CPAP and NIPPV no better than O2 in acute pulmonary edema (3CPO)

Clinical Question

Does noninvasive ventilation improve outcomes in patients with acute cardiogenic pulmonary edema?

Bottom Line

In patients with acute cardiogenic pulmonary edema, continuous positive airway pressure (CPAP) and noninvasive positive pressure support (NIPPV) do not reduce mortality or the risk of requiring intubation more than standard oxygen therapy. They may provide a small benefit in terms of greater relief of dyspnea. (LOE = 1b)


Gray A, Goodacre S, Newby DE, et al, for the 3CPO Trialists. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med 2008;359(2):142-151.  [PMID:18614781]

Study Design

Randomized controlled trial (nonblinded)






Inpatient (any location)


The optimal approach to noninvasive ventilation for patients with acute cardiogenic pulmonary edema remains unclear, with only a few small randomized controlled trials. CPAP provides the same level of positive airway pressure throughout the respiratory cycle, while NIPPV increases pressure more during inspiration than during expiration. There are theoretical reasons to think that NIPPV may be better, but it has also been associated with a greater risk of acute myocardial infarction. In this study, 1069 adults with acute cardiogenic pulmonary edema at 26 United Kingdom emergency departments were randomized to receive oxygen therapy, CPAP, or NIPPV. All patients had pulmonary edema on chest x-ray, a pH of less than 7.35, and a respiratory rate greater than 20 breaths per minute. Their mean age was 78 years and 57% were women. All patients received the assigned treatment for at least 2 hours, with the duration of further treatment determined by the treating physician. Groups were balanced at the start of the study and analysis was by intention to treat. Overall adherence to the assigned treatment was good, although patients initially assigned to oxygen were more likely to change therapy because of respiratory distress (8.4% vs 1.4% for CPAP and 3.4% for NIPPV; P < .001), while those assigned to NIPPV were more likely to change therapy because of patient discomfort (8.4% vs 5.2% for CPAP and 0.3% for oxygen; P < .001). After 7 days, there was no significant difference between groups regarding rates of mortality or need for intubation, or regarding mortality at 30 days. Patients receiving CPAP or NIPPV had a greater improvement on a 10-point dyspnea score than those receiving oxygen alone (4.6 vs 3.9 points), but this difference is of questionable clinical significance. There were also greater improvements in arterial pCO2 and pH, but again the clinical significance is uncertain.