Weaning failure in critical illness

Oxford Textbook of Critical Care (2 ed.)

Edited by: Andrew Webb , Derek Angus , Simon Finfer ,
Luciano Gattinoni , and Mervyn Singer

Publisher: Oxford University Press Print Publication Date: Apr 2016

Print ISBN-13: 9780199600830 Published online: Apr 2016
DOI: 10.1093/med/
9780199600830.001.0001

Weaning failure in critical illness  

Chapter: Weaning failure in critical illness

Author(s): Annalisa Carlucci and Paolo Navalesi

DOI: 10.1093/med/9780199600830.003.0103

Key points

◆ Weaning failure is defined as either unsuccessfull mechanical

ventilation discontinuation or extubation failure.
◆ Both are associated with increased morbidity and mortality.
◆ An impaired balance between respiratory muscles force and
respiratory system impedance (load) is the main cause of weaning
failure. Weak cough and increased upper airway resistances are
also implicated in the aetiology of extubation failure.
◆ A systematic approach to assess readiness by means of a
spontaneous breathing trial is crucial to reduce the risk of
extubation failure.

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Weaning failure in critical illness

◆ In selected cases, non-invasive ventilation and intensive

physiotherapy may facilitate discontinuation of mechanical
ventilation and avert extubation failure.

Definition and outcome

Weaning failure has been defined as either failure to discontinue

mechanical ventilation or a need for re-intubation within 48–72 hours
after extubation (extubation failure) [1].

The former is generally assessed as an inability to breath spontaneously

through an endotracheal tube for a relatively short period of time,
commonly 30–120 minutes, the so-called spontaneous breathing trial
(SBT) [1]. SBT failure is predominantly consequent to an excessive load
for the capacity of the respiratory muscles [1].

Extubation failure encompasses a more complex phenomenon. On the one

hand, it can be consequent to the incapacity to maintain the spontaneous
unassisted breathing after removal of the endotracheal tube, suggesting
an increase of the load imposed on the respiratory muscles after
extubation. On the other hand, it can be due to the inability to maintain
patent the upper airway without necessarily requiring mechanical
ventilation or to incapacity to adequately clear secretions [1].

Both discontinuation and extubation failure constitute major clinical and

economic burdens. Failure to discontinue mechanical ventilation is
associated with increased morbidity and mortality. In particular, patients
who require more than 7 days of mechanical ventilation after the first
attempt of withdrawal are characterized by a high rate of death [2].
Extubation failure is also associated with an increased risk of death,
ranging between 40 and 50% [3], which is correlated with the aetiology of
extubation failure and the delay in re-intubation [4]. A high incidence of
pneumonia and clinical deterioration before re-intubation are considered
to play a predominant role in worsening outcome [1,2,3]. Table 103.1
summarizes the major causes of weaning failure.

Table 103.1 Causes of weaning failure

Weaning failure

MV discontinuation failure Extubation failure

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Weaning failure in critical illness

Causes Increased load Deteriorated force/

(respiratory system load balance
impedance): Increased upper
◆ Increased airway airway resistance:
resistance ◆ Laryngeal
◆ Reduced respiratory inflammation
system compliance ◆ Laryngeal
◆ PEEPi oedema
◆ Tracheal
Decreased respiratory obstruction
muscle force: (stenosis,
◆ Neuromuscular granuloma)
disease
Inability to clear
◆ ICU-acquired CINM
secretions
◆ Prolonged controlled
MV
◆ Hyperinflation
◆ Poor nutritional status

Cardiac dysfunction
Cerebral dysfunction:

◆ Altered consciousness
◆ Psychological and
psychiatric disorders
(delirium, depression)
◆ Sedation

MV, mechanical ventilation; PEEPi, auto- or intrinsic positive end-

expiratory pressure; ICU, intensive care unit; CINM, critical illness
neuro-myopathy.

Epidemiology

The time for weaning accounts for 40–50% of the total

duration of mechanical ventilation, depending on the reason for initiating
mechanical ventilation [1]. In a recent observational multicentre study
including 2714 intubated patients who met criteria for weaning
readiness, 45% failed at least one attempt. Of these patients, 39% were
extubated within 7 days (difficult weaning) and 6% after 7 days
(prolonged weaning) after the first attempt [2].

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Weaning failure in critical illness

Extubation failure is reported to be as high as 15–18% of planned

extubations; about one-third of extubation failures occurs within the first
12 hours and approximately two-thirds within the first 24 hours [1,4].

Causes of failure of mechanical ventilation

discontinuation

Readiness for discontinuation of mechanical ventilation is commonly

assessed, when overall clinical stability is achieved, which implies that all
the acute problems are overcome, the patient is haemodynamically
stable, a high FiO2 is not required, positive end-expiratory pressure
(PEEP) values not exceeding 5 cmH2O are used, and comfortable
breathing and adequate gas exchange are obtained with no or minimal
(7–8 cmH2O) inspiratory support [1].

Discontinuation failure may depend on a multiplicity of factors and is

often consequent to more than one single cause. Irrespective of the
underlying disorder leading to the need for mechanical ventilation, the
most common mechanism is an unfavourable balance between the force
generating capacity of the respiratory muscles and the load they must
face [1,5]. Any treatment able to reduce the load and/or to augment
muscle force may favour discontinuation success [5]. A highly
unfavourable unbalance between force and load represents the most
common cause of early SBT failure, which is sometimes unpredictable
when the patient receives even a minimal assistance. Indeed, an
inspiratory support as low as 5 cmH2O can reduce the respiratory work
by nearly 40% [6].

Failure can occur later in the course of the trial. Sometimes an

inspiratory load that is tolerable at the beginning of the trial increases
throughout the SBT. In a series of chronic obstructive pulmonary disease
(COPD) patients undergoing SBT, Jubran et al. found that that airway
resistance significantly increased throughout the trial (from 9 ± 2 cmH2O
to 15 ± 2 cmH2O) within 45 minutes in the patients who failed, while it
did not vary in those who succeeded [7]. The increase in pulmonary
resistance in the course of the SBT may suggest a mechanism related to
the cardio-pulmonary interaction [7]. In fact, a remarkable increase of the
inspiratory negative intrathoracic pressure swings leads to a rise in both
cardiac preload (i.e. venous return) and afterload (i.e. left ventricular
transmural pressure), which may cause pulmonary congestion and
oedema of the bronchial wall, and consequently worsens pulmonary
mechanics and increases the magnitude of the load imposed on the
respiratory muscles. Thus, an unrecognized or latent cardiac dysfunction
can become evident when interrupting the ventilator support to resume
spontaneous breathing [1].

A critical reduction of the force-generating capacity of the respiratory

muscles may also lead to a failure to discontinue mechanical ventilation.
This is quite common in mechanically-ventilated patients with
neuromuscular diseases. Besides, the respiratory muscles can be

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Weaning failure in critical illness

weakened because of ICU-acquired critical illness neuromyopathy

(CINM), which may occur as a complication of sepsis and multiple organ
failure, hyperglycaemia and in patients receiving neuromuscular blocking
agents for days, aminoglycosides, and/or steroids [8]. Also, diaphragm
disuse atrophy complicates the clinical course of patients undergoing
controlled mechanical ventilation. After 5–6 days of controlled mechanical
ventilation the force-generating capacity of the diaphragm was found to
be reduced by two-third [9]. This was associated with histobiochemical
signs of diaphragmatic injury and atrophy, with a significant correlation
between duration of mechanical ventilation and magnitude of
diaphragmatic injury [9]. A physiological study performed on patients
who had received prolonged mechanical ventilation showed that the
recovery from inspiratory muscle weakness is a major determinant of
‘late’ weaning success [10]. A poor nutritional status may also play a role
in decreasing muscle force [1]. Finally, in patients with lung
hyperinflation because of diseases causing prolonged expiratory time
constant and/or expiratory flow limitation, such as asthma and COPD, the
force-generating capacity of the diaphragm is reduced because the
muscle fibres, though well-functioning, are already shortened at end
expiration [11].

Cerebral dysfunctions affecting the level of consciousness [12] or

determining psychological or psychiatric disorders, such as ICU-acquired
delirium and depression may contribute to discontinuation failure [1].

Causes of extubation failure

Any of the causes of discontinuation failure may also be

implicated in the pathogenesis of extubation failure. This holds especially
true whenever readiness for discontinuation of mechanical ventilation is
not systematically tested with a SBT [6,12].

In some cases, after removal of the endotracheal tube, the inspiratory

load may rise up consequent to an increase in upper airway resistance
due to laryngeal inflammation and oedema. However, a physiological
study showed that the work of breathing necessary to overcome
supraglottic airway resistance soon after extubation is on average rather
close to that formerly imposed by the endotracheal tube [13]. In patients
with prolonged intubation complications leading to tracheal obstruction,
such as tracheal stenosis, granuloma, and tracheomalacia may also cause
extubation failure [14].

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Weaning failure in critical illness

In patients successfully completing SBT, weak cough and the inability to

clear secretions may afterwards cause extubation failure not predicted by
the conventional parameters used to assess readiness for discontinuation
of mechanical ventilation [1]. In a prospective study on 115 patients who
passed the SBT and were ready to be extubated, a peak expiratory flow
during glotic-free cough ≤60 L/min was associated with a five-fold
increase in extubation failures [15].

Preventing strategies

Although conventionally considered as a specific period of the

time spent on mechanical ventilation, the process of weaning should start
as soon as mechanical ventilation is instituted and include any
intervention aimed at facilitating resumption of spontaneous breathing
through the native airway. If, on the one hand, discontinuation of
mechanical ventilation and extubation should be considered as soon as
possible to avoid the consequences of unnecessary prolonged intubation,
on the other hand, because of their detrimental consequences, both
discontinuation and extubation failures must be prevented.

The methodology used to assess readiness for withdrawal of mechanical

ventilation and extubation is crucial. A systematic approach to determine
readiness utilizing standardized meaningful physiological and clinical
criteria may improve weaning and extubation outcome [12]. Assessing
readiness by means of the SBT represents a cornerstone of this process.
Anyhow, the wide variability of the methods used to perform the SBT, i.e.
T-piece trial, minimal levels of CPAP and low values of inspiratory
support, may affect the SBT outcome [2].

Based on the aforementioned experimental data, although never proved

by clinical studies, a rapid switch from controlled to assisted modes of
mechanical ventilation should in principle reduce the risk of diaphragm
atrophy and injury. The ventilator settings are also important.
Unnecessarily high levels of mechanical support may result in excessively
low patient’s respiratory drive and effort, which is associated with poor
patient-ventilator interaction and increased risk of prolonged mechanical
ventilation [16]. Avoiding excessive sedation can also improve the
outcome of weaning [17].

In some patients with underlying chronic respiratory disorders intubated

for treatment of severe hypercapnic acute on chronic respiratory failure,
an early extubation followed by immediate application of non-invasive
ventilation (NIV) may help to speed up the process of discontinuation,
while reducing the risk of developing ventilator associated pneumonia
[18].

NIV can be also successfully used to decrease the re-intubation rate in

patients at increased risk of extubation failure, such as those with
underlying chronic or cardiac disorders, prior weaning failure, and
numerous comorbidities [19]. In particular, in patients who develop

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Weaning failure in critical illness

hypercapnia during the SBT, prophylactic application of NIV at extubation

reduces the rate of re-intubation and mortality [20].

In patients at risk of developing extubation failure because of ineffective

clearing of secretions, intensive physiotherapy may be helpful. The use of
mechanical cough assistance may prevent extubation failure consequent
to sputum retention, especially in patients with weak cough [1].

References
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personal use (for details see Privacy Policy and Legal Notice).

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Weaning failure in critical illness

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