Weaning from mechanical ventilation and post-extubation failure / Mekanik ventilatorden ayirma ve ekstubasyon sonrasi basarisizlik.
Subject: Lung diseases, Obstructive
Authors: Pierucci, Paola
Carlucci, Annalisa
Schreiber, Annia
Nava, Stefano
Pub Date: 03/01/2011
Publication: Name: Turkish Thoracic Journal Publisher: Aves Yayincilik Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Aves Yayincilik ISSN: 1302-7808
Issue: Date: March, 2011 Source Volume: 12 Source Issue: 1
Accession Number: 305562801

In the event of acute respiratory failure, invasive mechanical ventilation (IMV) is a required practice to support gas exchanges and to unload respiratory muscles. It is important to optimise the timing of effective need of IMV. Weaning is defined as the process of gradual removal of mechanical ventilation support toward spontaneous ventilation. Non-invasive ventilation (NIV) efficacy have been proved only in a selected population of patients such as people with acute-on-chronic respiratory failure (COPD exacerbation) to shorten the length of invasive mechanical ventilation, the intensive care unit (ICU) stay and to avoid intubation related complications such as VAP. The role of NIV in all the other conditions (i.e. hypoxic patients, post-surgical patients) remains unclear. In the event of unplanned extubations during the weaning period, NIV could be considered as a good option to prevent re-intubation. (Tur Toraks Der 2011; 12: 27-31)

Key words: Respiratory failure, noninvasive ventilation, invasive mechanical ventilation, weaning

Received: 06.10.2010 Accepted: 07.10.2010


Akut solunum yetmezligi durumlarinda, solunum kaslarinin yukunu azaltmak ve gaz degisiminin saglanmasi icin invaziv mekanik ventilasyon (IWV) yapilmasi gereken bir islemdir. IMV'un yararli olabilmesi icin en uygun zamanlama onemlidir. Mekanik ventilatorden ayirma (weaning) islemi mekanik ventilasyon desteginden spontan solunuma asamali olarak gecme ilemidir. Noninvaziv ventilasyonun etkinligi, kronik solunum yetmezligi Cizerine eklenmi akut solunum yetmezligi gibi (orn. KOAH alevlenmesi) secilmis hasta gruplarinda, invaziv mekanik ventilasyonda ve yogun bakim unitesinde kalma suresinde kisalma, ventilatorle iliskili pnomoni (VIP) gibi entubasyonla iliskill komplikasyonlardan korunmada etkili oldugu gosterilmistir. Ancak NIV'un baska patolojilerdeki (orn. hipoksik hastalar, cerrahi sonrasi hastalar) rolu net degildir. Weaning sirasinda planlanmamis ekstubasyonlarda, yeniden entubasyonu onlemek icin NIV iyi bir secenek olarak dusunulebilir. (Tur Toraks Der 2011; 12: 27-31)

Anahtar sozcukler: Solunum yetmezligi, noninvaziv ventilasyon, invaziv mekanik ventilasyon, weaning

Gelis Tarihi: 06.102010 Kabul Tarihi: 07.10.2010


In the event of acute respiratory failure, Invasive Mechanical Ventilation (IMV) is a required practice to support gas exchanges and to unload respiratory muscles. Even if it is a life-saving procedure, it is not free from complications such as ventilator associated pneumonia (VAP) (1) gastro-intestinal haemorrhages (2) and generalized myopathy (3). For these reasons it is important to optimise the timing of effective need of IMV, guaranteeing a safe and lasting extubation (4). Weaning is defined as the process of gradual removal of mechanical ventilation support toward spontaneous ventilation. There are no differences between the two most popular weaning methods, either the gradual progressive reduction of Pressure support level or T piece breathing. In fact, they have been shown to be equally effective and the operator confidence with one or the other technique should be the criteria of choice (5).


One third of IMV time is devoted to weaning (6) and it becomes close to 50% in patients affected by COPD, cardiac failure and neurological problems. When the weaning fails, it is usually associated with an increased risk of death, prolonged ICU stay, and transfer to long-term facilities (7).

Many investigators examined the possibility of weaning from IMV using Non Invasive Ventilation (NIV) to shorten the intubation time and to avoid intubation related complications such as ventilation associated pneumonia. Udwadia et al. (8) in 1992 published the first report describing the use of NIV to facilitate liberation from IMV and after this several studies, trials and meta-analysis have followed (9-15).

From a physiological point of view, NIV is similar to IMV, in fact, it reduces the breathing work and frequency, decreases the negative deflections of intrathoracic pressure, improves gas exchange, and rests respiratory muscles (16). Indeed, both invasive and non-invasive pressure support, are equally effective and NIV may be used as a "full alternative" for invasive ventilation.

NIV may also facilitate the weaning process in "difficult to wean patients". A randomised-controlled study (12) performed in severe COPD patients showed that the likelihood of weaning success increases while the ICU stay and duration of mechanical ventilation decrease, using NIV as a weaning technique compared to the above mentioned weaning protocols. A French study (18), conducted on patients intubated for acute respiratory failure due to COPD or restrictive diseases confirmed the finding of a shorter duration of invasive mechanical ventilation using NIV versus traditional weaning. However, no differences in terms of ICU and hospital length of stay, as well as 3-months survival were found between the two techniques.

Burns et al. (19) conducted a meta-analysis of five studies (12), (18), (20-22) considering "difficult to wean" patients (i.e. clinical stable patients who failed a weaning trial) randomly assigned from IMV to either continued IMV, or to prompt extubation followed by NIV as a weaning strategy. Although respiratory failure requiring IMV was the unifying enrolment criteria, severe COPD was identified as the responsible pathology among most patients enrolled.

Trevisan and his group in Brasil (23), obtained similar results in a more recent randomized controlled trial. An heterogeneous group of patients treated with IMV for more than 48 hours who failed a SBT, were randomly assigned to the NIV group or the IMV group. Comparison between the two groups showed that the percentage of complications was lower in the NIV group (28.6% vs 75.5%). Patients in the NIV group had a shorter length of stay in the ICU and a shorter duration of mechanical ventilation, but these results were not statistically significant. Blood gases showed no differences between the two groups.

On the other hand, Prasad and co-workers in India conducted a similar randomized controlled trial (24), evaluating NIV for weaning from IMV of COPD patients with acute-on-chronic hypercapnic respiratory failure. Patients after a SBT failure were randomized into two groups to receive either NIV or continued weaning with IMV in pressure support mode. However, in this study no statistically significant differences were found between the two groups in terms of duration of MV, hours of weaning, ICU stay, incidence of VAP and number of deaths at discharge from the ICU and at 30 days. A possible explanation for these results could be related to the small number of patients recruited in the trial.

Girault et al. (25) recently completed a randomized controlled trial with a large number of patients in 17 centers in France. Inclusion criteria were the same as reported in the previous study. Patients were randomized into 3 groups either to continue intubation in IMV, to start NIV or to receive standard medical therapy after extubation. There were no differences in weaning failure, complications, ICU or hospital stay, or hospital survival. Interestingly, NIV was used effectively as rescue therapy in patients weaned invasively and also in patients extubated with oxygen alone. Further larger studies will be needed in order to assess the real impact of NIV on heterogeneous population of ICU patients.

Ferrer et al. (20) in a randomized controlled trial compared NIV with conventional weaning strategy in patients with "persistent" weaning failure defined as a failure of a SBT for 3 consecutive days. They showed a significant reduction in duration of mechanical ventilation, ICU and hospital stay using NIV, but no difference in the incidence of reintubation between the two techniques. However, patients treated with NIV had a minor incidence of serious complications and a better ICU and 90 days survival.

Some small, nonrandomised trials have been performed using NIV for weaning trauma patients with hypoxemic respiratory failure (26) and non-COPD patients with persistent acute respiratory failure after early extubation (27). However, based on these studies, we cannot recommend NIV as a weaning strategy in severe hypoxic patients.

Through all these studies, strong support for NIV as a weaning strategy in the subgroup of COPD patients who experienced a failure of a SBT was provided, with the effect of reducing mortality, minimizing ventilatorassociated pneumonia, and shortening the length of hospital stay.

The poor tolerance of facial interfaces and the possible difficulties in fitting masks, has been considered as possible causes for failure of NIV in the weaning process (28). Lately, the helmet has been considered as a potential alternative for NIV. In a recent case report Klein et al. (29) described the possibility to rapidly wean a COPD patients intubated for an acute respiratory failure by using the helmet during NIV. They showed good patient compliance, lower costs and nurse workload and mostly, fewer complications related to sedation and infections compared to invasive ventilation. Further studies will be needed to assess the role of routine helmet NIV in IMV weaning.


Post-extubation failure is a major clinical problem in intensive care units (ICU) (30). Extubation attempts may fail in as many as 23.5% of patients and the inhospital mortality of these patients may reach 30-40%. The cause of extubation failure and the time elapsed before re-intubation are independent predictors of outcome (31), (32).

Few studies have evaluated the use of NIV as a means to prevent, rather than treat post-extubation respiratory failure. Jiang et al. (33) conducted a prospective study on 93 patients randomised to receive NIV or oxygen therapy after planned or unplanned extubation. They found no difference in the re-intubation rate between the two groups. Epstein et al. (32) showed that there is a certain subset of patients whose clinical characteristics at the time of extubation may predict re-intubation. Two randomised trials from Nava and Ferrer (34), (35) were therefore performed to assess whether NIV is effective in preventing the occurrence of post-extubation failure in patients at "highest risk" when compared to standard medical treatment. Both studies showed that the groups treated with NIV had a lower re-intubation rate and a lower ICU mortality than the groups treated with standard therapy. Furthermore, one study (36) found a better 90-days survival in a subgroup of hypercapnic patients treated with NIV. To confirm the result found in this subgroup of patients, Ferrer and colleagues (36) performed a multi-centre randomized controlled trial specifically designed for patients who developed hypercapnia during an SBT. They were randomly divided in order to receive NIV or conventional oxygen therapy after a successful SBT. The primary end point was to avoid respiratory failure within 72 h after extubation. They found that respiratory failure was less frequent in the NIV arm than in the other (15% vs 25%). NIV was also independently associated with a lower risk of respiratory failure after extubation and NIV as a rescue therapy, avoided re-intubation in patients with respiratory failure. The overall 90 days mortality was significantly lower in the group of NIV (11% vs 31%).

Obesity represents another important risk factor of post extubation respiratory failure. El Sohl and colleagues (37) evaluated NIV immediately after extubation in morbidly obese patients who had been ventilated for more than 48 hours. Compared to matched control patients treated with conventional medical therapy, they found a 16% absolute risk reduction of post extubation respiratory failure and a lower need for re-intubation in the NIV group (10 in the NIV group versus 26% in controls). A shorter length of ICU stay and a reduced mortality was found only in the sub-group of hypercapnic patients treated by NIV. In summary, routine use of NIV immediately after extubation is not recommended, except for patients at high risk for extubation failure.


The use of NIV has been suggested in an attempt to avoid re-intubation in patients that show signs of "incipient" or overt respiratory failure following extubation.

Hilbert and co-workers (38) demonstrated that NIV improved the outcome of patients with COPD and postextubation hypercapnic respiratory failure when compared to conventional treatment of matched subjects, by reducing the need for endotracheal intubation, the mean duration of ventilatory assistance and the duration of ICU stay.

In a randomised controlled trial (39), patients developing Acute Respiratory Failure (ARF) within 48 hours after extubation were randomised to receive standard medical therapy alone or NIV. The authors did not find any difference in re-intubation rate, hospital mortality rate, ICU and hospital stay, despite a trend of a shorter duration of hospital stay in the NIV group. It is therefore important to underline a few comments concerning the present study. Patients were considered eligible for the study when developing respiratory distress was defined, in the present study, as a respiratory rate greater than 30/min, presence of increased respiratory rate greater than 50% from baseline rate, use of respiratory accessory muscles or abdominal paradox. These criteria could be not necessarily related to apost extubation failure. Moreover, after the first year, patients with an acute exacerbation of COPD were excluded from this study even if the randomised trial, strongly supported the use of NIV for this class of patients. Esteban et al. (40) conducted a large multicenter, randomised trial to evaluate the effect of NIV on the mortality of patients who had respiratory failure. Within the subsequent 48 hours of IMV, they were randomly assigned to either NIV or standard medical therapy. The study was stopped prematurely during an interim analysis because the authors found a higher mortality rate in the NIV group compared to the standard therapy (25% vs 14% respectively, p=0.048). However the dissimilarity appeared to be due to differences in the rate of death among the patients who required reintubation (38% in NIV group vs 22% in SMT group, p=0.06). This could correlate with the result of a longer interval between the onset of ARE and reintubation in the NIV group (p=0.02). This study was performed in an unselected group of patients, consequently the authors concluded there was the potential that selected patients (i.e. those with COPD) may still benefit from NIV, but the sample was too small to allow meaningful conclusions. As a result, the authors concluded that NIV does not improve survival and may in fact be harmful. Although selected patients in specialized centres may benefit from this therapy, specific hypothesis need to be tested prospectively. What remains unclear is a result not discussed in the paper. Of the 114 patients assigned to SMT, 28 received NIV as rescue therapy; only 7 (25%) were subsequently intubated and 3 (11%) died. This means that patients who are treated with NIV as rescue therapy had a lower rate of failure and a lower rate of death than patients treated with NIV as a first attempt (failure rate=48%, rate of death=25%). In summary, up to the present, the literature does not support the routine use of NIV to treat an incipient post-extubation respiratory failure.


The weaning process is crucial and a recent review by Epstein et al. (41) underline that the majority of studies which focused on this topic, found NIV superior to IMV. Until now, if the weaning criteria are met, confirmed evidences of real NIV efficacy have been proved only in a selected population of patients such as people with acute-on-chronic respiratory failure (COPD exacerbation) to shorten the length of invasive mechanical ventilation, the ICU stay and to avoid intubation related complications such as VAP. The role of NIV in all the other conditions (i.e. hypoxic patients, post-surgical patients) remains unclear. Randomised controlled studies have demonstrated that it may even be harmful to treat an over episode of post-extubation respiratory failure with NIV, while promising results were obtained using NIV to prevent reintubation in patients considered at risk. In the event of unplanned extubations, during the weaning period, NIV could also be considered as a good option to prevent re-intubation.

Conflict of Interest

No conflict of interest is declared by the authors.



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Paola Pierucci, Annalisa Carlucci, Annia Schreiber, Stefano Nava

Pulmonary and Critical Care Sant'Orsola and Malpighi Hospital, Bologna, Italy

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