REVIEW

CURRENT
OPINION Weaning from mechanical ventilation and sedation
Alawi Luetz, Anton Goldmann, Steffen Weber-Carstens, and Claudia Spies

Purpose of review
Guidelines for weaning from sedation and weaning from ventilator gained increasing interest in recent
years. This includes patients with acute respiratory distress syndrome, as well as other mechanically
ventilated patients. This review will give an overview of the current literature and practice guidelines in
ventilator and sedation weaning.
Recent findings
Sedation and ventilator weaning are closely linked. Weaning protocols for both sedation and ventilator
weaning should be implemented in daily routine. The essential element of such algorithm should be a daily
spontaneous awakening trial and spontaneous breathing trial. Furthermore, regularly monitoring for
deepness of sedation and delirium should be implemented. Too deep sedation, as well as prolonged
delirium is associated with higher mortality.
Summary
The most important conclusion we come to from recent randomized controlled trials is that only using an
integrative algorithm for sedation and ventilator weaning can improve survival of ICU patients.
Keywords
delirium, protocol, sedation, ventilation, weaning

INTRODUCTION end-expiratory pressure is frequently necessary.

Treatment of patients with acute respiratory distress
syndrome (ARDS) requires a tremendous technical
and staffing effort. Increasing number of evidence-
based medicine (EBM) guidelines are being devel-
oped and ARDS-treatment algorithms have recently
been published by our group [1]. Patients are
usually treated in specialized centers. Nevertheless,
mortality among these patients remains approxi-
mately 50% [2]. Over the years, research has been
focusing on treatment strategies in the acute phase
(e.g. ventilation strategies, prone positioning, role
of extracorporeal lung support, selective pulmonary
vasodilators, etc). Yet, in recent times, an increasing
number of articles were published concerning wean-
ing from sedation and weaning from mechanical
ventilation. In survivors of ARDS, after a long time
on a ventilator and under sedation, problems in the
weaning phase, like weaning failure or delirium,
frequently occur. This article will give an overview
of the current literature and practice guidelines in
ventilator and sedation weaning.
WEANING FROM MECHANICAL
VENTILATION
During acute respiratory failure mechanical venti-
lation using positive airway pressure and positive
After acute treatment, the weaning process begins
and usually takes 40–50% of the overall ventilation
time [3]. In approximately 70% of the patients, the
weaning from a ventilator is simple [i.e. successful
weaning after one spontaneous breathing trial
(SBT) and first extubation]. In the rest of the
patients, the weaning is difficult or prolonged.
According to the international consensus confer-
ence held in 2005 [4], a difficult weaning is
defined as a successful weaning at least after the
third of two previously failed SBTs or within 7 days
after the first failed SBT. A weaning is considered as
prolonged after three failed SBTs or at least 7 days
ventilation after the first failed SBT. This classifi-
cation system (simple weaning, difficult weaning,
Department of Anesthesiology and Intensive Care Medicine, Campus
Virchow-Klinikum and Campus Charité Mitte, Charité-Universitaetsme-
dizin Berlin, Berlin, Germany
Correspondence to Claudia Spies, MD, PhD, Professor of Anesthesiol-
ogy and Intensive Care Medicine, Head of the Department, Department
of Anesthesiology and Intensive Care Medicine, Campus Virchow Klini-
kum and Campus Charité Mitte, Charité-Universitaetsmedizin Berlin,
Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49 30 450
551 001/2; fax: +49 30 450 551 909; e-mail: claudia.spies@charite.de
Curr Opin Anesthesiol 2012, 25:164–169
DOI:10.1097/ACO.0b013e32834f8ce7

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Number 2
April 2012

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 Weaning from mechanical ventilation and sedation Luetz et al.
KEY POINTS

Protocol-based weaning from ventilation (including
spontaneous breathing trials) reduces duration of
ventilation and ICU length of stay.

Protocol-based weaning from sedation (including
spontaneous awakening trials and avoiding
oversedation) reduces duration of ventilation and ICU
length of stay.

Using an integrated concept of protocol-based weaning
from sedation and ventilation improves survival and
cognitive outcome.
prolonged weaning) has been shown to be clinically
relevant and to correlate with ICU and hospital
& &
mortality [5 ]. In contrast, Sellares et al. [6 ] found
a worse outcome regarding mortality only for the
prolonged weaning group, whereas differentiation
between simple and difficult weaning had no
clinical impact. A weaning failure is defined as failed
SBT, reintubation or resumption of ventilatory assist
within 48 h or death within 48 h after extubation
[4].
Some patients (2–5%) cannot be weaned
completely and have to be discharged with a home
ventilator [7]. In specialized facilities, a prolonged
weaning after acute treatment can be continued
over months. Prolonged weaning is not only associ-
ated with higher healthcare expenses, it can also
be associated with psychic trauma for the patient
causing post-traumatic stress disorder after dis-
charge from ICU [8].
Practical guidelines
Weaning from mechanical ventilation should be
considered as early as possible: to avoid further
complications and unnecessary prolonged venti-
lation, it is essential to evaluate the readiness to
wean as early as possible. This should be done daily
and following a standardized weaning protocol.
A recent meta-analysis revealed that in most trials,
the use of a weaning protocol has been shown to
reduce time on a ventilator, duration of weaning
&
and duration of ICU stay [9 ]. In a medical ICU
setting, implementation of a weaning protocol
was able to reduce frequency of unplanned
extubations [10]. A recently published randomized
controlled trial (RCT) performed in a cardiac ICU
compared a new weaning protocol using SBT vs. the
standard of care [11]. Patients who were weaned
following the new protocol had a better outcome
compared with standard of care regarding duration
of weaning process and duration of ICU stay.
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An essential element of the weaning process
is the SBT. The SBT should be performed using a
T-piece (usually in patients with tracheostoma, i.e.
the patient is breathing independently) or with
low-pressure support (patients with endotracheal
tubus, breathing with CPAP/ASB). A SBT duration
of 30 min has been shown to be as sufficient to
predict successful extubation as a SBT duration of
2 h [12]. Su et al. [13], however, concluded from a
retrospective analysis that a longer SBT in older
critically ill patients (>70 years) is associated with
less frequency of reintubation. Despite that, a ques-
tionnaire-based analysis of 55 ICUs in Australia and
New Zealand [14] revealed that SBT was only used in
13% of patients to predict weaning and extubation
success. In most cases, respiratory rate (98%), effec-
tive cough (94%) and Glasgow Coma Score (92%)
were used to predict readiness for extubation.
A parameter that has been investigated as
a predictor of weaning success during SBT is the
Rapid Shallow Breathing Index (RSBI). The RSBI is
the respiratory rate to tidal volume ratio (RSBI ¼ RR/
TV). Patients with high RSBI (i.e. breathing fast with
low tidal volumes) during SBT seem to be at higher
risk for weaning or extubation failure. Recent
studies were not able to show a prognostic value
of RSBI [15]. Boutou et al. [16] tested two different
thresholds of RSBI (105 and 130 bpm/l) in
64 patients with chronic obstructive pulmonary
disease (COPD). RSBI was measured 5 min after
initiation of SBT (T-piece). Both thresholds had
a low sensitivity, low specificity and low diag-
nostic accuracy in predicting a successful T-piece
trial. Thus, the prognostic value of RSBI remains
unclear.
Neuromuscular weakness
There are several pathophysiologic factors that can
especially in combination with each other impact
the ability to wean and lead to a prolonged weaning
process. These factors can be pulmonary (e.g. COPD,
fibrosis, reduced compliance diffuse infiltration),
circulatory (pre-existing cardiac dysfunction, anae-
mia), neuropsychologic (e.g. delirium), metabolic
(e.g. obesity, malnutrition) and neuromuscular
(critical illness myopathy/neuropathy). Especially
neuromuscular weakness [ICU-acquired weakness
(ICUAW)], which is frequently observed after severe
sepsis can cause a prolonged weaning process
[17,18]. Diagnosis of ICUAW should be verified as
early as possible to facilitate further therapeutic
options [19] (e.g. transfer to a specialized weaning
facility). An inspiratory muscle strength training
has been shown to improve weaning outcome in
patients after weaning failure [20].
www.co-anesthesiology.com 165
 Intensive care and resuscitation
Practical approach for prevention of muscle
weakness
A strategy for whole-body rehabilitation consisting
of interruption of sedation and physical and
occupational therapy in the earliest days of critical
illness was safe and well tolerated and resulted
in better functional outcomes at hospital discharge,
a shorter duration of delirium and more ventilator-
free days compared with standard care [21]. There-
fore, unresponsive patients should undergo a
passive range of motion exercises for all limbs
(10 repetitions in all cardinal directions) by a
physical and occupational therapist. Once patient
interaction is achieved, sessions began with
active assisted (with manual assistance) and active
(independent) range of motion exercises in the
supine position. If these exercises are tolerated, treat-
ment should be advanced to bed mobility activities,
including transferring to upright sitting. Sitting
balance activities should be followed by participation
in activities of daily living and exercises that encour-
age increased independence with functional tasks.
The session should progress to transfer training (i.e.
repetition of sit-to-stand transfers from bed to chair
or bed to commode), and finally pregait exercises
and walking. Progression of activities is dependent
on patient tolerance and stability. Therapy inter-
vention continues on a daily basis throughout the
patient’s hospital stay until the patient returns to a
previous level of function or is discharged.
Role of tracheostomy
Percutaneous dilative tracheostomy is used as a
routine technique in the ICU and, if performed
correctly, is associated with a low rate of compli-
cations. Although the optimal timing is still
controversial, tracheostomy should be considered
early if prolonged weaning is expected. If there is
no option of extubation and continuing of weaning
with noninvasive ventilation (NIV), after third
weaning failure or after 4–7 days of ventilation,
tracheostomy should be performed (early tracheos-
tomy). Comorbidities like COPD or lung fibrosis
should be considered leading to an early decision
for tracheostomy after weaning failure. Currently
there is only poor evidence from the literature that
an early tracheostomy is associated with a better
outcome. A recently published randomized trial
showed that early tracheostomy did not result in
a significantly reduced incidence of ventilator-
associated pneumonia compared with late trache-
&
ostomy [22 ]. In contrast, a retrospective analysis
of Bickenbach et al. [23] showed a reduced inci-
dence of ventilator-associated pneumonia and
sepsis after early tracheostomy compared with late
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tracheostomy, whereas length of weaning and
mortality were not affected.
Comparing the conventional surgical tracheos-
tomy vs. dilative tracheostomy, there is no differ-
ence regarding overall complication rate, bleeding
complications or mortality [24]. Dilative tracheos-
tomy is more cost-effective, is perfomed faster and
has a better cosmetic result compared with surgical
tracheostomy. In patients with difficult airway or
marginal oxygenation (i.e. severe ARDS), a surgical
tracheostomy is the better choice as dislocation of
the tracheal canulla within the first days after a
dilative tracheostomy may lead to severe compli-
cations in these patients (impossible recanullation).
In conclusion, tracheostomy should be always
considered if a prolonged weaning or ventilation
time is expected. The optimal timing for tracheos-
tomy remains unclear. Dilative tracheostomy
should be always performed whenever there are
no contraindications and the airway access is
needed temporarily.
Role of noninvasive ventilation
The role of NIV as a method to continue weaning
after extubation in patients with difficult or
prolonged weaning remains controversial. There is
evidence that especially in patients with chronic
hypercapnic lung failure (e.g. exazerbated COPD),
NIV can be a useful weaning tool and reduce inci-
dence of pneumonia and improve mortality [25].
A new randomized multicenter trial showed that
NIV decreases the intubation duration and improves
weaning outcome in difficult to wean patients
&
with chronic hypercapnic lung failure [26 ]. Never-
theless, contraindications for NIV should always
be carefully considered (e.g. incooperative patient,
ileus and gastrointestinal bleeding). If a long-term
dependence from respiratory support is expected,
then NIV should not be used due to the decreased
patient comfort.
WEANING FROM SEDATION
The systematic evaluation of analgesia, sedation
and delirium is a fundamental part of evidence-
&
based treatment for critically ill patients [27,28 ].
Even though national and international guidelines
recommend a sedation-as-needed approach, includ-
ing monitoring of sedation at regular intervals,
42% of the ICUs still do not use a validated sedation
&
scale in clinical routine [29 ]. Although numerous
studies revealed that inadequate sedation (mostly
deep sedation) and increased consumption of
sedatives is significantly associated with worse out-
come, more than half of the ICU patients are most of
Volume 25
Number 2
April 2012
 Weaning from mechanical ventilation and sedation Luetz et al.
the time in a deep state of sedation. In 1996, Ely et al.
[30] published the first controlled trial to demon-
strate that, when compared with physician judg-
ment alone, the use of protocolized SBTs to assess
readiness for extubation, decreased ventilator days
by 1.5 days and led to 50% fewer ventilator-related
complications even when managed by nonphysi-
cian providers [31]. In 1999, Kress et al. [32] could
already show that performing daily spontaneous
awakening trials (SATs) significantly reduces time
of mechanical ventilation and the incidence of
ventilator-associated pneumonia. In a RCT, Girard
et al. [33] combined the SAT and SBT approach;
the intervention group received patient-targeted
sedation each day accompanied by protocolized,
paired SATs and SBTs. The control group only
received patient-targeted sedation and daily SBTs.
The use of this ‘awakening and breathing coordina-
tion’ protocol led to significant reductions in hos-
pital length of stay, a 14% absolute risk reduction in
death at 1 year and a reduction in the incidence
&
of long-term brain dysfunction at 3 months [34 ].
For that reason, a daily sedation goal should be
defined for every patient accompanied by assessing
the level of sedation (at least every 8 h) with a valid
and reliable sedation scale [e.g. Richmond Agitation
&
Sedation Scale (RASS)] [28 ]. Due to the reported
negative consequences for the patients’ outcome,
deep sedation (RASS <3) should be considered only
for a limited period and only for specific indications
(e.g. increased intracranial pressure in patients with
traumatic brain injury, prone-positioning in ARDS
patients). In all other patients, even no sedation
&
should be considered [35 ].
A multicenter RCT conducted by the ARDS
network revealed that applying a concept of low
tidal volume ventilation in patients with ARDS and
acute lung injury led to 22% relative reduction in
mortality [36]. One of the major concerns that arose
with the implementation of the low tidal volume
concept was that these patients may need high doses
of sedatives and opioids due to the low delivered
tidal volume that can cause hypercapnia-induced
dyspnea, breath stacking and patient–ventilator
asynchrony [37–40]. However, others could show
that applying a lower tidal volume of 6 ml/kg
of predicted body weight did not increase the
proportion of patients receiving benzodiazepines,
propofol, haloperidol and opioids, nor were there
differences in the doses of administered benzo-
diazepines and opioids [41].
The duration of administering propofol should
not exceed 7 days because of the risk of developing
rhabdomyolysis. That is probably one of the reasons
why benzodiazepines are still the preferred sub-
stances for medium-term and long-term sedation
0952-7907 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
[42]. This is particularly problematic because the
use of benzodiazepines is associated with worse
clinical outcomes when compared with either
propofol or with opioid-based sedation regimens
[43]. Moreover, the administration of benzo-
diazepines is the most consistent and significant
predictor for transitioning into delirium [44].
Delirium itself is associated with an increased inci-
dence of SAT and SBT failure, leading to a prolonged
time of mechanical ventilation and associated com-
plications. A study by Pisani et al. [45] could show an
association between days of delirium and mortality;
each additional day spent in delirium was associated
with a 20% increased risk of prolonged hospitaliz-
ation – translating to over 10 additional days – and
a 10% increased risk of death.
Dexmedetomidine combines sedative, analgesic
and anxiolytic effects and may induce a sedative
state similar to physiologic sleep without respiratory
depression by acting on a2 receptors in the locus
caeruleus [46,47]. At comparable sedation levels,
dexmedetomidine-treated patients spent less time
on the ventilator and experienced less delirium com-
pared with the midazolam group [48]. In addition,
dexmedetomidine reduced sedative requirements
and improved hemodynamic stability during bispec-
tral index-guided ICU sedation [49]. Even though
these results are promising, a first meta-analysis on
dexmedetomidine use in ICU patients [50] did not
reveal any significant outcome benefit for patients
treated with dexmedetomidine. This might be due to
the heterogeneity of patient cohorts in the included
studies. Further studies are needed to determine
which subgroups of critically ill patients are likely
to benefit most from using dexmedetomidine.
In a survey done by Novaes et al. [51], having
pain was identified as the principal stressor among
ICU patient’s. Data regarding the assessment and
the management of sedation and analgesia in the
ICU reveal that a large proportion of patients are
not assessed while receiving treatment for sedation
or for analgesia. Implementing the ‘awakening
and breathing coordination’ concept alone without
routine delirium monitoring and pain assessment
may not result in a significant improvement in
patient’s outcome – especially in the severe criti-
&&
cally ill, like the ARDS patient. Skrobik et al. [52 ]
evaluated the impact of a combined approach
including protocolized analgesia, sedation and
delirium management on patient’s outcome. This
combination of protocol implementation signifi-
cantly reduced the rate of medication-induced
coma, sedation levels, the prevalence of delirium,
the duration of mechanical ventilation, ICU and
hospital length of stay. In addition, the percentage
of patients able to go home increased.
www.co-anesthesiology.com 167
 Intensive care and resuscitation

Not possible Delirium monitoring No delirium SAT

Delirium Failure ü

Re-evaluate

<–1 Sedation↓
R
A Treatment of delirium SBT
0/–1
S
S Adequate analgesia
≥1
respirator adjustment

Re-evaluate

No Respiratory fatigue?

Start Extubation Yes

Stepwise reduction
Tolerance
of respiratory support

FIGURE 1. Algorithm for protocol-based weaning from sedation and ventilation.

CONCLUSION REFERENCES AND RECOMMENDED

Although some aspects of weaning from mechanical READING
Papers of particular interest, published within the annual period of review, have
ventilation remain controversial, the following been highlighted as:
recommendations can be made. Weaning should & of special interest
&& of outstanding interest

be considered as early as possible, a daily screening Additional references related to this topic can also be found in the Current
for readiness to wean should be implemented. World Literature section in this issue (p. 263).

A weaning protocol including a SBT should be used.
If prolonged weaning or ventilation is expected,
a tracheostomy should be considered early. Percuta-
neous dilative tracheostomy should be preferred if
there are no contraindications. However, the most
important conclusion we come to from recent
RCTs is that only the paired application of protocols
including protocol-based weaning from sedation
and ventilation are sufficient to have impact on
patients’ survival. The implementation of a core
model that combines awakening and breathing
coordination with target-based sedation, manage-
ment of delirium and analgesia as well as early
mobility must be part of routine care for every
&
critically ill patient [53 ]. A suggested algorithm is
shown in Figure 1.
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest.
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Outcomes of critically ill patients can be improved by applying evidence-based
therapies for the ‘liberation’ from mechanical ventilation and sedation, and the
‘animation’ through early mobilization.
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