Clinician Article

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema.

  • Berbenetz N
  • Wang Y
  • Brown J
  • Godfrey C
  • Ahmad M
  • Vital FM, et al.
Cochrane Database Syst Rev. 2019 Apr 5;4:CD005351. doi: 10.1002/14651858.CD005351.pub4. (Review)
PMID: 30950507
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  • Emergency Medicine
    Relevance - 7/7
    Newsworthiness - 4/7
  • Cardiology
    Relevance - 6/7
    Newsworthiness - 5/7
  • Intensivist/Critical Care
    Relevance - 6/7
    Newsworthiness - 5/7
  • Hospital Doctor/Hospitalists
    Relevance - 6/7
    Newsworthiness - 4/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 4/7
  • Respirology/Pulmonology
    Relevance - 6/7
    Newsworthiness - 4/7


BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE.

OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates.

SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and clinicaltrials.gov. We also reviewed reference lists of included studies. We applied no language restrictions.

SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations.

MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality.

AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.

Clinical Comments


At least we know it is a viable option that could have more research interest.

Emergency Medicine

NIPPV is the standard of care for ACPE.

Intensivist/Critical Care

This is an exhaustive review that is quite relevant to the management of cardiogenic pulmonary edema. The large amount of reading required may be a bit foreboding. Nevertheless, this is a great effort at providing a summary of data on the topic.

Intensivist/Critical Care

This rigorous and comprehensive meta-analysis provides a powerful affirmation of U.S. and European clinical practice in the management of acute cardiogenic pulmonary edema (ACPE) and is urgently needed. Current national U.S. and Canadian guidelines are out of step with the numerous RCTs, and this meta-analysis shows convincingly that NIV with CPAP or BiPAP in ACPE greatly reduces the need for intubation, mechanical ventilator support, and, most importantly, mortality. Current guidelines need immediate updating.


Cochrane meta-analysis showing that non-invasive ventilation reduces mortality and intubation rates in acute cardiogenic pulmonary edema. Updates previous 2013 review with several new trials. Most individual studies failed to reach statistical significance, so the meta-analysis generates new information.


Cochrane review finds that the current practice of using NPPV for respiratory failure due to acute pulmonary edema appears to reduce mortality and intubation rates. No new findings here to alter what has become standard practice in most institutions.


As an intensivist, this updated meta-analysis reinforces the previously accepted use of non-invasive positive pressure ventilation for decompensated heart failure. The point estimate (with narrow confidence intervals) suggests a mortality benefit of non-invasive positive pressure ventilation compared with standard medical care.

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