Failure of weaning:

Weaning failure

Weaning failure is defined as the failure to pass a spontaneous-breathing trial or

the need for reintubation within 48 hours following extubation
predicting success is important to reduce rates of reintubation
reintubation is associated with a 7-11x increase in hospital mortality
reintubation rates of 10 to 15% are typical for most well-run ICUs (a target of 0%
is unrealistic and would lead to prolonged ventilation)

According to the European Respiratory Society (ERS) Task Force,

Classification of weaning by duration

Simple ventilator discontinued after the first assessment

Difficult ventilator discontinued from 27d after initial assessment
Prolonged ventilator discontinued in >7d after initial assessment

Weaning is a two step process:

weaning parameters are assessed (wean screen)

perform weaning trial

Screening for ventilator weaning should be performed daily

Numerous objective indices have been studied to predict failure of ventilator

liberation or weaning.
None of these indexes alone are sufficiently sensitive and specific to be useful
in predicting the success of ventilation discontinuation in an individual patient.

They are not recommended for routine use, the Spontaneous breathing trial (SBT) remains the
de facto gold standard test.

INDICES THAT PREDICT SUCCESSFUL VENTILATOR DISCONTINUATION

Respiratory rate <30 breaths per minute

Tidal volume >5 ml/kg or >325 mL
FVC >15 mL/kg predicts success
Minute ventilation <15 L/min
Normal 5 6 L/min
Patient unlikely to wean if > 15 L/min
 Maximum inspiratory pressure (PImax) < -30 cmH20
Measure of respiratory muscle strength
Normal -90 to -120 cmH2O

Rapid shallow breathing index (RSBI) = f/VT <105 breaths/min/L

the ratio of respiratory rate : tidal volume
often used in conjunction with SBT to determine if it should continue
some evidence that its use in protocols delays ventilator discontinuation
CROP index (dynamic compliance, respiratory rate, oxygenation, maximum
inspiratory pressure index) >13
Cdyn x PImax x (PaO2/PAO2)/f
>13 good
Cdyn = dynamic compliance
IWI (integrative weaning index) >25
(CRS x SaO2)/(f/VT)
CRS = static compliance of the respiratory system
CORE index (dynamic compliance, oxygenation, rate, effort) >8
Cdyn x (PImax/P0.1) x (PaO2/PAO2)/f

the above indices focus on lung function

successful ventilar discontinuation and extubation also depends on 2 other
domains:
general medical condition (e.g. disease resolution, nutrition, anaemia,
conditioning, etc)
ability to protect airway post-extubation (extubation assessment, separate
from weaning assessment)

Spontaneous breathing trial (SBT):

METHOD

SBT involves the following steps:

It be conducted while the patient is still connected to the ventilator circuit, or the
patient can be removed from the circuit to an independent source of oxygen (T-
piece)
When using the ventilator a PS of 5 7 cmH2O and 1-5 cmH20 PEEP (so called
minimal ventilator settings) will overcome increased work of breathing through
the circuit (i.e. ETT)
If still on the ventilator the patient should have minimal ventilator settings
 Initial trial should last 30 120 minutes
If it is not clear that the patient has passed at 120 minutes the SBT should be
considered a failure
In general, the shorter the intubation time the shorter the SBT

80% of patients who tolerate this time can be permanently removed from the ventilator

CRITERIA TO STOP SBT

No single parameter should be used to judge SBT success or failure, but a combination
of the following are often used:

Respiratory rate RR >38 bpm for 5 minutes or <6bpm

SpO2 < 92%
Tidal volume < 325 mL
Heart rate: HR > 140 OR 25% above baseline OR HR<60
Blood pressure: SBP 40 mm Hg above baseline
Worsening agitation, anxiety or discomfort despite reassurance
RSBI: Most consistent and powerful predictor
-> RSBI > 105 min/L predicted failure well, but if used rigidly may slow the
weaning process

MINIMAL VENTILATOR SETTINGS

The concept of minimal ventilator settings is controversial:

Martin Tobin has argued that adding either 5 cm H2O as physiologic PEEP or
pressure support of 7 cm H2O to overcome the resistance in an endotracheal
tube (or both, as is usually done) may actually reduce the spontaneously
breathing patients workload by >40%
It has been shown experimentally that the work of breathing through an
endotracheal tube, compared to the work of breathing following extubation, is
almost identical due to upper airway edema resulting from an ETT being in place
for several days
Tobin argues for wider use of true T-piece spontaneous breathing trials,
especially in those at high risk of failed extubation and when the consequences
of failed extubation may be catastrophic
An alternative is to have the ventilator set on flow-by, with pressure support and
PEEP set at zero
There is no strong evidence in favour of any of these approaches

If patient failed SBT but passed wean screen':

 consider an extubation attempt to ensure that the irritant and loading effects (e.g.
demand-valve insensitivity/unresponsiveness) of the artificial airway are not the
cause of the SBT failure
careful reevaluation of the need(s) for ongoing ventilatory support should be
coupled with a daily reassessment for the appropriateness of repeat SBTs
Ventilatory support between SBTs should be comfortable interactive support that
does not necessarily have to be weaned
do not perform SBTs more often than daily (i.e. q24h) to avoid fatigue

The pathophysiology of weaning failure is complex and often multifactorial. Complex

clinical problems probably benefit from a structured approach. An 'ABC approach' is valuable in
training juniors in trauma management The following topics should be evaluated in a difficult-to-
wean patient airway and lung dysfunction, diaphragm dys-function ,brain dysfunction,
cardiac dysfunction, , and endocrine/metabolic dysfunctio

1) Patient airway and lung dysfunction

Factors affecting respiratory mechanics

Increased airway resistance Reduced compliance

Tube (small diameter, sputum retention) Chest wall

Central airways Edema

Tracheostomy malposition Elevated abdominal pressure

Sputum plug Pleural fluid and ascites

Corpus alienum (after trauma) Obesity

Tracheomalacia or tracheal stenosis Lung

Intrinsic positive end-expiratory

Small airways
pressure

Asthma and chronic obstructive pulmonary Alveolar filling (edema, pus, and
disease collapse)

Acute respiratory distress syndrome Pneumonia

A) Resistance:

Resistance of the upper airway should be considered in difficult weaning. Rumbak and
colleagues found that tracheal obstruction caused by tracheal injury may contribute to
weaning failure in patients who were on invasive mechanical ventilation for more than 4
weeks. Tracheal injury includes tracheal stenosis, tracheomalacia, and
granulation tissue formation. In intubated patients, the endotracheal tube could
increase airway resistance. Indeed, resistance of an endotracheal tube removed from a
patient is significantly higher than the resistance of a new tube when tested in a
laboratory setting and this is due to contamination of the tube with airway secretions. No
correlation between the duration intubation and the resistance of the tube was found.
However, in general, it is a misconception that, after extubation, upper airway
resistance decreases. In fact, the work of breathing in patients mechanically
ventilated for 5.5 days increased after extubation, and this increase was
probably due to edema of the upper airways.

Increased resistance of the small airways is a characteristic of chronic obstructive

pulmonary disease (COPD) and asthma but has been demonstrated in acute respiratory
distress syndrome (ARDS), and this latter increase was due to edema of bronchial
walls..

Diagnostic approach

Flexible bronchoscopy is the gold standard for diagnosing upper airway disease.
Patients should be disconnected from the ventilator during bronchoscopy so that the
presence of tracheomalacia can be assessed. Tracheomalacia may be treated with
(nocturnal) non-invasive ventilation or placement of endotracheal stents

The flow-time and pressure-time loops provide a qualitative assessment of the presence
of increased airway resistance and PEEPi
Figure 2

Tracings obtained from ventilator while operating in the volume-controlled mode. Flow,
pressure, and volume in time are presented from top to bottom. The dashed circle in the
upper panel shows the truncated expiratory flow tracing, indicating intrinsic positive end-
expiratory pressure (PEEP). Indeed, when expiration is interrupted (red solid arrow)
after the next inspiration, airway pressure rises (middle panel), reflecting total PEEP
(applied PEEP and intrinsic PEEP). To measure respiratory resistance, inspiratory hold
is applied (red dotted arrow), resulting in rapid decay in airway pressure from peak to
P1 and a subsequent slow decay to plateau pressure (P,plat).

Tracings obtained from ventilator while operating in the volume-controlled mode. Flow,
pressure, and volume in time are presented from top to bottom. The dashed circle in the upper
panel shows the truncated expiratory flow tracing, indicating intrinsic ...

R,aw=(PpeakPplat)/flow(normal is less than 5 cm H2O/L per second).

PEEPi is obtained by subtracting PEEPappl from PEEPtot. Unfortunately, this technique is

seldom satisfactory in spontaneously breathing patients. In those patients, the only way
that PEEPi can be measured adequately is by using an esophageal balloon.

Therapeutic strategies

In COPD patients being weaned with pressure support ventilation, appropriate setting of
the cycle-off criterion is of importance to limit PEEPi and the work of breathing,
asApplied PEEP may reduce inspiratory work of breathing imposed by PEEPi .Applied
PEEP should match the level of PEEPi, as estimated by the expiratory occlusion
technique.

Patients with asthma and COPD should be treated optimally to reduce

bronchoconstriction. The effect of bronchodilators in patients without a history of
COPD has not been tested, but if airway resistance appears elevated, latent
obstructive airway disease may be present. Attention should be paid to the optimal
delivery of inhaled medications as this will greatly influence its effect .Clinical studies
have shown that, in patients with COPD, the bronchodilating effect does not further
increase after four doses of 100 g of albuterol via metered dose inhaler.

B) Compliance

Respiratory compliance is determined by the compliance of the chest wall and lungs In
patients with ARDS, compliance was significantly lower at the time of weaning failure
compared with weaning success The static compliance of the respiratory system
can be calculated after measuring inspiratory and expiratory plateau pressure
and tidal volume

compliance respiratory system = TV/(Pplat - PEEPtot) (normal is 60 to 100 mL/cm

H2O). Optimizing compliance by reducing edema of the lung and chest wall, resolving
atelectasis and thoracocentesis, and removing ascites may facilitate weaning.

Most weaning patients still have considerable disturbances in gas exchange at the
time of weaning and it is important to limit instrumental dead space (for instance,
resulting from heat and moisture exchangers as much as possible.

2) Diaphragm/respiratory muscle function

Initiating a spontaneous-weaning trial puts an acute load on the inspiratory muscles.

The elevated load is imposed on a weakened respiratory muscle pump. When
considering the inspiratory muscles as a cause for weaning failure, it should be kept in
mind that dysfunction of the ventilatory pump may result from a lesion anywhere
between the afferent chemo-receptors of the respiratory centers and the
contractile proteins.

Drive, weakness, and fatigue

Impaired respiratory drive is an uncommon cause of weaning failure. In fact, in most

weaning-failure patients, respiratory drive is increased .Occasionally, clinically relevant
diaphragm dysfunction results from damage to the phrenic nerve(s). The most frequent
disorder affecting the phrenic nerves is critical illness polyneuropathy. As biopsy studies
have shown that critical illness poly-neuropathy and critical illness myopathy often
coexist ,the term 'ICU-acquired weakness' has gained popularity. There is
convincing evidence that contractility of the respiratory muscles is impaired in
mechanically ventilated patients. in a heterogeneous group of mechanically ventilated
patients ( 29 days), found profound muscle fiber atrophy accompanied by
activation of the proteolytic ubiquitin-proteasome pathway in the diaphragm of
patients mechanically ventilated for 18 to 96 hours. Although ICU-acquired
weakness is the most frequent neurological disorder in the ICU, other neurological
disorders may be associated with difficult weaning .

Diagnostic approach

The diagnostic approach of diaphragm dysfunction is sophisticated, and an in-depth

neurological examination should be performed by a neurologist. The most frequently
used test to evaluate respiratory drive in mechanically ventilated or spontaneously
breathing patients is the airway occlusion pressure at 100 ms (P0.1). To this end, the
inspiratory limb of the ventilator is occluded and the drop in airway pressure is
continuously monitored. In normal subjects, P0.1 is about 0.5 to 1.5 cm H2O.
Accordingly, a reduced P0.1 is not a very specific sign of impaired drive, but in patients
with normal/high P0.1, impaired drive is highly unlikely.

Generalized skeletal muscle weakness will guide the clinician to respiratory

muscle weakness but does not prove inspiratory muscle weakness, and vice
versa. A global assessment of inspiratory muscle function can be obtained by
measuring maximal inspiratory pressure.. As this test does not evaluate the endurance
of the inspiratory muscles, the value of maximal inspiratory pressure as a weaning
predictor is much more controversial .

The definite diagnosis of respiratory muscle fatigue after a trial of spontaneous

breathing is not feasible in routine clinical care. The development of hypercapnia
during a weaning trial is not a very specific finding, as hypercapnia may result
from causes other than muscle fatigue, such as central hypoventilation and rapid
shallow breathing. The absence of hypercapnia in a weaning-failure patient
virtually excludes inspiratory muscle fatigue.

Treatment strategies

I. Mechanical ventilation is a double-edged sword for the respiratory muscles

Unloading prevents the development of fatigue, but inactivity is associated with

the development of weak-ness. Very few studies have assessed the effect of
inspiratory muscle training on muscle strength and in particular on clinical outcome such
as duration of ventilatory assist.. However, from a physiological point of view, it seems
reasonable to train the inspiratory muscles, as part of a generalized training program .in
patients with inspiratory muscle weakness and prolonged weaning from mechanical
ventilation. When considering a training schedule, clinicians should keep in mind that
the diaphragm operates mostly at its submaximal force level. Therefore, when the
clinician decides that inspiratory muscle training may facilitate weaning from mechanical
ventilation, from a physiological point of view, an endurance training strategy is most
appropriate.

II. Antioxidants modulate respiratory muscle function in healthy subjects

In a large, randomized, non-blinded trial, surgical ICU patients received the

antioxidants alpha-tocopherol and ascorbic acid or only standard care from ICU
admission until discharge Antioxidant supplementation was associated with a reduction
in ventilator-dependent days from 4.6 to 3.7 (P < 0.05). Further trials are needed before
antioxidant treatment can be recommended.

III. Effects of tight glycemic control on clinically relevant outcome parameters

The effects of tight glycemic control on clinically relevant outcome parameters

(mortality and days of mechanical ventilation) in critically ill patients are complex and
well beyond the scope of this review. Notably, in a recent large prospective multicenter
study intensive glycemic control did not affect the duration of mechanical ventilation. the
clinical relevance of such findings would be controversial as tight glycemic control did
not favor weaning and reduced survival in this trial.

IV. Effect of growth hormone treatment

The effect of growth hormone treatment (0.07 to 0.13 mg/kg of body weight per day)
has been reported in two parallel studies published in 1999 .Growth hormone
treatment is associated with increased mortality (39% versus 20% in the Finnish
study and 44% versus 18% in the European study). In addition, growth hormone
increased time spent on the ventilator. However, the successful use of growth
hormone supplementation in ICU patients who are more chronic has been
described .Future studies are needed to address this issue, but today the safety
of growth hormone supplementation in weaning patients is unknown.

3) Brain dysfunction

Delirium and depression in weaning

Brain dysfunction in difficult-to-wean patients is related mostly to delirium. Only one

paper specifically studied the role of delirium in weaning, and the paper showed that
impaired cognitive function was associated with a more than fourfold higher risk
of failed extubation .Other psychological disturbances, such as anxiety and
depression, may interfere with successful weaning]. Sleep disruption frequently
occurs in intensive care unit (ICU) patients, but no data showing the effects of disturbed
sleep architecture on weaning are available.
Diagnostic approach

The confusion assessment method for ICU (CAM-ICU) is a well-validated screening

tool for delirium in mechanically ventilated patients and is available in numerous
languages, but other screening tools have been validated as well]. Diagnosing other
cognitive disorders in the ICU is best performed by psychologists or psychiatrists. In
general wards, reducing risk factors for delirium reduces the incidence of delirium
[Midazolam is considered a risk factor for the development of delirium .A recent
multicenter trial indicated that sedation with dexmedetomidine reduced the incidence
of delirium and reduced the duration of mechanical ventilation compared with
sedation with midazolam .

Therapeutic strategies

High levels of sedatives are associated with increased time spent on the
ventilator. Depression is associated with weaning failure in patients admitted to a
long-term weaning facility .and preliminary data suggest that pharmacological treatment
of depression favors weaning from mechanical ventilation.Sleep may be improved by
limiting noise and light during sleep hours and adequately treating pain/discomfort.

4) Cardiac dysfunction

The transition from mechanical ventilation to spontaneous breathing imposes an

additional load on the cardio-vascular system because of intrathoracic pressure
changes, which affect ventricular preload and afterload and increased oxygen
consumption by the respiratory muscles.

Cardiac function during weaning

In patients with COPD but without cardiac disease, weaning was associated with a
significant reduction in left ventricle ejection fraction and this reduction was probably
due to increased left ventricular afterload . In patients with COPD (FEV1 [forced
expiratory volume in 1 second] 1.0 0.2 L) but without a history of cardiac disease,
weaning was associated with a reduction in left ventricle ejection fraction (54%
12% versus 47% 13% during mechanical ventilation and spontaneous breathing,
respectively; P < 0.01.Moreover, in difficult-weaning patients with COPD and a
history of heart disease, spontaneous-breathing trials resulted in elevated
pulmonary artery occlusion pressure and left ventricular end diastolic pressure,
suggesting reduced ventricular compliance .. Elevated left ventricular end diastolic
pressure during weaning may induce pulmonary and bronchial wall edema and thus
increase the work of breathing.

Brain natriuretcic peptide (BNP) is a hormone released from the myocardium upon
stretch. In patients with failed-spontaneous breathing trials and in failed-extubation
patients, changes in BNP are significantly higher than in patients with successful
extubation.This response of BNP does support a role for cardiac failure in selected
difficult-weaning patients.

Diagnostic approach

The first step to assess cardiac dysfunction as a cause for weaning failure is
electrocardiography at the final stages of the weaning trial to detect ischemia.
Subsequently, SvO2 could be used as a screening tool for cardiac dys-function in
difficult weaning. Accordingly, in patients who do exhibit a decrease in SvO2 during
failed weaning, cardiac failure may play a role and measurement of pulmonary
artery occlusion pressure and cardiac output by means of a Swan-Ganz catheter
or echocardiography must be considered.

Treatment strategies

In difficult-to-wean patients with evidence of cardiac failure, afterload reduction and

ultimately the use of inotropes must be considered. Notably, amelioration of
pulmonary mechanics will reduce left ventricle afterload. No studies have compared the
different classes of inotropes in these patients. Levosimendan is a new inotropic
used in the treatment of cardiac failure One of the mechanisms of action is
enhanced calcium sensitivity of the cardiac contractile proteins, resulting in
elevated pressure generation. it was recently shown that levosimendan improves
contractility of human diaphragm muscle fibers as well

5) Endocrine and metabolic dysfunction

The role of endocrine disorders in difficult weaning has gained little interest in the
literature.. Cortisol supplementation The pathophysiological mechanisms for
improved clinical outcome in these cortisol-supplemented patients are, however,
unknown.

For a variety of reasons, including decreased central drive and respiratory muscle
weakness ,hypo-thyroidism may delay weaning from mechanical ventilation.

Malnutrition frequently occurs in mechanically ventilated patients and is associated

with poor prognosis but also with reduced muscle mass and as such contributes to
difficult weaning. Nutritional status should be evaluated by determining body mass
index, plasma albumin concentration, and nitrogen balance Ideally, energetic needs
should be determined by indirect calorimetry to prevent under-and overfeeding.

Electrolyte abnormalities, including very low plasma levels of phosphate and

magnesium, have been shown to affect skeletal muscle function. Although these
should be corrected in difficult-weaning patients, no studies have investigated the
role electrolyte abnormalities in weaning failure. Other metabolic disturbances that
increase the work of breathing and that therefore may be associated with difficult
weaning include metabolic acidosis and fever