REVIEW

CURRENT
OPINION Weaning from the ventilator and extubation in ICU
Arnaud W. Thille a,b, Irene Cortés-Puch a, and Andrés Esteban a

Purpose of review
The decision to extubate is a crucial moment for intubated patients. In most cases, the transition to
spontaneous breathing is uneventful, but in some patients, it implies a more challenging decision. Both
extubation delay and especially the need for reintubation are associated with poor outcomes. We aim to
review the recent literature on weaning and to clarify the role of certain interventions intending to help in
this process.
Recent findings
Cardiac dysfunction is probably one of the most common causes of weaning failure. Several studies have
evaluated the ability of B-natriuretic peptides and echocardiographic tools to predict weaning outcome due
to cardiac origin, attempting to prevent its failure. Noninvasive ventilation may have a potential benefit in
preventing respiratory failure after extubation of hypercapnic patients, although more studies are needed to
define a target population.
Summary
Current research is focusing on preventing extubation failure, especially in the most challenging cases. The
use of weaning protocols – written or computerized – attempts to early identify patients who are able to
breathe spontaneously and to hasten extubation, resulting in better outcomes. Nevertheless, individualized
care is needed in the most vulnerable patients, trying to prompt weaning without exposing patients to
unnecessary risks.
Keywords
extubation, ICU, spontaneous breathing trial, weaning from mechanical ventilation

INTRODUCTION THE FIRST STEP: TO BREATHE ON ONE’S

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 independ-
&&
ently 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 [10]. In a multicentre trial on the
use of noninvasive ventilation (NIV) to treat post-
extubation 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 stand-
ard group versus more than 12 h in the NIV group
[11].
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 follow-
ing criteria [12]: 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
a
Departamento de Cuidados Intensivos, Hospital Universitario de
Getafe, CIBER de Enfermedades Respiratorias, Madrid, España and
b
Réanimation Médicale, Centre Hospitalier Universitaire de Poitiers,
Université de Poitiers, Poitiers, France
Correspondence to Andrés Esteban, MD, PhD, Unidad de Cuidados
Intensivos, Hospital Universitario de Getafe, carretera de Toledo Km.
12.5, Getafe 28905, Madrid, España. Tel: +34 916834982; e-mail:
aesteban@ucigetafe.com
Curr Opin Crit Care 2013, 19:57–64
DOI:10.1097/MCC.0b013e32835c5095

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 Respiratory system

expected but nearly 50% of the ventilated patients

KEY POINTS

Failure of planned extubation occurs in about 10–20%
of cases, and patients who fail extubation have a high
mortality ranging around 25–50%.

Cardiac dysfunction, which could be detected using
B-natriuretic peptides or echocardiography, is probably
one of the most common causes of weaning failure.

Research efforts must focus in better identifying this
high-risk population who may benefit from noninvasive
ventilation in the postextubation period.
&&
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 [12]: ‘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
&&
[7 ,14–16] and up to 70% of the patients ventilated
for more than 2 days [15]. 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. [19] 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 [19] by increasing preload and afterload [20].
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 [23]. Several studies found that
high basal levels or an increase in B-type natriuretic
peptides measured at the end of spontaneous breath-
&
ing trial [24,25 ] could be related to weaning failure
due to cardiac origin or predict postextubation respir-
&
atory distress [26 ]/extubation failure [27]. A multi-
&&
centre 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 conser-
vative fluid strategy shortened the duration of mech-
anical ventilation in patients with acute lung injury
[29]. Echocardiographic indices (E/A, E/Ea ratio)
allow the detection of pulmonary occlusion artery
pressure elevation during the weaning trial [30].

Reintubation rate
Rate in %
In-ICU mortality rate of reintubated patients
60
50
50
43
40 35
33
30 27 26 28

19
20 15 14 15 16
13
10
10

0
Thille Esteban Esteban Epstein Vallverdú Peñuelas Frutos-Vivar
2011 [2] 1997 [3] 1999 [4] 1997 [5] 1998 [6] 2011 [7] 2011 [8]
N = 168 N = 397 N = 453 N = 287 N = 148 N = 2714 N = 1142

FIGURE 1. Rates of reintubation and in-ICU mortality of reintubated patients from studies focusing on weaning from
mechanical ventilation in ICU. Reintubation rate (white histograms) ranged from 10 to 19% of all planned extubations and
in-ICU mortality rate of reintubated patients (black histograms) ranged from 26 to 50% of them.

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 Weaning from the ventilator and extubation in ICU Thille et al.

Table 1. Proportion of patients, rates of intubation and outcomes according to the duration of weaning process
classified as simple, difficult and prolonged
Simple weaning Difficult weaning Prolonged weaning

Proportion of patients
Peñuelas et al. [7 ] 55% (N ¼ 1502) 39%(N ¼ 1058) 6% (N ¼ 154)
&&

Funk et al. [14] 59% (N ¼ 152) 26% (N ¼ 68) 14% (N ¼ 37)

Tonnelier et al. [15] 30% (N ¼ 34) 40% (N ¼ 47) 30% (N ¼ 34)
Sellares et al. [16] 43% (N ¼ 78) 39% (N ¼ 70) 18% (N ¼ 33)
Reintubation rates
Peñuelas et al. [7 ] 10% 10% 16%
&&

Funk et al. [14] 13% 7% 5%

Tonnelier et al. [15] 0% 9% 24%
Sellares et al. [16] 1% 19% 33%
In-ICU mortality rates
Peñuelas et al. [7 ] 7% 7% 13%
&&

Funk et al. [14] 3% 1% 22%

Tonnelier et al. [15] 0% 2% 18%
Sellares et al. [16] 13% 11% 42%


P < 0.05 between prolonged weaning and simple or difficult weaning.

Several studies suggest that patients who have dias-
tolic 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 echo-
cardiography.
However, the increase in capillary pulmonary
pressure occurring during the transition from mech-
anical to spontaneous ventilation depends on the
type of weaning trial. The standard test for extuba-
tion readiness is the spontaneous breathing trial
(SBT) performed using the T-tube by simply discon-
necting the patient from the ventilator and provid-
ing 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 con-
tinuously monitored on the ventilator screen.
Cabello et al. [21] 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 dys-
function [21]. 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 [3], 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 [34]. Overall, this suggests that
either the T-tube trial slightly delays weaning read-
iness 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 endo-
tracheal tube [35]. 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 [36]. Therefore, addition of even low levels of
pressure support may lead to underestimate the risk
of extubation failure in some patients [37].
The two goals of a weaning trial are the early
detection of patients who are able to breathe with-
out a ventilator, in order to avoid complications of
prolonged mechanical ventilation and the identifi-
cation of patients who are not able to breathe spon-
taneously 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 [4]. However, a more challenging SBT

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 Respiratory system

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 respir-
atory 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 [39]. A randomized controlled trial has
revealed that automated-weaning system shortened
overall ventilation time as compared with usual care
&&
[40], 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 proto-
col in units with a high nurse ratio and staffing [42],
most studies that have compared automated-wean-
ing 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 [43].
Factors that have been associated with extuba-
&&
tion 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
[48]. 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 reintu-
bation 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 [49]. 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 [50] and can affect both peripheral and
respiratory muscles [51] leading to prolonged

Table 2. Potential risk factors of extubation failure

Number of episodes
Study of extubation failure Risk factors of extubation failure

Thille et al. [2 ] N ¼ 26 Age >65 years or underlying chronic cardiorespiratory disease

&&

Epstein et al. [5] N ¼ 40 Age, higher severity at time of weaning and acute respiratory failure of cardiac origin
Vallverdu et al. [6] N ¼ 23 Patients intubated for neurologic disorders
Frutos-Vivar et al. [9] N ¼ 121 Pneumonia as the reason for intubation, high rapid shallow breathing index,
positive fluid balance
Chien et al. [27] N ¼ 19 Increase in B-type natriuretic peptide during a spontaneous breathing trial
Namen et al. [44] N ¼ 44 f/VT < 105, paO2/FiO2 < 200 mmHg, Glasgow Coma Score <8
Mokhlesi et al. [45] N ¼ 16 Abundant endotracheal secretions, Glasgow Coma Score 10, pCO2 44 mmHg
during spontaneous breathing trial
Smina et al. [46] N ¼ 13 Peak expiratory flow 60 l/min and rapid shallow breathing index 100
Khamiees et al. [47] N ¼ 18 Moderate or abundant endotracheal secretions, none or weak cough strength,
haemoglobin 10 g/dl

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 Weaning from the ventilator and extubation in ICU Thille et al.
weaning [51–53] and a higher risk of extubation
&&
failure [53]. A recent study [54 ] showed that dia-
phragm dysfunction assessed by ultrasonography
was associated with weaning failure. Diaphragm dys-
function 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 pres-
sure exerted by the endotracheal tube and is favoured
by the conditions of intubation and the duration of
mechanical ventilation [55]. 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 [60]. 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 postextuba-
tion 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 [61]. 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 focus-
ing on postextubation stridor [60]. In this latter
study, administration of methylprednisolone prior
to extubation reduced the incidence of stridor and
the rate of reintubation due to laryngeal oedema [60].
Recently, it has been found that a majority of patients
ventilated more than 24 h exhibited laryngeal
lesions, suggesting that this may favour postextuba-
tion respiratory distress by increasing work of breath-
ing 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 [10].
NONINVASIVE VENTILATION IN THE
POSTEXTUBATION PERIOD
The use of NIV to treat postextubation respiratory
distress or as a prophylactic measure to avoid respir-
atory distress needs to be distinguished. The
literature suggests that prophylactic NIV after extu-
bation may be useful to prevent acute respiratory
failure in selected populations [62–64], whereas
NIV employed for treating postextubation acute
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respiratory failure has no proven benefit [65] and
can even increase mortality by delaying reintuba-
tion [11]. However, NIV could reduce the risk of
reintubation in postoperative patients after major
elective abdominal surgery [66] or lung resection
[67], and could even reduce mortality in this latter
group. Indications and results of postextuba-
tion 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. [62] found that the use of NIV in patients at
a high risk resulted in a reduction for the need of
reintubation. Another study [63] 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 [64]. 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 extuba-
tion 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 recom-
mended 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.
www.co-criticalcare.com 61
 Respiratory system

Table 3. Studies evaluating the impact of noninvasive ventilation on outcome after planned extubation

Dose of NIV Reintubation (%) Mortality (%)

Study Number of patients Indication of NIV (duration) NIV versus O2 NIV versus O2

Esteban 114 NIV-107 standard Therapeutic By sessions of 4 h 48 versus 48% In ICU:

et al. [11] (P ¼ 0.99)
Patients with 25 versus 14%
postextubation ARF (P ¼ 0.048)
Nava 48 NIV-49 standard Prophylactic >8 h a day during 8 versus 24% In ICU:
et al. [62] the first 2 days (P ¼ 0.03)
Patients with prior failure 6 versus 18%
of SBT, paCO2>45 mmHg, (P ¼ 0.06)
cardiac failure, comorbidities
Ferrer 79 NIV-83 standard Prophylactic 19 h during the first 11 versus 22% In ICU:
et al. [63] 24 h (P ¼ 0.12)
Patients with age >65 years, 3 versus 14%
APACHE II >12 or cardiac (P ¼ 0.01)
failure as cause of intubation
Ferrer 54 NIV-52 standard Prophylactic 18 h during the first 11 versus19% In hospital:
et al. [64] 24 h (P ¼ 0.37)
Patients with pCO2 >45 mmHg 11 versus 22%
during SBT (P ¼ 0.25)
Keenan 39 NIV-42 standard Therapeutic Continue during 12 h 72 versus 69% In ICU:
et al. [65] (P ¼ 0.79)
Patients with postextubation ARF 15 versus 24%
(P ¼ 0.34)
Squadrone 104 NIV-105 standard Therapeutic Continue during 19 h 1 versus 10% In hospital:
et al. [66] (P < 0.01)
Patients with ARF after 0 versus 3%
abdominal surgery (P ¼ 0.12)
Auriant 24 NIV-24 standard Therapeutic 14 h a day during the 21 versus 50% In hospital:
et al. [67] first 2 days (P ¼ 0.03)
Patients with ARF after 12 versus 37%
thoracic surgery (P ¼ 0.04)
Su et al. 202 NIV-204 standard Prophylactic At least 12 h 10 versus 8% In ICU:
[68 ] (P ¼ 0.37)
&&

All planned extubation 1 versus 1%

(P ¼ 0.64)

NIV was prophylactic, that is systematically applied after extubation, or therapeutic, that is only applied in case of postextubation acute respiratory failure. ARF,
acute respiratory failure; NIV, noninvasive ventilation; SBT, spontaneous breathing trial.

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Volume 19
Number 1
February 2013