Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema. Randomized, prospective trial of oxygen, continuous positive airway pressure, and bilevel positive airway pressure by face mask in acute cardiogenic pulmonary edema. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term results and long-term follow-up. Noninvasive positive airway pressure and risk of myocardial infarction in acute cardiogenic pulmonary edema: continuous positive airway pressure vs noninvasive positive pressure ventilation. Continuous positive airway pressure versus bilevel noninvasive ventilation in acute cardiogenic pulmonary edema: a randomized multicenter trial. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial. Noninvasive continuous positive airway pressure in elderly cardiogenic pulmonary edema patients. High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema. Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial. Noninvasive pressure support ventilation vs. continuous positive airway pressure in acute hypercapnic pulmonary edema. Continuous positive airway pressure by face mask in acute cardiogenic pulmonary edema. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Randomised controlled trial of continuous positive airway pressure and standard oxygen therapy in acute pulmonary oedema; effects on plasma brain natriuretic peptide concentrations. Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial. Continuous positive airway pressure for cardiogenic pulmonary edema: a randomized study. Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. Continuous positive airway pressure vs. pressure support ventilation in acute cardiogenic pulmonary edema: a randomized trial. The efficacy of early continuous positive airway pressure therapy in patients with acute cardiogenic pulmonary edema. Myocardial infarction rate in acute pulmonary edema: noninvasive pressure support ventilation versus continuous positive airway pressure. The effect of nasal continuous positive airway pressure on plasma endothelin-1 concentrations in patients with severe cardiogenic pulmonary edema. Prehospital noninvasive pressure support ventilation for acute cardiogenic pulmonary edema. A prospective, randomized trial of BiPAP in severe acute congestive heart failure.
Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy.
                Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H(2)O), or bilevel ventilation (IPAP 15 cm H(2)O, EPAP 5 cm H(2)O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat.
                Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test).
                In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation. To compare the effects of oxygen, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (bilevel-PAP) on the rate of endotracheal intubation in patients with acute cardiogenic pulmonary edema.
                Randomized, controlled trial.
                Tertiary hospital emergency room.
                We randomly assigned 80 patients with severe cardiogenic acute pulmonary edema into three treatment groups. Patients were followed for 60 days after the randomization.
                Oxygen applied by face mask, CPAP, and bilevel-PAP.
                The rate of endotracheal intubation as well as vital signs and blood gases was recorded during the first 24 hrs. Mortality was evaluated at 15 days, at 60 days, and at hospital discharge. Complications related to respiratory support were evaluated before hospital discharge. Treatment with CPAP or bilevel-PAP resulted in significant improvement in the PaO2/FiO2 ratio, subjective dyspnea score, and respiratory and heart rates compared with oxygen therapy. Endotracheal intubation was necessary in 11 of 26 patients (42%) in the oxygen group but only in two of 27 patients (7%) in each noninvasive ventilation group (p = .001). There was no increase in the incidence of acute myocardial infarction in the CPAP or bilevel-PAP groups. Mortality at 15 days was higher in the oxygen than in the CPAP or bilevel-PAP groups (p < .05). Mortality up to hospital discharge was not significantly different among groups (p = .061).
                Compared with oxygen therapy, CPAP and bilevel-PAP resulted in similar vital signs and arterial blood gases and a lower rate of endotracheal intubation. No cardiac ischemic complications were associated with either of the noninvasive ventilation strategies. To evaluate whether bilevel positive airway pressure, by actively assisting inhalation, more rapidly improves ventilation, acidemia, and dyspnea than continuous positive airway pressure (CPAP) in patients with acute pulmonary edema.
                Randomized, controlled, double-blind trial.
                Emergency department in a university hospital.
                Twenty-seven patients, presenting with acute pulmonary edema, characterized by dyspnea, tachypnea, tachycardia, accessory muscle use, bilateral rales, and typical findings of congestion on a chest radiograph.
                In addition to standard therapy, 13 patients were randomized to receive nasal CPAP (10 cm H2O), and 14 patients were randomized to receive nasal bilevel positive airway pressure (inspiratory and expiratory positive airway pressures of 15 and 5 cm H2O, respectively) in the spontaneous/timed mode that combines patient flow-triggering and backup time-triggering.
                After 30 mins, significant reductions in breathing frequency (32 +/- 4 to 26 +/- 5 breaths/min), heart rate (110 +/- 21 to 97 +/- 20 beats/min), blood pressure (mean 117 +/- 28 to 92 +/- 18 mm Hg), and Paco2 (56 +/- 15 to 43 +/- 9 torr [7.5 +/- 2 to 5.7 +/- 1.2 kPa]) were observed in the bilevel positive airway pressure group, as were significant improvements in arterial pH and dyspnea scores (p < .05 for all of these parameters). Only breathing frequency improved significantly in the CPAP group (32 +/- 4 to 28 +/- 5 breaths/min, p < .05). At 30 mins; the bilevel positive airway pressure group had greater reductions in Paco2 (p = .057), systolic blood pressure (p = .005), and mean arterial pressure (p = .03) than the CPAP group. The myocardial infarction rate was higher in the bilevel positive airway pressure group (71%) compared with both the CPAP group (31%) and historically matched controls (38%) (p = .05). Duration of ventilator use, intensive care unit and hospital stays, and intubation and mortality rates were similar between the two groups.
                Bilevel positive airway pressure improves ventilation and vital signs more rapidly than CPAP in patients with acute pulmonary edema. The higher rate of myocardial infarctions associated with the use of bilevel positive airway pressure highlights the need for further studies to clarify its effects on hemodynamics and infarction rates, and to determine optimal pressure settings. Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy.
                40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat.
                Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality.
                In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure. To investigate whether serial incremental continuous positive airway pressure (CPAP) has any short-term or long-term advantages over face-mask oxygen therapy by way of intrapulmonary shunt reduction, 100 patients admitted to the coronary care unit for the treatment of acute cardiogenic pulmonary edema were studied. All patients received Swan-Ganz catheterization. Hemodynamic and pulmonary function parameters were recorded over the next 6 h, and the patients were followed until hospital discharge. All survivors received regular follow-up at 1-month intervals in the outpatient clinic. During the first-stage investigation period (3 h) PaO2 in the CPAP group showed a significant increase, whereas the intrapulmonary shunt and alveolar-arterial oxygen tension gradient (P[A-a]O2) was significantly reduced (p < 0.005). The CPAP group had significantly lower rate-pressure product and higher stroke volume index compared with the control group. The therapeutic failure rate over 6 h was 24% in the CPAP group and 50% in the control group (p < 0.01). The CPAP group had a significantly lower incidence of tracheal intubation and ventilator therapy than the control group; however, there was no significant difference in short-term mortality and hospital stay between the two groups. In conclusion, although study size was not large enough to demonstrate a difference in mortality, CPAP therapy resulted in physiologic cardiovascular and pulmonary function improvement and significantly reduced the need for intubation; however, it did not decrease mortality in patients with acute cardiogenic pulmonary edema, and a much larger study is needed to investigate this possibility. The addition of both noninvasive continuous positive airway pressure (n-CPAP) or noninvasive intermittent positive pressure ventilation (n-IPPV) to medical treatment has been shown to improve the outcome of patients with acute cardiogenic pulmonary edema (ACPE). Previous studies indicated a potential risk of new-onset acute myocardial infarction (AMI) associated with the use of n-IPPV. Although further studies did not confirm this observation, a few recent metaanalyses could not eliminate all the doubts at this regards because of the paucity of data available and the presence of confounding factors. This study aims to assess whether the application of n-IPPV, as opposed to n-CPAP, increases the rate of AMI in ACPE patients.
                Fifty-two patients with severe hypoxemia consequent to ACPE were randomized to receive n-CPAP (n = 27) or n-IPPV (n = 25) in addition to medical therapy. Patients with signs of acute coronary syndrome on hospital admission were excluded from the study. Cardiac markers, ECG, and clinical/physiologic parameters were assessed at study entry, after 30 and 60 min, and every 6 h for the first 2 days.
                No significant difference was observed in the rate of AMI (26.9% and 16% with n-CPAP and n-IPPV, respectively, p = 0.244). Rate of intubation (p = 0.481), death (p = 0.662), and hospital stay (p = 0.529) were not different between the two groups. Both techniques were effective in improving gas exchange and vital signs in patients with ACPE.
                The AMI rate was not different with n-CPAP and n-IPPV, which resulted to be equally effective in the treatment of ACPE. Trial registration: Clinicaltrials.gov Identifier: NCT00453947. 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.
                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.
                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.
                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. Continuous positive airway pressure (CPAP) is widely used in the belief that it may reduce the need for intubation and mechanical ventilation in patients with acute hypoxemic respiratory insufficiency.
                To compare the physiologic effects and the clinical efficacy of CPAP vs standard oxygen therapy in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency.
                Randomized, concealed, and unblinded trial of 123 consecutive adult patients who were admitted to 6 intensive care units between September 1997 and January 1999 with a PaO(2)/FIO(2) ratio of 300 mm Hg or less due to bilateral pulmonary edema (n = 102 with acute lung injury and n = 21 with cardiac disease).
                Patients were randomly assigned to receive oxygen therapy alone (n = 61) or oxygen therapy plus CPAP (n = 62).
                Improvement in PaO(2)/FIO(2) ratio, rate of endotracheal intubation at any time during the study, adverse events, length of hospital stay, mortality, and duration of ventilatory assistance, compared between the CPAP and standard treatment groups.
                Among the CPAP vs standard therapy groups, respectively, causes of respiratory failure (pneumonia, 54% and 55%), presence of cardiac disease (33% and 35%), severity at admission, and hypoxemia (median [5th-95th percentile] PaO(2)/FIO(2) ratio, 140 [59-288] mm Hg vs 148 [62-283] mm Hg; P =.43) were similarly distributed. After 1 hour of treatment, subjective responses to treatment (P<.001) and median (5th-95th percentile) PaO(2)/FIO(2) ratios were greater with CPAP (203 [45-431] mm Hg vs 151 [73-482] mm Hg; P =.02). No further difference in respiratory indices was observed between the groups. Treatment with CPAP failed to reduce the endotracheal intubation rate (21 [34%] vs 24 [39%] in the standard therapy group; P =.53), hospital mortality (19 [31%] vs 18 [30%]; P =.89), or median (5th-95th percentile) intensive care unit length of stay (6.5 [1-57] days vs 6.0 [1-36] days; P =.43). A higher number of adverse events occurred with CPAP treatment (18 vs 6; P =.01).
                In this study, despite early physiologic improvement, CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency primarily due to acute lung injury. JAMA. 2000;284:2352-2360. To compare the physiological effects and the clinical efficacy of continuous positive airway pressure (CPAP) vs standard medical treatment in elderly patients (> or =75 years) with acute hypoxemic respiratory failure related to cardiogenic pulmonary edema.
                A prospective, randomized, concealed, and unblinded study of 89 consecutive patients who were admitted to the emergency departments of one general, and three teaching, hospitals.
                Patients were randomly assigned to receive standard medical treatment alone ( n=46) or standard medical treatment plus CPAP ( n=43).
                Improvement in PaO(2)/FIO(2) ratio, complications, length of hospital stay, early 48-h and overall mortality, compared between the CPAP and standard treatment groups.
                Study groups were comparable with regard to baseline physiological and clinical characteristics (age, sex ratio, autonomy, medical history, cause of pulmonary edema). Within 1 h, noninvasive continuous positive airway pressure led to decreased respiratory rate (respiratory rate, 27+/-7 vs 35+/-6 breaths/min; p=0.009), and improved oxygenation (PaO(2)/F(I)O(2), 306+/-104 vs 157+/-71; p=0.004) compared with baseline, whereas no differences were observed within the standard treatment group. Severe complications occurred in 17 patients in the standard treatment group, vs 4 patients in the noninvasive continuous positive airway pressure group ( p=0.002). Early 48-h mortality was 7% in the noninvasive continuous positive airway pressure group, compared with 24% in the standard treatment group ( p=0.017); however, no sustained benefits were observed during the overall hospital stay.
                Noninvasive continuous positive airway pressure promotes early clinical improvement in elderly patients attending emergency departments for a severe pulmonary edema, but only reduces early 48-h mortality. To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy.
                Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities.
                We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival.
                Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee.
                High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema. The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus "placebo" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect. This study compared noninvasive pressure support ventilation (NIPSV) and continuous positive airway pressure (CPAP) in patients with acute hypercapnic pulmonary edema with regard to resolution time.
                Randomized prospective study in an emergency department.
                We randomly assigned 36 patients with respiratory failure due to acute pulmonary edema and arterial hypercapnia (PaCO(2) >45 mmHg) to NIPSV (n=18) or CPAP through a face mask (n=18).
                Electrocardiographic and physiological measurements were made over 36 h. There was no difference in resolution time defined as clinical improvement with a respiratory rate of fewer than 30 breaths/min and SpO(2)of 96% or more between CPAP and NIPSV groups. Arterial carbon dioxide tension was significantly decreased after 1 h of ventilation (CPAP, 60.5+/-13.6 to 42.8+/-4.9 mmHg; NIPSV, 65.7+/-13.6 to 44.0+/-5.5 mmHg); respective improvements were seen in pH (CPAP, 7.22+/-0.11 to 7.37+/-0.04; NIPSV, 7.19+/-0.11 to 7.38+/-0.04), SpO(2) (CPAP, 86.9+/-3.7% to 95.1+/-2.6%; NIPSV, 83.7+/-6.6% to 96.0+/-2.9%), and respiratory rate (CPAP, 37.9+/-4.5 to 21.3+/-5.1 breaths/min; NIPSV, 39.8+/-4.4 to 21.2+/-4.6 breaths/min). No significant differences were seen with regards to endotracheal intubation and in-hospital mortality.
                NIPSV proved as effective as CPAP in the treatment of patients with acute pulmonary edema and hypercapnia but did not improve resolution time. The therapeutic efficacy of continuous positive airway pressure (CPAP) administered by face mask was studied in 40 patients with acute cardiogenic pulmonary edema and respiratory failure. Arterial blood gas values and pH, systemic arterial pressure, heart rate and respiratory rate were measured during administration of 30% oxygen with a high-flow face mask apparatus at ambient airway pressure. Twenty patients were then randomly chosen to continue ambient airway pressure breathing and 20 received 10 cm H2O of CPAP. The measurements were repeated 10, 60 and 180 minutes after therapy was initiated. During the first 10 minutes of CPAP treatment, arterial blood oxygen partial pressure increased 8 +/- 9 mm Hg (mean +/- 1 standard deviation), (p less than 0.01) and respiratory rate decreased 5 +/- 5 breaths/min (p less than 0.001). Systolic arterial pressure decreased 12 +/- 21 mm Hg (p less than 0.05), and heart rate by 10 +/- 11 beats/min (p less than 0.001). A decrease in respiratory rate by 2 +/- 5 breaths/min (p less than 0.05) was the only change that occurred in the control group. The improvement in arterial blood oxygenation persisted throughout the investigation period (p less than 0.05). Thirteen patients (65%) in the control group and 7 patients (35%) in the CPAP group met our criteria for treatment failure during the study (p = 0.068). Thus, CPAP administered by face mask improves gas exchange, decreases respiratory work, unloads circulatory stress, and may reduce the need for ventilator treatment in acute cardiogenic pulmonary edema. Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p=0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients. The study aim was to compare the effects of continuous positive airway pressure (CPAP) on clinical outcomes and plasma neurohormonal concentrations in patients with acute pulmonary oedema.
                In addition to standard therapy, 58 consecutive patients were randomized to receive 60% inhaled oxygen with or without CPAP at 7.5 cmH(2)O pressure. Clinical variables, symptoms and oxygenation were monitored and plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) concentrations estimated at 0, 1, 6 and 24 h. CPAP was associated with less breathlessness at 1 h (P<0.001), no treatment failures and more rapid resolution in respiratory rate (P<0.001), heart rate (P<0.001) and acidosis (P<0.005). Length of hospital stay was similar but there was a trend for a reduction in overall hospital mortality in the CPAP group (0.10>P>0.05). Plasma BNP concentrations rose progressively (P<0.001) before falling below admission concentrations at 24 h. Plasma neurohumoral concentrations were unaffected by CPAP treatment but were elevated in patients who died or had acute myocardial infarction.
                CPAP produces a more rapid clinical and symptomatic improvement in patients with acute pulmonary oedema, particularly within the first hour. CPAP is a useful adjunctive treatment in the early management of acute heart failure.
                Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. Severe cardiogenic pulmonary edema is a frequent cause of respiratory failure, and many patients with this condition require endotracheal intubation and mechanical ventilation. We investigated whether continuous positive airway pressure delivered by means of a face mask had physiologic benefit and would reduce the need for intubation and mechanical ventilation.
                We randomly assigned 39 consecutive patients with respiratory failure due to severe cardiogenic pulmonary edema to receive either oxygen alone or oxygen plus continuous positive airway pressure delivered through a face mask. It was not possible to blind the investigators to the assigned treatment. Physiologic measurements were made over the subsequent 24 hours, and the patients were followed to hospital discharge.
                After 30 minutes, both respiratory rate and arterial carbon dioxide tension had decreased more in the patients who received oxygen plus continuous positive airway pressure. The mean (+/- SD) respiratory rate at 30 minutes decreased from 32 +/- 6 to 33 +/- 9 breaths per minute in the patients receiving oxygen alone and from 35 +/- 8 to 27 +/- 6 breaths per minute in those receiving oxygen plus continuous positive airway pressure (P = 0.008); the arterial carbon dioxide tension decreased from 64 +/- 17 to 62 +/- 14 mm Hg in those receiving oxygen alone and from 58 +/- 8 to 46 +/- 4 mm Hg in those receiving oxygen plus continuous positive airway pressure (P less than 0.001). The patients receiving continuous positive airway pressure also had a greater increase in the arterial pH (oxygen alone, from 7.15 +/- 0.11 to 7.18 +/- 0.18; oxygen plus continuous positive airway pressure, from 7.18 +/- 0.08 to 7.28 +/- 0.06; P less than 0.001) and in the ratio of arterial oxygen tension to the fraction of inspired oxygen (oxygen alone, from 136 +/- 44 to 126 +/- 47; oxygen plus continuous positive airway pressure, from 138 +/- 32 to 206 +/- 126; P = 0.01). After 24 hours, however, there were no significant differences between the two treatment groups in any of these respiratory indexes. Seven (35 percent) of the patients who received oxygen alone but none who received oxygen plus continuous positive airway pressure required intubation and mechanical ventilation (P = 0.005). However, no significant difference was found in in-hospital mortality (oxygen alone, 4 of 20 patients; oxygen plus continuous positive airway pressure, 2 of 19; P = 0.36) or the length of the hospital stay.
                Continuous positive airway pressure delivered by face mask in patients with severe cardiogenic pulmonary edema can result in early physiologic improvement and reduce the need for intubation and mechanical ventilation. This short-term study could not establish whether continuous positive airway pressure has any long-term benefit or whether a larger study would have shown a difference in mortality between the treatment groups. To determine whether non-invasive ventilation reduces mortality and whether there are important differences in outcome by treatment modality.
                Multicentre open prospective randomised controlled trial.
                Patients presenting with severe acute cardiogenic pulmonary oedema in 26 emergency departments in the UK.
                Inclusion criteria were age > 16 years, clinical diagnosis of acute cardiogenic pulmonary oedema, pulmonary oedema on chest radiograph, respiratory rate > 20 breaths per minute, and arterial hydrogen ion concentration > 45 nmol/l (pH < 7.35).
                Patients were randomised to standard oxygen therapy, continuous positive airway pressure (CPAP) (5-15 cmH2O) or non-invasive positive pressure ventilation (NIPPV) (inspiratory pressure 8-20 cmH2O, expiratory pressure 4-10 cmH2O) on a 1:1:1 basis for a minimum of 2 hours.
                The primary end point for the comparison between NIPPV or CPAP and standard therapy was 7-day mortality. The composite primary end point for the comparison of NIPPV and CPAP was 7-day mortality and tracheal intubation rate. Secondary end points were breathlessness, physiological variables, intubation rate, length of hospital stay and critical care admission rate. Economic evaluation took the form of a cost-utility analysis, taken from an NHS (and personal social services) perspective.
                In total, 1069 patients [mean age 78 (SD 10) years; 43% male] were recruited to standard therapy (n = 367), CPAP [n = 346; mean 10 (SD 4) cmH2O] or NIPPV [n = 356; mean 14 (SD 5)/7 (SD 2) cmH2O]. There was no difference in 7-day mortality for standard oxygen therapy (9.8%) and non-invasive ventilation (9.5%; p = 0.87). The combined end point of 7-day death and intubation rate was similar, irrespective of non-invasive ventilation modality (CPAP 11.7% versus NIPPV 11.1%; p = 0.81). Compared with standard therapy, non-invasive ventilation was associated with greater reductions (treatment difference, 95% confidence intervals) in breathlessness (visual analogue scale score 0.7, 0.2-1.3; p = 0.008) and heart rate (4/min, 1-6; p = 0.004) and improvement in acidosis (pH 0.03, 0.02-0.04; p < 0.001) and hypercapnia (0.7 kPa, 0.4-0.9; p < 0.001) at 1 hour. There were no treatment-related adverse events or differences in other secondary outcomes such as myocardial infarction rate, length of hospital stay, critical care admission rate and requirement for endotracheal intubation. Economic evaluation showed that mean costs and QALYs up to 6 months were 3023 pounds and 0.202 for standard therapy, 3224 pounds and 0.213 for CPAP, and 3208 pounds and 0.210 for NIPPV. Modelling of lifetime costs and QALYs produced values of 15,764 pounds and 1.597 for standard therapy, 17,525 pounds and 1.841 for CPAP, and 17,021 pounds and 1.707 for NIPPV. These results suggest that both CPAP and NIPPV accrue more QALYs but at higher cost than standard therapy. However, these estimates are subject to substantial uncertainty.
                Non-invasive ventilatory support delivered by either CPAP or NIPPV safely provides earlier improvement and resolution of breathlessness, respiratory distress and metabolic abnormality. However, this does not translate into improved short- or longer-term survival. We recommend that CPAP or NIPPV should be considered as adjunctive therapy in patients with severe acute cardiogenic pulmonary oedema in the presence of severe respiratory distress or when there is a failure to improve with pharmacological therapy.
                Current Controlled Trials ISRCTN07448447. The purpose of this randomized controlled trial was to determine the immediate and delayed effects of noninvasive ventilation for patients in acute cardiogenic pulmonary edema (ACPE) in addition to aggressive usual care in a medical prehospital setting.
                Out-of-hospital patients in severe ACPE were eligible for the study. Patients were randomized to receive either usual care, including conventional optimal treatment with furosemide, oxygen, and high-dose boluses of isosorbide dinitrate plus oxygen, or conventional medications plus out-of-hospital continuous positive airway pressure (CPAP). The primary outcome was the treatment success defined as all of respiratory rate less than 25 breaths per minute and oxygen saturation of greater than 90% at the end of 1-hour study. Secondary end points included death during 30 days after inclusion. Lengths of intensive care unit and hospital stays were also recorded.
                In total, 124 patients were enrolled into the study. The 2 groups had similar baseline characteristics. For the primary outcome analysis, 22 (35.5%) of 62 patients were considered as experiencing a treatment success in the usual care group vs 19 (31.7%) of 60 in the CPAP group (P = .65). Seven patients died within 30 days in the usual care group vs 6 in the CPAP group (P = .52). There were no statistically significant differences between the treatment groups for length of stay either in hospital or in the intensive care unit.
                In the prehospital setting, in spite of its potential advantages for patients in ACPE, CPAP may not be preferred to a strict optimal intravenous treatment.
                Copyright © 2011 Elsevier Inc. All rights reserved. The efficacy of noninvasive ventilation (NIV) to avoid intubation and improve survival was assessed in 105 patients with severe acute hypoxemic respiratory failure (arterial O2 tension or saturation persistently 60 mm Hg or less or 90% or less, respectively; breathing conventional Venturi oxygen at a maximal concentration [50%]), excluding hypercapnia, admitted into intensive care units of three hospitals. Patients were randomly allocated within 24 hours of fulfilling inclusion criteria to receive NIV (n=51) or high-concentration oxygen therapy (n=54). The primary end-point variable was the decrease in the intubation rate. Both groups had similar characteristics. Compared with oxygen therapy, NIV decreased the need for intubation (13, 25% vs. 28, 52%, p=0.010), the incidence of septic shock (6, 12% vs. 17, 31%, p=0.028), and the intensive care unit mortality (9, 18% vs. 21, 39%, p=0.028) and increased the cumulative 90-day survival (p=0.025). The improvement of arterial hypoxemia and tachypnea was higher in the noninvasive ventilation group with time (p=0.029 each). Multivariate analyses showed NIV to be independently associated with decreased risks of intubation (odds ratio, 0.20; p=0.003) and 90-day mortality (odds ratio, 0.39; p=0.017). The use of noninvasive ventilation prevented intubation, reduced the incidence of septic shock, and improved survival in these patients compared with high-concentration oxygen therapy. Both non-invasive continuous positive airway pressure (nCPAP) and non-invasive pressure support ventilation (nPSV) have been shown to be effective treatment for acute cardiogenic pulmonary edema (ACPE). In patients with severe ACPE who are treated with standard medical treatment, the baseline intubation rate is approximately 24%.
                This study was conducted to compare the endotracheal intubation (ETI) rate using two techniques, nCPAP vs. nPSV. In addition, mortality rate, improvement in gas exchange, duration of ventilation, and hospital length of stay were also assessed.
                This prospective, multi-center, randomized study enrolled 80 patients with ACPE who were randomized to receive nCPAP or nPSV (40 patients in each group) via an oronasal mask. Inclusion criteria were severe dyspnea, respiratory rate > 30 breaths/min, use of respiratory accessory muscles, or PaO(2)/FiO(2) < 200.
                ETI was required in 0 (0%) and in 3 (7.5%) patients in the nCPAP group and in the nPSV group, respectively (p = 0.241). No significant difference was observed in in-hospital mortality: 2 (5%) vs. 7 (17.5%) in nCPAP and nPSV groups, respectively (p = 0.154). No difference in hospital length of stay was observed between the two groups, nor was there a difference observed in duration of ventilation, despite a trend for reduced time with nPSV vs. nCPAP (5.91 ± 4.01 vs. 8.46 ± 7.14 h, respectively, p = 0.052). Both nCPAP and nPSV were effective in improving gas exchange, including in the subgroup of hypercapnic patients.
                Both methods are effective treatment for patients with ACPE. Non-invasive CPAP should be considered as the first line of treatment because it is easier to use and less expensive than non-invasive PSV.
                Copyright © 2010 Elsevier Inc. All rights reserved. Although continuous positive airway pressure (CPAP) therapy using a face mask is known to improve oxygenation, the intrapulmonary shunt reduction remains unsettled. Our study was designed to explore this issue. From 1985 to 1987 80 patients with acute cardiogenic pulmonary edema were randomly chosen to receive either serial CPAP therapy or high-flow face mask oxygen therapy without CPAP (control) for the purpose of evaluating the efficacy of CPAP therapy. After screening for exclusion, only 55 patients were included in the first 3-hour investigation period. PaO2 in the CPAP group showed a significant increase by the end of the initial study; whereas intrapulmonary shunt and alveolar-arterial oxygen tension gradient AaDO2 revealed simultaneously a significant reduction. Conversely, neither PaO2 nor intrapulmonary shunt (or AaDO2) in the control group demonstrated any significant beneficial changes. As for cardiovascular function, only the CPAP therapy achieved a significant reduction in rate pressure product in contrast to the control (face mask) therapy alone. In terms of therapeutic failure, 10 patients in the control group failed. However, in the CPAP group only 5 patients had failed at the end of the first 3-hour study period. Overall, the cumulative therapeutic failure rate was 28% in the CPAP group and 60% in the control group during a 6-hour observation study. However, there was no significant difference between the two groups in 24-hour hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS) Noninvasive pressure support ventilation (NIPSV) delivered by face mask has proved an effective treatment for patients with acute pulmonary edema. However, an increase in acute myocardial infarction rate has been reported with this ventilation modality. We investigated whether the use of NIPSV increases the incidence of acute myocardial infarction compared with continuous positive airway pressure (CPAP) in patients with acute pulmonary edema.
                Randomized, prospective, controlled study.
                Emergency Department, Niguarda Hospital of Milano (Italy).
                Forty-six patients affected by acute pulmonary edema.
                The patients received either NIPSV (24 patients) or CPAP (22 patients) through a face mask.
                Cardiac enzymes (myoglobin, creatine kinase isoenzyme MB, and troponin I) were determined and electrocardiographic and physiologic measurements made over the subsequent 36 hrs. No significant differences were observed in the incidence of acute myocardial infarction in the CPAP group (13.6%) compared with the NIPSV group (8.3%). Both modalities of noninvasive ventilation improved ventilation and vital signs in patients with acute pulmonary edema. Two patients of the NIPSV group (8.3%) and one of the CPAP group (4.5%) required endotracheal intubation because vital signs and arterial blood gases worsened 1 hr after the start of noninvasive ventilation. No significant differences were found in in-hospital mortality rate.
                NIPSV proved to be equally effective in improving vital signs and ventilation without increasing acute myocardial infarction rate in patients with nonischemic acute pulmonary edema in comparison to CPAP alone. However, because the study lacked statistical power and excluded patients with acute coronary syndromes, caution is still advised when applying NIPSV to the latter subgroup of patients. We investigated the effects of nasal continuous positive airway pressure (CPAP) on plasma endothelin-1 (ET-1) concentrations in patients with cardiogenic pulmonary edema. Thirty patients were randomly assigned to two groups: 15 patients who received oxygen plus nasal CPAP (CPAP group), and 15 patients who received only oxygen by face mask (oxygen group). The heart rate and the mean pulmonary artery pressure decreased significantly in the CPAP group. The PaO2/ fraction of inspired oxygen (FIO2) ratio increased in the CPAP group (163 +/- 70 to 332 +/- 104, P < 0.01) after 6 h and was significantly higher than that in the oxygen group. Arterial plasma ET-1 concentrations decreased from 6.2 +/- 2.0 pg/mL to 4.8 +/- 1.7 pg/mL (P < 0.05) after 6 h and to 3.3 +/- 0.7 pg/mL (P < 0.01) after 24 h in the CPAP group. Arterial plasma ET-1 concentrations in the CPAP group compared with the oxygen group were significantly lower at 24 h. There was a correlation between the arterial plasma ET-1 concentrations and mean pulmonary artery pressure (r = 0.62, P < 0.001), and PaO2/FIO2 (r = -0.46, P < 0.01). Nasal CPAP led to an early decrease in plasma ET-1 concentrations, and improvement in oxygenation and hemodynamics. Severe acute cardiogenic pulmonary edema (ACPE) can successfully be treated with noninvasive pressure support ventilation (NIPSV) in a clinical setting. Whether prehospital NIPSV starting early at patients' home and being continued until hospital arrival is feasible and improves ACPE emergency care is examined in this study. End points of the study were oxygen saturation at hospital admission and clinical outcome. Twenty-three patients suffering from severe cardiac pulmonary edema with severe dyspnea, an oxygen saturation of less than 90% and basal rales were included in this controlled prospective randomized trial. All patients received standard medical treatment and 10 patients were additionally treated with NIPSV (pressure support level, 12 cmH2O; positive endexpiratory pressure, 5 cmH2O; FiO2, 0.6) whereas the other patients received oxygen (8 l/min) via Venturi face mask. Improvement in oxygen saturation was significantly faster in the NIPSV group and oxygen saturation was higher at the time of the hospital admission (NIPSV=97.3+/-0.8%; standard=89.5+/-2.7%, P=0.002). A trend toward higher troponin T levels was seen in the standard treatment group. The need for intensive care treatment did not differ, and one patient of each treatment group died in hospital. No complications were noted during the treatment with NIPSV. Prehospital NIPSV is feasible and able to improve emergency management of ACPE. Noninvasive positive pressure ventilation has been found to be efficacious in the setting of acute respiratory failure, specifically in chronic obstructive pulmonary disease exacerbations. Its use in congestive heart failure (CHF) is less well established. Additionally, it has been reported that there is an increase in acute myocardial infarction (AMI) rate with the use of bilevel positive pressure ventilation (BiPAP) in CHF patients. This study examined whether BiPAP decreases the intubation rate or improves cardiopulmonary parameters in severe CHF patients compared to high flow O(2) by mask (MASK), and whether there is an increase in AMI rate with the use of BiPAP. A prospective, randomized clinical trial at a county hospital teaching Emergency Department was conducted by enrolling 38 patients who were in severe CHF. Patients were randomized to receive either BiPAP or MASK in addition to adjunct therapy. Age and gender were not different between the groups. Heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, and pulse oximetry all showed no significant difference in change over time between groups, but there was a significant change over time within groups. Arterial pH, pCO(2), and pO(2) also showed no significant difference in change over time between groups, but there was a significant change over time within groups. The intubation rate for BiPAP was 23.8% (5) vs. MASK at 41.2% (7). The AMI rate was 19% (4) in the BiPAP group and 29.4% (5) in the MASK group. No true differences were detected between groups for increased oxygenation or a reduction in intubation rate. An increase in AMI rate with BiPAP was not found in this study as previously reported. This study provides support for a larger clinical trial assessing the safety and efficacy of BiPAP in acute CHF.
NPPV in addition to standard medical care is an effective and safe intervention for the treatment of adult patients with acute cardiogenic pulmonary oedema. The evidence to date on the potential benefit of NPPV in reducing mortality is entirely derived from small-trials and further large-scale trials are needed.