Effect of Continuous Positive Airway Pressure and Noninvasive Positive Pressure Ventilation in Acute Cardiogenic Pulmonary Oedema - 3CPO


The goal of the trial was to evaluate the efficacy of active, noninvasive ventilation compared with passive ventilation with standard oxygen therapy in patients with acute cardiogenic pulmonary edema.


Noninvasive ventilation will improve survival compared with passive ventilation.

Study Design

Study Design:

Patients Enrolled: 1,069
Mean Follow Up: 30 days
Mean Patient Age: 78 years
Female: 57

Patient Populations:

• Age >16 years
• Signs and symptoms consistent with acute cardiogenic pulmonary edema as the primary clinical complaint, including acute dyspnea and bilateral crackles on chest auscultation
• Chest radiograph confirming the diagnosis of acute cardiogenic pulmonary edema
• Arterial blood gas analysis with a pH of
• Respiratory rate of >20 breaths per minute


• Severely altered consciousness
• Need for immediate lifesaving intervention
• Requiring thrombolysis or percutaneous coronary intervention for acute ST-segment elevation myocardial infarction
• Clear alternative primary diagnosis
• Inability to provide informed consent at any time during the trial period

Primary Endpoints:

• Mortality comparing standard oxygen therapy and noninvasive ventilation (CPAP or NIPPV) at 7 days
• Mortality or intubation at 7 days comparing CPAP and NIPPV

Secondary Endpoints:

• Dyspnea
• Physiological variables
• Intubation within 7 days
• Duration of hospital stay
• Admission to the critical care unit
• Mortality at 30 days

Drug/Procedures Used:

Patients were randomized to standard oxygen therapy given via facial mask (n = 367), continuous positive airway pressure (CPAP; n = 346), or noninvasive intermittent positive pressure ventilation (NIPPV; n = 356). Use of nitrate and diuretic therapy was encouraged.

Principal Findings:

At study entry, 63% of patients had ischemic heart disease and 44% had congestive heart failure. Nitrate therapy was used in 90% of patients and diuretic therapy in 89%. Mean inspired oxygen was 12 L/min. Mean ventilation pressure was 10 cm H20 in the CPAP group and 14 cm H20 in the NIPPV group.

Treatment of allocated therapy was completed in 83.2% of the standard oxygen therapy group, 84.5% of the CPAP group, and 77.7% of the NIPPV group (p = 0.016). Reason of stopping treatment due to nontolerance of therapy occurred in 0.3% of the standard oxygen therapy group, 5.4% of the CPAP group, and 8.8% of the NIPPV group (p

One hour after the intervention, pulse rate was lower in the CPAP or NIPPV groups combined compared with the standard oxygen therapy group (96 vs. 102 bpm, p 2 (6.2 vs. 6.7 kPA, p

There was no difference in the primary endpoint of mortality at 7 days comparing the CPAP or NIPPV groups combined with the standard oxygen therapy group (9.5% vs. 9.8%, p = 0.87). There was also no difference in the co-primary endpoint of mortality or intubation at 7 days comparing the CPAP group with the NIPPV group (11.7% vs. 11.1%, p = 0.81). Results were similar for mortality at 30 days comparing standard oxygen therapy with noninvasive ventilation (16.4% vs. 15.2%, p = 0.64).

Other clinical characteristics were similar between the three groups, including need for admission to the intensive care unit (8.8% of the standard oxygen therapy group, 9.1% of the CPAP group, and 6.6% of the NIPPV group; p = 0.411) and median length of hospital stay (8 days for the oxygen therapy group and 9 days for both the CPAP and NIPPV groups; p = 0.313).


Among patients with acute cardiogenic pulmonary edema, treatment with noninvasive ventilation was not associated with a difference in mortality compared with standard oxygen therapy; there was also no difference in mortality or need for intubation comparing the two types of noninvasive ventilation, CPAP and NIPPV.

Despite improvement in early physiologic parameters such as oxygen saturation and arterial PCO2 with noninvasive ventilation, as well as reductions in respiratory distress, no mortality benefit was observed when compared with passive ventilation with standard oxygen therapy. The mode of noninvasive ventilation, either CPAP or NIPPV, did not appear to have an impact on either clinical or physiologic parameters. Mortality associated with acute cardiogenic pulmonary edema presentation is as high as 15-20% in-hospital.

The findings of the present study are quite different from a meta-analysis published in 2005 (JAMA 2005;294:3124-30), which suggested a nearly 50% reduction in mortality with noninvasive ventilation compared with control (relative risk 0.53, 95% confidence interval 0.35-0.81), although the majority of the trials in the meta-analysis were small, with all but two enrolling less than 100 patients. The present study enrolled more patients than all of the earlier combined trials to date.


Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J, on behalf of the 3CPO Trialists. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med 2008;359:142-51.

Presented by Dr. David Newby at the European Society of Cardiology Congress, September 2007, Vienna, Austria.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Intermittent Positive-Pressure Ventilation, Blood Gas Analysis, Pulmonary Edema, Myocardial Ischemia, Noninvasive Ventilation, Auscultation, Respiratory Rate, Diuretics, Dyspnea, Heart Rate, Length of Stay, Oxygen Inhalation Therapy, Intubation, Heart Failure, Continuous Positive Airway Pressure, Respiratory Sounds

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