11.05 to 1.80 mmHg; N = 8 studies).
“Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the non-invasive ventilation group than in the usual care group).”
Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of non-invasive ventilation on PaCO2.
Treatment intolerance was significantly greater in the non-invasive ventilation group than in the usual care group (risk difference [RD] 0.11, 95% CI, 0.04-0.17; N = 6 studies) and there was a nonsignificant trend towards reduction in dyspnea with non-invasive ventilation compared with usual care (standardized mean difference [SMD] -0.16, 95% CI, -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences.
“Data from good-quality randomized controlled trials show that non-invasive ventilation is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD),” the Cochrane authors concluded.
“The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when non-invasive ventilation is applied within the intensive care unit or ward setting.”