Treatment of Acute Hypoxemic Nonhypercapnic Respiratory Insufficiency With Continuous Positive Airway Pressure Delivered by a Face Mask (2024)

ContextContinuous positive airway pressure (CPAP) is widely used in the beliefthat it may reduce the need for intubation and mechanical ventilation in patientswith acute hypoxemic respiratory insufficiency.

ObjectiveTo compare the physiologic effects and the clinical efficacy of CPAPvs standard oxygen therapy in patients with acute hypoxemic, nonhypercapnicrespiratory insufficiency.

Design, Setting, and PatientsRandomized, concealed, and unblinded trial of 123 consecutive adultpatients who were admitted to 6 intensive care units between September 1997and January 1999 with a PaO₂/FIO₂ ratio of 300 mm Hgor less due to bilateral pulmonary edema (n = 102 with acute lung injury andn = 21 with cardiac disease).

InterventionsPatients were randomly assigned to receive oxygen therapy alone (n =61) or oxygen therapy plus CPAP (n = 62).

Main Outcome MeasuresImprovement in PaO₂/FIO₂ ratio, rate of endotrachealintubation at any time during the study, adverse events, length of hospitalstay, mortality, and duration of ventilatory assistance, compared betweenthe CPAP and standard treatment groups.

ResultsAmong the CPAP vs standard therapy groups, respectively, causes of respiratoryfailure (pneumonia, 54% and 55%), presence of cardiac disease (33% and 35%),severity at admission, and hypoxemia (median [5th-95th percentile] PaO₂/FIO₂ 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) andmedian (5th-95th percentile) PaO₂/FIO₂ ratios were greaterwith CPAP (203 [45-431] mm Hg vs 151 [73-482] mm Hg; P= .02). No further difference in respiratory indices was observed betweenthe groups. Treatment with CPAP failed to reduce the endotracheal intubationrate (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 lengthof 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 vs6; P = .01).

ConclusionIn this study, despite early physiologic improvement, CPAP neither reducedthe need for intubation nor improved outcomes in patients with acute hypoxemic,nonhypercapnic respiratory insufficiency primarily due to acute lung injury.

Patients with severe hypoxemic acute respiratory insufficiency oftenrequire life-supporting mechanical ventilation (MV). The placement of an endotrachealtube to allow for MV is associated with a significant risk of local airwayinjury and ventilator-associated pneumonia. Several studies found that noninvasiveventilation (NIV) reduced the need for endotracheal intubation in patientswith acute exacerbations of chronic obstructive pulmonary disease (COPD).^1,2

In addition, reports published over many years have suggested that patientswith cardiogenic pulmonary edema (CPE) or non-CPE may benefit from continuouspositive airway pressure (CPAP) delivered by a face mask.^3-16Most of these studies were nonrandomized, and in the few randomized studies,the primary end point was often based on gas exchange criteria after a predeterminedduration of CPAP treatment.^7,13These studies demonstrated the ability of CPAP to improve hypoxemia but notits ability to reduce the need for intubation and MV. However, one single-center,randomized study found strong evidence that CPAP use reduced the need forendotracheal intubation in patients with severe hypercapnic CPE.¹⁰

In patients with acute lung injury (ALI), applying positive pressureto the airway opening has been shown to lessen the reduction in functionalresidual capacity and to improve respiratory mechanics and gas exchange.¹⁷ These data have led intensive care unit (ICU) physiciansto widely use CPAP to prevent subsequent clinical deterioration and to reducethe need for endotracheal intubation.^5,6,8,9,11However, the efficacy of this practice has not been evaluated. In particular,uncertainty continues to surround the potential clinical benefits of CPAPdelivered by a face mask to patients with acute hypoxemic, nonhypercapnic,respiratory insufficiency due to bilateral pulmonary edema, with or withoutunderlying cardiac disease.

We conducted a multicenter, prospective, randomized trial to comparethe efficacy of CPAP delivered through a full face mask with standard oxygentherapy in ICU patients admitted with ALI with or without underlying cardiacdisease.

Between September 28, 1997, and January 19, 1999, 123 consecutive adultsadmitted with acute respiratory insufficiency secondary to pulmonary edemawere recruited prospectively at the medical ICUs of 6 hospitals (Henri Mondor,Créteil, France; La Cavalle Blanche, Brest, France; Croix Rousse, Lyon,France; Sant Pau, Barcelona, Spain; Monastir Hospital, Monastir, Tunisia;and La Sapienza University, Rome, Italy), which previously had participatedin NIV studies and had experience with the various NIV techniques.^1,16,19,20 Thestudy protocol was approved by the appropriate institutional review boards.Informed consent was obtained from all the patients.

Inclusion criteria were as follows: (1) acute respiratory insufficiency,defined as the PaO₂/FIO₂ ratio of 300 mm Hg or lessafter breathing oxygen at 10 L/min or more for 15 minutes, with the inspiredfraction of oxygen determined by a portable oxygen analyzer (MiniOX I; MineSafety Appliances Co, Pittsburgh, Pa); (2) the presence of bilateral lunginfiltrates on a posteroanterior chest radiograph; and (3) randomization within3 hours after the criteria were first fulfilled.

Exclusion criteria were patients younger than 18 years; intubation wasrefused or contraindicated; history of COPD; acute respiratory acidosis (definedas a pH <7.30 and a PaCO₂ >50 mm Hg); systolic blood pressureless than 90 mm Hg under optimal therapy (fluid repletion); ventricular arrhythmias;coma or seizures; life-threatening hypoxemia (defined as an SaO₂<80% with an oxygen mask); use of epinephrine or norepinephrine; and theinability to clear copious airway secretions.

The precipitating cause of acute respiratory insufficiency and the presenceof a chronic or acute cardiac disease were recorded at admission. Patientswere randomly assigned to standard treatment (oxygen alone) or standard treatmentplus CPAP delivered by a face mask. Patients with ALI and no history of chroniclung disease constituted the primary group of interest. Since increased pulmonarypermeability may coexist with left atrial or pulmonary capillary hypertension,¹⁸ patients with a history of cardiac disease also wereincluded. The coronary care unit (CCU), independent from the medical ICU,treated patients with ischemic myocardial disease and those with heart failuredeemed unlikely to require MV. Patients with obvious cardiac disease wereprimarily treated in the CCU, however, the only ones who were considered forthe study were those patients with cardiac disease who had a possible superimposednoncardiac cause of respiratory failure, patients with extreme severity andno response to treatment, or patients in whom cardiac insufficiency previouslywas not known.

Because a cardiogenic mechanism contributing to the pulmonary edemamight have had a substantial influence on the study results, the randomizationwas stratified based on whether there was an underlying cardiac disease (chroniccardiac disease with class II, III, or IV of the New York Heart Associationfunctional classification or acute de novo cardiac disease). The stratificationwas not based on whether it was CPE or non-CPE because in severely ill patientswith chronic cardiac disease admitted for acute respiratory insufficiency,it is sometimes difficult to determine on admission whether decompensatedheart failure is the only cause of the episode of respiratory insufficiency.Including patients with a history of cardiac disease, it was likely that usingclinical examination and simple biological criteria a proportion of thesepatients would be eventually diagnosed as having cardiac disease. The stratificationwas to ensure that patients with an underlying cardiac disease were equallydistributed between the 2 study groups. Sealed envelopes were used to randomlyassign patients to their treatment group.

Patients assigned to the standard treatment group (n = 61) receivedoxygen delivered through a face mask. The FIO₂ was measured usingthe same oxygen analyzer in each center: the tip of the oxygen analyzer wasintroduced via a small hole in the face mask. The goal was to achieve a pulseoximetry SaO₂ greater than 90%. Oxygen was delivered until endotrachealintubation, death, or fulfillment of oxygen delivery cessation criteria (anSaO₂ ≥ 92% without oxygen and a respiratory rate < 30/min).

All patients with suspected cardiac insufficiency received diureticsas required. Infectious causes were treated with antibiotics. Gastrointestinaltract prophylaxis was administered to patients who were intubated with MVor in patients with a history of gastrointestinal tract ulcer.²¹Patients did not receive systematic ulcer prophylaxis under CPAP therapy.

Patients assigned to the CPAP plus oxygen group (n = 62) received periodsof CPAP in addition to the standard treatment. All study centers used a VitalSigns, Inc (Totowa, NJ) device.²² The deviceincluded (1) a Vital Flow 100 CPAP Flow Generator that delivered a flow (rate0-130 L/min) that could be adjusted to the patient's inspiratory flow requirement,with an adjustable FIO₂ within the 34% to 100% range; (2) a spring-loaded,positive end-expiratory pressure (PEEP) valve that provided a fixed end-expiratorypressure (5, 7.5, or 10 cm H₂O) with minimal resistance to airflow;(3) a full face mask composed of a transparent mask and a soft inflatablecushion; and (4) a dedicated headstrap. Airway humidification was achievedby using a heated humidifier (MR640; Fisher & Paykel, Auckland, NZ).

For at least the first 6 to 12 hours, CPAP was given continuously andthen discontinuously as indicated based on patient tolerance and on whetherthe pulse oximetry SaO₂ was greater than 90% under oxygen alone.

For all patients, CPAP was started at 7.5 cm H₂O. The levelcould be decreased to 5 cm H₂O or increased to 10 cm H₂Oas needed based on the clinical response and tolerance. Continuous positiveairway pressure was delivered for at least 6 h/d and was continued until endotrachealintubation, death, or fulfillment of the following cessation criteria: PaO₂/FIO₂ ratio greater than 300 mm Hg, or SaO₂ between95% and 100% and FIO₂ of 40% or less without CPAP, or CPAP durationless than 6 h/d. The criteria for oxygen delivery cessation were the sameas in the standard therapy group.

Endotracheal intubation was performed in patients with any of the following:decreased alertness or major agitation requiring sedation, clinical signsof exhaustion (active contraction of the accessory muscles of respirationwith paradoxical abdominal or thoracic motion), hemodynamic instability, cardiacarrest, or refractory hypoxemia (SaO₂ <85% with FIO₂of 100%).

Arterial blood gas values, respiratory rate, systolic blood pressure,and pulse rate were collected at baseline, after 1 hour, and between the 6thand 12th hours; the worst value of each of these variables was recorded oncea day. The response to treatment was recorded 1 hour after the initiationof CPAP or oxygen treatment by asking patients to grade the effect of treatmenton their dyspnea: + 2, marked improvement; + 1, slight improvement; 0, nochange; − 1, slight deterioration; and − 2, marked deterioration.The Simplified Acute Physiologic Score II²³(SAPS II) and the Logistic Organ Dysfunction score²⁴were calculated 24 hours after ICU admission and 24 hours after study inclusion.Since CPAP use is assigned a specific weight in both scoring systems, thetreatment assigned by randomization could in itself modify the scores; consequently,both scores were calculated without including the points for respiratory failure.

The following adverse events were recorded during spontaneous ventilation:facial skin necrosis, conjunctivitis, sinusitis, gastric distension, aspiration,pneumothorax, nosocomial pneumonia (based on clinical criteria), stress gastrointestinaltract ulcer and bleeding, and cardiac arrest; and during MV: cardiac arrestat endotracheal intubation, tracheal injury, pneumothorax, sinusitis, nosocomialpneumonia (based on clinical criteria and quantitative cultures of protectedbacteriological sampling of the lungs), and stress gastrointestinal tractulcer and bleeding. Among these events, only adverse events not present atadmission were counted as those that occurred during the ICU stay.

The primary outcome variable was endotracheal intubation and MV at anytime during the study. The patient was used as the randomization unit. Therandomization protocol, computer-generated by the Department of Biostatisticsof Henri Mondor Hospital, was stratified based both on the study center andthe presence or absence of an underlying cardiac disease. Based on a preliminaryretrospective evaluation of medical charts of patients fulfilling the inclusioncriteria, the predicted intubation rate was approximately 40%. Sixty patientsper group were required to demonstrate a difference in the rate of endotrachealintubation from 40% to 15% between the 2 groups, with a type I risk of errorof 5% and a power of 80%. The 15% rate of intubation was chosen because previousstudies had shown that 0% to 6% of patients receiving CPAP to treat CPE wereeventually intubated, but that a lower efficacy could be expected in non-CPE.^10,13 Secondary outcome variables werethe length of ICU and hospital stays, number of adverse events during spontaneousventilation or MV (not present at admission; see above), duration of ventilatoryassistance, and hospital mortality rate.

Values are reported as medians with the 5th to 95th percentiles. Allstatistical analyses were performed on an intention-to-treat basis, that is,including all randomized patients. χ² Tests or Fisher exacttests were used to compare categorical variables between the 2 treatment groups.Continuous variables were compared using the Wilcoxon rank sum test or Wilcoxonmatched pairs signed rank test when appropriate. Pvalues for all statistical tests were 2-tailed.

The Kaplan-Meier curve for intubation rates was plotted during the entirefollow-up. The log-rank test was used to compare the 2 randomized groups.Independent factors associated with endotracheal intubation were analyzedusing a Cox regression model and then used to adjust treatment comparisonsconsidering both a stratified model based on the preexistence of cardiac diseaseand a nonstratified model. In the nonstratified model, the interaction betweenthe treatment group and the cardiac disease group was formally tested by enteringan indicator interaction in the Cox regression model and by using a test forheterogeneity.²⁵ In the multivariate analysis,in addition to baseline data, the persistence of respiratory failure (definedas a PaO₂/FIO₂ ratio ≤200 mm Hg at 1 hour of treatment)also was evaluated as an index of respiratory severity. This index was determinedat admission and at 1 hour, since most patients with fluid overload are alreadyimproved at 1 hour, whereas patients with nonhydrostatic lung edema are stillhypoxemic. All computations were done using SAS software (SAS Institute, Cary,NC).

The individuals responsible for assessing and recording the outcomes(E.L'H., J.M., F.A., G.C., C.G., F.S., Y.L., and M.A.) only had access topatient medical charts; biostatisticians (C.A. and E.L.) were responsiblefor the computer database; and patient data were collected by the other investigators(C.D., F.L., and L.B.).

The baseline characteristics of the 123 patients included in this studyare shown in Table 1. Patientswith an underlying cardiac disease were equally distributed between the 2treatment groups (11 for oxygen alone and 11 for oxygen plus CPAP). The follow-upwas complete for all patients (Figure 1).

At study entry, all 123 patients had acute respiratory insufficiency(defined as a PaO₂/FIO₂ ratio ≤300 mm Hg and thepresence of bilateral infiltrates on chest radiograph). Of these 123 patients,21 (17%) eventually were classified as having pure cardiac decompensation;102 patients (83%) had ALI (PaO₂/FIO₂ ratio ≤300mm Hg due to increased lung permeability), among whom 74 (60%; 59 patientswithout cardiac disease plus 15 with associated cardiac disease) had a PaO₂/FIO₂ ratio of 200 mm Hg or lower, indicating acute respiratorydistress syndrome (ARDS). Precipitating causes of pulmonary edema were equallydistributed between the 2 treatment groups (Table 2). Infectious causes represented 37 (61%) of the 61 patientstreated with oxygen alone and 42 (68%) of the 62 patients treated with oxygenplus CPAP; direct lung injury due to pneumonia was the most frequent cause(55% and 54%, respectively).

After 1 hour of treatment, patients receiving oxygen plus CPAP had asignificantly greater PaO₂/FIO₂ ratio increase (P = .02) and a significantly greater subjective responseto treatment than patients receiving oxygen alone (P<.001)(Table 3 and Figure 2). Compared with baseline values at entry, CPAP also wasassociated with a significant reduction in respiratory rate (P<.001) and a significant increase in pH levels (P = .01) at the end of the first treatment hour. During the remainderof the study, however, these indices showed no significant differences betweenthe 2 treatment groups.

Nine of the 62 patients (14%) were unable to tolerate CPAP treatment:2 of the 9 tolerated CPAP for less than 10 minutes and 7 for longer than 6hours. Three of the 9 patients eventually required intubation.

The median percent SaO₂ over time was consistently above90% in both treatment groups (Figure 3).In the oxygen plus CPAP group, the median daily duration of CPAP was significantlylonger in patients who eventually required intubation than in those who didnot (P = .03 at day 2, P= .048 at day 3, and P = .02 at day 4) (Figure 4).

No significant differences were found between the 2 treatment groupsfor any of the clinical outcome variables studied, including rate of endotrachealintubation, length of hospital stay, and hospital mortality (Table 4 and Figure 5).The indications for endotracheal intubation were similar in the 2 treatmentgroups (Table 5). Four patientsrandomized to the oxygen alone group subsequently were given oxygen plus CPAPtreatment, and another patient received NIV pressure support. Two patients(1 in each group) were found a posteriori to meet an exclusion criterion (contraindicationto endotracheal intubation); neither patient was intubated and both died inthe ICU. Excluding these patients or switching them to the other group hadno significant effects on outcomes.

A multivariate analysis demonstrated that the SAPS II score (hazardratio [HR] per 1 SAPS II point, 1.05; 95% confidence interval, [1.03-1.07]),absence of a cardiac disease (HR, 2.27 [1.08-4.75]), and PaO₂/FIO₂ ratio 200 mm Hg or less at 1 hour of treatment (HR, 2.35 [1.20-4.60])were independently associated with endotracheal intubation. Treatment groupassignment as well as a PaO₂/FIO₂ ratio of 200 mm Hgor less on admission were not associated with endotracheal intubation. Theabsence of treatment effect remained unchanged when the stratified analysison preexistence of cardiac disease was performed. Moreover, there was no interactionbetween the treatment and the cardiac disease groups.

When patients with and without an underlying cardiac disease were analyzedseparately, no significant benefits of oxygen plus CPAP treatment were foundfor the need for endotracheal intubation, length of hospital stay, or hospitalmortality (Table 4).

Adverse events that occurred during spontaneous and MV were significantlymore common in the CPAP group (P = .01) (Table 6).

This multicenter, randomized, concealed, but unblinded trial of 123patients showed that, despite early physiologic benefits, treatment with oxygenplus CPAP delivered by a face mask did not reduce the need for intubationin patients with acute, hypoxemic, and nonhypercapnic respiratory insufficiency,among whom a majority had ALI, and it did not impact the length of hospitalstay or hospital mortality. A higher number of adverse events occurred withthe use of CPAP.

All centers were experienced in the delivery of face-mask ventilationand had previously participated in NIV studies.^1,16,19,20Analysis of daily CPAP treatment duration data showed that CPAP was used forat least 6 h/d, as required by the study protocol. Use of intubation in patientsin the oxygen plus CPAP group was not explained by a low compliance with CPAPtreatment. On the contrary, patients who eventually required intubation hadsignificantly longer daily CPAP treatment durations (Figure 3). In addition, SaO₂ goals were achieved in bothgroups (Figure 2). The fact thata longer duration of CPAP use per day was associated with intubation couldraise the hypothesis that additional respiratory load due to CPAP use mayfavor intubation. To minimize this problem, we used a continuous flow systemwith adequate airway humidification and minimal loads imposed by the circuit.Because the CPAP device was an adjustable-flow venturi, when high FIO₂ is used, a slight reduction in total outflow may occur.²²Thus, it is possible that the CPAP system was less efficient for the mostsevere patients needing the highest FIO₂ and the highest flow.Nevertheless, the multivariate analysis demonstrated that a PaO₂/FIO₂ ratio at 1 hour of 200 mm Hg or lower was an independent risk factorfor intubation whatever the treatment type. This index was taken at 1 hourto more accurately identify patients with ARDS, since most patients with fluidoverload are already improved at 1 hour. This parameter was a marker of severity,and this could not be reversed by CPAP treatment despite increasing its use.

Oxygen plus CPAP therapy was associated with a significantly greaterimprovement of PaO₂/FIO₂ ratio within the first hourthan oxygen alone therapy. As a result, oxygenation was improved after 1 hourin the CPAP group and of patient dyspnea. Similar results were obtained withCPAP treatment in patients with cardiac disease or in the short-term studiesin patients with ALI.^7,13,17During the remainder of the study, no differences in oxygenation were demonstrated.

The leading cause of acute respiratory insufficiency in our study wasnonhydrostatic edema, that is, ALI (101 [82%] of the patients). The largeproportion of these patients with criteria for ARDS is representative of therelative distribution of these 2 degrees of severity found in previous studies(ALI [with no criteria for ARDS]: 1.8% vs ARDS: 6.9%, among all ICU admissionsin a recent multicenter prevalence survey).²⁶Our population included patients with cardiac dysfunction, a factor that mayhave influenced the efficacy of CPAP treatment. Results were similar in patientswith and without cardiac disease (Table4). Our study was not powered to determine the efficacy of oxygenplus CPAP treatment in the subgroup of patients with pure CPE nor in specificsubsets of patients with non-CPE.

Bersten et al¹⁰ reported that oxygenplus CPAP treatment in patients with severe hypercapnic CPE resulted in earlyphysiologic improvement and significantly reduced the need for intubation;the PaO₂/FIO₂ ratio improvement with CPAP use was significantonly at 30 minutes, as compared with oxygen alone. The prompt improvementwith CPAP use was probably because the patients had rapidly resolving conditions:mean (SD) CPAP duration of use was only 9.3 (4.9) hours and mean (SD) ICUstay length was 1.2 (0.4) days. These results suggest that the patients hadextremely acute conditions in which CPAP treatment was beneficial becausethe rapid improvement it afforded, although transient, lasted long enoughto give drug therapy time to act. Similar benefits were suggested by L'Heret al.¹⁶ In these studies, most patients hadhypercapnic CPE, indicating frank ventilatory failure (patients with hypercapniawere not included in our study). Hypoxemic nonhypercapnic pulmonary edemain cardiac patients seems to respond to CPAP treatment differently for 2 possiblereasons: because the evolution may be spontaneously favorable under medicaltherapy alone in patients with pure CPE or because the evolution may becomesimilar to ALI when the disease is triggered by a noncardiac event in cardiacpatients. The existence of ventilatory failure, with hypercapnia and respiratoryacidosis, indicates that the immediate prognosis depends on the ability ofthe ventilatory function to cope with the loads. This can be obtained by reducingthe loads on the system (medications) or by assisting the respiratory musclefunction (CPAP or NIV therapy). The absence of frank ventilatory failure mayexplain why these patients do not clearly benefit from CPAP therapy. Therefore,CPAP may be beneficial in patients with a poorly tolerated but transient hypercapnicepisode of CPE but may be less advisable in patients with longer-lasting hypoxemia.

Confalonieri and colleagues²⁷ recentlyreported beneficial effects of NIV in patients with severe community-acquiredpneumonia, but this result was essentially explained by the subgroup of patientswith COPD. In a study by Wysocki et al²⁸ ofNIV in patients without COPD admitted for acute respiratory failure, the needfor endotracheal intubation and the time from study entry to endotrachealintubation affected were not decreased by NIV. In addition, the results suggestedthat benefits occurred only in the subgroup of patients with hypercapnia.

Antonelli et al²⁰ recently reported thebeneficial effects of NIV in selected patients with hypoxemia and acute respiratoryfailure deemed to require intubation. They used pressure support ventilationin addition to PEEP (mean [SD], 5.1 [1.4] cm H₂O) and found thatthis treatment improved gas exchange and was less likely to cause adverseeffects compared with conventional MV. Mean (SD) duration of NIV was only2 (1) days in the patients who did not require intubation. It remains unclearwhether the higher level of support provided by the concomitant use of pressuresupport and PEEP may explain the better results in the study by Antonelliet al²⁰ as compared with our study. Differencesin selection criteria also may have contributed to the differences in resultsbetween these 2 studies.

If CPAP therapy does not reduce the need for endotracheal intubation,then it may carry its own risks. Oxygen plus CPAP treatment was accepted by86% of our patients, initially produced few adverse effects, and improvedsubjective response compared with oxygen therapy. Nevertheless, of 8 patientstreated with CPAP, 4 experienced cardiac arrest and 4 who were treated withCPAP experienced upper gastrointestinal tract bleeding. Continuous positiveairway pressure was not associated with a significant increase in adverseevents during spontaneous ventilation (7 vs 1, P= .06). However, it may be difficult to ensure that the adverse effects occurringduring MV may not be explained by the period of spontaneous ventilation, forinstance, for gastrointestinal tract bleeding (4 patients in the oxygen plusCPAP group and 0 in the oxygen alone group). In some cases, CPAP may prolongthe stressful period of spontaneous breathing, which could have been reducedby MV, allowing to rest the patient. Although this study was not powered enoughto detect small benefits of CPAP therapy, it found a significantly highernumber of adverse events in centers well trained in the NIV technique.

In conclusion, CPAP provided rapid but transient improvements in oxygenationand dyspnea compared with standard therapy but did not decrease endotrachealintubation in patients with acute, nonhypercapnic respiratory insufficiency.However, we found significantly more adverse events with CPAP.