10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Official reprint from UpToDate®

www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Management of the difficult-to-wean adult patient in

the intensive care unit
Authors: Scott K Epstein, MD, Martin F Joyce-Brady, MD
Section Editor: Polly E Parsons, MD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2020. | This topic last updated: Aug 14, 2020.

INTRODUCTION

Many patients in intensive care units (ICUs) are difficult-to-wean off of mechanical
ventilation, thereby delaying extubation. The management of patients who are difficult-to-
wean in the ICU is reviewed here. Details regarding readiness testing, methods of weaning,
and the management of patients who require prolonged mechanical ventilation in long-term
care facilities are provided separately. (See "Management and prognosis of patients
requiring prolonged mechanical ventilation".)

DEFINITION AND INCIDENCE

Weaning can be classified as simple, difficult, or prolonged.

● Simple wean – Patients are considered to have undergone a simple wean when they
pass their first spontaneous breathing trial (SBT). Approximately half to two-thirds of
patients in intensive care units (ICUs) undergo simple weaning, many of which will
proceed with extubation. Details regarding what constitutes an SBT and extubation
management are discussed separately [1,2]. (See "Initial weaning strategy in
mechanically ventilated adults" and "Extubation management in the adult intensive care
unit".)

● Difficult-to-wean – Patients are considered difficult-to-wean if they fail their first SBT and
then require up to three SBTs or seven days to pass an SBT [3]. The incidence ranges
from 26 to 39 percent [1,2]. This population mostly includes patients intubated in the
first few weeks of acute ICU admission. This population is discussed in this topic review.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 1/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

● Prolonged weaning – Patients are considered to have undergone prolonged weaning if

they fail at least three SBTs or require more than seven days to pass an SBT. The
incidence ranges from 6 to 14 percent [1,2]. Patients who require more than seven days
to wean are at increased risk for death [2] and are also more likely to fail extubation
compared with those who undergo simple weaning [4]. While in the ICU, many of these
patients are managed similarly to patients who are difficult to wean, many will require
tracheostomy and be managed accordingly. (See "Overview of tracheostomy" and
"Management and prognosis of patients requiring prolonged mechanical ventilation".)

IDENTIFY AND CORRECT THE CAUSE

Repeat unsuccessful attempts at weaning usually signify incomplete resolution of the illness
that precipitated mechanical ventilation and/or the development of one or more new
problems that prevent weaning. The clinician should identify and treat these issues before
resuming further weaning trials.

● Identify the cause(s) – Numerous factors contribute to failure to wean ( table 1) by

causing an imbalance between respiratory muscle strength and the work of breathing.
Respiratory and cardiac issues are common while psychological, ventilator, or nutrition-
related issues are less common. Most of the etiologies are apparent on routine clinical
examination, laboratory testing, arterial blood gas analysis, electrocardiography, and
chest radiography, as well as an assessment of sedative medications and the ventilator
circuit. Additional investigations may be indicated depending upon the suspicion for
select etiologies. (See 'Respiratory or ventilatory causes' below and 'Cardiac causes'
below and 'Psychological causes' below and 'Ventilator circuit issues' below and
'Nutritional issues' below.)

● Treat the cause – When feasible, identified etiologies that contribute to difficult weaning
should be treated to improve the probability of successful weaning. As an example, in a
series of 12 difficult-to-wean patients who failed weaning due to the development of
hypertension during their spontaneous breathing trial (SBT), antihypertensive therapy
during the SBT was associated with successful weaning in the majority (92 percent) [5].
In another study of 42 patients who failed weaning, nine of whom were assessed as
having heart failure succeeded on a later occasion after diuretic therapy [6].

● Resume weaning – Once it is felt that the likely cause of ventilator dependency has been
corrected, readiness testing ( table 2) should be performed to determine whether
weaning can be resumed. (See "Weaning from mechanical ventilation: Readiness
testing".)

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 2/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Respiratory or ventilatory causes — Respiratory/ventilatory causes of failure to wean, their

detection and treatment are listed in the table ( table 1).

Manifestations are often nonspecific and include tachycardia, tachypnea, respiratory

distress, or oxygen desaturation during a breathing trial.

Routine testing including chest, cardiac, and neurological examination (including an

assessment for delirium), complete blood count and chemistries (including calcium,
magnesium, and phosphate), chest radiography, arterial blood gas analysis, and
nutrition assessment will narrow the differential considerably. Additional testing is
individualized and targeted at specific suspected etiologies (eg, computed tomography
[CT] of the chest and/or abdomen, CT pulmonary angiography, nerve conduction
studies, bronchoscopy [to look for airway pathology]).

Frequently overlooked causes include:

● Auto-positive end-expiratory pressure (auto-PEEP) – The detection and treatment of

auto-PEEP are discussed separately. (See "Positive end-expiratory pressure (PEEP)",
section on 'Auto (intrinsic) PEEP'.)

● Overventilation – A common mistake made is to ventilate patients who have chronic

hypercapnia with a minute ventilation that normalizes the arterial carbon dioxide
tension (PaCO2). This causes the pH to rise and prompts renal excretion of bicarbonate
over three to five days until the pH normalizes. When the patient resumes spontaneous
ventilation, such as that during an SBT, an acute respiratory acidosis will result because
there is insufficient bicarbonate for buffering (thereby constituting a failed SBT). Thus,
patients with chronic hypercapnia should be mechanically ventilated in between SBTs
with a minute ventilation that maintains the patient's usual PaCO2.

● Imposed work of breathing by endotracheal tubes – Small-sized endotracheal tubes

(ETTs) or ETTs narrowed by secretions can significantly increase the work of breathing
and produce a pattern of rapid shallow breathing observed in patients with weaning
failure (akin to breathing through a straw) [7]. Use of a pressure support SBT may
overcome the imposed work of breathing by the ETT, and facilitate successful weaning
[8].

Moderate to large pleural effusions are common in ventilated patients at the time of
spontaneous breathing trials and in one prospective observational study were found to be
an independent predictor of weaning failure [9]. However, while drainage may improve
oxygenation and lung volumes [10], it has not been conclusively shown to reduce
mechanical ventilation days. Thus, we typically avoid large volume thoracentesis in this
setting unless indicated for another reason.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 3/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Cardiac causes — Weaning-induced myocardial ischemia or cardiac dysfunction (ie, heart

failure) may contribute to difficult weaning in 20 to 60 percent of patients and when
identified, should be treated accordingly (eg, optimize beta-blockade, diuresis) ( table 1)
[11,12]. Because of the increased work involved in spontaneous breathing, myocardial
demand increases, thereby resulting in ischemia in susceptible individuals, and pulmonary
edema in those with underlying cardiac dysfunction. Ischemia and/or pulmonary edema, in
turn, further increase the work of breathing, creating a vicious cycle.

Because PEEP is a treatment for heart failure, weaning-induced cardiac dysfunction may be
hard to detect when SBT strategies that include PEEP, rather than a t-tube or non-PEEP
strategies, are used [13]. Thus, cardiac dysfunction should be suspected in patients who pass
an SBT that included PEEP but who fail extubation and require re-intubation because of
acute heart failure.

Manifestations include tachycardia, tachypnea, oxygen desaturation, hypertension or even

hypotension during a breathing trial. Patients rarely complain of chest pain, and ST
depressions are only occasionally appreciated on a bedside monitor. Risk factors identified in
one retrospective study included chronic obstructive pulmonary disease, previous
cardiomyopathy, and obesity [11].

When ischemia is suspected, most experts use continuous multi-lead electrocardiography

(EKG) during the SBT, or record an EKG pre- and post-the trial. Rarely, patients require
cardiac catheterization for diagnosis. If ischemia is identified, it should be treated. The
treatment of myocardial ischemia and cardiac dysfunction are described separately. (See
"Overview of the acute management of non-ST elevation acute coronary syndromes".)

When cardiac dysfunction is suspected, transthoracic echocardiography is used in

conjunction with clinical examination and brain natriuretic peptide (BNP) to justify optimizing
cardiac medications and altering fluid management. (See "Treatment and prognosis of heart
failure with preserved ejection fraction" and "Overview of the management of heart failure
with reduced ejection fraction in adults".)

● BNP levels – The possibility that weaning is limited by cardiac dysfunction is suggested
by an elevated BNP or N-terminal pro-BNP prior to the weaning trial, an elevated N-
terminal pro-BNP at the end of the trial, or a >20 percent increase in BNP during the SBT
[6,14-16]. Interventions based upon BNP levels alone are not typically routine. However,
one randomized trial reported that BNP-guided fluid management, particularly in
patients with left ventricular systolic dysfunction, and reduced time to extubation (59
versus 42 hours) [17].

● Echocardiography – The identification of systolic or diastolic dysfunction by transthoracic

echocardiography (TEE) may favor cardiac dysfunction as cause of failure to wean.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 4/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

However, TEE is nonspecific and only identifies patients who are at risk of failure to wean
[16], rather than proving that failure to wean in an individual is due to cardiac
dysfunction. (See "Transthoracic echocardiography: Normal cardiac anatomy and
tomographic views".)

While not routine, some echocardiographic parameters and stress echocardiography

have been described as potentially useful in identifying weaning-induced cardiac
dysfunction. One retrospective study reported that an elevated ratio of early ventricular
filling velocity (E) to late ventricular filling velocity (A) measured by echocardiography
during weaning was associated with an elevated pulmonary artery occlusion pressure
during weaning; whether this increased the likelihood of failure to wean was not
determined [18]. In another study of 161 patients mechanically ventilated for
cardiogenic shock who were stable and had an ejection fraction of 45 percent,
dobutamine stress echocardiography was useful in identifying silent systolic and
diastolic dysfunction in patients with weaning failure compared with those who
successfully passed an SBT [19].

● Other reported methods that require further validation include:

• Passive leg raising (PLR) – One study reported that patients who fail to increase
cardiac output by >10 percent during PLR (negative PLR test) are significantly more
likely to fail an SBT with a pulmonary artery occlusion pressure (PAOP) >18 mmHg at
the end of the trial [20]. In another trial, a positive PLR was associated with a
successful weaning trial while a negative one was associated with failure [11]. (See
"Novel tools for hemodynamic monitoring in critically ill patients with shock",
section on 'Passive leg raising or fluid bolus challenge'.)

• Others – Other methods include the demonstration of a >5 to 6 percent increase in

plasma protein and hemoglobin during an SBT [21] and carbon dioxide rebreathing
[22]. Lung ultrasound, by the demonstration of B lines has also been reported to
identify pulmonary edema during weaning [23].

Psychological causes — Psychological issues (eg, depression, anxiety, delirium, pain) can be

significant impediments to successful weaning. When suspected as contributors to difficult
weaning, sedative medications should be adjusted and the psychological issue treated, if
feasible (eg, anti-psychotic, anxiolytic, analgesic).

Depression, anxiety, and delirium are common in ventilated individuals. Depressive

disorders are present in approximately 40 percent of patients undergoing weaning from
prolonged mechanical ventilation and their presence adversely affects weaning success [24].
In another study, patients with delirium were twice as likely to be difficult-to-wean compared
with those without delirium [25].

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 5/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Such disorders may be hard to assess and may simply manifest as agitation, grimacing,
disorientation, tachycardia, and hypertension during the trial.

Interventions that may minimize these factors include explaining the weaning plan to the
patient, family, and other caretakers; arranging for a trusted caretaker to provide
reassurance and explanation during weaning trials; biofeedback (if feasible or available) that
displays the breathing pattern [26]; ensuring adequate sleep; and environmental stimulation
during the trial, such as television, radio, or books. Efforts to optimize medications for
treating delirium, anxiety (eg, switching anxiolytic to dexmedetomidine), and pain should
also be performed. Oversedation should be avoided. (See "Sedative-analgesic medications in
critically ill adults: Selection, initiation, maintenance, and withdrawal" and "Sedative-
analgesic medications in critically ill adults: Properties, dosage regimens, and adverse
effects".)

Ventilator circuit issues — Ventilator circuit-related problems can increase the work of

breathing and contribute to SBT failure. Potential problems include equipment dead space,
poor circuit compliance, low gas compression volume, exhalation valve function, and
increased resistance caused by the ETT, inspiratory circuit, or expiratory circuit [27].
Consulting respiratory therapy and examining the pressure and flow tracings on the
ventilator screen can help identify and eliminate potential ventilator-related problems. As
examples:

● An elevated peak inspiratory airway pressure (Ppeak) with a sizeable difference between
the Ppeak and plateau pressure (Pplat) may suggest an obstructed ETT or abnormally
increased resistance in ventilator circuit tubing (assuming that the patient is on volume
cycled ventilation). Examining the ETT and circuit for obstructions or secretions may
reveal an obvious source that needs to be treated accordingly (eg, replace ETT or tubing,
frequent suctioning, remove the obstruction).

● An increase in both Ppeak and Pplat may suggest a malfunction of the exhalation valve,
which should be checked if this waveform abnormality is found. However, such changes
may also result from issues not related to the ventilator circuit (ie, processes that
decrease respiratory system compliance such as pulmonary edema, pneumothorax,
pleural effusion).

● Ventilator asynchrony may be evident on waveforms. This manifests as minimal or no

inspiratory flow, despite patient inspiratory effort due to continued neural inspiration
(contraction of inspiratory muscles) after the ventilator has cycled to the expiratory
phase (ie, premature opening of the exhalation valve). This may lead to a transient but
prominent decrease in peak expiratory flow, followed by increase and then a slow
decrease again as neural expiration ends [28]. Such inspiratory effort increases the work
of breathing and may injure the inspiratory muscles as they contract eccentrically (eg,

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 6/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

the muscle contracts while lengthening). If suspected, the cause of ventilator

asynchrony should be sought and treated (eg, auto-PEEP).

Nutritional issues — Protein catabolism induced by critical illness leads to decreased

respiratory muscle mass, strength, and endurance, which may lead to difficulty weaning
from mechanical ventilation [29]. Although it is rare for malnutrition to be the sole cause, it
can contribute to difficulty weaning such that this population should be evaluated by a
nutrition expert and their nutrition support optimized. This approach is based upon studies
that report a possible increase the number of ventilator-free days when adequate nutrition
is provided, the details of which are discussed separately. (See "Nutrition support in critically
ill patients: An overview".)

Overfeeding with excessive carbohydrates can impair weaning success [30], presumably by
leading to excess carbon dioxide production and an increased ventilatory load on the
respiratory muscles. While in the past overfeeding was common, it is now a rare
phenomenon.

RESUMING WEANING TRIALS

Once the potential causes have been identified and treated, weaning trials may resume.

General strategies

Posture — Patients should be placed in the posture that they prefer during a weaning
trial. For example, patients with diaphragmatic paralysis generally prefer and perform better
in an upright position because their vital capacity decreases when they are horizontal. In
contrast, patients with intercostal muscle weakness (eg, due to a low cervical cord lesion)
may prefer being supine because their lung volumes tend to increase when they move from
an upright to a supine position. In patients with chronic obstructive pulmonary disease, the
optimal posture varies. Some patients have less dyspnea when they are lying supine,
whereas others prefer to lean forward.

Airway management — Airway secretions should be suctioned before every weaning

trial.

Theoretically, bronchodilators may facilitate weaning in patients with airway obstruction by

reducing airway resistance and the work of breathing [31,32]. We use short-acting inhaled
beta-adrenergic and/or anticholinergic agents prior to a weaning trial in patients with
airflow obstruction unrelated to the artificial airway. (See "Invasive mechanical ventilation in
acute respiratory failure complicating chronic obstructive pulmonary disease", section on
'Bronchodilators'.)

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 7/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Trials longer than 30 minutes — In patients who are difficult-to-wean, spontaneous

breathing trials (SBTs) are the same as those in patients who are weaning for the first time
with one major difference, that trials are longer than the typical 30 minutes in duration
(often up to two hours long). Data to support this strategy are discussed separately. (See
"Initial weaning strategy in mechanically ventilated adults".)

Importantly, a weaning trial should be terminated early if the patient is failing, since
respiratory muscle fatigue may develop and further decrease the chances of successful
weaning. Rest is the only treatment for such fatigue, and recovery can take several days.

Method of weaning trial — In our clinical practice, we favor once daily SBTs to wean
patients who have failed an initial weaning attempt. We return the patients to a supportive
mode of mechanical ventilation after a failed SBT, look for and correct reversible causes of
weaning intolerance, and reassess their readiness to wean the next day. We typically use SBT
with pressure support (5 to 8 cm H2O) and positive expiratory pressure PEEP; (5 cm H2O) with
one exception, that in patients with weaning failure due to cardiac dysfunction, some
experts prefer to resume SBTs using a T-tube or pressure support without PEEP; this
preference ensures that weaning-induced heart failure is not concealed by the use of PEEP
(which is a therapy for heart failure). We do not use intermittent mandatory ventilation
weaning. (See "Initial weaning strategy in mechanically ventilated adults", section on
'Choosing a weaning method'.)

A strategy of extubation with immediate application of noninvasive ventilation (NIV) may

facilitate earlier extubation in select patients who might otherwise be difficult to wean. While
this approach is not necessary as a routine, it is an option for patients who fail the initial SBT
and are at risk of failing extubation, including patients with COPD or chronic hypercapnic
respiratory failure. This approach should not be used in patients with difficult airways,
excessive secretions, or an impaired mental status.

The practice of early extubation to NIV is supported by randomized trials and meta-analyses
[33-36]. In a meta-analysis of 16 trials (1156 patients), hospital mortality was lower in the NIV
weaning group compared with control (14 versus 20 percent; odds ration [OR] 0.58, 95% CI
0.29–0.89) [35]. However, the difference was largely accounted for by the large effect size in
trials involving patients with COPD (10 versus 20 percent; OR 0.43, 95% CI 0.13–0.81);
whereas mortality rates were similar in both groups in trials involving mixed ICU populations
(18 versus 20 percent; OR 0.88, 95% CI 0.25–1.48). NIV weaning also reduced MV duration
and ICU length of stay, with little to no effect on hospital length of stay. The effect on these
outcomes was also largely accounted for by the effect in trials involving patients with COPD,
with smaller effect sizes or no effect in trials involving mixed ICU populations. NIV weaning
reduced rates of ventilator-associated pneumonia (VAP) both in trials involving patients with
COPD and trials in mixed ICU populations (overall VAP rates 10 versus 38 percent; OR 0.22,

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 8/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

95% CI 0.13-0.33). However, VAP definitions varied between trials and many trials had
unusually high rates of VAP in the control arm.

One randomized trial of 364 patients with respiratory failure predominantly due to
pneumonia or post-surgical complications who were deemed ready to wean, but who had
failed a spontaneous breathing trial [34]. Patients were either extubated without passing an
SBT and treated with NIV or were extubated only when an SBT was passed. Although the
median time to liberation from ventilation (invasive or noninvasive) was no different (4.3
versus 4.5 days), the NIV group, as expected, received fewer days of invasive mechanical
ventilation (1 versus 4 days) and had a lower ICU length of stay (10.8 versus 12.2 days).
However, despite fewer invasive and total ventilation days, early extubation to NIV had no
impact on mortality or rates of reintubation or tracheostomy. Notably, most of the included
patients had hypoxemic non-hypercapnic respiratory failure and only 4 percent had an
admission diagnosis of chronic obstructive pulmonary disease (COPD) or asthma
exacerbation. Similarly, in a small randomized study of hypoxemic patients early extubation
to NIV reduced the duration of mechanical ventilation and length of hospital stay without
reducing mortality [37].

Mechanical ventilation between weaning trials — Appropriate ventilator settings in

between SBTs allow the muscles to rest and recover from the fatigue caused by the weaning
trial. In contrast, inappropriate settings can create more work than is required for
spontaneous breathing, leading to respiratory muscle fatigue and impairing successful
weaning.

● Mode, tidal volume, respiratory rate, and/or pressure level – Any mode may be used, as
long as the settings (ie, tidal volume, respiratory rate, and/or pressure level) are such
that the patient is comfortable and performing minimal work. Reasonable settings are
those that result in a respiratory rate between 12 and 20 breaths per minute, a tidal
volume between 6 and 8 mL/kg, and a minute volume between 6 and 12 L/min. For
those on pressure-controlled ventilation a reasonable goal is a plateau pressure <30 cm
H2O (the lower the better). For those on pressure support ventilation (PSV), a pressure of
7 to 15 cm H2O usually achieves these goals. Most patients who undergo weaning have
a PEEP between 5 and 8 cm H2O. Importantly, patients who have chronic hypercapnia
should receive a minute ventilation that targets their baseline arterial carbon dioxide
tension. (See "Overview of initiating invasive mechanical ventilation in adults in the
intensive care unit", section on 'Settings' and 'Respiratory or ventilatory causes' above
and "Weaning from mechanical ventilation: Readiness testing".)

● Trigger method, trigger sensitivity, and inspiratory flow – A reasonable initial approach is
to use flow triggering in patients receiving intermittent mandatory ventilation and in
patients receiving PSV who have increased inspiratory effort during triggering. Either
pressure or flow triggering is acceptable in other patients. A trigger sensitivity of -1 to -2
https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?sear… 9/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

cm H2O during pressure triggering or -1 to -2 L/min during flow triggering is

appropriate. An initial inspiratory flow rate of 60 L/min reasonable for most patients. The
flow rate can be increased to as needed if a patient appears to be struggling. (See
"Overview of initiating invasive mechanical ventilation in adults in the intensive care
unit", section on 'Flow rate and pattern' and "Overview of initiating invasive mechanical
ventilation in adults in the intensive care unit", section on 'Trigger sensitivity'.)

IMPROVING RESPIRATORY MUSCLE STRENGTH

Respiratory muscle weakness is common among mechanically ventilated patients; it may be

present at the time of intubation or result from intensive care unit (ICU)-acquired paresis or
ventilator-induced respiratory muscle weakness. One study found diaphragm dysfunction,
defined by vertical excursion of <10 mm or paradoxical motion during inspiration, in 29
percent of patients ready for weaning. Another study found that 27 percent of patients
demonstrated less than a 30 percent increase in diaphragm thickening during inspiration, an
indication of dysfunction [38]. Another study reported that 41 percent of patients developed
signs of diaphragm atrophy (>10 percent decrease in thickness) by day four of mechanical
ventilation [39].

Respiratory muscle strength is typically evaluated by clinical examination at the bedside by

asking the patient to take a maximal inspiratory effort; weak effort or low lung volumes
suggest respiratory muscle weakness. While not routine, more objective bedside measures
such as a low negative inspiratory force (eg, <60 cm H2O) and poor diaphragmatic excursion
by ultrasound can be used to support clinical findings. (See "Respiratory muscle weakness
due to neuromuscular disease: Clinical manifestations and evaluation" and "Tests of
respiratory muscle strength".)

Physical therapy is the mainstay of treatment. Inspiratory muscle strength training (IMST) is
of unclear benefit and not routinely used. Importantly, methods that improve muscle
strength typically take days to weeks for efficacy.

Physical therapy — Early mobilization/physical therapy in mechanically ventilated patients

is supported by the American Thoracic Society and American College of Chest physicians as a
preventive measure to promote liberation from mechanical ventilation [33,40]. However,
specific therapeutic strategies for difficult-to-wean patients have not been studied. Data
discussing early ambulation in the ICU are provided separately. (See "Post-intensive care
syndrome (PICS)", section on 'Prevention and treatment'.)

Investigational strategies (respiratory muscle training) — Inspiratory muscles can be

trained to improve strength and endurance so that fatigue occurs less easily. However,

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 10/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

whether IMST consistently results in earlier liberation from mechanical ventilation remains
unproven. Consequently, it is not routinely used.

IMST is performed by adding a resistance device to the inspiratory limb of the ventilator
circuit. A systematic review of small randomized trials and observational studies reported
that compared with sham or no training, inspiratory muscle training improved maximal
inspiratory pressures (increase by -7 cm H2O), rapid shallow breathing index (+15
breaths/minute/L) (see "Weaning from mechanical ventilation: The rapid shallow breathing
index") and weaning success (risk ratio 1.34) [41]. Duration of mechanical ventilation
improved only in the subgroup with known weaning difficulty. However, there was significant
heterogeneity among trials suggesting that larger trials are needed to confirm or exclude
this benefit.

REFRACTORY PATIENTS

Some patients remain difficult-to-wean even though their acute illness and factors
contributing to failure to wean have been resolved. In such patients, a tracheostomy is
frequently placed and the patient transferred to a long term acute care facility/hospital
(LTAC/LTACH) where further weaning efforts can be undertaken (ie, prolonged weaning).
(See 'Definition and incidence' above.)

Tracheostomy — A tracheostomy can be advantageous in those in whom weaning is

expected to be prolonged. The advantages, disadvantages and timing of tracheostomy are
discussed in detail separately. (See "Overview of tracheostomy".)

Transfer to long-term acute care — The number of patients in specialized weaning units

increased three-times between 1997 and 2006, reflecting the trend to manage such patients
outside of the intensive care unit (ICU) [42]. However, one single institution LTAC ventilator
weaning trial reported that as many as a third of this population could have completed their
wean in the ICU [43].

Several factors are considered when determining whether a patient is appropriate for
transfer to a specialized weaning center. First, the acute illness should be resolved. Second,
the patient should not be dyspneic or hypoxemic during mechanical ventilation. Third,
patients should have a stable airway and route to receive nutrition, which usually consists of
a tracheostomy and enteral feeding tube, respectively [44].

LTAC facilities provide a site where weaning and rehabilitation are the primary focus of care.
They foster involvement of the patient in decision-making and provide an environment that
integrates the family and other caregivers into a supportive health care team. This team
includes intensivists, internists, nurses, and respiratory therapists who identify weaning
goals and coordinate the weaning process. In addition, there is daily patient-centered
https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 11/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

rehabilitation that includes physical exercise for regaining muscle strength and practice
performing activities of daily living. Skilled therapists are also available to focus on issues
such as speech and communication, nutrition support, physical and recreational activities,
and counseling. Strategies for weaning patients who are in an LTAC facility for prolonged
mechanical ventilation and their outcomes are described in detail separately. (See
"Discussing goals of care" and "Management and prognosis of patients requiring prolonged
mechanical ventilation".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Weaning from
mechanical ventilation".)

SUMMARY AND RECOMMENDATIONS

● Patients are considered difficult-to-wean if they fail their first spontaneous breathing
trial (SBT) and then require up to three SBTs or seven days to pass an SBT. Up to 40
percent of patients mechanically ventilated for an acute illness in the intensive care unit
(ICU) are difficult-to-wean. (See 'Definition and incidence' above.)

● Repeat unsuccessful attempts at weaning usually signify incomplete resolution of the

illness that precipitated mechanical ventilation and/or the development of one or more
new problems that prevent weaning. The clinician should identify and treat these issues
(eg, respiratory, cardiac, psychological, circuit, nutritional) ( table 1) before resuming
further weaning trials. (See 'Identify and correct the cause' above.)

● Once the potential causes have been identified and treated, weaning trials may resume.
SBTs are similar to those undergoing first time weaning except special attention should
be paid to comfortable posture, airway management, and appropriate ventilation in
between trials; in addition trials are typically longer (up to two hours) and T-piece trials
may be preferred in those with cardiac dysfunction. (See 'Resuming weaning trials'
above.)

● Early mobilization/physical therapy in mechanically ventilated patients should be used

as a preventive measure to promote liberation from mechanical ventilation. However,
specific therapeutic strategies for difficult-to-wean patients have not been studied.
Inspiratory muscle training is of unclear benefit and therefore, not typically used. (See
'Investigational strategies (respiratory muscle training)' above and 'Improving
respiratory muscle strength' above.)

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 12/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

● Some patients remain difficult-to-wean even though their acute illness and factors
contributing to failure to wean have been resolved. In such patients, a tracheostomy is
frequently placed and the patient transferred to a long term acute care facility/hospital
where further weaning efforts can be undertaken (ie, prolonged weaning). (See 'Transfer
to long-term acute care' above and 'Refractory patients' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Funk GC, Anders S, Breyer MK, et al. Incidence and outcome of weaning from
mechanical ventilation according to new categories. Eur Respir J 2010; 35:88.

2. Peñuelas O, Frutos-Vivar F, Fernández C, et al. Characteristics and outcomes of

ventilated patients according to time to liberation from mechanical ventilation. Am J
Respir Crit Care Med 2011; 184:430.

3. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J
2007; 29:1033.

4. Jeong BH, Ko MG, Nam J, et al. Differences in clinical outcomes according to weaning
classifications in medical intensive care units. PLoS One 2015; 10:e0122810.

5. Routsi C, Stanopoulos I, Zakynthinos E, et al. Nitroglycerin can facilitate weaning of

difficult-to-wean chronic obstructive pulmonary disease patients: a prospective
interventional non-randomized study. Crit Care 2010; 14:R204.

6. Mekontso-Dessap A, de Prost N, Girou E, et al. B-type natriuretic peptide and weaning

from mechanical ventilation. Intensive Care Med 2006; 32:1529.

7. Valentini I, Tonveronachi E, Gregoretti C, et al. Different tracheotomy tube diameters

influence diaphragmatic effort and indices of weanability in difficult to wean patients.
Respir Care 2012; 57:2012.

8. Ezingeard E, Diconne E, Guyomarc'h S, et al. Weaning from mechanical ventilation with

pressure support in patients failing a T-tube trial of spontaneous breathing. Intensive
Care Med 2006; 32:165.

9. Razazi K, Boissier F, Neuville M, et al. Pleural effusion during weaning from mechanical
ventilation: a prospective observational multicenter study. Ann Intensive Care 2018;
8:103.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 13/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

10. Razazi K, Thille AW, Carteaux G, et al. Effects of pleural effusion drainage on
oxygenation, respiratory mechanics, and hemodynamics in mechanically ventilated
patients. Ann Am Thorac Soc 2014; 11:1018.

11. Liu J, Shen F, Teboul JL, et al. Cardiac dysfunction induced by weaning from mechanical
ventilation: incidence, risk factors, and effects of fluid removal. Crit Care 2016; 20:369.

12. Li S, An YZ, Ren JY, et al. Myocardial injury after surgery is a risk factor for weaning
failure from mechanical ventilation in critical patients undergoing major abdominal
surgery. PLoS One 2014; 9:e113410.

13. Cabello B, Thille AW, Roche-Campo F, et al. Physiological comparison of three

spontaneous breathing trials in difficult-to-wean patients. Intensive Care Med 2010;
36:1171.

14. Grasso S, Leone A, De Michele M, et al. Use of N-terminal pro-brain natriuretic peptide
to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients
with chronic obstructive pulmonary disease. Crit Care Med 2007; 35:96.

15. Chien JY, Lin MS, Huang YC, et al. Changes in B-type natriuretic peptide improve
weaning outcome predicted by spontaneous breathing trial. Crit Care Med 2008;
36:1421.

16. Konomi I, Tasoulis A, Kaltsi I, et al. Left ventricular diastolic dysfunction--an

independent risk factor for weaning failure from mechanical ventilation. Anaesth
Intensive Care 2016; 44:466.

17. Mekontso Dessap A, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid

management during ventilator weaning: a randomized controlled trial. Am J Respir Crit
Care Med 2012; 186:1256.

18. Lamia B, Maizel J, Ochagavia A, et al. Echocardiographic diagnosis of pulmonary artery

occlusion pressure elevation during weaning from mechanical ventilation. Crit Care
Med 2009; 37:1696.

19. Ruiz-Bailén M, Cobo-Molinos J, Castillo-Rivera A, et al. Stress echocardiography in

patients who experienced mechanical ventilation weaning failure. J Crit Care 2017;
39:66.

20. Dres M, Teboul JL, Anguel N, et al. Passive leg raising performed before a spontaneous
breathing trial predicts weaning-induced cardiac dysfunction. Intensive Care Med 2015;
41:487.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 14/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

21. Dres M, Teboul JL, Anguel N, et al. Extravascular lung water, B-type natriuretic peptide,
and blood volume contraction enable diagnosis of weaning-induced pulmonary edema.
Crit Care Med 2014; 42:1882.

22. Tanios M, Epstein S, Sauser S, Chi A. Noninvasive monitoring of cardiac output during
weaning from mechanical ventilation: a pilot study. Amer J Crit Care 2016; 25:257.

23. Ferré A, Guillot M, Lichtenstein D, et al. Lung ultrasound allows the diagnosis of
weaning-induced pulmonary oedema. Intensive Care Med 2019; 45:601.

24. Jubran A, Lawm G, Kelly J, et al. Depressive disorders during weaning from prolonged
mechanical ventilation. Intensive Care Med 2010; 36:828.

25. Jeon K, Jeong BH, Ko MG, et al. Impact of delirium on weaning from mechanical
ventilation in medical patients. Respirology 2016; 21:313.

26. Holliday JE, Hyers TM. The reduction of weaning time from mechanical ventilation using
tidal volume and relaxation biofeedback. Am Rev Respir Dis 1990; 141:1214.

27. Girault C, Breton L, Richard JC, et al. Mechanical effects of airway humidification devices
in difficult to wean patients. Crit Care Med 2003; 31:1306.

28. Georgopoulos D, Prinianakis G, Kondili E. Bedside waveforms interpretation as a tool to

identify patient-ventilator asynchronies. Intensive Care Med 2006; 32:34.

29. Laghi F, Tobin MJ. Disorders of the respiratory muscles. Am J Respir Crit Care Med 2003;
168:10.

30. Krishnan JA, Parce PB, Martinez A, et al. Caloric intake in medical ICU patients:
consistency of care with guidelines and relationship to clinical outcomes. Chest 2003;
124:297.

31. Mancebo J, Amaro P, Lorino H, et al. Effects of albuterol inhalation on the work of
breathing during weaning from mechanical ventilation. Am Rev Respir Dis 1991;
144:95.

32. Dhand R, Jubran A, Tobin MJ. Bronchodilator delivery by metered-dose inhaler in

ventilator-supported patients. Am J Respir Crit Care Med 1995; 151:1827.

33. Girard TD, Alhazzani W, Kress JP, et al. An Official American Thoracic Society/American
College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical
Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation
Protocols, and Cuff Leak Tests. Am J Respir Crit Care Med 2017; 195:120.

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 15/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

34. Perkins GD, Mistry D, Gates S, et al. Effect of Protocolized Weaning With Early
Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From
Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe
Randomized Clinical Trial. JAMA 2018; 320:1881.

35. Burns KE, Adhikari NK, Keenan SP, Meade MO. Noninvasive positive pressure ventilation
as a weaning strategy for intubated adults with respiratory failure. Cochrane Database
Syst Rev 2010; :CD004127.

36. Yeung J, Couper K, Ryan EG, et al. Non-invasive ventilation as a strategy for weaning
from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis.
Intensive Care Med 2018; 44:2192.

37. Vaschetto R, Longhini F, Persona P, et al. Early extubation followed by immediate

noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized
clinical trial. Intensive Care Med 2019; 45:62.

38. DiNino E, Gartman EJ, Sethi JM, McCool FD. Diaphragm ultrasound as a predictor of
successful extubation from mechanical ventilation. Thorax 2014; 69:423.

39. Goligher EC, Dres M, Fan E, et al. Mechanical Ventilation-induced Diaphragm Atrophy
Strongly Impacts Clinical Outcomes. Am J Respir Crit Care Med 2018; 197:204.

40. Schmidt GA, Girard TD, Kress JP, et al. Official Executive Summary of an American
Thoracic Society/American College of Chest Physicians Clinical Practice Guideline:
Liberation from Mechanical Ventilation in Critically Ill Adults. Am J Respir Crit Care Med
2017; 195:115.

41. Elkins M, Dentice R. Inspiratory muscle training facilitates weaning from mechanical
ventilation among patients in the intensive care unit: a systematic review. J Physiother
2015; 61:125.

42. Kahn JM, Benson NM, Appleby D, et al. Long-term acute care hospital utilization after
critical illness. JAMA 2010; 303:2253.

43. Jubran A, Grant BJ, Duffner LA, et al. Effect of pressure support vs unassisted breathing
through a tracheostomy collar on weaning duration in patients requiring prolonged
mechanical ventilation: a randomized trial. JAMA 2013; 309:671.

44. Scheinhorn DJ, Hassenpflug MS, Votto JJ, et al. Ventilator-dependent survivors of
catastrophic illness transferred to 23 long-term care hospitals for weaning from
prolonged mechanical ventilation. Chest 2007; 131:76.

Topic 1646 Version 19.0

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 16/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 17/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

GRAPHICS

Etiologies of the difficult-to-wean patient

Etiologies Investigations Treatment

Respiratory/ventilatory

Increased Hypoxemia (eg, atelectasis, morbid obesity, Clinical examination Treat underlying
ventilator abdominal distension, lung disease, sepsis), elevated including neurological etiology (eg,
demand dead space (eg, hyperinflation, pulmonary embolism, examination, chest bronchodilation,
dehydration), excess carbon dioxide production (eg, radiograph, arterial antibiotics,
fever, infection, overfeeding [refer to nutritional, blood gases, routine pulmonary toilet,
below], metabolic acidosis, or neuropsychiatric chemistries, thyroid fluids, diuresis).
factors [eg, delirium, anxiety, pain]). function tests, Administer oxygen.
Increased Bronchoconstriction (eg, COPD, asthma), airway nutrition assessment, Adjust mechanical
resistive load edema (eg, lower respiratory infection), secretions and occasionally CT ventilator settings,
(eg, tracheobronchitis, pneumonia), equipment chest and/or when indicated
issues (refer to ventilator circuit below). abdomen or CT (eg, for auto-PEEP).
angiography. Rarely, Correct feeding or
Increased Dynamic hyperinflation (eg, COPD, asthma, increased nerve conduction metabolic
elastic load minute ventilation), alveolar filling (eg, pulmonary studies or disturbances.
edema), atelectasis, pleural disease (eg, pleural bronchoscopy.
Optimize sedative
effusion, pneumothorax), chest wall disease, or
analgesics.
abdominal distension (eg, morbid obesity, ileus,
ascites). Rarely, ETT change,
physical therapy,
Reduced Electrolyte abnormalities (eg, hypophosphatemia, thoracocentesis.
neuromuscular hypomagnesemia, hypocalcemia, hypokalemia),
capacity medications (eg, steroids, neuromuscular blocking
agents), malnutrition (refer to nutritional below),
hypothyroidism, systemic inflammation (eg, sepsis),
neuropathy (eg, Guillain-Barré syndrome, critical
illness polyneuropathy), and myopathy (eg, critical
illness myopathy).

Decreased Excess sedation, metabolic alkalosis (eg, nasogastric

ventilatory suctioning, volume depletion, diuretics and other
drive causes of chloride depletion), central nervous system
disease (eg, stroke, encephalopathy), central sleep
apnea, or obesity hypoventilation syndrome.

Cardiac

  Weaning may induce myocardial ischemia in A continuous multi- Maximize cardiac

susceptible patients. lead EKG during
spontaneous
breathing trials or EKG
  Pulmonary edema may develop in patients with pre-and post-weaning
cardiac dysfunction or ischemia. trial. BNP or N-
terminal pro-BNP pre-
and post-weaning
  Fluid overload may present similarly in patients with trial. Transthoracic
normal cardiac function. echocardiography.
Rarely, cardiac
catheterization.
medications (eg,
beta blockade,
diuresis, ACE
inhibition, or
vasodilators before
or during SBT).
Rarely, coronary re-
perfusion
interventions or
inotropic agents.

Psychological

  Psychologic issues (eg, depression, anxiety, delirium, Clinical history and Patients education,
pain) and oversedation may limit ventilation and examination including optimize sedative
impede cooperation with a SBT. pain assessment. analgesia
medications, which
may involve
increasing,
adjusting, or
weaning

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 18/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

psychoactive
medications.

Ventilator circuit

  Equipment dead space, circuit compliance, gas Examine waveforms Equipment

compression volume, exhalation valve dysfunction, (eg, ventilator modifications (eg,
and increased resistance (eg, endotracheal tube asynchrony), change tubing,
luminal narrowing due to inspissated secretions and ventilator pressures ventilator,
debris or small-sized ETT). (eg, peak inspiratory endotracheal tube,
pressure, plateau etc), pulmonary
pressure), and toilet.
equipment (eg,
blocked exhalation
valve, excess
condensation).

Nutritional

  Protein catabolism and underfeeding leading to Calculate nutrition Administer

respiratory muscle weakness. Overfeeding leading to needs. adequate nutrition.
increased carbon dioxide production and increased
ventilatory load.

COPD: chronic obstructive pulmonary disease; CT: computed tomography; PEEP: positive end-expiratory pressure; ETT:
endotracheal tube; EKG: electrocardiogram; BNP: brain natriuretic peptide; ACE: angiotensin converting enzyme; SBT: spontaneous
breathing trial.

Graphic 115677 Version 1.0

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 19/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Clinical criteria used to determine readiness for trials of spontaneous breathing

Required criteria
1. The cause of the respiratory failure has improved

2. PaO 2 /FiO 2 ≥150* or SpO 2 ≥90 percent on FiO 2 ≤40 percent and positive end-expiratory pressure (PEEP) ≤5 cmH 2 O

3. pH >7.25

4. Hemodynamic stability (no or low dose vasopressor medications)

5. Able to initiate an inspiratory effort

Additional criteria (optional criteria)

1. Hemoglobin ≥7 mg/dL

2. Core temperature ≤38 to 38.5°Centigrade

3. Mental status awake and alert or easily arousable

* A threshold of PaO 2 /FiO 2 ≥120 can be used for patients with chronic hypoxemia. Some patients require higher levels of PEEP to
avoid atelectasis during mechanical ventilation.

Adapted from: MacIntyre, NR, Cook, DJ, Ely, EW, Jr., et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: a
collective task force facilitated by the American College of Chest Physicians, the American Association for Respiratory Care, and the
American College of Critical Care Medicine. Chest 2001; 120:375S.

Graphic 62377 Version 3.0

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 20/21
10/12/2020 Management of the difficult-to-wean adult patient in the intensive care unit - UpToDate

Contributor Disclosures
Scott K Epstein, MD Nothing to disclose Martin F Joyce-Brady, MD Nothing to disclose Polly E
Parsons, MD Nothing to disclose Geraldine Finlay, MD Consultant/Advisory Boards: LAM Board of
directors, LAM scientific grant review committee for The LAM Foundation.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

https://www-uptodate-com.bvcscm.a17.csinet.es/contents/management-of-the-difficult-to-wean-adult-patient-in-the-intensive-care-unit/print?se… 21/21