Noninvasive Positive Pressure Ventilation for Cardiogenic Pulmonary Edema

Reduces hospital mortality and endotracheal intubations

Benefits in NNT

1 in 17 were helped (deaths prevented)
1 in 13 were helped (endotracheal intubations prevented)
5.9% lower risk of death
7.7% lower rate of endotracheal intubations

Harms in NNT

No one was harmed
No one was harmed
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Berbenetz N, Wang Y, Brown J, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev. 2019;4(4):CD005351.

Study Population: 2664 adult participants (>18 years of age) with respiratory distress due to acute cardiogenic pulmonary edema not requiring immediate mechanical ventilation treated either prehospital, in the ED, or in the intensive care unit

Efficacy Endpoints

Mortality, need for endotracheal intubation

Harm Endpoints

Acute myocardial infarction, increased length of hospital stay


Acute cardiogenic pulmonary edema (ACPE) has traditionally been treated pharmacologically, with a combination of nitrates, diuretics, morphine, and inotropes. Since the introduction of noninvasive positive pressure ventilation (NIPPV), a method of providing mechanical ventilation that does not bypass the upper airway, this modality has been widely used as an important addition to the acute care of ACPE. NIPPV encompasses both CPAP (continuous positive airway pressure) and BiPAP (bilevel positive airway pressure), two slightly varied modalities of breathing support where oxygen and additional pressure are delivered most commonly through a facial mask. CPAP delivers a constant pressure throughout the respiratory cycle, while BiPAP delivers independent levels of pressure support set by the clinician for both inspiratory and expiratory phases.

Noninvasive positive pressure ventilation provides multiple benefits in ACPE including improving respiratory dynamics, hemodynamic effects, and decreasing work of breathing. Beneficial respiratory effects include recruitment of additional alveolar units for gas exchange, correction of hypoxemia, reduction in hypoxia-induced pulmonary vascular resistance, and improvement in lung compliance. Hemodynamic effects are complex, however, and ultimately lead to a reduction in afterload and increased LV emptying. Decreasing work of breathing will in turn reduce myocardial oxygen demand and allow for improvement in overall cardiopulmonary dynamics. A 2013 meta-analysis of patients with ACPE found no significant differences in clinical outcomes when comparing CPAP to BiPAP.1

Common contraindications to the use of NIPPV include cardiac or respiratory arrest, inability to cooperate or to remove own mask in an emergency, inability to tolerate or clear secretions, facial trauma, high aspiration risk, and anticipation of a prolonged duration of mechanical ventilation. Canadian and European guidelines differ in their recommendations regarding NIPPV; Canadian guidelines suggest initiating NIPPV only if hypoxia persists despite standard medical care, whereas European guidelines recommend early initiation of NIPPV for those presenting with tachypnea (RR > 25) and hypoxia (SpO2 < 90). American guidelines do not provide clear recommendations for the treatment of ACPE.2

This is an updated review utilizing the 2019 Cochrane review by Berbenetz et al.,3 which sought to evaluate the safety and effectiveness of NIPPV compared to standard medical care for adults with ACPE. The review included 24 studies with 2,664 adult participants (>18 years of age) with respiratory distress due to ACPE who did not require immediate mechanical ventilation. Patients in the included studies were randomized to standard medical care or standard medical care plus NIPPV. NIPPV included both continuous (CPAP) and bilevel (BiPAP) positive pressure support. Standard medical care was supplemental oxygen and pharmacologic treatments that included various combinations of loop diuretics, nitrates, opioids, and inotropes. The median follow-up for determining hospital mortality was 13 days and for endotracheal intubation was 1 day.

In the meta-analysis, NIPPV was associated with statistically significantly lower mortality than standard care (relative risk [RR] = 0.65, 95% confidence interval [CI] = 0.51 to 0.82, absolute risk difference [ARD] = 5.9%, number needed to treat [NNT] = 17, quality of evidence = low). NIPPV was also associated with lower intubation rates (RR = 0.49, 95% CI = 0.38 to 0.62, ARD = 7.7%, NNT = 13, quality of evidence = moderate).3

The risks of myocardial infarction and increased length of stay (potential harms) were not significantly different between the groups. Two RCTs reported a shortened ICU length of stay for NIPPV. However, the quality of the pooled evidence was very low. Other risks or limitations of NIPPV such as inability to tolerate the mask, aspiration, etc., were inconsistently defined and reported in the included trials.


diuretics was not defined, and it is possible that the benefits of NIPPV might have been different (reduced or null), based on the clinician providing the care. In addition, the studies included in the analysis followed different protocols for intubation, and it is unclear if this affected the reduction in intubation rates appreciated in the NIPPV group. It is worth noting that patients presenting with need for immediate intubation, depressed GCS scores, hypotension, need for PCI, and evidence of infectious sources were broadly excluded from the studies. It remains to be seen if there is a certain phenotype of patient with ACPE (e.g., more severe ACC/ AHA heart failure grade) who might benefit more from the initiation of NIPPV. These are all potential areas for further research.

The evidence for reduced intubation was of moderate quality and for reduction in mortality and mean length of hospital stay was of low quality. Overall there was low statistical heterogeneity among studies.

Not all patients with ACPE are suitable for NIPPV and the contraindications must be considered prior to initiating therapy; these contraindications include obtunded and uncooperative patients, poor mask fit, facial trauma/burns, facial/esophageal/gastric surgeries, and vomiting or inability to handle secretions.

In conclusion, NIPPV in ACPE (for those not requiring immediate ETI) appears to provide beneficial effects, including reduced mortality and decreased intubation rates, without an apparent increase in clinically significant harms. We thus assign a color rating of green (benefits > harms) to this treatment.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between and AEM.

See's previous reviews of this topic:
Non-Invasive Positive Pressure Ventilation for Acute Pulmonary Edema, August 22, 2010


Brian M. Killeen, MD; Allan B. Wolfson, MD
Supervising Editors: Shahriar Zehtabchi, MD


December 1, 2020