Several complications may occur during invasive mechanical ventilation (IMV), the most important of which is pneumonia associated with mechanical ventilation 1 . To avoid tracheal intubation and its complications, noninvasive positive-pressure mechanical ventilation (NPPV) has been suggested as an alternative for the management of patients with acute respiratory failure (ARF), particularly during the course of acute pulmonary edema and chronic obstructive pulmonary disease (COPD) 2 3 4 5 6 7 8 .

One third of IMV time is spent in weaning, defined as the process of gradual removal of mechanical ventilation support toward spontaneous ventilation 9 . Most patients are weaned with no difficulties. However, a significant percentage (5% to 30%) of patients in intensive care units (ICUs) fail spontaneous ventilation trials, characterizing difficult weaning 10 . In the last few years, NPPV has been tested in these situations. Nava and colleagues 11 , in a randomized clinical trial, used NPPV or IMV in 50 patients with COPD aggravation who failed spontaneous ventilation trials. The authors found shorter ventilation time and lower mortality with the use of NPPV. Girault and colleagues 12 compared NPPV with pressure support ventilation in 33 COPD patients who failed a 2-hour T-piece trial and found a reduction in total mechanical ventilation time in the NPPV group. However, remaining time in the ICU and survival rates at 3 months were similar in the two groups. Vitacca and colleagues 13 assessed diaphragm energy expenditure (diaphragmatic pressure-time product [PTPdi]), lung resistance and elastance, arterial blood gases, and dyspnea during invasive and noninvasive pressure support ventilation. They found that, in patients with COPD who were not ready to sustain spontaneous breathing, the use of invasive or noninvasive ventilation was equally effective in reducing PTPdi and improving arterial blood gases but that noninvasive ventilation seemed to be better tolerated. In a later study, Ferrer and colleagues 14 suggested that NPPV be assessed as a means to facilitate IMV weaning for patients who failed spontaneous ventilation trials, regardless of the underlying disease. They confirmed the results of the previous study and additionally reported a reduction in remaining hospitalization time and in the need for tracheotomy. Later, a meta-analysis revealed that NPPV facilitates weaning and reduces mortality comparatively to IMV 15 . Quite recently, another two studies showed that the early use of NPPV was efficient in preventing respiratory failure after tracheal extubation in patients at risk for complications and that it reduced mortality in the ICU 16 17 . In all of those trials, most patients had COPD.

Studies assessing NPPV in weaning are still insufficient and generally include a small number of patients. Therefore, questions remain about NPPV benefits in weaning, particularly in heterogeneous groups of patients, which is a usual characteristic of patients admitted to the ICU. Therefore, new controlled and randomized studies are warranted. This study assessed the use of NPPV during weaning from mechanical ventilation in an ICU and compared this procedure with IMV by analyzing cardiac and respiratory parameters, clinical course, and complications.

Of the 156 patients submitted to SBT, 84 (53.8%) were randomly assigned to IMV and 72 (46.2%) to NPPV. After SBT, 91 patients were successfully extubated, but 26 (29.5%) had to be reintubated (Figure 1). Sixty-five patients (41.7%) failed SBT and were included in this study: 28 had been randomly assigned to NPPV and 37 to IMV. The patients in the NPPV group tended to be older. Other clinical characteristics were similar in the two groups. COPD aggravation, post-operative respiratory failure, and heart disease were the most frequent causes for the use of invasive ventilation support (Table 1) in both groups.

The distribution of associated diseases was not significantly different between the NPPV and IMV groups, and the most frequent diseases were systemic hypertension (50% versus 27%), heart diseases (21.4% versus 21.6%), and diabetes mellitus (17.9% versus 21.6%). Moreover, respiratory characteristics of patients on mechanical ventilation, before the spontaneous breathing trial, were not statistically different between the groups, as shown in Table 2.

During the spontaneous ventilation trial, 22 patients of the NPPV group and 20 of the IMV group were able to complete the test within 30 minutes and failed at 30 minutes, whereas 8 patients of the NPPV group and 17 of the IMV group failed before 30 minutes. The patient's final measurements were carried out at the failure moment. No statistically significant differences in cardiorespiratory parameters were found between groups at 1 minute or at the end of the trial, as shown in Table 3. Values of SpO₂ measured during ventilation support were not statistically different between the two groups (Figure 2), which shows that both techniques were effective in keeping oxygenation.

The comparisons of gas measurements between the NPPV and IMV groups showed no significant differences. The pH values were as follows: before spontaneous breathing trial, 7.41 ± 0.07 for both groups; after up to 2 hours of spontaneous breathing trial, 7.39 ± 0.06 versus 7.40 ± 0.05; after 24 hours of ventilation support, 7.38 ± 0.08 versus 7.39 ± 0.07; and at the end of ventilation support removal, 7.38 ± 0.06 for both groups. PaCO₂ before spontaneous ventilation trial for the two groups was 45.1 ± 11.5 versus 40.1 ± 11.1; up to 2 hours after failure, it was 43.2 ± 10.8 versus 41.6 ± 10.2; after 24 hours of support, it was 42.1 ± 11.3 versus 42.4 ± 11.2; and at final removal of ventilation support, it was 41.2 ± 10.9 versus 42.2 ± 10.8. PaO₂ before spontaneous ventilation trial was 88.7 ± 23.2 versus 99.7 ± 29.5; after failure, it was 87.5 ± 22.4 versus 89.8 ± 25.1; after 24 hours of ventilation support, it was 88.6 ± 24.1 versus 92.5 ± 25.6; and at the removal of ventilation support, it was 89.2 ± 24.2 versus 95.5 ± 26.2.

Table 4 compares lengths of stay in the ICU and the hospital and mortality rate in both groups. Patients of the NPPV group had a shorter stay in the ICU and in the hospital. Duration of mechanical ventilation after random assignment amounted to 10.02 days for the IMV group and 7.5 days for the NPPV group. However, these differences were not statistically significant, even though the duration of mechanical ventilation was slightly reduced in the NPPV group. For the 6 patients returned to IMV, duration of mechanical ventilation amounted to 8 days. Mortality was similar in the two groups. Of the 28 patients in the NPPV group (Figure 1), 16 had no serious complications and were not on ventilatory support when discharged from the ICU. One of these patients died from pulmonary embolism. Six patients returned to invasive ventilation support because of abdominal sepsis (n = 2), worsening of congestive heart failure (n = 3), or pneumonia (n = 1). Two of these patients died, both due to sepsis and multiple organ dysfunction syndrome (MODS), whereas the remaining patients were discharged. Of the 37 patients in the IMV group (Figure 1), 8 patients died in the ICU due to sepsis and MODS and 2 died from kidney failure and sepsis. Discharged patients were not on ventilatory support when discharged from the ICU. However, 7 patients had to undergo tracheotomy and showed a greater incidence of complications, particularly infections. This higher rate of complications, chiefly pneumonia, in the IMV group, is shown in Table 5.

The most important results of this study showed that, in patients who failed spontaneous ventilation trial when weaning was attempted, the combination of earlier tracheal extubation and NPPV ventilation support is a useful alternative. They decreased the incidence of pneumonia associated with mechanical ventilation, as well as the need for tracheotomy, in comparison with patients who were conventionally weaned from IMV.

Strong evidence supports the use of NPPV to avoid placement of an invasive airway and to reduce complications and mortality due to IMV 2 28 29 . However, few randomized clinical trials evaluated early use of NPPV to accelerate mechanical ventilation weaning. Older studies used this resource, but it was applied at a later stage in patients ventilated for a long time 30 31 . NPPV was recently used at earlier stages for mechanical ventilation weaning, and the results were favorable, particularly when used in selected patients, such as those with COPD and hypercapnic respiratory failure or respiratory acidosis 28 29 . Our study with a heterogeneous population of patients confirmed the beneficial effects of NPPV in comparison with IMV during weaning.

The process of gradual removal of mechanical ventilation poses an important clinical challenge, particularly in patients with pulmonary diseases, and its failure rates range from 35% to 67% 32 . Weaning failure during SBT in our study was not an infrequent clinical situation in patients on mechanical ventilation for an average of 7.3 days and was observed in 41.7% of the cases, which is in agreement with findings in the literature. Also in accordance with the literature, chronic pulmonary diseases were the most frequent causes of mechanical ventilation in our patients.

The NPPV group had shorter lengths of stay in the ICU and in the hospital, although this difference was not statistically significant. We did not observe any reductions in mortality, as did Ferrer and colleagues 14 . During the clinical course, the two treatment groups showed similar gas parameters, which is consistent with the literature 11 . In addition, there were no statistically significant differences in cardiorespiratory parameters measured in the first minute and at failure of the spontaneous breathing trial, which indicates that the groups had very similar baseline conditions. These findings indicate that NPPV is at least as safe a strategy as IMV.

There were significantly fewer complications in the NPPV group, with an important decrease in the incidence of pneumonia associated with mechanical ventilation and less need for tracheotomy. These results are similar to those of Nava and colleagues 11 and Ferrer and colleagues 14 . As in our study, those authors used NPPV after tracheal extubation and maintained it as long as necessary. On the other hand, Girault and colleagues 12 used intermittent periods of NPPV and did not observe any significant differences in the incidence of complications. The increased incidence of pneumonia which is observed in cases submitted to IMV for more than 3 days is associated with a high mortality rate 33 34 35 . Therefore, the decrease in its incidence, as observed in our study, is an important result. In addition, the decrease in the need for tracheotomy may result in fewer complications. These beneficial effects of NPPV, reducing the incidence of pneumonia and the need for tracheotomy, may also be correlated to cost reductions, but we did not analyze this possible correlation. It is important to note that the return to IMV of patients who did not benefit from the use of NPPV was due to aggravation of heart failure and abdominal sepsis and was not directly linked to the ventilation strategy used.

One of the limitations of this study was that our sample size was relatively small, though larger than samples in previous studies. A study with a greater number of patients might have yielded other significant results such as a reduction in the lengths of stay in the ICU and in the hospital. Also, although it is important to understand the role of NPPV in different groups of patients, a stratified analysis per subgroup was not possible because of the heterogeneity of our population as well as the small number of patients. Another limitation was that no data were collected after patients were discharged, and the analysis of late mortality was not possible. New studies should be carried out, with longer follow-up times and larger samples, to evaluate the effects of NPPV on the quality of life of patients on weaning ventilation support and to understand how the cause of ARF could affect the results of different weaning ventilation methods. Cost evaluation should also be included in these studies.

The results of this study suggest that the combination of early extubation and NPPV is a good alternative for ventilation in a group of heterogeneous patients who initially failed weaning. NPPV use resulted in efficient gas exchange, a tendency to decrease ICU and hospital stays, and principally an important reduction in the incidence of pneumonia as well as in the need for tracheotomy when compared with conventional IMV weaning. Therefore, NPPV is a useful and safe strategy that may be considered during mechanical ventilation weaning.

• The combination of early extubation and noninvasive positive-pressure mechanical ventilation (NPPV) is a useful and safe alternative for ventilation in patients who fail initial weaning attempts.

• NPPV use resulted in efficient gas exchange, a tendency to decrease intensive care unit and hospital stays, and principally an important reduction in the incidence of pneumonia as well as in the need for tracheotomy.

ARF = acute respiratory failure; bpm = beats per minute; COPD = chronic obstructive pulmonary disease; CPIS = clinical pulmonary infection score; DBP = diastolic blood pressure; FiO₂ = fraction of inspired oxygen; HR = heart rate; ICU = intensive care unit; IMV = invasive mechanical ventilation; MODS = multiple organ dysfunction syndrome; NPPV = noninvasive positive-pressure mechanical ventilation; PaCO₂ = arterial partial pressure of carbon dioxide; PaO₂ = arterial partial pressure of oxygen; PEEP = positive end-expiratory pressure; PI_max = maximal inspiratory pressure; PTPdi = diaphragmatic pressure-time product; f = respiratory rate; f/V_T = respiratory rate to tidal volume ratio; SBP = systolic blood pressure; SBT = spontaneous breathing T-piece trial; SIRS = systemic inflammatory response syndrome; SpO₂ = peripheral oxygen saturation; V_e = minute volume; V_T = tidal volume.

The authors declare that they have no competing interests.

CT and SV made substantial contributions to the study conception and design, analysis and interpretation of data, as well as drafting of the manuscript. The Research Group in Mechanical Ventilation Weaning was responsible for data collection. Both authors read and approved the final manuscript.