Ventilatorweaningand Extubation: Karen E.A. Burns,, Bram Rochwerg, Andrew J.E. Seely

Ven t i l a t o r We a n i n g a n d
Extubation
Karen E.A. Burns, MD, FRCPC, MSca,b,c,d,*, Bram Rochwergd,e,f,
Andrew J.E. Seelyg,h,i
KEYWORDS
Ventilator weaning Noninvasive ventilation High flow nasal cannulae Extubation
KEY POINTS
Increasing evidence supports specific approaches to liberate patients from invasive venti-
lation including the use of liberation protocols, inspiratory assistance during spontaneous
breathing trials (SBTs), early extubation of patients with chronic obstructive pulmonary
disease to noninvasive ventilation, and prophylactic use of noninvasive support strategies
after extubation.
Additional research is needed to elucidate the best criteria to identify patients who are
ready to undergo an SBT and to inform optimal screening frequency, the best SBT tech-
nique and duration, extubation assessments, and extubation decision-making.
Additional clarity is also needed regarding the optimal timing to measure and report extu-
bation success and to standardize reporting of weaning (SBT outcome) and extubation
outcomes.
INTRODUCTION
For critically ill patients who are recovering from critical illness requiring invasive venti-
lation, liberation from mechanical ventilation refers to the processes of weaning and
a
Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario,
Canada; b Department of Medicine and Division of Critical Care, Unity Health Toronto, St.
Michaels Hospital, Toronto, Ontario, Canada; c Li Ka Shing Knowledge Institute, Unity Health
Toronto, St. Michael’s Hospital, Toronto, Ontario, Canada; d Department of Health Research
Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada;
e
Department of Medicine, Hamilton Health Sciences, Juravinski Hospital, Hamilton, Ontario,
Canada; f Department of Critical Care, Hamilton Health Sciences, Juravinski Hospital, Hamilton,
Ontario, Canada; g Department of Critical Care, Ottawa Hospital, Ottawa, Ontario, Canada;
h
Division of Thoracic Surgery, Department of Surgery, University of Ottawa, Ottawa, Ontario,
Canada; i Clinical Epidemiology Program, Ottawa Hospital Research Institute, University of
Ottawa, Ottawa, Ontario, Canada
* Corresponding author. Unity Health Toronto, St. Michael’s Hospital, 30 Bond Street, Office 4-
045 Donnelly Wing, Toronto, Ontario M5B 1W8, Canada.
E-mail address: [email protected]
Twitter: @KarenBurnsK (K.E.A.B.); @Bram_Rochwerg (B.R.)
Crit Care Clin 40 (2024) 391–408

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392 Burns et al
extubation and includes efforts made by clinicians to reduce and ultimately remove
the need for invasive or noninvasive ventilation (NIV). The liberation process includes
reversal or improvement of the factors that precipitated respiratory failure and identi-
fication of the earliest time that patients can resume the work of breathing (liberation
from the ventilator) and maintain a patent airway (liberation from the artificial airway).
Extubation is the act of endotracheal tube removal. Patients with acute respiratory fail-
ure spend approximately 40% of the time on invasive mechanical ventilation in the
liberation phase.1 Timely and successful liberation has been identified as a key priority
for critical care.2 An inherent trade-off exists in liberating critically ill patients from
invasive ventilation. Premature failed attempts at liberation may result in airway
compromise, ineffective gas exchange, aspiration, nosocomial respiratory infections,
respiratory muscle fatigue,3 and increase the risk for ventilator-associated pneumonia
(VAP).4 Conversely, delayed and prolonged attempts at liberation may contribute to
patient harm related to ventilator-associated lung injury, diaphragmatic dysfunction,
development of VAP and neuromuscular weakness, and increase costs of care.5 In
this article, we summarize how to identify, test, and optimize patients for liberation
from mechanical ventilation. Additionally, we highlight the use of NIV and high flow
nasal cannulae (HFNC) in liberation and summarize evidence related to assessments
for extubation readiness.
DISCUSSION
Identifying Candidates for Liberation from Mechanical Ventilation
Liberation from invasive ventilation ideally begins when the underlying cause of acute
respiratory failure that led to the need for invasive ventilation has improved or resolved
and the patient is able to initiate spontaneous breaths.2,6 Clinicians aim to use spon-
taneous modes of ventilation as early as possible in the course of recovery from critical
illness provided that patients do not demonstrate insufficient or excessive effort during
weaning attempts.7 The multistep process typically includes ascertaining patient’s
readiness to undergo a spontaneous breathing trial (SBT), conduct of an SBT, and
extubation after successful completion of an SBT8 (Fig. 1).
Assessing Readiness to Undergo Spontaneous Breathing Trials

Invasively ventilated patients should be screened once daily to determine whether
they meet selected criteria to undergo a SBT9,10 or a test of their capacity to breathe
spontaneously for up to 120 minutes. Compared with physician judgment, weaning
protocols have been shown to reduce the duration of mechanical ventilation by
25 hours (95% confidence interval [CI], 12.5–35.5 hours) and intensive care unit
(ICU) length of stay by approximately 1 day (95% CI, 0.24–1.7 days; low certainty
evidence).9,10 Similarly, a Cochrane Review found that protocolized weaning reduced
the mean duration of ventilation especially in medical, surgical, and mixed ICUs but
not in neurosurgical ICUs, as well as, weaning, and ICU length of stay.11 The American
Thoracic Society (ATS)/American College of Chest physicians (ACCP) guidelines pro-
vided a conditional recommendation for the use of a ventilator liberation protocol for
the management for acutely hospitalized patients who have been mechanically venti-
lated for more than 24 hours.9,10
The parameters used in screening protocols to identify patients who are ready to
undergo an SBT vary across studies and with regard to their positive and negative pre-
dictive values. Parameters often include objective parameters (ie, the respiratory rapid
shallow breathing index [RSBI],12 tidal volume [VT], respiratory rate (RR), inspiratory
effort and maximal pressures, and blood gas and hemodynamic measurements);
Ventilator Weaning and Extubation 393
Fig. 1. The process of liberation from invasive ventilation. The weaning path. FiO2, fractional
inspired concentration of oxygen; GCS, Glasgow comas scale; O2 saturation, oxygen satura-
tion; PaO2/FiO2, partial pressure of oxygen/fractional inspired concentration of oxygen; PEEP,
positive end-expiratory pressure; RR, respiratory rate; RSBI, rapid shallow breathing index;
SBT, spontaneous breathing trial.
subjective parameters that may evaluate weaning and extubation readiness (ie,
reversal of the underlying cause of respiratory failure, cough strength, and secretion
volume); and other parameters (ie, hemodynamic status, no or minimal vasopressor
or inotropic support required, and so forth).13
The RSBI evaluates whether patients can avoid rapid shallow breathing as ventilator
support is reduced. The RSBI is the ratio of the patient’s breathing frequency (f or RR)
divided by the patient’s VT in liters measured during 1 minute of unassisted, sponta-
neous breathing.12 As originally described by Yang and Tobin, an RSBI less than
105 breaths/min/L, measured using a Wright’s spirometer attached to the end of an
endotracheal tube without ventilator support, had a sensitivity of 97% and specificity
of 64% for predicting extubation success.12 Subsequent studies have brought into
question the utility of the RSBI to predict extubation success recognizing that this
outcome confounds both liberation from the ventilator and the artificial airway.14,15
A meta-analysis found that the RSBI had limited value in predicting successful extu-
bation (positive likelihood ratio of 1.49).14 A more recent meta-analysis of 48 studies
found that the RSBI had a sensitivity of 83% and a specificity of 58% for predicting
extubation success.15 In sensitivity analyses, RSBI sensitivity and specificity did not
vary significantly with the use of different thresholds (<80 vs <105 breaths/min/L),
ventilator support used during RSBI measurement (T-piece, Pressure Support [PS]),
or the timing of RSBI measurement.15
The RSBI has also been assessed as a permissive criterion to decide whether inva-
sively ventilated patients area ready to undergo an SBT (RSBI <105 breaths/min/L
along with other safety criteria). An international survey of intensivist’s stated practices
in liberating critically ill adults from invasive ventilation identified that only one-third of
respondents reported using an RSBI threshold of 105 breaths/min/L to determine pa-
tient readiness to undergo an SBT.16 In a randomized trial, Tanios and colleagues
found that inclusion of the RSBI in an SBT protocol delayed successful extubation
and did not reduce the rate of extubation failure.17
394 Burns et al
Criteria to determine SBT outcome (pass/fail) have largely been derived from clinical
trials and clinical practice guidelines.18–21 Additional research is needed to elucidate
the best combination of criteria for clinicians to identify patients who are ready to un-
dergo an SBT and the optimal screening frequency, SBT technique, and SBT duration.
Moreover, the impact of specific interventions on both liberation from the ventilator
(time to first successful SBT) and the endotracheal tube (time to successful extubation)
require clarification and standardization. Additional clarity is also needed regarding the
optimal timing to measure and report extubation success (48 hours vs 72 hours vs
7 days).
Conduct of Spontaneous Breathing Trials

SBTs represent a formal assessment of extubation readiness performed using
reduced or no ventilator support as a test of a patient’s capacity to breathe spontane-
ously for 30 to 120 minutes. SBTs may be conducted using a variety of techniques
including T-piece, low levels of PS with or without positive end-expiratory pressure
(PEEP), continuous positive airway pressure (CPAP), automatic tube compensation,
and other less frequently used techniques.16,22
Data regarding the optimal SBT technique for clinicians to use are conflicting. A phys-
iologic systematic review that examined effort to breathe using alternative SBT tech-
niques found that SBTs conducted with PS decreased work of breathing more than
SBTs conducted with other techniques including T-piece or CPAP.23 Conversely, a
meta-analysis of randomized trials that compared alternative SBT techniques and
reported clinical outcomes found that although patients were not more likely to pass
an SBT using PS with or without PEEP SBTs versus T-piece SBTs, they were 6%
more likely to remain successfully extubated with PS SBTs (number needed to treat
of 22).22 Aligned with these findings, the ATS/ACCP guidelines made a conditional
recommendation for the conduct of SBTs with augmentation of inspiratory pressure.9,24
More recently, Subira and colleagues25 conducted an RCT that compared 30-min-
ute SBTs with PS 8 cm H2O without PEEP (less-demanding technique) to a 2-hour SBT
with T-piece (more demanding technique) for patients who received invasive ventila-
tion for at least 24 hours in 18 Spanish ICUs. The authors found that the less-
demanding SBT technique had an 8.2% absolute increase in the rate of successful
extubation, defined as remaining free of mechanical ventilation 72 hours after first
SBT, without an increase in the rate of reintubation.25 In this trial, participants received
the assigned SBT technique during the first SBT. Subsequently, Thille and colleagues
compared PS (without PEEP) versus T-piece SBTs for patients who were invasively
ventilated for more than 24 hours and deemed to be at “high risk” for reintubation
(>65 years of age or with any underlying chronic cardiac or lung disease) in 31 ICUs
in France.26 The authors found no differences between the alternative SBT techniques
in the median number of ventilator-free days at day 28, and in the rates of extubation
(within 24 hours and within 7 days) and reintubation.26 A large-scale observational
study found that initial SBTs are most commonly conducted using PS with PEEP
(457/930 [49.1%]) or T-piece (236/930 [25.4%]) and less frequently with CPAP (100/
930 [10.8%]) or PS without PEEP (88/930 [9.5%]).27 Four trials, including the aforemen-
tioned trial by Subira and colleagues have compared shorter (20 or 30 minute) versus
longer (120 minute) SBTs and found no important differences in SBT outcome, extuba-
tion outcome, and reintubation rates.25,28–30
Important study design features including the use of daily screening and incorpora-
tion of extubation criteria among criteria to identify SBT candidates, whether SBT
techniques were applied once or repeated until a trial end-point was achieved, and
the reporting of weaning (ie, time to successful SBT) versus extubation (ie, time to
successful extubation) outcomes remain poorly characterized. In addition, no trial

comparing alternative SBT techniques was powered to assess equivalency. Uncer-
tainty remains regarding the role for more frequent screening to identify SBT candi-
dates and the best SBT technique and duration for clinicians to use. Additionally,
we do not know which patients may benefit from longer SBTs and whether certain
patients (ie, chronic obstructive pulmonary disease [COPD], congestive heart failure,
or neuromuscular disease) may benefit from the use of specific SBT techniques.
Optimizing Patients for Liberation from Invasive Ventilation

Analgesics and sedatives are frequently used to enhance patient comfort and prevent
self-extubation. Trials examining the effects of sedation strategies have shown that
sedation protocols focused on minimizing sedation in mechanically ventilated patients
result in shorter duration of ICU stay and a trend toward reduced duration of mechan-
ical ventilation and received a conditional recommendation for patients invasively
ventilated for more than 24 hours in a clinical practice guideline.24 Conflicting evidence
exists regarding the benefits associated with sedation interruption for critically ill pa-
tients. A trial of 336 invasively ventilated patients randomized to either a daily sponta-
neous awakening trial (SAT) followed by an SBT or with sedation as per usual care plus
a daily SBT found that patients in the combined SAT plus SBT (vs usual care plus SBT)
group spent more days breathing without assistance during the 28-day study period
and were discharged from ICU and hospital earlier. Although more patients in the
intervention group self-extubated compared with the control group, a similar number
of patients in both groups required reintubation.31 Conversely, a trial of 430 invasively
ventilated patients randomly allocated to either protocolized sedation plus daily seda-
tion interruption or protocolized sedation alone did not find between-group differences
in the median time to successful extubation, ICU and hospital lengths of stay. Daily
sedation interruption was associated with higher mean daily doses of fentanyl and
midazolam and more daily boluses of opiates and benzodiazepines.32 In a secondary
analysis of this trial, the authors found that patients received higher doses of benzo-
diazepines and opioids at night and higher nighttime doses were associated with
more SBT failures and delayed extubation.33
Critically ill patients, especially those who are severely ill and those who receive pro-
tracted ventilation, are at high risk for the development of ICU-acquired weakness34
and sequelae of immobility may contribute to delayed weaning and extubation failure.
For patients who are invasively ventilated for more than 24 hours, a conditional recom-
mendation (low certainty evidence) supports the use of protocolized rehabilitation
directed toward early mobilization.9
Laryngeal edema is also associated with postextubation stridor and an increased
risk for reintubation. Although a cuff leak test may help to identify laryngeal edema
before extubation and decrease the risk of postextubation stridor,35,36 this approach
may also delay extubation due to false-positive test results.9,10 Guidelines provide a
conditional recommendation to perform a cuff leak test for patients who meet extuba-
tion criteria and are deemed to be at high risk for postextubation stridor (traumatic
intubation, large endotracheal tubes, women, and those ventilated for 1 week or
more).9,10 For patients who have failed a cuff leak test and who are at high risk for post-
extubation stridor, a conditional recommendation supports administration of systemic
steroids 4 hours before extubation.9
Use of Noninvasive Positive Pressure Ventilation for Weaning

Although life-saving, invasive ventilation is associated with ventilator-related compli-
cations, especially VAP. VAP, in turn, is associated with morbidity and an attributable
396 Burns et al
mortality of approximately 13%.37 Cumulative exposure to invasive ventilation is also

associated with the development of long-term sequelae including muscle weak-
ness,38,39 reduced health-related quality of life,40,41 depression,42 delirium,43 posttrau-
matic stress disorder,44,45 and cognitive impairment.46 For these reasons, minimizing
patients’ exposure to invasive ventilation has been identified as a key research priority
by critical care and respiratory societies.2
Investigators have studied the use of NIV as a method to reduce patients’ exposure
to invasive ventilation during weaning by prematurely extubating selected patients to
NIV. NIV, administered with a patient–ventilator interface, provides partial ventilator
support and preserves patients’ ability to cough, swallow, and speak47 but does not
provide airway protection. NIV can augment tidal volumes, reduces RRs, enable appli-
cation of PEEP, and improve gas exchange.48,49 Studies demonstrate that patients
who are treated with NIV receive less-invasive monitoring and sedation50 and experi-
ence less psychological distress.51 In the periextubation period, NIV can be used to
facilitate weaning (direct extubation to NIV for the purpose of weaning); applied
prophylactically for patients who are at risk for extubation failure; or applied after post-
extubation respiratory failure has developed. When NIV is used to facilitate earlier
extubation and weaning, patients who do not meet conventional criteria for extubation
(ie, fail an SBT or are too early to undergo an SBT) are extubated directly to NIV. In
pressure mode, noninvasive support (the difference between inspiratory positive
airway pressure and expiratory positive airway pressure [EPAP]) and EPAP are
reduced over time in a manner similar to reductions in invasive PS in intubated pa-
tients. As such, NIV replaces invasive PS and reduces patients’ exposure to invasive
ventilation and its associated complications.
Noninvasive weaning may be ideally suited to patients with COPD because failure to
wean in this population is characterized by respiratory muscle weakness, gas trapping,
and increased intrinsic PEEP. With NIV, clinicians can administer oxygen, augment
inhaled volume, and apply extrinsic PEEP to counteract intrinsic PEEP.49 NIV has
been shown to augment VT, reduce breathing frequency, improve gas exchange, and
rest the muscles of respiration.48 An international survey of self-reported practices in
liberating critically ill patients from invasive ventilation found that many intensivists
(>50% of respondents in most regions) reported using noninvasive weaning in patients
with COPD but were less likely to use NIV for other indications such as cardiogenic pul-
monary edema or in the postoperative setting.16
A recent systematic review and meta-analysis, including 28 trials (n 5 2066)
compared extubation with NIV for the purpose of weaning versus continued invasive
weaning in critically ill patients.52 Compared with invasive weaning, noninvasive wean-
ing reduced mortality (Fig. 2), VAP (Fig. 3), and weaning failures—all with high-quality
evidence. Compared with invasive weaning, noninvasive weaning also reduced length
of stay in the ICU and hospital, and rates of tracheostomy. Moreover, the noninvasive
(vs invasive) approach to weaning significantly reduced the duration of invasive (endo-
tracheal) ventilation, total duration of ventilation, and the duration of ventilation related
to weaning. Subgroup analysis suggested that the benefits of noninvasive weaning
were greater in COPD versus mixed patient populations, with significant between-
group differences in mortality, ICU length of stay, and reintubation favoring patients
with COPD.52 In this review, patients with COPD were the focus of half of the included
trials and 44.6% of the patients.52 The lack of blinding and inconsistent use of stan-
dardized weaning protocols in both treatment arms and the absence of a sedation
protocol in the invasive weaning arms raises the possibility that control patients
may not have received optimal care in some trials, biasing in favor of the noninvasive
approach to weaning.
Fig. 2. Effect of noninvasive weaning (vs invasive weaning) on mortality. COPD, chronic
obstructive pulmonary disease; M-H, Mantel-Haenszel. (Granton, David MD, et al., High-
Flow Nasal Cannula Compared With Conventional Oxygen Therapy or Noninvasive Ventilation
Immediately Postextubation: A Systematic Review and Meta-Analysis. Critical Care Medicine
48(11):p e1129-e1136, November 2020. https://doi.org/10.1097/CCM.0000000000004576.)
In the largest single trial conducted to date comparing the alternative weaning
strategies, Perkins and coworkers found significant differences in the duration of
invasive ventilation and total duration of ventilation.53 In contrast to the aforemen-
tioned meta-analysis, the authors of this trial did not find differences in rates of mor-
tality or tracheostomy.53 It is important to note 2 key differences in the design of this
trial. First, the trial by Perkins and colleagues enrolled patients with various reasons
for acute respiratory failure and only 4% of their participants included patients with
COPD. Second, the authors were diligent in using protocolized weaning strategies in
both groups and thereby may have reduced performance bias. The difference in
duration of invasive ventilation is, in part, directed by the protocol and early extuba-
tion of patients in the NIV arm. Similarly, the total duration of ventilation is of greatest
interest when it is restricted to the postrandomization period because the preran-
domization period does not reflect the interventions being studied. These factors,
may in part, explain the discordant findings between the results of this large trial
and the meta-analysis.
Compared with a prior meta-analysis conducted by Yeung and colleagues published
in 2018,54 the more recent meta-analysis52 included more trials and documented similar
beneficial effects of NIV on mortality, VAP, duration of invasive ventilation, and ICU stay.
In a sensitivity analysis of 9 trials involving 788 patients who failed an initial SBT, Yeung
398 Burns et al
Fig. 3. Effect of noninvasive weaning (vs invasive weaning) on ventilator-associated pneu-

monia. COPD, chronic obstructive pulmonary disease; M-H, Mantel-Haenszel. (Burns KEA,
Stevenson J, Laird M, et al. Non-invasive ventilation versus invasive weaning in critically ill
adults: a systematic review and meta-analysisThorax 2022;77:752-761. https://doi.org/10.
1136/thoraxjnl-2021-216993.)
and coworkers also identified beneficial effects of noninvasive weaning on hospital

mortality but wide “highest posterior density intervals,” from Bayesian estimates, pre-
cluded a definitive statement regarding the effect of NIV on this outcome.54 The more
recent meta-analysis also identified beneficial effects of noninvasive (vs invasive) wean-
ing on the proportion of weaning failures and tracheostomies, as well as, hospital length
of stay and the duration of ventilation related to weaning; however, these summary
estimates had considerable heterogeneity.52 Aligned with these findings, a recent sys-
tematic review and individual patient meta-analysis of 6 trials highlighted the potential
beneficial effect of NIV after early extubation in reducing the total days spent on invasive
ventilation, although this was not associated with a significant reduction in ICU
mortality.55
The ATS/ACCP guidelines provided a strong recommendation (moderate certainty
evidence) in favor of extubation to preventative NIV for patients who received mechan-
ical ventilation for more than 24 hours and passed an SBT but were considered to be at
high risk of extubation failure.9 The guidelines; however, did not address early extuba-
tion to NIV for patients who failed an initial SBT or were too early to undergo an SBT.
On balance, the above findings support beneficial effects of noninvasive (vs invasive)
weaning on important clinical outcomes especially for patients with COPD. Notwith-
standing, the benefits of noninvasive weaning are unclear in non-COPD patients
and represents an area for future investigation. Enthusiasm for noninvasive weaning
should be tempered by local considerations including the need for standalone
noninvasive ventilators or ventilators capable of providing both forms of ventilation,

and the experience of physicians, nurses, and respiratory therapists to safely imple-
ment noninvasive weaning and perform reintubation if required.
Extubation Decision-Making and Extubation

An international survey found that diverse health-care providers participate in various
aspects of weaning and extubation; however, intensivists are largely responsible for
extubation decision-making.16 During extubation decision-making, clinicians aim to
avoid extubation failure (ie, need for reintubation within hours to days) because it
has been associated with an increased risk of death, ICU length of stay, need for reha-
bilitation following ICU discharge, and hospital costs (US$34,000 per failed extuba-
tion).56–64 Although few studies have examined how extubation decisions are made,
clinicians should use a patient-centered, stepwise to extubation decision-making
including (1) dynamic evaluation of individual patient’s extubation readiness and his/
her risks and consequences of extubation failure, (2) establishing a plan should extu-
bation fail, and (3) mitigating the risk for extubation failure with strategic interventions
performed preextubation or postextubation.
Determining the risk for extubation failure (ie, estimation of future prevalence) in-
volves the science of prediction of extubation outcomes. Readiness for extubation
usually but not always involves an SBT. Surgical patients who are intubated for pro-
cedural general anesthesia and undergo a short period of ventilation may not need a
formal SBT because the likelihood of success is exceptionally high and an SBT may
unnecessarily prolong ventilation.22 However, for acutely hospitalized patients inva-
sively ventilated for less than 24 hours, current guidelines suggest that an SBT be
performed with inspiratory pressure augmentation (conditional recommendation)
as part of the liberation assessment.9,24 In this manner, an SBT not only aids clini-
cians to assess patient’s capacity to assume spontaneous breathing but also in-
forms clinician’s prediction of extubation outcome. Clinicians may perceive that
some patients are at greater risk for the consequences of failed extubation. For
example, patients with advanced coronary artery disease and documented myocar-
dial ischemia, or frail patients recovering from respiratory failure may suffer greater
potential harm following a failed attempt at extubation. In contrast, other patients
may be at lower risk for the consequences of a failed attempt at extubation (eg, sur-
gical patients). The balance of the risks and consequences of a failed extubation aids
clinicians in determining when a trial of extubation should not be attempted, and a
tracheostomy may be considered. Tracheostomy without a trial of extubation is a
feasible option when both the risk and consequences of extubation failure are pro-
hibitive. Identifying patients who benefit from direct tracheostomy remains an impor-
tant area of investigation.27
Several of the previously discussed parameters used in screening protocols to iden-
tify SBT candidates (ie, RSBI) are also used to predict extubation outcome, in addition
to, other routinely performed, bedside assessments, and more novel approaches to
prediction. Bedside assessments, typically performed by respiratory therapists and
nurses, include a patient’s handgrip strength, cough strength, lift his/her head off the
pillow, and ability to follow commands. Although an active area of investigation, several
studies have demonstrated that loss of respiratory variability is associated with65–71 and
is predictive of extubation failure.72–74 In this field of investigation, loss of respiratory
and heart rate variability represent diminished physiologic reserve and/or increased
illness severity.75
Although extubation decisions are made by ICU clinicians daily in practice, few
studies have examined physician’s ability to predict extubation outcomes. A survey
400 Burns et al
of 45 intensivists in the United States identified only fair agreement between physicians
in extubation decision-making but with low accuracy (receiver operating characteristic
area under the curve of 0.35, sensitivity [57%], and specificity [31%]).76 Additionally, a
single-center longitudinal study found that protocolized assessments of extubation
readiness decreased extubation failure rates.77
Postextubation management must be planned before extubation to ensure clarity of
action in the event of patient deterioration. Prompt reintubation is warranted for patients
who demonstrate signs of impending respiratory failure postextubation. However, rein-
tubation and prolonged life-support with a tracheostomy may not be aligned with the
goals of care of some patients. Therefore, a discussion with the patient’s family and le-
gally authorized representatives to clarify goals of care is warranted before extubation.
Occasionally, based on the patient’s preexpressed wishes or values, optimal care may
include extubation with full care while optimizing conditions for success; yet with a clear
plan not to pursue reintubation in the event that the patient deteriorates or is unable to
tolerate breathing on his/her own. A “one-way extubation” may be used for patients
who want an opportunity to recover and regain their prior functional status but do not
wish for prolonged life support, hospitalization, tracheostomy, and rehabilitation.
Risk mitigation of extubation failure involves recognizing specific risk factors and tar-
geting therapies to address modifiable factors. Risk factors may be airway-related (eg,
airway obstruction, excessive secretions, impaired cough, aspiration, and decreased
level of consciousness) or breathing-related (eg, congestive heart failure, hypoxemia,
hypoventilation, pulmonary disease, and impaired consciousness).78 Once identified
these factors should be addressed, where feasible, before extubation. For example,
patients with hypertension, especially in the presence of left ventricular systolic func-
tion, should undergo afterload reduction before and after extubation.79 Diuresis is
commonly used to mitigate risk of extubation failure in the setting of a positive cumula-
tive fluid balance.80 Delirium may increase the risk for extubation failure and should be
treated based on clinical judgment. Instituting risk mitigation strategies before extuba-
tion is appropriate, and it is reasonable to delay extubation if the risk of extubation failure
may be meaningfully reduced.59 Finally, for patients who are at an increased risk for
extubation failure, clinicians must decide whether to apply HFNC81 or NIV82,83 prophy-
lactically after extubation.
Use of High Flow Nasal Cannula After Extubation

HFNC uses a single-limb inspiratory setup and is able to deliver humidified oxygen at
flows much higher than traditional soft plastic nasal cannula. This high flow oxygen, as
high as 60 to 70 L/min, is able to achieve reliably high FiO2 delivery and also more
adequately match the inspiratory demands of a dyspneic patient. Previous random-
ized controlled trials and systematic reviews84 have demonstrated the benefit of
HFNC in patients with acute hypoxemic respiratory failure and newer data have shown
similar benefit in hypercarbic respiratory failure.85 As compared with bilevel NIV,
HFNC is better tolerated by patients, more comfortable, and usually allows patients
to eat and speak during treatment.
Because HFNC is a relatively new oxygen-delivery strategy in adults, the evidence
base is less well developed compared with that of NIV. Few studies have examined
HFNC as a tool for weaning or to facilitate early extubation and, as opposed to NIV.
However, there are some data to support delivery of high flow oxygen in tracheostom-
ized patients to increase airway pressure and reduce work of breathing during trache-
ostomy collar trials; however, these data are limited to small physiology-based
crossover trials.86 Use of high flow for these indications remains variable given the
sparse evidence supporting its use.
HFNC is more widely used to help with the transition off invasive mechanical
ventilation after extubation. The sudden loss of positive pressure during extubation
may be abrupt, and many patients experience postextubation dyspnea with a
smaller proportion require reintubation. NIV is used in this setting but is associated
with limitations, especially related to patient comfort and delivery of care. When
considering oxygen support in the postextubation period, prophylaxis is key
because data suggest once postextubation respiratory failure develops, the use
of noninvasive supports may just delay reintubation and worsen patient out-
comes.87 When used for prophylaxis following extubation, data demonstrate that
HFNC probably reduces the need for reintubation (pooled RR, 0.46; 95% CI,
0.30–0.70; moderate certainty, Fig. 4) although with no effect on mortality (RR,
0.93; 95% CI, 0.57–1.52; moderate certainty). Based on this, a recent guideline
suggested that the use of HFNC as opposed to conventional oxygen therapy
(COT) for patients who are intubated more than 24 hours and have any high-risk
feature (conditional recommendation, moderate certainty evidence).84 The data un-
derpinning these recommendations were derived from 5 trials81,88–91 that
compared HFNC to COT and 3 trials92–94 that compared HFNC with NIV (bilevel
or CPAP). The definition for high risk varied with the largest trial92 defining high
risk as at least one of the following: age older than 65 years, congestive heart fail-
ure, moderate–severe COPD, Acute Physiology and Chronic Health Evaluation II
score greater than 12, body mass index greater than 30, airway patency or secre-
tion problems, difficulty weaning, 2 or more comorbidities, or duration of ventilation
greater than 7 days. The guideline panel also suggested continued use of NIV as
opposed to HFNC (conditional recommendation, low certainty evidence) for pa-
tients who clinicians would normally extubate to NIV, especially those with
COPD. This practice is supported by recently updated meta-analysis that demon-
strated a reduction in mortality (RR, 0.57; 95% CI, 0.44–0.74; high certainty), wean-
ing failure (RR, 0.59; 95% CI, 0.43–0.81; high certainty), and ICU/hospital length of
stay when using NIV to facilitate weaning from invasive mechanical ventilation in
selected patients, mostly those with underlying structural lung disease such as
COPD.52
Fig. 4. Effect of postextubation HFNC on risk of reintubation. df, degrees of freedom;

HFNC, high flow nasal cannula; NIV, noninvasive ventilation. (Burns KEA, Stevenson J,
Laird M, et al. Non-invasive ventilation versus invasive weaning in critically ill adults: a sys-
tematic review and meta-analysisThorax 2022;77:752-761. https://doi.org/10.1136/thoraxjnl-
2021-216993.)
402 Burns et al
SUMMARY
Increasing evidence supports specific approaches to liberate patients from invasive

ventilation including the use of liberation protocols, inspiratory assistance during
SBTs, early extubation of patients with COPD to NIV, and prophylactic use of noninva-
sive support strategies after extubation. Additional research is needed to elucidate the
best criteria to identify patients who are ready to undergo an SBT and to inform optimal
screening frequency, the best SBT technique and duration, extubation assessments,
and extubation decision-making. Additional clarity is also needed regarding the optimal
timing to measure and report extubation success (48 hours vs 72 hours vs 7 days) and
to standardize reporting of weaning (SBT outcome) and extubation outcomes.
CLINICS CARE POINTS
Clinicians should use a protocolized approach to weaning and extubation with

individualized consideration of patient’s goals and values, as well as, the risks and
consequences of extubation failure. Liberation from invasive ventilation is a multistep
process involving optimizing patients for liberation from invasive ventilation, screening to
identify candidates who are ready to undergo a breathing trial (SBT), conduct of an SBT,
assessment for extubation, and extubation where feasible.
An updated meta-analysis supports the beneficial effects of early extubation to NIV (vs
continued invasive weaning) on important clinical outcomes especially for patients with
COPD. The benefits of noninvasive weaning are unclear in non-COPD patients. Application of
noninvasive weaning in practice should be tempered by local considerations.
A patient-centered, stepwise approach to extubation decision-making involves (1) dynamic
evaluation of individual patient’s extubation readiness and his/her risks and consequences
of extubation failure, (2) establishing a plan should extubation fail, and (3) mitigating the
risk for extubation failure with strategic interventions performed before or after extubation.
HFNC is a noninvasive oxygenation strategy that can aid in transitioning patients off of
invasive ventilation.
DISCLOSURE
K.E.A. Burns holds a Canadian Institutes of Health Research grant to investigate

weaning strategies and Physician Services Incorporated Mid Career Research Award.
A.J. Seely is the founder and CEO of Therapeutic Monitoring Systems, which holds
global licensing rights for intellectual property related to Extubation Advisor (a tool
designed to aid extubation assessment) and tools being developed in the Ottawa Hos-
pital Research Institute Dynamical Analysis Laboratory that require regulatory
approval and commercialization for bedside application. B. Rochwerg has no conflicts
of interest to declare.
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Ven t i l a t o r We a n i n g a n d

Crit Care Clin 40 (2024) 391–408

Assessing Readiness to Undergo Spontaneous Breathing Trials

Conduct of Spontaneous Breathing Trials

successful extubation) outcomes remain poorly characterized. In addition, no trial

Optimizing Patients for Liberation from Invasive Ventilation

Use of Noninvasive Positive Pressure Ventilation for Weaning

mortality of approximately 13%.37 Cumulative exposure to invasive ventilation is also

Fig. 3. Effect of noninvasive weaning (vs invasive weaning) on ventilator-associated pneu-

and coworkers also identified beneficial effects of noninvasive weaning on hospital

noninvasive ventilators or ventilators capable of providing both forms of ventilation,

Extubation Decision-Making and Extubation

Use of High Flow Nasal Cannula After Extubation

Fig. 4. Effect of postextubation HFNC on risk of reintubation. df, degrees of freedom;

Increasing evidence supports specific approaches to liberate patients from invasive

CLINICS CARE POINTS

 Clinicians should use a protocolized approach to weaning and extubation with

K.E.A. Burns holds a Canadian Institutes of Health Research grant to investigate

1. Esteban A, Alia I, Ibanez J, et al. Modes of mechanical ventilation and weaning. A

of in 596 patients following adult cardiac surgery. Eur J Anaesthesiol 1997;14:

invasive ventilation for acute hypercapnic respiratory failure in adults: a system-

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