Continuous Positive Airway Pressure Versus Bilevel Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema: A Randomized Multicenter Trial

doi:10.1016/j.annemergmed.2007.06.488

Annals of Emergency Medicine

Volume 50, Issue 6, December 2007, Pages 666-675.e1

https://doi.org/10.1016/j.annemergmed.2007.06.488 Get rights and content

Study objective

Patients with acute cardiogenic pulmonary edema may develop respiratory failure. Noninvasive respiratory support should be initiated rapidly to avoid tracheal intubation. The aim of this study is to compare the efficacy of continuous positive airway pressure (CPAP) delivered by the Boussignac CPAP device and bilevel positive airway pressure (bilevel PAP) in patients with acute respiratory failure caused by acute cardiogenic pulmonary edema.

Methods

This prospective multicenter randomized study was conducted in 3 emergency departments. Patients were assigned to Boussignac CPAP through a facemask or to bilevel PAP, in addition to standard therapy. The main outcome was a combined criterion (tracheal intubation, death, or acute myocardial infarction). Complications, durations of ventilation, and hospitalization were also assessed.

Results

After 1 hour of ventilation and at the end of the ventilation period, clinical parameters of respiratory distress and blood gas exchange significantly improved in each treatment arm. No significant differences were observed between the Boussignac CPAP and bilevel PAP arms for the combined criterion (5% versus 12%, respectively; odds ratio [OR] 0.4; 95% confidence interval [CI] 0.0 to 1.9) and also for severe complications (9% versus 6%; OR 1.5; 95% CI 0.3 to 9.9), duration of ventilation (median for both groups 2 hours; interquartile range [IQR] 1.2 to 3.0 hours), duration of hospitalization (CPAP 8.5 [IQR 6 to 14] days; bilevel PAP 10 [IQR 7 to 16] days), or intrahospital mortality (8% versus 14%; OR 1.8 [IQR 0.4 to 8.8]). Similar results were obtained among hypercapnic patients (PaCO₂ >45 mm Hg). Whatever the ventilation support used, the combined criterion and severe complications were more frequently observed among hypercapnic patients.

Conclusion

Both Boussignac CPAP and bilevel PAP appeared effective in rapidly improving respiratory distress even in hypercapnic patients, but they were not different in terms of patient outcome.

Introduction

Acute cardiogenic pulmonary edema is the first cause of acute respiratory distress worldwide.¹ In patients with acute respiratory failure, standard treatment, including diuretics, nitroglycerin, morphine, and oxygen, may not be sufficient to reduce respiratory distress.² In this setting, noninvasive ventilation support should be initiated rapidly, with the main goals to improve oxygenation, avoid invasive ventilation, and permit a sufficient period for medical therapy to decrease pulmonary vascular congestion.³ Moreover, noninvasive ventilation support, per se, has been shown to improve cardiogenic pulmonary edema by the establishment of a positive intrathoracic pressure and the reduction of left ventricular afterload. This nonpharmacologic form of treatment of acute cardiogenic pulmonary edema results in an improvement in gas exchange, a decreased need for intubation, and a decreased relative risk of mortality in comparison to standard medical treatment.3, 4, 5, 6, 7, 8, 9

Patients with severe acute cardiogenic pulmonary edema may benefit from noninvasive ventilation support either with continuous positive airway pressure (CPAP) or with bilevel positive airway pressure (PAP).9, 10 CPAP increases functional residual capacity, which results in a reduction of atelectasis and intrapulmonary shunt.¹¹ Efficacy of CPAP in reducing intubation and invasive ventilation was first demonstrated by Bersten et al.⁴ Randomized controlled studies of acute cardiogenic pulmonary edema patients have demonstrated significant improvements in vital signs and gas exchange, as well as a drastic reduction in tracheal intubation rates and mortality attributable to CPAP, in comparison with standard medical treatment.4, 12, 13, 14, 15 Despite these convincing results, the use of CPAP has gained interest only recently with the extensive use of the Boussignac CPAP device. This device is of major interest because it does not require specific technical skills or the use of a flow generator or a ventilator, as does other CPAP or bilevel PAP, which explains its low cost16, 17 (See Appendix E1, available online at http://www.annemergmed.com; Figure 1).

Bilevel PAP provides inspiratory pressure support coupled with positive end-expiratory pressure. Bilevel PAP theoretically confers the same benefits as CPAP and inspiratory assistance that unloads the respiratory muscles in acute cardiogenic pulmonary edema.¹⁸ Compared to CPAP, bilevel PAP is more effective at reducing the work of breathing, although its use in acute cardiogenic pulmonary edema remains controversial because results from reported studies are inconsistent.3, 5, 7, 13, 19, 20 In a large multicenter study, Nava et al²¹ did not find bilevel PAP superior to medical treatment in avoiding intubation, although it improved dyspnea, respiratory rate, and gas exchange. In contrast, a meta-analysis showed that bilevel PAP reduced the need for invasive mechanical ventilation.²² However, this meta-analysis underscored the potential increase of myocardial infarction in the bilevel PAP group, which may be explained by the inspiratory effort of the patient, patient-ventilator asynchrony, and the rapid correction of PaCO₂ values with potential coronary vasoconstriction.²²

This study aimed to compare the efficacy of CPAP delivered by the Boussignac device, adjusted on a full facemask, with bilevel PAP in patients admitted to the emergency department (ED) with respiratory failure caused by acute cardiogenic pulmonary edema.

Section snippets

Study Design

This randomized, prospective, nonblinded, multicenter study compared the adjuvant effects of Boussignac CPAP to bilevel PAP on respiratory distress in acute cardiogenic pulmonary edema patients treated in the ED. The recommended treatment for pulmonary edema consisted of furosemide 40 mg intravenously, or twice the patient's normal dose, and isosorbide dinitrate infusion 2 to 4 mg/h, with possible additional boluses of 1 mg isosorbide dinitrate and morphine 0.05 mg/kg. Investigators were free

Characteristics of Study Subjects

Among the 357 patients presenting with acute cardiogenic pulmonary edema during the study period in the 3 centers, 237 were not included, 68 of them because they had ventilation support with CPAP or with bilevel PAP before their arrival to the hospital, 154 because they had mild forms of acute cardiogenic pulmonary edema, and 15 because they were already intubated (Figure 3). Thus, 120 patients were enrolled in the study. Eleven patients were withdrawn from the study analysis because no

Limitations

The fact that we did not have a group with oxygen alone, applied with a facemask, might be considered a limitation. This point was discussed during the planning phase of the study, but it was not deemed ethical to include a group with oxygen alone because CPAP and bilevel PAP had already been shown to improve respiratory distress and to reduce the intubation rate in patients with acute cardiogenic pulmonary edema.4, 19

The 2 treatment arms were slightly imbalanced with respect to potential

Discussion

The present multicenter randomized study compares for the first time, to our knowledge, the efficacy of the Boussignac CPAP to bilevel PAP in the treatment of patients with acute cardiogenic pulmonary edema. After 1 hour of ventilation and at the end of the ventilation period, clinical characteristics of respiratory distress and blood gas exchange improved in each study group. Boussignac CPAP and bilevel PAP are both effective modalities for rapidly improving respiratory distress in patients

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Cited by (77)

Is hypocapnia a risk factor for non-invasive ventilation failure in cardiogenic acute pulmonary edema?
2022, Journal of Critical Care
Citation Excerpt :
On the other hand, hypocapnia was associated with an increased NIV failure and a higher in-hospital mortality. The prevalence of hypercapnia in our patients being 49%, consistent with what was previously published (20%–65%) [9,12-14,16,19-24]. Even in patients without a history of chronic respiratory disease, nearly one half developed hypercapnia during an episode of acute cardiogenic pulmonary edema [16].
The impact of hypocapnia in the prognosis of cardiogenic acute pulmonary edema (CAPE) has not been sufficiently studied. The aim of this study was to analyse whether hypocapnia is a risk factor for non-invasive ventilation (NIV) failure and hospital mortality, in CAPE patients CAPE.
Retrospective observational study of all patients with CAPE treated with NIV. Patients were classified in three groups according to PaCO₂ level (hypocapnic, eucapnic and hypercapnic). NIV failure was defined as the need for endotracheal intubation and/or death.
1138 patients were analysed, 390 (34.3%) of which had hypocapnia, 186 (16.3%) had normocapnia and 562 (49.4%) had hypercapnia. NIV failure was more frequent in hypocapnic (60 patients, 15.4%) than in eucapnic (16 pacientes, 8.6%) and hypercapnic group (562 pacientes, 10.7%), with statistical significance (p = 0.027), as well as hospital mortality, 73 (18.7%), 19(10.2%) and 83 (14.8%) respectively (p = 0.026). The predicted factors for NIV failure were the presence of do-not-intubate order, complications related to NIV, a lower left ventricular ejection fraction, higher SAPS II and SOFA score and a higher HACOR score at one hour of NIV initiation.
Hypocapnia in patients with CAPE is associated with NIV failure and a greater in-hospital mortality.
Acute respiratory failure in randomized trials of noninvasive respiratory support: A systematic review of definitions, patient characteristics, and criteria for intubation
2020, Journal of Critical Care
Citation Excerpt :
A total of 53 trials were included in our review, yielding a total of 7225 patients. The groups of respiratory failure studied in trials were all cause ARF (20 trials) [10–29], cardiogenic pulmonary edema (11 trials) [30–40], COPD (12 trials) [41–52], immune compromise (6 trials) [53–58], and postoperative (4 trials) [59–62]. The median sample size was 83 patients (IQR 56 to 130 patients).
To examine the definitions of acute respiratory failure, the characteristics of recruited patients, and the criteria for intubation used in randomized trials.
We searched MEDLINE for randomized trials of noninvasive respiratory support modalities in patients with de novo respiratory failure. We included trials from 1995 to 2017 that enrolled 40 or more patients and used intubation as an outcome.
We examined the reports of 53 trials that enrolled 7225 patients. There was wide variation in the use of variables for defining acute respiratory failure. Dyspnea was rarely measured and the increase in breathing effort was poorly defined. The characteristics of patients enrolled in trials changed over time and differed by the cause of respiratory failure. Intubation was poorly characterized. The criteria for intubation had more variables than the criteria for respiratory failure.
We identified deficiencies in the design and reporting of randomized trials, some of which can be remedied by investigators. We also found that patient characteristics differ by the type of respiratory failure. This knowledge can help clinician identify patients at the right moment to benefit from the tested interventions and investigators in developing criteria for enrollment in future trials.
Pressure support ventilation vs Continuous positive airway pressure for treating of acute cardiogenic pulmonary edema: A pilot study
2018, Respiratory Physiology and Neurobiology
Non-invasive ventilation is usually adopted as a support to medical therapy in patients with acute pulmonary edema, but which modality between Pressure Support Ventilation (PSV) and Continuous Positive Airway Pressure (CPAP) has better favourable effects is not been yet well known. Aim of this observational study was to provide data on these different non-invasive ventilation modalities in the management of acute cardiogenic pulmonary edema. One-hundred-fifty-three patients consecutively admitted to the Emergency Room of two different Center were enrolled and randomly assigned to CPAP or PSV. Data relative to mortality, need of endotracheal intubation, sequential blood gas analysis were compared. Furthermore, there were no significant differences regarding mortality in the two groups, but patients treated with PSV had a significant lower rate of endotracheal intubation and a higher improvement of blood gas analyses parameters. In conclusion, our data support only a slight advantage in favour to PSV versus CPAP.
Non-Invasive Mechanical Ventilation Versus Continuous Positive Airway Pressure Relating to Cardiogenic Pulmonary Edema in an Intensive Care Unit
2017, Archivos de Bronconeumologia
Citation Excerpt :
These data justify systematically ruling out NIV in hypercapnic patients with no chronic pulmonary disease, despite elevated PaCO2 levels. Similarly to other studies, in our study duration of both NIV and CPAP ventilation was longer in the hypercapnic group.13,29,31 Unlike other clinical trials,36 our study protocol did not allow switching from CPAP to NIV; however, this was violated in the case of 1 patient who was switched from CPAP to NIV in order to avoid endotracheal intubation.
To compare the application of non-invasive ventilation (NIV) versus continuous positive airway pressure (CPAP) in the treatment of patients with cardiogenic pulmonary edema (CPE) admitted to an intensive care unit (ICU).
In a prospective, randomized, controlled study performed in an ICU, patients with CPE were assigned to NIV (n=56) or CPAP (n=54). Primary outcome was intubation rate. Secondary outcomes included duration of ventilation, length of ICU and hospital stay, improvement of gas exchange, complications, ICU and hospital mortality, and 28-day mortality. The outcomes were analyzed in hypercapnic patients (PaCO₂ > 45 mmHg) with no underlying chronic lung disease.
Both devices led to similar clinical and gas exchange improvement; however, in the first 60 min of treatment a higher PaO₂/FiO₂ ratio was observed in the NIV group (205±112 in NIV vs. 150±84 in CPAP, P=.02). The rate of intubation was similar in both groups (9% in NIV vs. 9% in CPAP, P=1.0). There were no differences in duration of ventilation, ICU and length of hospital stay. There were no significant differences in ICU, hospital and 28-d mortality between groups. In the hypercapnic group, there were no differences between NIV and CPAP.
Either NIV or CPAP are recommended in patients with CPE in the ICU. Outcomes in the hypercapnic group with no chronic lung disease were similar using NIV or CPAP.
Comparar la efectividad de la ventilación no invasiva (VNI) frente a la presión positiva continúa en la vía aérea (CPAP) en pacientes ingresados por edema agudo de pulmón (EAP) cardiogénico en una unidad de cuidados intensivos (UCI).
Ensayo clínico donde 56 pacientes fueron asignados a VNI y 54 pacientes a CPAP. El objetivo primario fue la tasa de intubación. Los objetivos secundarios fueron: duración de ventilación, estancia en UCI y en el hospital, mejoría gasométrica, complicaciones y mortalidad en UCI, hospitalaria y a los 28 días. Los objetivos fueron analizados en pacientes hipercápnicos (PaCO₂ >45 mmHg) sin patologia pulmonar.
Ambos dispositivos obtuvieron similar mejoría clínica y del intercambio gaseoso, sin embargo, la VNI mostró un aumento más rápido de la oxigenación (medido por el cociente PaO₂/FiO₂) en los primeros 60 minutos de aplicación (205 ± 112 en VNI vs. 150 ± 84 en CPAP, p= 0,02). La tasa de intubación fue similar en ambos grupos (9% en VNI vs. 9% en CPAP, p= 1,0). No hubo diferencias en la duración de la ventilación, ni en la estancia en UCI ni hospitalaria. Tampoco hubo diferencias significativas en la mortalidad en UCI, hospitalaria y a los 28 días entre ambos grupos. En el subgrupo de pacientes hipercápnicos tampoco se observaron diferencias significativas en los objetivos analizados.
La VNI como la CPAP se pueden emplear en pacientes con EAP en la UCI. En pacientes hipercápnicos sin patología pulmonar no se observa beneficio de la VNI sobre la CPAP.
Noninvasive Ventilation
2015, Murray and Nadel's Textbook of Respiratory Medicine: Volume 1,2, Sixth Edition
Randomized trial of bilevel versus continuous positive airway pressure for acute pulmonary edema
2014, Journal of Emergency Medicine
Studies have shown different clinical outcomes of noninvasive positive pressure ventilation (NPPV) from those of continuous positive airway pressure (CPAP).
We evaluated whether bilevel positive airway pressure (BPAP) more rapidly improves dyspnea, ventilation, and acidemia without increasing the myocardial infarction (MI) rate compared to continuous positive pressure ventilation (CPAP) in patients with acute cardiogenic pulmonary edema (APE).
Patients with APE were randomized to either BPAP or CPAP. Vital signs and dyspnea scores were recorded at baseline, 30 min, 1 h, and 3 h. Blood gases were obtained at baseline, 30 min, and 1 h. Patients were monitored for MI, endotracheal intubation (ETI), lengths of stay (LOS), and hospital mortality.
Fourteen patients received CPAP and 13 received BPAP. The two groups were similar at baseline (ejection fraction, dyspnea, vital signs, acidemia/oxygenation) and received similar medical treatment. At 30 min, PaO₂:FIO₂ was improved in the BPAP group compared to baseline (283 vs. 132, p < 0.05) and the CPAP group (283 vs. 189, p < 0.05). Thirty-minute dyspnea scores were lower in the BPAP group compared to the CPAP group (p = 0.05). Fewer BPAP patients required intensive care unit (ICU) admission (38% vs. 92%, p < 0.05). There were no differences between groups in MI or ETI rate, LOS, or mortality.
Compared to CPAP to treat APE, BPAP more rapidly improves oxygenation and dyspnea scores, and reduces the need for ICU admission. Further, BPAP does not increase MI rate compared to CPAP.

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: Supervising editor: J. Stephan Stapczynski, MD

: Author contributions: FM, BB, and JB conceived and designed the study. AC performed the data collection and data entry. MFH and JB performed the statistical analysis. FM, BB, BG, and EL were responsible for patient inclusions. FM and JB were responsible for the overall direction of the text and discussion. FM and JB takes responsibility for the paper as a whole.

: Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Financial support was provided by grant 01/059HP (French Department of Health). This financial support provided the study logistics and the equipment for continuous positive airway pressure treatment in each hospital, with the Boussignac CPAP, the specific flowmeters, and manometers used. The authors do not report any financial connection or conflict of interest with the manufacturers, in particular Vygon Society. Financial support also provided the independent statistical analysis.

: Reprints not available from the authors.

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Airway/original researchContinuous Positive Airway Pressure Versus Bilevel Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema: A Randomized Multicenter Trial

Study objective

Methods

Results

Conclusion

Introduction

Section snippets

Study Design

Characteristics of Study Subjects

Limitations

Discussion

Lancet

Lancet

Chest

Chest

Ann Fr Anesth Reanim

J Am Coll Cardiol

Lancet

J Emerg Med

Chest

Chest

Incidence and epidemiology of heart failure

Heart Fail Rev

Continuous versus bilevel positive airway pressure in acute pulmonary edema? a good question

Crit Care Med

Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask

N Engl J Med

Randomized, prospective trial of oxygen, continuous positive airway pressure, and bilevel positive airway pressure by face mask in acute cardiogenic pulmonary edema

Crit Care Med

Non-invasive continuous positive airway pressure in acute hypoxaemic respiratory failure: experience of an emergency department

Eur J Emerg Med

Positive end-expiratory pressure

Anaesthesist

Airway/original research
Continuous Positive Airway Pressure Versus Bilevel Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema: A Randomized Multicenter Trial