Intensive and Critical Care Nursing (2015) 31, 189—195

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ANNIVERSARY SERIES: THE STATE OF THE SCIENCE

Strategies for weaning from mechanical

ventilation: A state of the art review
Louise Rose a,b,c,d,e,f,g,∗

a
Critical Care Research, Sunnybrook Health Sciences Centre, Canada
b
Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Canada
c
Provincial Centre of Weaning Excellence, Toronto East General Hospital, Canada
d
Institute for Clinical Evaluative Sciences, Canada
e
Li Ka Shing Institute, St Michael’s Hospital, Canada
f
West Park Healthcare Centre, Canada
g
Canadian Institutes of Health Research (CIHR) New Investigator, Canada

Accepted 28 June 2015

KEYWORDS Summary Identification and adoption of strategies to promote timely and successful wean-
ing from mechanical ventilation remain a research and quality improvement priority. The most
Weaning;
important steps in the weaning process to prevent unnecessary prolongation of mechanical
Mechanical
ventilation are timely recognition of both readiness to wean and readiness to extubate. Strate-
ventilation;
gies shown to be effective in promoting timely weaning include weaning protocols and use of
Spontaneous
spontaneous breathing trials. This review explores various other strategies that also may pro-
breathing trial;
mote timely and successful weaning including bundling of spontaneous breathing trials with
Closed loop;
sedation and delirium monitoring/management as well as early mobility, the use of auto-
Patient—ventilator
mated weaning systems and modes that improve patient—ventilator interaction, mechanical
interaction
insufflation—exsufflation as a weaning adjunct, early extubation to non-invasive ventilation
and high flow humidified oxygen. As most critically ill patients requiring mechanical ventilation
will tolerate extubation with minimal weaning, identification of strategies to improve manage-
ment of those patients experiencing difficult and prolonged weaning should be a priority for
clinical practice, quality improvement initiatives and weaning research.
© 2015 Elsevier Ltd. All rights reserved.

∗ Correspondence to: 155 College Street, Rm 276, Toronto, ON, Canada M5T 1P8. Tel.: +1 416 978 3492; fax: +1 416 946 0665.
E-mail address: louise.rose@utoronto.ca

http://dx.doi.org/10.1016/j.iccn.2015.07.003
0964-3397/© 2015 Elsevier Ltd. All rights reserved.
190
Implications for Clinical Practice
• Clinicians should seek to identify strategies to promote timely recognition of weaning and extubation readiness
appropriate to their clinical environment and the needs of individual patients.
• Patients experiencing difficult and prolonged weaning require careful consideration with a graduated, consistent
approach using a tracheostomy mask recommended for tracheostomised patients.
• Strategies such as early extubation to non-invasive ventilation and cough augmentation using mechanical
insufflation—exsufflation may be effective in certain subpopulations.
Introduction
What is known about weaning from mechanical
ventilation?
It is undisputed that mechanical ventilation, though lifesav-
ing is associated with complications resulting in risk to the
critically ill patient (Adamides et al., 2009; Boles et al.,
2007; MacIntyre, 2001). Therefore weaning from mechan-
ical ventilation has been a long-standing priority in terms
of research to identify the most effective and efficient
methods and quality improvement initiatives designed to
implement evidence and best practices. Existing data indi-
cate the most important steps in the weaning process to
prevent unnecessary prolongation of mechanical ventilation
are timely recognition of both readiness to wean and readi-
ness to extubate (Brochard et al., 1994; Esteban et al.,
1995). Inappropriate decision making regarding weaning
and extubation readiness also is not without risk. Patients
may experience respiratory and cardiac failure associated
with increased work of breathing during the reduction
of ventilatory support for weaning (Jeganathan et al.,
2015; Vagheggini et al., 2015). Reintubation due to post-
extubation respiratory failure has been shown to increase
mortality from 2.5 to 10 times compared to patients that
do not require reintubation (Rothaar and Epstein, 2003).
However, despite numerous studies attempting to identify
predictors of weaning and extubation readiness that have
high levels of sensitivity and specificity, no one predic-
tor or combination of predictor variables, either objective
or subjective, has been shown to be particularly accurate
(Meade et al., 2001). In some contexts weaning protocols
that provide structured guidance to weaning and incorpo-
rate timely assessment of weaning and extubation readiness
may reduce the time to wean and overall duration of venti-
lation (Blackwood et al., 2014).
A spontaneous breathing test (SBT) or weaning test
(Perren and Brochard, 2013) that comprises a focused
assessment of a patient’s capacity to breathe, currently
is advocated as the best method to ascertain extubation
readiness (Boles et al., 2007). A SBT generally comprises
30—60 minutes on either low levels of pressure support or
continuous positive airway pressure (CPAP) via the ventila-
tor, or using a T-piece attached to the endotracheal tube.
A recent Cochrane systematic review and meta-analysis
confirms the results of earlier studies that report no differ-
ence in terms of weaning success based on the SBT method
(Ladeira et al., 2014). Most patients, approximately 60—70%,
will require minimal to no weaning of ventilatory support
and are extubated without difficulty after the first SBT (Boles
L. Rose
et al., 2007). These patients may be classified as simple
weaning (Boles et al., 2007). The remaining 30—40% may
be classified as difficult weaning, defined as requiring up
to three SBTs and seven days to achieve weaning success
or prolonged weaning defined as requiring more than three
SBTs and more than seven days of weaning (Boles et al.,
2007). These patients require a more graduated approach
to reducing the amount of support provided by the ventila-
tor or prolonging the time spent off the ventilator using a
T-piece or tracheostomy mask (Boles et al., 2007).
This state of the art review of weaning from mechan-
ical ventilation will discuss recent evidence for strategies
to promote weaning success including the bundling of SBTs
with other complex interventions including sedation and
delirium monitoring and management and early exercise;
automated weaning systems and ventilator modes that
promote improved patient—ventilator interaction; manage-
ment of difficult and prolonged weaning; use of mechanical
insufflation—exsufflation (MI-E) as a weaning adjunct; early
extubation to non-invasive ventilation; and the role of high
flow humidified oxygen in weaning.
Spontaneous breathing trials, spontaneous
awakening trials and the rest of the alphabet
As discussed earlier, a SBT or a weaning test is consid-
ered the best method to ascertain extubation readiness.
In 2008, Girard and colleagues (Girard et al., 2008) pub-
lished a multi-centre randomised controlled trial (the ABC
trial) that paired a SBT with a spontaneous awakening trial
(SAT), also referred to as sedation interruption. Duration of
mechanical ventilation, intensive care unit (ICU) and hospi-
tal length of stay were reduced with the study intervention
when compared to the usual sedation and weaning prac-
tices prevalent in the participating units at that time. A
key feature of studies evaluating the effectiveness of SBTs,
SATs and those evaluating weaning and sedation protocols is
the shifting of responsibility from physicians to nurses and
other allied health professionals such as physiotherapists
and respiratory therapists (Ely et al., 1999). More recently,
Klompas and colleagues (2015) in a surveillance study of
3425 ventilation episodes, reported that the pairing of an
SBT with an SAT resulted in a reduction in ventilator associ-
ated events (VAEs) as well as reductions in the duration of
mechanical ventilation, ICU and hospital length of stay. In
2013 VAEs replaced ventilator associated pneumonia (VAP)
as the surveillance target for mechanical ventilation recom-
mended by the Centers for Disease Control and Prevention
(CDC) (Magill et al., 2013). A VAE is defined as two days or
Strategies for weaning from mechanical ventilation
more of increased ventilator settings after two days or more
of stable or decreasing ventilator settings.
In recent years, awakening and breathing coordina-
tion (ABC) has been bundled with delirium monitor-
ing/management and early exercise/mobilisation to form
the ABCDE bundle (Pandharipande et al., 2010). The bundle
approach combines a set of evidence based practices shown
to be effective for improving patient outcomes (Resar et al.,
2005) such as reducing the duration of mechanical venti-
lation. Monitoring for delirium using a validated screening
tool such as the CAM-ICU (Ely et al., 2001) or the Intensive
Care Delirium Screening Checklist (Bergeron et al., 2001)
was recommended in the 2013 Pain, Agitation and Delirium
(PAD) guidelines endorsed by several professional societies
(Barr et al., 2013). Early mobilisation was shown to reduce
the duration of ventilation (Schweickert et al., 2009) as well
as to improve physical functional and cognitive functioning
(Hopkins et al., 2012; Winkelman et al., 2012). The com-
bination of these activities in a bundled approach can be
viewed as an effective strategy for weaning as it has been
shown to decrease ventilation time potentially not only due
to timely recognition of weaning and extubation readiness
but also through reductions in the administration of seda-
tion and delirium incidence (Balas et al., 2014; Khan et al.,
2014).
Automated weaning systems
Automated weaning systems theoretically enable more effi-
cient weaning when compared to clinician-directed weaning
by providing improved adaptation of ventilatory support
to patients’ needs through continuous monitoring and
real-time intervention (Dojat et al., 1996; Lellouche and
Brochard, 2009) (see Table 1 for description of commercially
available automated weaning systems). A recent Cochrane
systematic review and meta-analysis of 10 trials reporting
data on only those automated weaning systems that conduct
a SBT as part of their protocol reported that, compared to
non-automated weaning methods, these systems decreased
weaning time, time to successful extubation, ICU length
of stay and the number of patients requiring prolonged
mechanical ventilation (7 and 21 days) (Burns et al., 2014). A
second Cochrane systematic review and meta-analysis that
included 21 trials of all automated systems regardless of SBT
capability also demonstrated a reduction in the duration of
weaning as well as total duration of ventilation compared to
non-automated weaning methods (Rose et al., 2014). Auto-
mated weaning systems can be viewed as a computerised
version of a written weaning protocol. As such, trials of
automated weaning systems were included in a Cochrane
systematic review and meta-analysis of weaning protocols
that demonstrated reductions in weaning and ventilation
duration with use of a protocol (Blackwood et al., 2014).
However, despite evidence to suggest their effectiveness for
improving the efficiency of weaning, adoption of automated
weaning systems into clinical practice is modest at this time
(Rose et al., 2011, 2015).
Patient—ventilator interaction
Unlike pressure support ventilation (PSV) that provides
the same level of pre-set pressure for every inspiration
191
regardless of the patient’s inspiratory effort, effort adapted
automated modes such as Proportional Assist Ventilation
(PAV) (The University of Manitoba, Canada) and Neurally
Adjusted Ventilatory Assist (NAVA) (Maquet, Solna, Sweden)
adjust the amount of assistance based on continuous mea-
surement of inspiratory effort (Schmidt et al., 2015). This
enables physiologic variation in tidal volume, inspiratory
pressure and inspiratory time that is more similar than
PSV to breathing without ventilatory support (Akoumianaki
et al., 2014). With PAV, the amount of assistance provided
by the ventilator is automatically adjusted and propor-
tional to respiratory compliance and resistance measured
throughout the inspiratory cycle (Branson, 2004). Therefore
pressure assistance adapts on a breath-by-breath basis to
the patient’s needs. The degree of assistance is set by the
% support setting. As well as its potential use as a weaning
mode (Elganady et al., 2014; Xirouchaki et al., 2008), PAV+
has been shown to reduce patient—ventilator asynchrony
compared to PSV thus promoting patient comfort, ventilator
tolerance and decreasing the need for sedation. Prevention
of asynchrony that includes ineffective inspiratory efforts
during expiration, double-triggering, aborted inspirations,
and short and prolonged cycling may also impact patient
mortality (Blanch et al., 2015).
With NAVA, pressure delivered to the airways is pro-
portional to inspiratory diaphragmatic electrical activity
measured via an oesophageal catheter (Sinderby et al.,
1999). As with PAV, NAVA has been shown to reduce
over-assistance provided by the ventilator and improve
patient—ventilator interaction (Vagheggini et al., 2013).
A recent randomised controlled trial comparing NAVA to
conventional ventilation modes (pressure control and pres-
sure regulated volume control) in 170 critically ill children
reported a halving in the ventilation duration with NAVA
(3.3 hours compared to 6.6 hours) though this did not reach
statistical significance. Sedative doses were also lower in
children admitted for medical reasons though not when sur-
gical patients were included in the analysis (Kallio et al.,
2015). This trial suggests NAVA is a feasible and safe venti-
lator mode for children at least. At present, similar studies
have not been reported for critically ill adults though trials
are underway (Rose et al., 2014).
Difficult and prolonged weaning
Patients that experience difficult or prolonged weaning are
at increased risk of reintubation, are more likely to require
tracheostomy, have a higher hospital mortality and are less
likely to be discharged home (Jeong et al., 2015). In a recent
systematic review and meta-analysis of studies reporting
outcomes of patients requiring mechanical ventilation for 14
days or more, only 50% were successfully weaned, 19% were
able to return home and the one year mortality rate was 50%
(Damuth et al., 2015). These are important data for clini-
cians to consider that can inform discussions with patients
and family members about the trajectory of care and poten-
tial anticipated reductions in quality of life. There is limited
evidence regarding the most effective method for difficult
and prolonged weaning. Indeed a recent Canadian survey
reporting on weaning methods for patients ventilated over
21 days found of the 48% of ICUs that indicated they used
192 L. Rose

Table 1 Automated closed loop systems.

Name Manufacturer/Patent Brief description

Smartcare/PSTM
Adaptive Support
Ventilation (ASV)
Automode
Proportional Assist
Ventilation (PAV)
Mandatory Minute
Ventilation (MMV)
Proportional Pressure
Support (PPS)
Neurally Adjusted
Ventilatory Assist
Intellivent-ASV®
Mandatory Rate
Ventilation (MRV)
Dräger Medical, Lübeck,
Germany
Hamilton Medical,
Bonaduz, Switzerland
Siemens, Solna, Sweden
The University of
Manitoba, Canada
Dräger Medical, Lübeck,
Germany
Dräger Medical, Lübeck,
Germany
Maquet, Solna, Sweden
Hamilton Medical,
Rhäzüns, Switzerland
Taema-Horus Ventilator®
Air Liquide, France
Closed loop control of pressure support based on
monitoring of respiratory rate, tidal volume and end-tidal
carbon dioxide. Tests for extubation readiness using a one
hour spontaneous breath trial
Closed loop control of inspiratory pressure and mandatory
breath rate on a breath-by-breath basis to maintain pre-set
minimum minute ventilation. Automatically switches to
pressure support ventilation and adapts pressure support
based on respiratory rate and tidal volume
Switches from a controlled mode (for example pressure
control ventilation) to a support mode such (for example
pressure support ventilation) based on detection of patient
triggering of two consecutive breaths
Adjusts airway pressure based on measurement of
compliance and resistance throughout the inspiratory cycle
to maintain an clinician selected % degree of support
Closed loop control of the mandatory breath rate while
considering the patient’s spontaneous breath rate based on
a clinician predetermined minute ventilation
Pressure support is provided proportionately to changes in
airway resistance and lung compliance. PPS is based on the
PAV algorithm
Partial ventilatory support proportional to inspiratory
diaphragmatic electrical activity measured via an
oesophageal catheter
Extension of ASV that uses closed loop control to adjust
minute ventilation using end tidal carbon dioxide and
oxygenation by adjusting positive end-expiratory pressure
and the fraction of inspired oxygen
Closed loop control to adjust pressure support based on a
respiratory rate target

a weaning protocol, only 25% had guidance specific to pro-
longed weaning (Rose et al., 2015). A randomised controlled
trial comparing PSV weaning with progressively extended
tracheostomy mask trials found decreased weaning time
and increased weaning success with the tracheostomy mask
(Jubran et al., 2013). This trial was conducted in tra-
cheostomised patients requiring mechanical ventilation for
greater than 21 days and admitted to a single long term
acute care hospital (LTACH) in the United States. LTACHs
admit medically stable patients from acute care hospitals
including ventilated patients from the ICU after 21 days and
have a lower intensity staffing model (Kahn et al., 2013).
An important incidental finding of this study that used a five
day screening window to assess the need for weaning prior to
randomisation, was that 32% of the 500 patients passed the
weaning screen. This suggests that, as highlighted above,
the most important steps to weaning are timely recognition
of weaning and extubation readiness, which still does not
necessarily occur in a consistent and optimal fashion.
Mechanical insufflation: exsufflation
Patients with neuromuscular disease and those with ICU
acquired weakness comprise an important subset of patients
experiencing difficult or prolonged weaning in ICUs and
other care locations such as weaning units, respiratory
intermediate care units and LTACHs. These patients, along
with those with spinal cord injury or restrictive lung dis-
ease may experience impaired mucociliary clearance as the
result of ineffective cough associated with respiratory mus-
cle weakness or paralysis (Gonçalves et al., 2012). For these
patients, cough augmentation techniques such as lung vol-
ume recruitment, manually assisted cough and mechanical
insufflation—exsufflation (MI-E) (see Table 2) may be useful
strategies to promote successful weaning. Two studies by
Bach and colleagues (Bach et al., 2010, 2015) report suc-
cessful extubation to continuous NIV using a mouthpiece
with MI-E used both before and after extubation for patients
considered unweanable due to profound respiratory muscle
weakness and unable to pass a SBT. Continuous NIV and MI-E
may offer a preferred option to tracheostomy and long-term
invasive ventilation. However the success reported in these
two studies may not be generalisable to other settings as
both were conducted in a specialised centre highly experi-
enced with MI-E and mouthpiece NIV. Additionally MIE was
performed on a half hourly basis and utilised family mem-
bers to aid in its delivery which is beyond the capabilities
of the average ICU. However a randomised controlled trial
Strategies for weaning from mechanical ventilation
Table 2 Cough augmentation techniques.
Technique Description
Lung volume Patient inhales a volume of gas
recruitment and retains it
Procedure is repeated until
maximum insufflation capacity is
reached
Gas can be delivered via a
self-inflating resuscitation bag
adapted with a one-way valve to
facilitate breath holding or a
volume targeted ventilator
Manually assisted Cough timed with an abdominal
cough thrust or lateral costal
compression once maximal air
stacking is achieved and can be
timed to glottic opening in
non-intubated patients
Mechanical Alternates delivery of positive
insufflation— (inflation) and negative pressures
exsufflation (rapid deflation)
Delivered via an oronasal
interface, mouthpiece,
endotracheal or tracheostomy
tube
Manual or automatic cycling
Pressures of 40 cm H2 O
(insufflation) to −40 cm H2 O
(exsufflation) are usually most
effective
A cycle comprises one inspiration,
expiration, and a pause with 4—6
consecutive cough cycles
recommended for adults
that used MI-E three times a day after extubation in a more
heterogeneous group of ICU patients able to pass a SBT has
also reported lower rates of reintubation compared to a
conventional extubation protocol (Gonçalves et al., 2012).
Early extubation to non-invasive ventilation
Non-invasive ventilation (NIV) is the provision of (usually)
positive pressure via an interface such as a mask, mouth-
piece or helmet. As such, NIV avoids the complications
associated with artificial airways such as aspiration, VAP,
sinusitis, pharyngo-laryngeal dysfunction and laryngeal or
tracheal wall injuries (Elmer et al., 2015). Non-invasive ven-
tilation may be used in three ways to optimise weaning and
extubation success (Perren and Brochard, 2013). First, to
facilitate early extubation from invasive mechanical ven-
tilation thereby reducing associated risks. When used in
this manner, patients generally cannot pass a SBT or meet
standard extubation criteria. A recent Cochrane systematic
review and meta-analysis of NIV as a weaning strategy iden-
tified 16 trials including 994 participants, most of whom had
a diagnosis of COPD (Burns et al., 2013). This meta-analysis
reported that NIV, when compared to traditional weaning
strategies via invasive mechanical ventilation, resulted in
193
reduced mortality, weaning failure, VAP, ICU and hospital
length of stay and total duration of ventilation. Second,
early use of NIV as a prophylactic intervention can be used
to prevent reintubation for patients considered at high risk
(Bajaj et al., 2015). Third, NIV can be used as an unplanned
rescue therapy for respiratory failure that develops follow-
ing extubation. In this situation NIV may be harmful if it
delays reintubation (Esteban et al., 2004).
High flow humidified oxygen
High flow humidified oxygen delivered via nasal cannula pro-
vides heated and humidified gas (up to 100% oxygen) at a
maximum flow of 60 L/minute. This high flow rate reduces
air entrainment that occurs with other oxygen delivery sys-
tems thereby facilitating consistent delivery of high oxygen
concentrations (Sim et al., 2008; Wagstaff and Soni, 2007).
High-flow nasal cannulae have the capacity to generate low
levels of positive end expiratory pressure (PEEP), though this
is dependent on the gas flow rate, trachea size and mouth
closing (Chanques et al., 2013). Generation of PEEP may
reduce work of breathing and associated tachypnoea (Groves
and Tobin, 2007; Kernick and Magary, 2010).
Recently high flow humidified oxygen administered via
nasal cannula has been proposed as an alternative to
non-invasive ventilation for patients experiencing hypoxic
respiratory failure and as a strategy to avoid reintubation.
The BiPOP trial (Stéphan et al., 2015) compared high flow
humidified oxygen via Optiflow (Fisher and Paykel Health-
care, Auckland, New Zealand) to noninvasive ventilation
using Biphasic Positive Airway Pressure (BIPAP) via facemask
after extubation in 830 patients following cardiac surgery.
Patients were eligible if they either failed a SBT; or passed
the SBT but had preexisting risk factors for post-extubation
failure such as body mass index greater than 30, left ventri-
cular ejection fraction less than 40% and failure of previous
extubation; or passed the SBT and then failed extubation.
This non-inferiority trial showed no difference in the primary
outcome of treatment failure defined as either reintuba-
tion, switch to the other treatment, or premature treatment
discontinuation (21.9% with high flow humidified oxygen
therapy and 21% with BiPAP). There was also no difference in
secondary outcomes with the exception of skin breakdown
during the first two days which occurred more frequently in
the BiPAP group.
Implications for clinical practice and critical care
research
Undoubtedly the most effective strategies to promote wean-
ing success in the majority of critically ill patients requiring
mechanical ventilation are those that promote timely recog-
nition of weaning and extubation readiness and that remove
contextually specific barriers to this recognition. When
considering ways to optimise weaning success, clinicians and
decision makers need to assess weaning practices within
their own clinical environment to identify opportunities for
change and strategies likely to be most effective such as
a weaning protocol, the ABCDE bundle approach or use
of an automated weaning system. Patients that experi-
ence difficult or prolonged weaning present a significant
194
clinical challenge and further research is required in terms
of weaning strategies for these patients. At present, evi-
dence suggests a simplified, graduated and consistent
approach using a tracheostomy mask for tracheostomised
patients may be the best approach. In some cases,
modes such as PAV and NAVA may be useful in improving
patient—ventilator synchrony, comfort and reducing seda-
tion requirements, though more studies are required to
confirm their effectiveness as weaning strategies. Strate-
gies such as MI-E and early extubation to NIV more be useful
weaning adjuncts in certain subpopulations but again fur-
ther evidence of their effectiveness is required. High flow
humidified oxygen therapy offers an intermediate step in the
continuum of oxygen delivery devices that promotes comfort
and patient tolerance while enabling delivery of high oxygen
concentrations. Again, further evidence is required to con-
firm its role as an effective weaning strategy and for which
patients.
Conclusion
Identification and adoption of strategies to promote timely
and successful weaning from mechanical ventilation remain
a research and quality improvement priority. This state of
the art review has explored evidence related to a variety
of strategies designed to promote weaning success. Further
studies are required to identify the effectiveness of strate-
gies to promote success in patients experiencing difficult
and prolonged weaning. Use of MI-E as a weaning adjunct,
early extubation to NIV and high flow humidified oxygen may
offer solutions in certain patient subgroups, though again
further studies are required to confirm effectiveness, iden-
tify risks and those patients for whom these strategies are
most beneficial.
Conflict of interest
Dr. Louise Rose has received consulting fees from Covi-
dien who market PAV+ and has conducted a trial of
SmartCare/PSTM that was included in the Cochrane system-
atic review of automated weaning systems referred to in this
paper.
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