By Leslie A. Hoffman, RN, PhD
Professor Emeritus,
Nursing and Clinical & Translational Science,
University of Pittsburgh

Leslie Hoffman reports no financial relationship in this field of study.

This article originally appeared in the February 2015 issue of Critical Care AlertIt was edited by Betty Tran, MD, MS, and peer reviewed by William Thompson, MD. Dr. Tran is Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago, and Dr. Thompson is Associate Professor of Medicine, University of Washington, Seattle. Drs. Tran and Thompson report no financial relationships relevant to this field of study.

SYNOPSIS: In a large cohort study, patients with chronic obstructive pulmonary disease managed with noninvasive ventilation had lower inpatient mortality, shorter length of stay, and lower costs compared to those managed with invasive ventilation.

SOURCE: Lindenauer PK, et al. Outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations. JAMA Intern Med 2014;174:1982-1993.

Prior studies, including several meta-analyses, have concluded that nonivasive ventilation (NIV) can reduce the need for intubation and improve short-term survival of patients experiencing a chronic obstructive pulmonary disease (COPD) exacerbation. Little is known, however, about the effectiveness of NIV in routine clinical practice. To determine effectiveness, this study compared outcomes in 25,628 patients hospitalized with a severe exacerbation of COPD who received mechanical ventilation on the first or second ICU day in 420 U.S. hospitals. Patients were included if they were > 40 years of age, had a principal discharge diagnosis of COPD, or a secondary diagnosis of COPD with a principal diagnosis of acute respiratory failure (determined by ICD-9 codes). Patients were excluded who were not treated with short-acting bronchodilators or systemic corticosteroids (to reduce misclassification), received palliative or hospice care, or were diagnosed with sleep apnea. Data retrieved from electronic medical records were used to compare outcomes in patients managed using NIV (n = 17, 978; 70%) or invasive mechanical ventilation (IMV), and subgroups were defined by age, comorbidity, and comorbid pneumonia. Two additional analyses were performed to address differences among hospitals and control for unmeasured confounders.

The primary study outcome was in-hospital mortality. When compared with those initially managed with IMV, NIV managed patients were older, more likely to have been admitted for COPD in the past year, and had a lower comorbidity score. The incidence of NIV failure was 15.3%. NIV was associated with a lower risk of mortality than IMV (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.48-0.61), lower risk of hospital-acquired pneumonia (OR, 0.53; 95% CI, 0.44-0.64), a 19% shorter length of stay (OR, 0.81; 95% CI, 0.79-0.82), and 32% lower costs, which averaged $5673 per patient (OR, 0.68; 95% CI, 0.67-0.69). There was no difference in 30-day all-cause readmission (OR, 1.04; 95% CI, 0.94-1.15) or COPD-specific readmission (OR, 1.05; 95% CI, 0.91-1.22). The benefits of NIV were similar in a sample restricted to patients younger than 85 years. Benefits were less for patients with higher levels of comorbidity and comorbid pneumonia, but remained significant. Using the hospital as an instrumental variable, the strength of association between NIV and mortality was modestly less (OR, 0.66; 95% CI, 0.47-0.91). In sensitivity analyses, the benefit of NIV was robust in the face of a strong hypothetical unmeasured confounder.


A major strength of this study is the use of a large, externally generalizable population. Patients were recent admissions (January 2008-June 2011) to 420 geographically diverse hospitals; all were participants in a fee-supported data repository designed to support quality improvement (Premier Healthcare Informatics). This data-sharing repository enabled access to an extensive database and sophisticated analytic techniques.

Findings supported benefits reported from randomized, controlled trials. NIV was associated with lower mortality, a lower risk of hospital-acquired pneumonia, a shorter hospital length of stay, and no increase in COPD-specific or all-cause readmission within 30 days of discharge. Although NIV has been strongly endorsed in clinical guidelines, surveys suggest that many eligible patients are not managed using NIV. One frequently cited reason relates to concern that benefits seen in a carefully selected sample of patients managed by experienced clinicians might not transfer to the “real world” of clinical practice. Successful implementation of NIV requires appropriate patient selection, 24-hour availability of an experienced team, close patient monitoring, and the ability to quickly to convert to IMV if NIV fails.

 In this study, patients spent a median of 2 (range 1-4) days on NIV and 3 (range 2-5) days on IMV. In-hospital mortality rates were 4.8%, 8.6%, and 13.8% among those initially treated with NIV, IMV, and those who failed NIV, respectively. The higher mortality rate in those who fail NIV supports the need for careful patient selection. Notably, the relative advantage of NIV was less in patients with COPD if pneumonia was present at admission, a finding that has potential clinical significance. Unlike an acute exacerbation of COPD, patients with pneumonia are less likely to experience a rapid reversal of acute respiratory failure. In such situations, NIV may not be the optimum choice, given the likely longer recovery interval and higher patient acuity. Findings of this study are subject to the limitations of all observational studies, namely inability to identify causality. They suggest that, among patients hospitalized for a COPD exacerbation, NIV is a prudent initial choice given its many benefits with the caveat that benefits may be more limited or absent when pneumonia is present at admission.