Thille, Arnaud W.a,b; Cortés-Puch, Irenea; Esteban, Andrésa
The day of extubation is a critical moment in the ICU stay. Despite meeting all weaning criteria and succeeding in a weaning trial, failure of planned extubation occurs in about 10–20% of cases [1,2▪▪,3–6,7▪▪,8▪,9], and patients who fail extubation have a high mortality ranging around 25–50% [2▪▪,3–6,7▪▪,8▪] (Fig. 1). Although this high mortality rate may be ascribable to a greater severity at the time of extubation, there is some evidence that extubation failure and/or reintubation can directly worsen the patients’ outcome independently of their underlying severity [2▪▪,8▪]. The timing of reintubation also seems to influence the outcome, given that the mortality rate increases in proportion to the delay between extubation and reintubation . In a multicentre trial on the use of noninvasive ventilation (NIV) to treat postextubation respiratory distress, mortality was found higher in the group using NIV, and the only result that could explain the difference in mortality was the delay in reintubation: around 2 h in the standard group versus more than 12 h in the NIV group .
THE FIRST STEP: TO BREATHE ON ONE'S OWN WITHOUT THE VENTILATOR
An international consensus conference on weaning emphasized that the first weaning trial must be performed as soon as the patient meets the following criteria : resolution of disease for which the patient was intubated, cardiovascular stability with no need or minimal vasopressors, no continuous sedation and adequate oxygenation defined as paO2/FiO2 of at least 150 mmHg with positive end-expiratory pressure (PEEP) up to 8 cmH2O. This last point is crucial and could explain the higher failure rates of the first weaning trial reported in the more recent studies [7▪▪,13–16]. In earlier studies [6,17,18], patients were screened later to pass a weaning trial, which was not performed until the paO2/FiO2 was above 200 mmHg with PEEP 5 cmH2O or less. This conference also proposed to categorize ventilated patients into three groups according to the difficulty of their weaning process : ‘simple weaning’ includes patients who succeed the first weaning trial and are extubated without difficulty, ‘difficult weaning’ includes patients who fail the first weaning trial and require up to three trials or 7 days to achieve successful weaning and ‘prolonged weaning’ includes patients who require more than 7 days of weaning after the first weaning trial. According to the literature [6,17,18], approximately 70% of mechanically ventilated patients fall into the simple weaning group. However, four recent studies have evaluated the proportion of patients in each group using this strategy of daily screening and early weaning (Table 1) [7▪▪,14–16]. The failure rate of the first weaning trial in these studies was not 30% as expected but nearly 50% of the ventilated patients [7▪▪,14–16] and up to 70% of the patients ventilated for more than 2 days . In these four studies, only prolonged weaning was independently associated with an increased mortality [7▪▪,14–16], and the risk of reintubation tended to increase in this group [7▪▪,16] although the difference was not significant.
In 1988, Lemaire et al. demonstrated the development of pulmonary oedema and subsequent respiratory distress shortly after the beginning of spontaneous breathing, leading to unsuccessful weaning. Switching from mechanical to spontaneous ventilation can unmask latent left ventricular heart failure  by increasing preload and afterload . Cardiac dysfunction is probably one of the most common causes of weaning failure [21,22] and should be diagnosed by all means because it can be effectively treated by diuretics and/or vasodilators and sometimes even by coronary angioplasty in case of cardiac ischaemia . Several studies found that high basal levels or an increase in B-type natriuretic peptides measured at the end of spontaneous breathing trial [24,25▪] could be related to weaning failure due to cardiac origin or predict postextubation respiratory distress [26▪]/extubation failure . A multicentre study [28▪▪] using diuretics guided by brain natriuretic peptide (BNP) measurements allowed shortening duration of weaning suggesting that negative fluid balance using diuretics could hasten extubation. Also, it has been shown in a large randomized controlled trial that the use of a conservative fluid strategy shortened the duration of mechanical ventilation in patients with acute lung injury . Echocardiographic indices (E/A, E/Ea ratio) allow the detection of pulmonary occlusion artery pressure elevation during the weaning trial . Several studies suggest that patients who have diastolic dysfunction, as indicated by an increase in E/Ea ratio with normal systolic function, could be at a high risk of weaning failure [31,32▪]. Interestingly, a recent innovative study [33▪] found that the loss of lung aeration measured using pulmonary echography may be more helpful in predicting postextubation respiratory distress than BNP measurement or echocardiography.
However, the increase in capillary pulmonary pressure occurring during the transition from mechanical to spontaneous ventilation depends on the type of weaning trial. The standard test for extubation readiness is the spontaneous breathing trial (SBT) performed using the T-tube by simply disconnecting the patient from the ventilator and providing additional oxygen. The weaning trial can also be performed without disconnecting the patient from the ventilator using a low level of pressure support, although respiratory rate and tidal volume are continuously monitored on the ventilator screen. Cabello et al. compared three modalities of trial before extubation in a selected population of patients with difficult weaning. A SBT on a T-tube was compared with a low pressure support level (7 cmH2O) with or without PEEP. They showed that the patient effort was higher during a T-tube trial than during a pressure support trial. During the pressure support trial, addition of PEEP further decreased both the effort and capillary pulmonary pressure, suggesting that weaning trials must be done without PEEP to unmask latent cardiac dysfunction . In a large, multicentre, randomized controlled trial, although the proportion of patients who failed the first trial was higher using T-tube than using a pressure support trial , the rate of patients who were extubated after 48 h was similar when the weaning trial was performed using T-tube or pressure support trial. Other studies suggested that some patients who failed a T-tube trial could immediately succeed a pressure support trial [21,34] and could be extubated without an increased risk of extubation failure . Overall, this suggests that either the T-tube trial slightly delays weaning readiness due to higher respiratory muscle effort or, on the contrary that the pressure support trial may expose to a higher risk of reintubation. The use of pressure support was justified by reducing the imposed work of the ventilator circuit and the endotracheal tube . However, the postextubation period is characterized by a relatively high upper airway resistance and an overall work of breathing similar before and after removal of endotracheal tube . Therefore, addition of even low levels of pressure support may lead to underestimate the risk of extubation failure in some patients .
The two goals of a weaning trial are the early detection of patients who are able to breathe without a ventilator, in order to avoid complications of prolonged mechanical ventilation and the identification of patients who are not able to breathe spontaneously to avoid extubation failure and its potential complications. In the vast majority of patients, the main objective is the early detection of weaning trial success and a short trial is fully effective . However, a more challenging SBT using prolonged T-tube trial might be especially interesting in a population in which the risk of reintubation is particularly high [2▪▪,5].
Regardless of the weaning strategy used in ICUs, early identification of patients who are able to breathe spontaneously results in better outcomes, and it has been clearly demonstrated that the use of a weaning protocol, including daily screening followed by weaning trial and systematic extubation if successful, shortened intubation time without an increased risk of reintubation [13,38]. This strategy is usually caregiver-driven but can also be computer-driven by an automatic system, keeping the patient in a ‘respiratory comfort zone’ on the basis of respiratory rate, tidal volume and end-tidal CO2. This automated-weaning system allows to facilitate the weaning by gradually decreasing the level of pressure support and to perform a pressure support weaning trial when the lower level of assistance has been reached, suggesting to the clinician that the patient can be separated from the ventilator when this test is successful . A randomized controlled trial has revealed that automated-weaning system shortened overall ventilation time as compared with usual care , and a recent study [41▪▪] found similar results in postsurgical patients, but only in those after cardiac surgery. Although automated weaning could have no beneficial results compared to a nurse-driven protocol in units with a high nurse ratio and staffing , most studies that have compared automated-weaning system versus standard weaning found either reduction or similar duration of intubation time.
SECOND STEP: TO BREATHE WITHOUT THE ENDOTRACHEAL TUBE
The SBT is meant to accurately predict the tolerance of unassisted breathing after extubation. However, it does not predict well the consequences of the tube removal in terms of upper airway patency and lower airway protection, removal of secretions and, ultimately, the ability to sustain spontaneous breathing. Interestingly, it has been suggested that extubation success may be well correlated to the patient's subjective perception of his ability to breathe without the ventilator .
Factors that have been associated with extubation failure include age [2▪▪,5,9], primary reason for intubation [5,6,9], neurological dysfunction [6,44,45], cough efficacy [46,47] and amount of secretions [27,45,47] (Table 2). Although some studies found that a depressed mental status was a good predictor of extubation failure [44,45], some neurosurgical comatose patients with a GCS of 8 or less and even 4 or less could be extubated without delay and without an increased risk of reintubation . Most studies point out that usual ICU severity scores are not good predictors of extubation failure even when measured at the time of extubation [2▪▪,45]. Recently, patients older than 65 years who had underlying chronic cardiac or respiratory diseases were identified as a subset of patients at a high risk of extubation failure with a rate of reintubation of 34% compared with only 9% for the other patients [2▪▪].
Extubation failure may be caused by hidden factors such as delirium, prolonged sedation or ICU-acquired weakness. Delirium is frequent in the ICU and is a predictor of higher mortality . Acute brain dysfunction may favour extubation failure through disturbance of consciousness, agitation or sedation induced by medications, aspiration or refusal of treatment. ICU-acquired paresis occurs in about 25% of patients after prolonged mechanical ventilation  and can affect both peripheral and respiratory muscles  leading to prolonged weaning [51–53] and a higher risk of extubation failure . A recent study [54▪▪] showed that diaphragm dysfunction assessed by ultrasonography was associated with weaning failure. Diaphragm dysfunction at the time of extubation may correlate clinically with alveolar hypoventilation and cough inefficacy, subsequently increasing the risk of failure.
UPPER AIRWAY OBSTRUCTION AFTER EXTUBATION
Postextubation laryngeal oedema is due to the pressure exerted by the endotracheal tube and is favoured by the conditions of intubation and the duration of mechanical ventilation . Laryngeal oedema occurs in about 5–15% of the patients [56–60], more often in women [56,60], with a low patient's height/tube diameter ratio . A good marker of severe laryngeal oedema is the absence of air leak when the sealing balloon cuff of the endotracheal tube is deflated. A low cuff-leak volume (<110–130 ml) measured by the difference between the insufflated volume and the expired volume in assist-control volume mode after deflating the balloon may be useful in identifying patients at risk for postextubation stridor [57,58]. However, although the absence of air leak is a good predictor of laryngeal oedema, the presence of detectable leak does not rule out the occurrence of upper airway obstruction . Upper airway obstruction was found to be the cause of extubation failure in 7–20% of the cases [3,10,61], but reached 38% in a large multicentric study focusing on postextubation stridor . In this latter study, administration of methylprednisolone prior to extubation reduced the incidence of stridor and the rate of reintubation due to laryngeal oedema . Recently, it has been found that a majority of patients ventilated more than 24 h exhibited laryngeal lesions, suggesting that this may favour postextubation respiratory distress by increasing work of breathing and/or favouring aspiration through glottis dysfunction. Interestingly, unlike other causes, when reintubation is purely linked to transient laryngeal oedema, it does not seem to be associated with a poor prognosis .
NONINVASIVE VENTILATION IN THE POSTEXTUBATION PERIOD
The use of NIV to treat postextubation respiratory distress or as a prophylactic measure to avoid respiratory distress needs to be distinguished. The literature suggests that prophylactic NIV after extubation may be useful to prevent acute respiratory failure in selected populations [62–64], whereas NIV employed for treating postextubation acute respiratory failure has no proven benefit  and can even increase mortality by delaying reintubation . However, NIV could reduce the risk of reintubation in postoperative patients after major elective abdominal surgery  or lung resection , and could even reduce mortality in this latter group. Indications and results of postextubation NIV on outcome are summarized in Table 3[11,62–67,68▪▪].
In a recent study [68▪▪] including more than 400 nonselected ICU patients, the rate of reintubation was similar in patients treated with prophylactic NIV or oxygen therapy, and studies that have shown beneficial effects of prophylactic NIV included patients considered at a high risk of reintubation. Nava et al. found that the use of NIV in patients at a high risk resulted in a reduction for the need of reintubation. Another study  found that use of NIV averted postextubation respiratory failure and decreased ICU mortality in hypercapnic patients, although the reintubation rate was surprisingly not significantly decreased. More recently, NIV was found to be effective in preventing postextubation respiratory failure in patients having hypercapnia at the end of the SBT . A significantly lower 90-day mortality rate was found in this study, although the use of this late outcome instead of in-ICU or in-hospital mortality is controversial. Prophylactic NIV should probably be systematically applied immediately after extubation of hypercapnic patients, although the potential benefit may differ whether it is performed in the setting of a specialized unit rather than in a standard one. Furthermore, research efforts must focus in better identifying this high-risk population who may benefit from NIV.
Finally, a few studies [69–71,72▪▪] reported the use of NIV as a weaning method to hasten extubation in chronic obstructive pulmonary disease patients difficult-to-wean despite the failure of a weaning trial. A recent multicentre study [72▪▪] compared conventional weaning versus extubation followed by NIV or standard oxygen therapy in patients who failed a 2-h T-tube trial. NIV reduced the risk of postextubation respiratory failure, but both rates of weaning success and reintubation were similar regardless of the weaning method. The time of intubation was shortened, but the overall time on mechanical ventilation taking into account NIV was even more prolonged in this group [72▪▪]. Given the results, this method of weaning cannot be recommended in clinical practice. Moreover, because patients were included after failure of a 2-h SBT, it would be interesting to know whether they would have succeeded an easier pressure support trial, meaning that this ‘hard’ and prolonged weaning trial could have delayed extubation.
The results of large randomized controlled trials give an overall incidence of extubation failure relatively ‘low’ (10–20%) for the general ICU population. However, the individual risk of reintubation can become unacceptably high in some at-risk populations with an extremely high mortality in case of extubation failure.
Conflicts of interest
The authors have not disclosed any potential conflict of interest.
No funding or support was received for this study.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 72).
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