In this randomized controlled trial, a sequential and early use of NIV was associated with a significant reduction of post-extubation respiratory failure in patients with chronic respiratory disorders. However, this strategy did not result in lowered mortality or reintubation in our population.

Patients at risk of post-extubation respiratory failure

One important research objective regarding the indication for early use of NIV immediately after extubation in the absence of evidence of respiratory failure is to identify the high-risk population of patients most likely to benefit from this intervention [1]. This “prophylactic” NIV seems beneficial only in patients at high risk for reintubation. Indeed, in a study including more than 400 ICU patients extubated after a successful 2-h spontaneous breathing trial, extubation failure rate was similar in patients treated with early NIV or oxygen therapy [23]. The result of this study suggests that their patients in general were at lower risk for extubation failure than those in the studies of Nava et al. [12] and Ferrer et al. [8, 11]. In addition, the composition of their patient population, with fewer patients with COPD, may also explain the lack of efficacy. The existing data suggest that early use of NIV after extubation might be indicated in patients older than 65 years, high severity score, heart failure [7] or in hypercapnic patients [8, 11]. However, patients with underlying chronic respiratory disease are identified as being at high risk for extubation failure [11]. For patients at high risk for extubation failure (patients with hypercapnia, COPD, chronic heart failure, or other serious comorbidities) who have been receiving mechanical ventilation for more than 24 h, and who have passed an SBT, an official clinical practice guideline from the American College of Chest Physicians and from the American Thoracic Society recommend extubation to preventive NIV [24]. Our study confirms these data and seems to indicate that nearly 30% of patients with chronic respiratory disorders, not exclusively hypercapnic, will develop respiratory failure after extubation. Another strength of the present trial is to confirm the benefits of prophylactic NIV in these patients. However, a subgroup analysis shown that, in patients without hypercapnia, the randomization group was not a predictor of respiratory failure after extubation in multivariate analysis. We observed the same results in patients with hypercapnia. This can be explained by a lack of power.

Mortality

In our study, neither ICU mortality rate nor the 90-day mortality rate were reduced with NIV. The reintubation rate of each group was similar compared with the difference in rate of respiratory failure after extubation between groups suggesting a protective effect of NIV as rescue therapy. In the study performed by Ferrer et al. in hypercapnic patients, the 90-day mortality rate was reduced with NIV. The authors provide several relevant explanations: only few patients from the NIV group needed reintubation; differences in mortality between groups arose later after discharge from the ICU, suggesting a long-term benefit of NIV [25]. We have not observed the same results. Our patients are likely to be less severe, not exclusively hypercapnic. Indeed, hypercapnia is associated with poor survival in mechanically ventilated patients particularly when no ventilatory support is provided after extubation [26, 27]. Another explanation, probably the most logical, is the fortuitously low number of deaths.

Reintubation

In our study, reintubation did not differ significantly between groups. Indeed, patients who did not require immediate reintubation escaped from reintubation after NIV was used as rescue therapy. Thille et al. performed a recent before–after study to assess the impact of a prophylactic NIV protocol on reintubation in a population of at-risk patients [28]. The reintubation rate was significantly decreased from 28% in the control cohort to 15% in the NIV cohort. However, as expressed by the authors, many changes may have impacted the reintubation rate such an improvement in the process of weaning or the use of NIV as rescue therapy.

NIV as recue therapy

There is some evidence that reintubation and prolongation of mechanical ventilation adversely affect survival independently of the underlying illness severity [6, 11]. In a large case-series study of planned extubation, Fructos-Vivar et al. showed that reintubation was independently associated with ICU mortality [6]. Results are disappointing in patients in whom NIV was used as rescue therapy, i.e. after they developed respiratory failure [29–31]. In our study, 20 patients, who developed respiratory failure after extubation but who did not need immediate reintubation, received NIV as rescue therapy. This strategy makes sense, because it has been consistently shown that patients with chronic pulmonary disease benefit from NIV [18, 32]. However, this remains a high-risk situation. Indeed, NIV used to avoid reintubation was successful in a few patients (7/17) in the usual care group and ineffective in the preventive NIV group (0/3). We can reasonably assume that some patients would have been reintubated for respiratory failure after extubation if NIV was not applied as rescue therapy. These positive results with NIV as rescue therapy confirm those previously reported, particularly in patients with chronic respiratory disease [8, 11, 17], although reintubation after rescue therapy with NIV occurred later than direct reintubation in our study. ICU mortality rate of patients who were reintubated directly (3/6 patients) was similar to that of patients who were reintubated after failure of rescue therapy with NIV (5/13 patients).

Sequential use of NIV

Most of the studies about preventive use of NIV after extubation performed the technique in a continuous way during a duration from 12 to 24 h [8, 11, 23, 33, 34]. In those studies, the facial skin was assessed regularly every 4 h to prevent damage from the face mask. Although in these studies NIV’ tolerance was satisfactory, in the study performed by Ferrer et al., 10% of patients assigned to continuous NIV for 24 h after extubation tolerated the procedure for only 6 h or less [11]. Some authors have emphasized that NIV is not easily accepted by patients with acute respiratory failure [35, 36]. This explains at least partly why in many studies the objectives of either continuous ventilation or prolonged periods of ventilation have not been achieved. We chose a different strategy, because NIV was applied following the so-called sequential protocol proposed by Hilbert et al. [13]. All the goals of NIV can also be achieved by a sequential use, and in our study tolerance of NIV was excellent with no specific complication.

Duration of NIV and late post-extubation failure

In ARF in patients with chronic respiratory disease, the mean number of hours of treatment per day is close to 8 h [37–39]. In most of the studies about the preventive use of NIV after extubation, the number of hours of treatment was paradoxically much more important, even though it is a preventive process in patients who are not in ARF. Our protocol of ventilation is appreciated by our nursing staff and it has not been necessary to modify the organization of our unit. Another point to discuss is the interest to perform NIV for 48 h in post-extubation. This attitude make sense, because roughly 20% of those patients who developed a respiratory failure did so on the second day after extubation. However, only four patients in each group developed respiratory failure the second day after extubation. Taking into account the small sizes of those subgroups, it is difficult to conclude to the interest to perform NIV for 48 h in post-extubation. Nevertheless, the tolerance to NIV was high and the rate of complications low, in keeping with our previous experiences. Giving the fact that NIV was maintained for 2 days, its suspension may have caused a relapse of acute respiratory failure. Indeed six patients in the NIV group versus four in the usual care group developed a late respiratory failure. It seemed difficult to compare those data. In addition, it could be questionable to establish a link between late failure and extubation.

High flow nasal cannula

Another point to discuss is the role of high-flow nasal cannula at the light of the recent randomized trials. Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation [40]. In patients at risk of post-extubation respiratory failure, Hernandez et al. recently performe a multicenter randomized clinical trial to test if high-flow oxygen therapy was noninferior to NIV for preventing post-extubation respiratory failure [41]. High-flow nasal cannula was not inferior to NIV for risk of reintubation. As noted by the authors, one possible limitation is the criteria used to select patients who were at high risk of reintubation. In fact, it could explain the very high and unusual percentage (close to 40%) of post-extubation respiratory failure in the NIV group.

Limitations of the study

Several limitations of our study should be acknowledged. It was not possible to conduct a double-blind investigation. Despite clearly predefined evaluation criteria, interventional procedure and clinical decisions during the trial, it was not possible to entirely control this bias. The use of rescue NIV in cases of post-extubation ARF might have contributed to reduce the difference in patient outcomes between the two groups. Nevertheless, it seemed difficult not to offer to the patients the opportunity of rescue NIV before having to reintubate. Patients in the usual care group presented more underlying diseases than in the NIV group. Nevertheless, there was no significant statistical difference. This lack of difference could be due to the small size of both populations. The present study was conducted in centers with experience with NIV. This factor could have affected the success of this technique. In our opinion, a skilled staff is crucial to apply the technique with efficiency and security in the post-extubation period.