Protocolos Weaining 2011

RESEARCH
BMJ: first published as 10.1136/bmj.c7237 on 13 January 2011. Downloaded from http://www.bmj.com/ on 23 January 2019 by guest. Protected by copyright.
Use of weaning protocols for reducing duration of
mechanical ventilation in critically ill adult patients: Cochrane
systematic review and meta-analysis
Bronagh Blackwood, lecturer in nursing,1 Fiona Alderdice, director,1 Karen Burns, clinician scientist,2 Chris
Cardwell, lecturer in medical statistics,3 Gavin Lavery, consultant in intensive care medicine,4 Peter
O’Halloran, lecturer in nursing1
1
Nursing and Midwifery Research ABSTRACT INTRODUCTION
Unit, Queen’s University Belfast, Objective To investigate the effects of weaning protocols
Belfast, BT9 5BN, Northern Ireland
Observational studies have shown that prolonged
2
St Michael’s Hospital,
on the total duration of mechanical ventilation, mortality, mechanical ventilation of critically ill patients is asso-
Interdepartmental Division of adverse events, quality of life, weaning duration, and ciated with adverse clinical outcomes. Patients who are
Critical Care Medicine, Toronto, length of stay in the intensive care unit and hospital. slower to breathe without mechanical ventilation have
Ontario, Canada
3 Design Systematic review. higher rates of mortality1 2 and morbidity, including
Centre for Public Health, Queen’s
University Belfast, Belfast Data sources Cochrane Central Register of Controlled ventilator associated pneumonia3-5 and ventilator asso-
4
Belfast Health and Social Care Trials, Medline, Embase, CINAHL, LILACS, ISI Web of ciated lung injury.6-8 Mechanical ventilation should
Trust, Royal Victoria Hospital, Science, ISI Conference Proceedings, Cambridge therefore probably be discontinued as soon as patients
Belfast, Belfast are capable of breathing independently. Moreover,
Correspondence to: B Blackwood
Scientific Abstracts, and reference lists of articles. We did
[email protected] not apply language restrictions. patients who are dependent on a ventilator generally
remain in intensive care, requiring specialised care and
Review methods We included randomised and quasi-
Cite this as: BMJ 2011;342:c7237 frequent monitoring. In the current climate of limited
doi:10.1136/bmj.c7237 randomised controlled trials of weaning from mechanical
availability of intensive care beds, maximising the use
ventilation with and without protocols in critically ill
of limited intensive care resources (including nursing
adults.
and equipment costs) is an important goal of providing
Data selection Three authors independently assessed
care to critically ill patients. For these reasons, discon-
trial quality and extracted data. A priori subgroup and
tinuing mechanical ventilation in a timely and safe way
sensitivity analyses were performed. We contacted study
should lead to desirable outcomes for patients and clin-
authors for additional information.
icians alike, and strategies that assist discontinuation
Results Eleven trials that included 1971 patients met the should be robustly evaluated.
inclusion criteria. Compared with usual care, the The process leading to discontinuing mechanical sup-
geometric mean duration of mechanical ventilation in the port is known as weaning. Identifying when the patient
weaning protocol group was reduced by 25% (95% is ready to wean and deciding on the most appropriate
confidence interval 9% to 39%, P=0.006; 10 trials); the method of weaning is influenced by the judgment and
duration of weaning was reduced by 78% (31% to 93%, experience of the doctor.9 Doctors tend to underesti-
P=0.009; six trials); and stay in the intensive care unit mate the probability of successfully stopping mechani-
length by 10% (2% to 19%, P=0.02; eight trials). There cal ventilation10 and predictions, based on judgment
was significant heterogeneity among studies for total alone, have low sensitivity (ability to predict success)
duration of mechanical ventilation (I2=76%, P<0.01) and and specificity (ability to predict failure).11 Until
duration of weaning (I2=97%, P<0.01), which could not be recently, there have been few standards of care in this
explained by subgroup analyses based on type of unit or area that are based on scientifically sound data. As a
type of approach. result, wide variation exists in weaning practice. There
Conclusion There is evidence of a reduction in the are several options, or weaning methods, for decreasing
duration of mechanical ventilation, weaning, and stay in support. They include intermittent T piece trials invol-
the intensive care unit when standardised weaning ving short time periods of spontaneous breathing
protocols are used, but there is significant heterogeneity through a T piece circuit while the patient is still intu-
among studies and an insufficient number of studies to bated; synchronised intermittent mechanical ventila-
investigate the source of this heterogeneity. Some studies tion involving gradual reductions in the ventilator rate,
suggest that organisational context could influence by increments of 1 to 4 breaths/min; pressure support
outcomes, but this could not be evaluated as it was ventilation involving the gradual reduction of pressure
outside the scope of this review. by increments of 2 to 6 cm H2O; spontaneous breathing
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ventilator output to the patient’s needs with closed

Records identified through other sources (n=29): Records identified through database search loop systems. These systems measure and interpret
Cambridge Scientific abstracts (n=15) (n=5987):
www.controlled-trials.com (n=14) CENTRAL (n=406) respiratory data in real time and provide continual
Contact with first authors (n=0) ISI Web of Science and Conference adjustment of the level of assistance within targeted
Reference search of included studies (n=0) Proceedings (n=1381)
LILACS (n=776)
values. It is suggested that through enabling “inter-
CINAHL (n=107) action” between the patient and the ventilator, the
Embase (n=2324) closed loop systems can improve tolerance of mechan-
ical ventilation and reduce the work of breathing.20
Multiple commercial computerised ventilation and
Further information Records excluded Full paper Records excluded due
sought (n=7) due to not review (n=14) to overlap or not weaning programs have been developed, including
meeting inclusion meeting inclusion adaptive support ventilation, proportional assist venti-
criteria (n=22) criteria (n=5973)
lation, and pressure support ventilation (SmartCare).21
Several studies have explored the use of weaning
Excluded (n=4)41 42 47 48 Excluded (n=5)43-46 49 protocols in clinical practice and shown that they can
be safe and effective in reducing the time spent on
Ongoing (n=1) mechanical ventilation.22 Other studies in various
populations, however, have not shown benefit.23-25
Included (n=11)10 16-18 23 24 31-34 36 The discordant results of these studies might reflect
the fact that protocols vary in more ways than in com-
Fig 1 | Identification of studies on weaning from mechanical ventilation position alone. While many protocols include criteria
for readiness to wean and guidelines for reducing ven-
tilator support, the specific criteria and guidance vary.
through a ventilator circuit with the application of con- Furthermore, not all protocols include extubation cri-
tinuous positive airway pressure; and combinations of teria. Protocols are implemented in different environ-
these and newer options, such as bi-level positive airway ments by healthcare professionals (including nurses,
pressure. The evidence is equivocal as to which method respiratory therapists, and doctors) and by automated
is superior, though it has been suggested that synchro- (computerised) systems. Limited evidence suggests
nised intermittent mechanical ventilation is the least that nurses and allied health professionals might
effective method.12-14 adhere to protocols more than physicians.26 Conse-
Doctors have different experiences, skills, and wean- quently, recent studies have compared weaning proto-
ing philosophies, and, in view of the potential for var- cols led by nurses or respiratory therapists with
iation, there has been an increasing interest in traditional or medical directed weaning.16-18
providing more consistent practice in intensive care We synthesised the best current evidence for the
units by developing weaning protocols that provide effectiveness of weaning protocols compared with no
structured guidance. Protocols are intended to protocols in weaning critically ill adults from invasive
improve efficiency of practice by following an expert mechanical ventilation. The protocol and the review
consensus to reduce variation produced by the appli- can be found in the Cochrane Database of Systematic
cation of individual judgment and experience.15 In Reviews.27
general, there are three components to a weaning pro-
tocol. The first component is a list of objective criteria METHODS
(often referred to as “readiness to wean” criteria) based Criteria for inclusion of studies
on general clinical factors to help to decide if a patient is Studies and participants
ready to breathe without the help of a ventilator, such We included randomised and quasi-randomised con-
as that used by Ely and colleagues.16 The second com- trolled trials. The study population included adults
ponent consists of structured guidelines for reducing receiving invasive mechanical ventilation with a naso-
ventilatory support. This might be abrupt (for exam- tracheal or orotracheal tube. We excluded studies in
ple, spontaneous breathing trials on a T piece) or gra- children, non-invasive ventilation as a weaning strat-
dual with a stepwise reduction in mechanical support egy, or patients with tracheotomies.
(for example, synchronised intermittent mechanical
ventilation or pressure support ventilation) such as Interventions
that used by Brochard et al,12 Esteban et al,14 Kollef et Weaning per protocol was defined as a method of limit-
al,17 and Marelich et al.18 The third component is a list ing the duration of invasive ventilation that included at
of criteria for deciding if the patient is ready for extuba- least the first two of: a list of objective criteria based on
tion, such as that used by Hendrix et al.19 In many general clinical factors for deciding if a patient is ready
intensive care units, protocols are presented as written to discontinue mechanical ventilation; structured
guides or algorithms, and ventilator settings are manu- guidelines for reducing ventilatory support, such as a
ally adjusted by healthcare professionals. More trial of spontaneous breathing or a stepwise reduction
recently, progress in ventilator microprocessor tech- in support (for example, synchronised intermittent
nology has enabled the development of computer mechanical ventilation or pressure support ventila-
assisted management of ventilation and weaning. tion); and a list of criteria for deciding if the patient is
Computerised ventilatory management adapts the ready for extubation.
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Table 1 | Characteristics of studies on weaning from mechanical ventilation excluded analysis design, setting and participants, inclusion and exclusion
criteria, and interventions and outcomes. In addition, we
Reason for exclusion
41
assessed risk of bias using the Cochrane Collaboration’s
Beale et al, 2008 Control group subject to weaning protocol
domain based evaluation tool for assessing the risk of
Butler et al, 200742 Trial stopped because of recruitment problems, unable to obtain data bias.28 We assessed adequacy of the generation of the
Donglemans et al, 200943 Control group subject to weaning protocol allocation sequence; concealment of allocation; blinding
East et al, 199944 Unable to identify weaning practice in control group procedures; whether or not outcome data were ade-
Lellouche et al, 200645 Control group subject to weaning protocol quately addressed; whether the study was free from sug-
McKinley et al, 200146 Unable to identify weaning practice in control group gestion of selective outcome reporting; and whether it
Papirov et al, 200847 Control group subject to weaning protocol was free from other problems that could put it at risk of
Scholz et al, 200848 Control group subject to weaning protocol bias. BB contacted authors of included studies if insuffi-
Taniguchi et al, 200949 Control group subject to weaning protocol cient information was available in the publications to
obtain missing data. Disagreement was resolved through
consultation with a fourth author (FA).
We did not exclude studies that did not include for-
mal extubation criteria as not all studies included this
Data synthesis
component. Furthermore, delay in extubation can be
Data were processed in accordance with the Cochrane
caused by organisational factors and not necessarily by
handbook.29 Intervention effects were expressed with
delays in weaning. Usual weaning practice was defined
odds ratios and 95% confidence intervals for dichoto-
as the usual practice in an intensive care unit (as stated
mous data and mean differences and 95% confidence
by the authors) where no written guidelines were
intervals for continuous data. The degree of heteroge-
applied. neity was informally evaluated by visual inspection of
forest plots, and more formally by measuring the
Outcome measures
impact of heterogeneity with the I2 statistic (I2 >50%
The primary outcome measure was the duration of indicates significant heterogeneity), and tested with
mechanical ventilation. Secondary outcome measures the χ2 statistic (P<0.05).30 We used a fixed effects
included mortality (intensive care unit and hospital); model for meta-analysis, except where we identified
adverse events (re-intubation, tracheostomy, pro- statistical heterogeneity when we used a random effects
tracted mechanical ventilation); weaning duration; model. The data for duration of mechanical ventila-
length of stay in intensive care unit; length of stay in tion, duration of weaning, and length of stay in the
hospital; and cost. intensive care unit and hospital were skewed so we
log transformed these data for the primary analyses.
Search methods for identification of studies In three studies the authors provided the means and
We used the standard search strategy of the Cochrane standard deviations on the log scale.16 31 32 In four stu-
Anaesthesia Review Group of the Cochrane Colla- dies in which only means and standard deviations of
boration. The search included the Cochrane Central the un-logged data were available10 17 33 34 we used
Register of Controlled Trials (CENTRAL) (Cochrane approximations to calculate the mean and standard
Library 2010, Issue 1), Medline (1950 to January 2010), deviation on the log scale using method 1 in Higgins
Embase (1988 to January 2010), CINAHL (1937 to et al.35 In four studies we could obtain outcomes
January 2010), ISI Web of Science and Conference reported only as medians and interquartile
Proceedings (1970 to January 2010), and LILACS ranges18 23 24 36 so we approximated the mean using the
(1982 to January 2010). The search strategy and terms median37 and calculated approximate standard devia-
are detailed in the online review at http://onlinelibrary. tion estimates from the interquartile range on the log
wiley.com/o/cochrane/clsysrev/articles/CD006904/ scale.38 The difference between the intervention and
frame.html. In addition, we searched reference lists of control group in the mean of a variable on the log
all identified study reports, contacted authors for scale was exponentiated to give the ratio of geometric
further information on ongoing trials, and searched means of the variable on the un-logged scale. This was
the meta-register of controlled trials at www.con generally reported as a percentage increase (or reduc-
trolled-trials.com. No language restrictions were tion) in geometric mean in the treatment group com-
applied. pared with the control group for ease of understanding
(see Bland and Altman39 for more details).
Selection of studies, data extraction, and quality We performed a sensitivity analysis to examine two
assessment areas of uncertainty. Firstly, we examined the impact of
Two authors (BB and POH) independently scanned titles excluding studies with a high risk of bias (in one or
and abstracts identified by electronic searching, manual more of the six domains) on the total duration of
searches, and contacts with experts. Three authors (BB, mechanical ventilation and weaning. Secondly, we
KB, POH) retrieved and evaluated the full text versions examined the results using the un-logged data. We per-
of potentially relevant studies and independently extra- formed a subgroup analysis to assess the impact of the
cted data using a modified paper version of the Cochrane approach to delivering the protocol (professional led
Anaesthesia Review Group’s data extraction form (ver- or computer driven) and type of intensive care unit
sion 3 January 2007). Data were extracted on study (medical, surgical, neurological, or mixed) on total
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Table 2 | Summary of included studies of weaning in critically ill adults on mechanical ventilation
Study Methods No of patients Interventions Outcomes Country, setting
16
Ely, 1996 RCT 300 Protocol delivered by RNs and RTs v physician Total duration of MV, weaning duration, length of stay in US, one medical and one
judgment ICU, adverse events, ICU and hospital costs, length of stay coronary ICU, closed units
in hospital, mortality
Kollef, 199717 RCT 357 Protocol delivered by RNs and RTs v physician Total duration of MV, reintubation, length of stay in US, two medical and two
judgment hospital, hospital mortality, hospital cost, MV time before surgical ICUs
weaning, protracted weaning >7 days
Krishnan, 200423 Quasi- 299 Protocol delivered by RNs and RTs v physician Total duration of MV, duration of SBT preceding MV US, one medical ICU
RCT judgment discontinuation, length of stay in ICU, location after ICU
discharge, ICU and hospital mortality, reinstitution of MV
Marelich, 200018 RCT 335 Protocol delivered by RNs and RTs v physician Total duration of MV, incidence of VAP, weaning duration, US, one medical and one
judgment (medical ICU) and standardised ventilator discontinuation failure rate surgical/trauma ICU
approach (surgical ICU)
Namen, 200124 RCT 100 Protocol delivered by RTs v practice (not stated) Total duration of MV, length of stay in ICU, time to US, neurosurgical patient
successful extubation, adverse events, ICU and hospital population
costs
Navalesi, 200831 RCT 318 Protocol v daily evaluation and physician Rate of extubation, duration of MV, length of stay in ICU and Italy, one closed neuro ICU
judgment hospital, ICU mortality, tracheostomy
Piotto, 200834 Quasi- 36 Protocol delivered by RT v gradual reduction in Reintubation rate, length of stay in CCU, time from Brazil, one CCU
RCT RR and PS possible SBT according to RT intubation to start of weaning, start of weaning to
physician judgment extubation, SBT to extubation, presence of respiratory
infection in patients requiring reintubation, mortality of
reintubated patients
Rose, 200832 RCT 102 Computerised protocol (SmartCare) v weaning Time to separation, total duration of MV, intubation to first Australia, one mixed medical,
of PS and PEEP according to usual local practice extubation and successful extubation, length of stay in ICU surgical, trauma ICU
and hospital, ICU mortality, rate of successful extubation,
rate of reintubation, rate of non-invasive ventilation after
extubation.
Simeone, 200233 RCT 49 Protocol v physician judgment Total duration of MV, length of stay in ICU, No of Italy, one cardiac surgical ICU
postoperative complications
Stahl, 200936 RCT 60 Computerised protocol (SmartCare) v weaning Duration of ventilator weaning, total duration of MV, length Germany, one surgical ICU
of PS according to physician judgment of stay in ICU, reintubation within 48 hours, physician and
nursing workload, ICU and hospital mortality
Strickland, RCT 15 Computerised protocol (Supersport model) v Time spent with RR 8 or >30, time spent with TV <5 mL/kg, no US, one medical ICU
199310 SIMV and PS weaning according to physician of arterial blood gases drawn, weaning duration, MV time
judgment before weaning.
RCT=randomised controlled trial; CCU=coronary care unit; ICU=intensive care unit; MV=mechanical ventilation; PEEP=positive end expiratory pressure; PS=pressure support; RN=registered
nurse; RR=respiratory rate; RT=respiratory therapists; SBT=spontaneous breathing trial; SIMV=synchronised intermittent mechanical ventilation; TV=tidal volume.
duration of mechanical ventilation. We could not do a Germany, 36 and Australia. 32 Participants were
subgroup analysis on type of protocol because only recruited from various intensive care units including
two studies used the same protocol.16 24 medical, 10 16-18 23 coronary, 16 34 surgical, 17 36 surgical/
The data were entered into Review Manager soft- trauma, 18 mixed (including medical, surgical/trauma
ware by BB, and POH checked data entry. All analyses patients), 32 neurosurgical, 24 31 and cardiac surgical. 33
were conducted with Review Manager.40 Three trials were conducted in multiple units 16-18 and
seven in single units. 10 23 31-34 36 One trial specified the
RESULTS population (neurosurgical) rather than the unit. 24 Four
Description of studies studies described the ventilatory modes used in “usual
Search results—The search of electronic databases practice” in the control group, and these involved a
retrieved 6016 citations: 5987 references from the reduction in respiratory rate in synchronised inter-
database search and 29 relevant references from web mittent mechanical ventilation and a reduction in pres-
based sources. After reviewing the titles and abstracts, sure support in pressure support ventilation, 19 34 a
we identified and retrieved 14 database references in reduction in positive end expiratory pressure and pres-
full text for review and obtained further information on sure support ventilation, 32 and a reduction in pressure
seven unpublished trials located on the controlled support ventilation. 36 The seven remaining described
trials website. Figure 1 summarises the study selection usual practice as weaning according to the physician’s
process, and table 1 provides details of excluded discretion without describing what this constituted.
studies 41-49 and reasons for their exclusion. Protocols were delivered by registered nurses and
Included studies—We included 11 studies with 1971 respiratory therapists,16-18 23 respiratory therapists,24 or
participants (table 2). The sample sizes ranged from physicians, registered nurses, and respiratory
15 to 357 participants. All studies took place in inten- therapists,31 or computer driven10 32 36 or not
sive care units in hospitals. Trials were conducted in stated.33 34 All studies used criteria on readiness to
the United States, 10 16-18 23 24 Brazil, 34 Italy, 31 33 wean for protocol entry, but the criteria varied greatly.
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Table 3 | Criteria for readiness to wean in critically ill adults on mechanical ventilation
Inflammatory response
Study Assessment Oxygenation Other respiratory factors Cardiovascular Neurological (temperature) Medication Other
Ely, 199616 Daily screen PaO2/FIO2 >200 mm Hg PEEP ≤5 cm H2O, f/VT ≤105 — — — No vasopressors or Adequate cough
breaths/L/min sedation
Kollef, 199717 Protocol entry PaO2/FIO2 >200 mm Hg PEEP ≤5 cm H2O, RR ≤35 HR <140 beats/min Awake and — No vasoactive or —
criteria breaths/min orientated inotropic agents
Krishnan, 200423 Daily screen SpO2 ≥92%, FIO2 ≤0.5 PEEP ≤5 cm H2O Stable CAD, HR <140 No raised ICP — No paralytics Cough and gag reflex present.
beats/min Responsive to stimulus
Marelich, 200018 Two daily screens PaO2/FIO2 ≥200 mm Hg — MAP ≥60 mm Hg GCS ≥10 or — No vasopressors, 5 µg/ Adequate cough not limited by
tracheostomy kg/min dopamine pain
Namen, 200124 Daily screen PaO2/FIO2 >200 mm Hg PEEP ≤5 cm H2O, f/VT=105 — — — No vasopressors or Adequate cough
sedation
Navalesi, 200831 Daily screen PaO2/FIO2 >200 mm Hg, FIO2 PEEP ≤5 cm H2O HR ≤125 beats/min, SBP GCS ≥8 <38.5°C No vasopressors, 5 µg/ Adequate cough. Suctioning
≤0.4, pH ≥7.35, PaCO2 ≥90 mm Hg kg/min dopamine <2/hour. Normal Na blood
≤50 mm Hg values
Piotto, 200834 Daily screen PaO2/FIO2=150-300 mm Hg, — MAP ≥60 mm Hg, HR Awake GCS ≥9 <37.8°C Minimum sedation. No or Cause of MV resolved.
FIO2 ≤0.4, PaO2 ≥60, Hb=80- ≤140 beats/min low vasopressors Effective cough. Metabolic
100 g/L stability. No hydroelectrolyte
disorders
Rose, 200832 Inclusion criteria PaO2/FIO2 >150 mm Hg or PEEP ≤8 cm H2O. Plateau Haemodynamically GCS >4 36-39°C — No surgery anticipated. MV
SaO2 ≥90% with FIO2=0.5 pressure ≤30 cm H2O. stable >24 hour
Successful 30 min SBT with PS
20 cm H2O to achieve VT >200
mL
Simeone, 200233 Inclusion criteria PaO2/FIO2 >200 mm Hg, FiO2 PEEP <4 cm H2O, RR <35 Haemodynamically Awake and >35<38°C — Urine output >100 ml/hour.
<0.5, pH 7.3-7.5, PaO2 30- breaths/min (2 min after MV stable conscious Normal satisfactory chest x ray
50 mm Hg, SaO2 >90%, discontinuation). Dynamic result
Hb >80 g/L. Pulse oximeter compliance >22 mL/cm H2O.
oxygenation stable. Static compliance >33 mL/cm
Cardiopulmonary bypass H2O. Vital capacity >10 ml/kg.
time <150 min MIP ≥−15 cm H2O
Stahl, 200936 Inclusion criteria FIO2 ≤0.5, PaO2 >75 mm Hg or PEEP ≤10 cm H2O Haemodynamically — — 5 µg/kg/min dopamine MV >24 hour. Breathing
SaO2 >90%, pH ≤7.2, stable spontaneously. Ramsey
Hb ≥70 g/L sedation score ≤3
Strickland, 199310 Inclusion criteria FIO2 ≤0.4, pH ≥7.3-7.5, PcO2 NIF ≤−20 cm H2O, FVC ≥10 mL/ Haemodynamically — 37°C — Judged ready to wean by
≥30-50, SaO2 ≥90% with kg, TV=10-15 mL/kg stable physician. Feeding: parenteral
SIMV rate between 6-10, or tube. Stable renal function.
PS=20 cm H2O Normal electrolytes
PaO2=arterial oxygen tension; FIO2=fractional inspired oxygen; SpO2=pulse oximeter oxygen saturation; CAD=coronary artery disease; CXR=chest x ray; GCS=Glasgow coma scale; FVC=forced vital capacity; Hb=haemoglobin; HR=heart rate;
MAP=mean arterial pressure; MIP=maximal inspiratory pressure; MV=mechanical ventilation; NIF=negative inspiratory force; PEEP=positive end expiratory pressure; PS=pressure support; RR=respiratory rate; SBP=systolic blood pressure;
SIMV=synchronised intermittent mechanical ventilation; f/TV=frequency to tidal volume.
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Table 4 | Characteristics of weaning methods for critically ill adults on mechanical ventilation
Extubation
Study Screen Weaning method criteria
Ely, 199616 Daily SBT two hour on CPAP 5 cm H2O Notify doctor
Kollef, 199717 SBT 30-60 min on CPAP 5 cm H2O, PS to 6 cm H2O. PS stepwise reduction to 6 cm H2O. All yes
IMV stepwise reduction to 0 breaths/min, on PEEP 5 cm H2O and PS 6 cm H2O for 30-60
min
Krishnan, 200423 Daily SBT one hour on CPAP 5 cm H2O Notify doctor
Marelich, 200018 Twice daily <72 hour admissions: SBT 30 min on PS=8 cm H2O and PEEP=8 cm H2O. >72 hour Both notify doctor
admissions: PEEP, IMV, and PS stepwise reductions to achieve FIO2 0.5, PEEP=8 cm H2O,
IMV=6 b/min, PS=8 cm H2O then SBT as above
Namen, 200124 Daily SBT two hour on CPAP 5 cm H2O Notify doctor
Navalesi, 200831 Daily SBT one hour on CPAP 2-3 cm H2O, FIO2 0.4 Yes
Piotto, 200834 Daily SBT two hour on PS 7 cm H2O, PEEP=5 cm H2O, FIO2=0.4, RR=1b/min Yes
Rose, 200832 None Computer automated SmartCare stepwise reductions to PS 7 cm H2O & PEEP 5 cm H2O No
Simeone, 200233 None SIMV and PS stepwise reductions to SIMV 0 breaths/min and PS 4 cm H2O Yes
Stahl, 200936 None Computer automated SmartCare stepwise reductions to PS Yes
Strickland, 199310 None Computer automated stepwise reductions in SIMV and PS to RR 2 b/min and PS 5 cm H2O No
CPAP=continuous positive airway pressure; IMV=intermittent mechanical ventilation; PEEP=positive end expiratory pressure; PS=pressure support;
SBT=spontaneous breathing trial; SIMV=synchronised intermittent mechanical ventilation; RR=respiratory rate.
They ranged from a list of five to 19 criteria, and the pressure support of 6 or 7 cm H2O. In pressure support
variables measured were not consistent among studies. weaning protocols, pressure support was reduced to
All studies included criteria that measured oxygena- levels ranging from 4 to 8 cm H2O before extubation.
tion (namely, PaO2 and FIO2), but not all included cri- With protocols for synchronised intermittent mechani-
teria relating to cardiovascular, neurological, cal ventilation weaning, there was a reduction in respira-
inflammatory response, medication, or other factors tory rate to rates of between zero and six breaths a
(table 3). Readiness for weaning was assessed twice minute before a trial of spontaneous breathing or extu-
daily, 18 daily, 16 23 24 31 34 or stated as inclusion or proto- bation. In automated weaning protocols pressure sup-
col entry criteria. 10 17 32 33 36 port was reduced to levels between 5 or 7 cm H2O and
There was also considerable variation in the weaning synchronised intermittent mechanical ventilation to two
methods (table 4). In three trials the intervention was breaths a minute.
delivered by a computer controlled weaning system:
two used an automated computerised protocol
delivered by Draeger EvitaXL ventilator with Smart-
Incomplete outcome data addressed

CareTM/PS software that titrated pressure support and
Adequate sequence generation
initiated spontaneous breathing trials, 32 36 and one used
Free from selective reporting

an early computer prototype (Supersport model 2) that
Allocation concealment
titrated respiratory rate and pressure support. 10 Six stu-

dies used protocol based weaning that included a trial of Free from other bias
spontaneous breathing. 16 18 23 24 31 34 For patients who had
been ventilated for more than 72 hours, Marelich et al 18
Blinding
used a stepwise reduction in positive end expiratory

pressure, synchronised intermittent mechanical ventila-
tion, and pressure support before the spontaneous Ely 199616 + + + + + +
breathing trial. Two trials used weaning protocols con-
Kollef 199717 + + + + + +
sisting of stepwise reductions in synchronised inter-
23
mittent mechanical ventilation and pressure support Krishnan 2004 – – ? + + +
with extubation. 33 34 Kollef et al implemented the proto- Marelich 200018 + + + + + +

cols in four intensive care units and used several different Namen 2001 24
? ? ? + + ?
protocols: spontaneous breathing trial and extubation; Navalesi 200831 + ? + + + +
synchronised intermittent mechanical ventilation reduc-
Piotto 200834 – – – ? + ?
tion and extubation; pressure support reduction and
extubation. 17 Methods of trials of spontaneous breathing Rose 200832 + + + + + +
and the lower parameters stated by authors as end points Simeone 200233 + + + ? ? ?
before discontinuation or extubation varied greatly Stahl 200936 + + + + + ?
among trials. The duration of spontaneous breathing 10
Strickland 1993 + + + + + +
trial ranged from 30 to 120 minutes through a T tube
or ventilator circuit with continuous positive airway
pressure ranging from 2 to 5 cm H2O, with or without Fig 2 | Summary of risk of bias assessment

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Weaning protocol Usual care
Type of intensive care unit Mean (SD) Total Mean (SD) Total Mean difference Weight Mean difference
log hours log hours (95% CI) (%) (95% CI)
Mixed
Kollef 199717 3.3 (1.2) 179 3.6 (0.9) 178 12 -0.23 (-0.46 to -0.00)
Marelich 200018 4.2 (1.2) 166 4.8 (1.4) 169 11 -0.60 (-0.87 to -0.33)
Piotto 200834 4.3 (1.4) 18 3.8 (1.4) 18 4 0.46 (-0.46 to 1.38)
Rose 200832 4.8 (0.8) 51 4.8 (0.9) 51 11 -0.04 (-0.35 to 0.28)
Subtotal (95% CI) 414 416 38 -0.23 (-0.54 to 0.09)
Test for heterogeneity: χ2=10.20, df=3, P=0.02, I2=71%
Test for overall effect: z=1.42, P=0.16
Neurosurgical
Namen 200124 5.0 (0.8) 49 5.0 (1.4) 51 9 0.00 (-0.44 to 0.44)
Navalesi 200831 4.3 (0.9) 165 4.3 (1.0) 153 12 -0.01 (-0.22 to 0.20)
Subtotal (95% CI) 214 204 21 -0.01 (-0.20 to 0.18)
Surgical
Simeone 200233 1.7 (0.5) 24 2.1 (0.4) 25 12 -0.36 (-0.62 to -0.10)
Stahl 200936 4.9 (0.8) 26 5.9 (0.4) 26 10 -0.97 (-1.31 to -0.63)
Subtotal (95% CI) 50 51 22 -0.66 (-1.25 to -0.06)
Medical
Ely 199616 4.2 (2.1) 149 4.8 (1.3) 151 9 -0.59 (-0.99 to -0.19)
Krishnan 200423 4.1 (1.3) 115 4.2 (1.4) 109 10 -0.12 (-0.47 to 0.23)
Subtotal (95% CI) 264 260 19 -0.35 (-0.81 to 0.11)
Total (95% CI) 942 931 100 -0.29 (-0.50 to -0.09)

Test for heterogeneity: χ2=37.71, df=9, P<0.001, I2=76%
-1.5 -1.0 -0.5 0 0.5 1.0 1.5
Favours Favours
weaning protocol usual care
Fig 3 | Duration of mechanical ventilation with and without weaning protocol; subgroup analysis by type of unit. Mean
difference calculated with fixed effects model
Risk of bias in included studies protocol, 10 16-18 23 24 31 34 and two described the automated
Most trials had low risk of bias across the six domains computer system 32 36 and reported all pre-specified out-
(fig 2). In eight trials, the allocation sequence was ade- comes: one trial published the weaning algorithm but did
quately generated and concealed. 10 16-18 31-33 36 Two trials not pre-specify outcomes so there was insufficient infor-
used inadequate allocation generation and concealment: mation to permit a judgment. 33 Seven trials seemed free
one allocated by using odd and even hospital numbers, 23 from “other sources of bias” as defined in the Cochrane
and one allocated sequentially on recruitment. 34 The Collaboration’s domain based evaluation, 10 16-18 23 31 32
remaining trial did not report the method used, and we two were stopped early for ineffectiveness, 24 36 one
were unable to obtain this information. 24 Given the nat- reported unsubstantiated findings, 33 and one was unpub-
ure of the intervention, blinding of participants and staff lished so there was insufficient information to permit a
to the intervention is not feasible, but in seven trials the judgment. 34 Five studies conducted a priori calculations
outcome assessors were independent from the indivi- of sample size, 17 24 31 34 36 two studies mentioned power
duals administering the intervention: this was confirmed calculations but were unclear, 18 23 and four studies did
in publications 10 17 and through personal communication not mention this. 10 16 32 33
with authors. 16 18 31-33 36 Blinding of outcome assessors was
unclear in one study, 23 not done in one study, 34 and Effects of interventions
could not be confirmed in one study despite attempts to Total duration of mechanical ventilation (hours)
obtain this information. 24 Most trials reported complete Ten trials reported on the total duration of mechanical
outcome data: two trials insufficiently reported on ventilation.16-18 23 24 31-34 36 One trial did not report on
recruitment, attrition, and exclusion to permit this outcome measure as the trial lasted only 48 hours
judgment. 33 34 Eight trials published the weaning for each patient.10 The pooled result for duration of
RESEARCH
Study or subgroup Mean (SD) Total Mean (SD) Total Mean difference Weight Mean difference
Professional led
Ely 199616 4.2 (2.1) 149 4.8 (1.3) 151 9 -0.59 (-0.99 to -0.19)
Kollef 199717 3.3 (1.2) 179 3.6 (0.9) 178 12 -0.23 (-0.46 to -0.00)
Krishnan 200423 4.1 (1.3) 115 4.2 (1.4) 109 10 -0.12 (-0.47 to 0.23)
Marelich 200018 4.2 (1.2) 166 4.8 (1.4) 169 11 -0.60 (-0.87 to -0.33)
Namen 200124 5.0 (0.8) 49 5.0 (1.4) 51 9 0.00 (-0.44 to 0.44)
Navalesi 200831 4.3 (0.9) 165 4.3 (0.9) 153 12 -0.01(-0.22 to 0.20)
Piotto 200834 4.3 (1.4) 18 3.8 (1.4) 18 4 0.46 (-0.46 to 1.38)
Simeone 200233 1.7 (0.5) 24 2.1 (0.4) 25 12 -0.36 (-0.62 to -0.10)
Subtotal (95% CI) 865 854 79 -0.25 (-0.43 to -0.06)
Computer driven
Rose 200832 4.8 (0.8) 51 4.8 (0.9) 51 11 -0.04 (-0.35 to 0.28)
Stahl 200936 4.9 (0.8) 26 5.9 (0.4) 26 10 -0.97 (-1.31 to -0.63)
Subtotal (95% CI) 77 77 21 -0.50 (-1.42 to 0.42)
Total (95% CI) 942 931 100 -0.29 (-0.50 to -0.09)

-1.5 -1.0 -0.5 0 0.5 1.0 1.5
Favours Favours
Fig 4 | Duration of mechanical ventilation with and without weaning protocol; subgroup analysis by type of approach. Mean
difference calculated with fixed effects model
mechanical ventilation, with the random effects model protocol group (−0.66, −1.25 to −0.06; P=0.03), corre-
because of significant substantial heterogeneity sponding to a reduction of 48% (6% to 71%) in the geo-
(I²=76%, P=0.0001), showed that weaning protocols metric mean; and the two medical intensive care
were associated with significantly reduced mean log units 16 23 showed a non-significant reduction in the
total duration of mechanical ventilation (mean log mean log (−0.35, −0.81 to 0.11; P=0.14), correspond-
−0.29, 95% confidence interval −0.5 to −0.09 ; ing to a reduction of 30% (−12% to 56%) in the geo-
P=0.006), corresponding to a reduction of 25% (9% to metric mean.
39%) in the geometric mean (fig 3). We also performed a subgroup analysis to assess the
We performed a subgroup analysis to assess the impact of type of approach: professional led or compu-
impact of type of intensive care unit on the total dura- ter driven (fig 4). The eight studies that used a profes-
tion of mechanical ventilation (fig 3). The subgroups
sional led approach 16-18 23 24 31 33 34 showed a significant
were small, with two to four studies in each, and
reduction in the mean log, favouring the weaning pro-
included mixed units that incorporated medical, surgi-
tocol group (mean log −0.25, −0.43 to −0.06; P=0.009),
cal and trauma patients; neurosurgical units; and sur-
corresponding to a reduction of 22% (6% to 35%) in the
gical units and medical units. The neurosurgical
geometric mean, and there was significant heterogene-
intensive care unit subgroup was introduced post hoc
ity (P=0.008, I2=63%). The two studies that used a com-
because we were unaware of these specific studies
puter driven approach 32 36 showed a non-significant
when writing the protocol and their weaning progress
is different to other groups of patients because of neu- reduction in the mean log in the weaning protocol
rological impairment. Pooled analysis of the four trials group (−0.5, −1.42 to 0.42; P=0.28), corresponding to
in the mixed intensive care unit group 17 18 32 34 showed a a reduction of 39% (−52% to 76%) in the geometric
non-significant reduction in the mean log in the wean- mean. For this outcome, the average percentage differ-
ing protocol group (mean log −0.23, −0.54 to 0.09; ence in geometric mean of 25% is consistent with esti-
P=0.16), corresponding to a reduction of 21% (−9% to mates in all subgroups in both subgroup analyses (that
42%) in the geometric mean. Pooled analysis of the two is, it is contained within the 95% confidence intervals).
neurosurgical studies 24 31 also showed a non-significant Therefore, the heterogeneity cannot be explained by
reduction in the mean log in the weaning protocol type of unit or type of approach.
group (−0.01, −0.2 to 0.18; P=0.93), corresponding to
a reduction of 1% (−20% to 18%) in the geometric Mortality
mean. The surgical intensive care units 32 36 showed a We found no significant differences between groups in
significant reduction in the mean log in the weaning hospital mortality (odds ratio 1.10, 0.86 to 1.41; six trials,
RESEARCH
Mortality Weaning protocol Usual care Odds ratio Weight Odds ratio
Events/total Events/total (95% CI) (%) (95% CI)
Hospital
Ely 199616 56/149 60/151 32 0.91 (0.57 to 1.45)
Kollef 199717 40/179 42/178 28 0.93 (0.57 to 1.53)
Krishnan 200423 56/115 48/109 22 1.21 (0.71 to 2.04)
Marelich 200018 17/166 10/169 8 1.81 (0.81 to 4.09)
Namen 200124 20/49 16/51 8 1.51 (0.66 to 3.43)
Stahl 200936 5/26 5/26 3 1.00 (0.25 to 3.97)
Subtotal (95% CI) 194/684 181/684 100 1.10 (0.86 to 1.41)
Intensive care unit

Navalesi 200831 2/165 6/153 41 0.30 (0.06 to 1.51)
Piotto 200834 7/18 10/18 41 0.51 (0.13 to 1.92)
Rose 200832 7/51 1/51 6 7.95 (0.94 to 67.21)
Stahl 200936 3/26 2/26 12 1.57 (0.24 to 10.24)
Subtotal (95% CI) 19/260 19/248 100 0.98 (0.48 to 2.02)
0.02 0.1 1 10 50
Favours Favours
Fig 5 | Mortality in hospital and intensive care unit according to weaning with and without protocol. Odds ratio calculated with
fixed effects model
n=1368)16-18 23 24 36 or mortality in the intensive care unit (fig 8). 16 17 24 32 There was minimal heterogeneity
(0.98, 0.48 to 2.02; four trials, n=508,)31 32 34 36 (fig 5). (I2=11%) (mean log −0.01, −0.11 to 0.1; P=0.9, corre-
sponding to an average percentage difference in geo-
Adverse events metric mean of −1%, −11% to 10%).
We found no significant differences between groups
(table 5) in the odds of reintubation (eight trials, Economic costs
n=1314), 16 17 24 31-34 36 self extubation (two trials, n=198), 16 24 Three trials from the US evaluated economic costs.
and tracheostomy (six trials, n=1191). 16 18 24 31 32 34 The odds There were no significant differences between groups
of requirement for protracted weaning were significant for for intensive care unit costs16 24 (mean difference $3600
weaning lasting over 21 days in one trial (n=300) 16 but not (£2300, €2700), −$1228 to $1948; P=0.66) or hospital
in another (n=100) 24 and not significant for weaning lasting costs16 17 24 ($−590, −$467 to $349; P=0.78).
over 14 days (n=102) 32 or seven days (n=357). 17
Sensitivity analyses
Weaning duration (hours) Exclusion of studies with a high risk of bias23 34 from the
In the random effects model for significant substantial analyses did not change the effects observed in the
heterogeneity (I²=97%, P<0.001), the pooled result for primary analysis for duration of mechanical
duration of weaning (six trials, n=834)10 16 18 32 34 36 showed ventilation and weaning duration. Similarly, analysis
that weaning per protocol significantly reduced the mean of the un-logged data for studies reporting total
log by an average of 1.52 (mean log −1.52, −2.66 to duration of mechanical ventilation (10 trials,
−0.37; P=0.009), corresponding to a reduction of 78% n=1873),16-18 23 24 31-34 36 weaning duration (six trials,
(31% to 93%) in the geometric mean (fig 6). n=706),10 16 18 32 34 36 length of stay in intensive care
(eight trials, n=1256),16 23 24 31-34 36 and length of stay in
Length of stay in intensive care unit (hours) hospital (four trials, n=859) 16 17 24 32 did not change the
Eight trials reported on length of stay in the intensive effects observed in the primary analysis.
care unit (fig 7), 16 23 24 31-34 36 and there was no statistical
heterogeneity among studies (I2=0%). Two trials DISCUSSION
showed a significant reduction in length of stay in the Principal findings
weaning protocol group, 23 33 and six did not. The In this systematic review we assessed evidence from 11
pooled estimate, however, was significant (mean log trials on the effect of weaning protocols on the duration
−0.11, −0.21 to −0.02; P=0.02), corresponding to an of mechanical ventilation in critically ill adults. We
average percentage difference in geometric mean of found that use of weaning protocols was associated
−10% (−19% to −2%). with significant reductions in geometric mean values
of 25% for the total duration of mechanical ventilation;
Length of stay in hospital (days) 78% for weaning duration; and 10% for length of stay
Weaning per protocol produced no significant reduc- in intensive care. We recognise that results reported in
tion in mean hospital length of stay in four trials percentage geometric mean values are difficult to
RESEARCH
Table 5 | Summary of adverse events associated with weaning from mechanical ventilation not adversely affect mortality in intensive care or hos-
pital. We found no effect on adverse events including
with and without weaning protocol in critically ill adults on mechanical ventilation
reintubation, self extubation, tracheostomy, and pro-
No of patients with events/total
Adverse event No of events Odds ratio (95% CI), P value tracted weaning, though our meta-analysis was under-
Reintubation16 17 24 31-34 36 1314 0.76 (0.40 to 1.42), P=0.39 powered to investigate the impact of the interventions
Self extubation16 300 0.40 (0.08 to 2.08), P=0.25 on these outcomes, which were infrequent. Further-
Self extubation24 100 0.50 (0.09 to 2.86), P=0.68 more, basic costing exercises in intensive care units
Tracheostomy16 18 24 31 32 34 1191 0.74 (0.45 to 1.22), P=0.24
and hospital in three US studies showed no significant
Protracted weaning (days):
difference between the alternative weaning strategies.
>2116 300 0.42 (0.19 to 0.96), P=0.04
Strengths and limitations of the review
>2124 100 0.18 (0.02 to 1.63), P=0.21
>1432 102 0.68 (0.20 to 2.31), P=0.54
In this systematic review and meta-analysis of weaning
>717 357 0.63 (0.35 to 1.15), P=0.13
protocols, most trials had sound methods and had a
low risk of bias. Based on GRADE,51 however, the
quality of evidence was low, mainly because of sub-
interpret clinically. To illustrate these findings in mean stantial variability in the effect estimates. As a result
differences that are clinically relevant we can use data of this heterogeneity, our findings should be inter-
on ventilation times from a large epidemiological preted with caution. The methods in trials were limited
study (n=5183) of characteristics and outcomes in by the inability to blind clinical staff to the method of
patients receiving mechanical ventilation.50 The weaning; therefore it is possible that clinician’s deci-
mean duration of mechanical ventilation in this study sions and actions could have been influenced, resulting
was 144 hours. The corresponding risk for a weaning in biased estimates of treatment effect. As it is not fea-
protocol is the mean that one would expect based on sible to blind staff in these weaning studies, we assessed
the effect estimates in this review. With this method, blinding of investigators collecting outcome data and
reductions can be found in the total duration of found risk of bias to be low in eight of 11 included
mechanical ventilation from an assumed risk of 144 studies. Six of the 11 studies originated in the US,
hours to a corresponding risk of 108 hours (88 to 131 which could limit the extent to which findings can be
hours); duration of weaning from 96 hours to 21 hours generalised to other healthcare systems.
(7 to 66 hours); and length of stay in intensive care from
11 days to 10 days (9 to 11 days). Implications for clinical practice
Though the data from the pooled summaries alone Ventilator weaning is a complex process, and it is not
seem to support benefit with weaning protocols, they easy to isolate the reasons for heterogeneity. The dis-
should be viewed with caution because of the signifi- cordance in results among studies could be caused by
cant heterogeneity among studies, particularly in rela- contextual factors (differences in populations of
tion to total duration of mechanical ventilation patients and usual practice within units) or intervention
(I2=76%) and duration of weaning (I2=97%). We factors (differences in determining readiness to wean,
explored heterogeneity through subgroup analyses ventilator modes, and variables used in weaning pro-
on the impact of type of intensive care unit (mixed, tocols). Though we attempted to examine the impact of
neurosurgical, surgical, medical) and type of approach different populations of patients on duration of
(professional led or computer driven). We found mechanical ventilation by exploring types of intensive
inconsistency among results and little statistical evi- care units, we could not isolate populations in all stu-
dence of difference in treatment effect, possibly dies because some units were “mixed” and included
because of the small number of studies with subgroups medical, surgical, neurosurgical, and trauma patients.
for analysis. The use of protocols to guide weaning did Clearly, the population of patients can affect the

Study Mean (SD) Total Mean (SD) Total Mean difference Weight Mean difference
Ely 199616 0.3 (3.8) 149 3.6 (2.6) 151 16 -3.35 (-4.09 to -2.61)
Marelich 200018 3.6 (1.4) 166 4.6 (1.4) 169 17 -0.93 (-1.24 to -0.62)
Piotto 200834 0.7 (0.2) 18 3.9 (0.8) 18 17 -3.20 (-3.58 to -2.82)
Rose 200832 3.4 (1.5) 51 3.4 ( 1.9) 51 17 0.00 (-0.65 to 0.65)
Stahl 200936 2.7 (2.3) 26 4.0 (1.9) 26 15 -1.29 (-2.42 to -0.16)
Strickland 199310 2.9 (0.3) 7 3.2 (0.2) 2 17 -0.34 (-0.72 to 0.04)
Total (95% CI) 417 417 100 -1.52 (-2.66 to -0.37)
-4 -2 0 2 4
Favours Favours
Fig 6 | Duration of weaning with and without weaning protocol. Mean difference calculated with fixed effects model

RESEARCH
Ely 199616 3.7 (2.4) 149 3.8 (2.1) 151 4 -0.06 (-0.57 to 0.45)
Krishnan 200423 4.7 (1.0) 154 5.0 (0.9) 145 19 -0.24 (-0.46 to -0.02)
Namen 200124 5.9 (0.4) 49 5.8 (0.8) 51 16 0.07 (-0.18 to 0.32)
Navalesi 200831 4.9 (0.8) 165 5.0 (0.8) 153 31 -0.11 (-0.28 to 0.06)
Piotto 200834 6.1 (0.7) 18 6.2 (0.7) 18 5 -0.09 (-0.54 to 0.36)
Rose 200832 5.1 (0.7) 51 5.2 (0.8) 51 12 -0.09 (-0.37 to 0.19)
Simeone 200233 3.2 (0.5) 24 3.6 (0.7) 25 9 -0.37 (-0.70 to -0.04)
Stahl 200936 6.3 (0.8) 26 6.2 (0.7) 26 6 0.10 (-0.31 to 0.51)
Total (95% CI) 636 620 100 -0.11 (-0.21 to -0.02)
-0.75 -0.50 -0.25 0 0.25 0.50 0.75
Favours Favours
Fig 7 | Length of stay in intensive care unit with and without weaning protocol. Mean difference calculated with fixed effects model
duration of weaning. For example, weaning a surgical care unit, which comprised unlimited assessment of
patient in intensive care after elective major surgery weaning by experienced autonomous critical care
might be more straightforward than weaning a medical nurses, a 1:1 nurse to patient ratio supported by 24
patient in intensive care with respiratory failure after hour medical staff, and twice daily rounds by an
acute exacerbation of chronic pulmonary disease. In intensivist.32 The association between staffing in inten-
addition, because of the wide variety of protocols sive care units and clinical outcomes has been studied
used in included studies, we could not examine the previously. High intensity of medical staffing with
impact of specific weaning protocols on specific popu- mandatory intensivist consultation (such as that
lations of patients. What remains unknown and war- found in intensive care units in the United Kingdom)
rants further investigation is whether or not specific has been associated with reduced mortality and
protocols are more beneficial than others in particular reduced length of stay in hospital and the intensive care
populations of patients. unit53; higher doctor to patient ratios are significantly
Another important contextual factor, and one that associated with higher rates of success of weaning and
causes controversy in studies of non-pharmacological home discharge in patients receiving prolonged
interventions in intensive care units, is the use of the mechanical ventilation54; and an optimum number of
“usual care” group as a control in randomised trials.52 qualified intensive care nurses led to a reduction in the
Usual care in intensive care units can encompass a duration of weaning for patients with exacerbation of
wide variety of practices—for example, usual care chronic obstructive pulmonary disease.55 These exam-
might be standardised around high level evidence ples suggest that in units where the organisational cul-
and thus represent best practice or it might be highly ture and context supports optimum trained staff
variable and include unfavourable practices.52 Conse- numbers, there might not be additional benefit from
quently, if the culture of a unit is such that usual care is a the use of weaning protocols compared with standar-
standardised high level approach to weaning, albeit not dised high level approaches to weaning. Notwithstand-
formally laid out in guidelines, then it might not differ ing, full descriptions of usual care in the control groups
greatly from that delivered by a weaning protocol. were not provided in the included studies, and there-
Thus, in a trial of effectiveness, the gap between usual fore we cannot be certain that this is the case.
care and weaning with a protocol might be too small to In relation to intervention factors, there were many
show a significant difference between groups. differences in methods among studies that could have
For example, Marelich et al conducted a study in one contributed to heterogeneity. The number and type of
medical and one surgical/trauma intensive care unit criteria used to determine readiness to wean within
and reported variable practice between units: the med- protocols varied considerably (ranging from five to
ical unit had no standardised approach to weaning 17) and the broadness or restrictiveness of criteria
whereas the surgical unit had a standardised approach used could have contributed to differences in results.
to ventilator management, though extubation was In relation to the protocols themselves, only two used
based on the judgment of individual physicians.18 an identical weaning protocol.18 24 Despite this, these
Thus, while combined data from both units showed a trials reported conflicting results in both the duration
reduction in the duration of mechanical ventilation, of mechanical ventilation and weaning, possibly
when we analysed data separately for each unit the because of differences in the populations of patients
reduction was significant only in the medical intensive studied or usual practice within the intensive care units.
care unit where no standard approach to weaning We focused solely on the impact of weaning proto-
existed. Similarly, the study by Rose et al attributed cols, but it is worth noting that sedation practices influ-
their lack of effect to usual practice in their intensive ence the duration of ventilation and must be
RESEARCH
Ely 199616 5.8 (0.8) 149 5.9 (1.2) 151 20 -0.10 (-0.33 to 0.13)
Kollef 199717 5.6 (0.7) 179 5.6 (0.7) 178 53 0.00 (-0.14 to 0.14)
Namen 200124 6.9 (0.6) 49 6.6 (0.9) 51 12 0.23 (-0.07 to 0.53)
Rose 200832 2.9 (0.7) 51 3.0 (0.7) 51 15 -0.09 (- 0.36 to 0.18)
Total (95% CI) 428 431 100 -0.01 (-0.11 to 0.10)
-0.75 -0.50 -0.25 0 0.25 0.50 0.75
Favours Favours
Fig 8 | Length of stay in hospital with and without weaning protocol. Mean difference calculated with fixed effects model
considered in trials of weaning protocols. The process support to the needs of individual patients during
of weaning can be affected by use of sedative agents. To weaning and to reduce the time spent on ventilation,
this end, the manner in which sedative agents are used costs, and staff workload.61 Computers can continu-
has been shown to be just as important as the pharma- ously monitor changes in ventilation, interpret real
cological properties of the agents themselves. Shorter time physiological changes, and adapt ventilation in
durations of ventilation and length of stay in the inten- response to these changes. As shown in this review,
sive care unit and hospital have been associated with however, compared with usual care their efficacy in
intermittent boluses of sedation and analgesia instead reducing the duration of mechanical ventilation has
of continuous infusions,56 daily interruption of infu- yet to be established. Nevertheless, the use of weaning
sions (sedation breaks) and subsequent assessment for protocols is increasing to the point where it is “usual
weaning,57 and a protocol combining daily sedation practice” in many units, and we are now beginning to
breaks with trials of spontaneous breathing.58 A recent see more studies that compare automated weaning
pilot trial of a protocol for no sedation found that with weaning with a protocol.41 43 45 47-49
patients with no sedation had significantly more days Non-invasive ventilation (where the endotracheal
without ventilation than those receiving daily sedation tube is removed, but the patient continues to receive
breaks (mean difference 4 days, 0.3 to 8; P=0.019).59 ventilatory support delivered by face or nasal mask) is
Sedation practice in intensive care units typically fol- gaining popularity as a weaning strategy. To date the
lows an agreed protocol or guideline60 involving number of trials are small (around five), but a recent
assessment of the patient’s response to administration systematic review has shown the clinical benefit of
of sedation/analgesia with a sedation scoring system this strategy in reducing the total duration of mechan-
and an algorithm that uses sedation scores to modify ical ventilation support in cases of difficult weaning,
drug delivery. The studies included in our review pro- particularly in patients with chronic obstructive pul-
vided little or no information regarding their sedation monary disease.62
practices. To interpret changes in weaning success or In patients in intensive care, mechanical ventilation
time to successful weaning, future studies should and immobilisation contribute to complications such
include detailed information on sedation practices as delirium and weakness, which can affect the dura-
including the agents used, use of a sedation protocol tion of mechanical ventilation and length of stay in
(or lack of one) and scoring system, and whether or intensive care and hospital.63-65 A recent randomised
not daily interruptions in sedation were permitted. controlled trial of early mobilisation instigated during
periods of daily sedation breaks showed significantly
New developments in weaning shorter durations of delirium (median 2 v 4 days,
Weaning and sedation protocols have contributed to P=0.02) and more ventilator-free days (median 23.5
the management of weaning in important ways over v 21.1 days, P=0.05).66
the past 15 years. New developments in this specialty
are targeted at discontinuing invasive ventilatory sup- Implications for research
port in a timely manner by using automated systems or The studies we included varied in the details they pre-
non-invasive ventilation as a weaning strategy, and sented regarding weaning protocols, the degree to
awakening and mobilising critically ill patients as which they described usual practice within their inten-
soon as possible. Applying protocols to real life clinical sive care units, and the settings in which they were con-
practice can be difficult because their effectiveness ducted. In many studies, neither usual weaning practice
depends on many factors, including their acceptability nor organisational context (for example, staffing ratios
to clinicians, the workload of the intensive care unit, and frequency of medical rounds) were described in suf-
the requirement for frequent assessments, and moni- ficient detail, thus it is difficult to ascertain the extent to
toring to ensure compliance. Thus, automated compu- which weaning practice differed between the experi-
terised systems are increasingly being used in an mental and control groups in the individual studies. It
attempt to improve the adaptation of mechanical is important that future trials fully report the details of
RESEARCH
evidence emerges and in response to feedback, and the Cochrane Library

WHAT IS ALREADY KNOWN ON THIS TOPIC should be consulted for the most recent version of the review.
Contributors: BB, FA, and PO’H were involved in the design of the review.
Prolonged mechanical ventilation can be associated with adverse outcomes for patients
BB developed the search strategy. BB, PO’H, KB, and FA conducted the
Weaning from mechanical ventilation according to standardised protocols is purported to be screening, and BB, PO’H, and KB undertook assessment of risk of bias and
safe and effective in reducing the duration of mechanical ventilation, though trials have data extraction. BB, PO’H and CC were involved in data entry and data
conflicting results analysis. BB wrote the first draft of the review, and all authors contributed
to the various drafts of the report. BB is guarantor.
Funding: The review was funded through a Cochrane Fellowship Award
WHAT THIS STUDY ADDS for BB from the Research and Development Office, Northern Ireland, and
Compared with usual care, use of weaning protocols can reduce the duration of mechanical the Health Research Board, Ireland.
ventilation by 25%, weaning duration by 78%, and length of stay in intensive care unit by Competing interests: All authors have completed the Unified Competing
Interest form at www.icmje.org/coi_disclosure.pdf (available on request
10%
from the corresponding author) and declare: no support from any
As there was significant heterogeneity in included trials and most were conducted in the US, organisation for the submitted work, no financial relationships with any
the findings might not be generalisable organisations that might have an interest in the submitted work in the
previous three years, no other relationships or activities that could appear
to have influenced the submitted work.
Ethical approval: Not required.
weaning protocols, usual weaning practice (including Data sharing: No additional data available.
sedation practice), and the context into which weaning
protocols are introduced (such as staffing ratios and 1 Dries DJ. Weaning from mechanical ventilation. J Trauma
organisation of care) as this would enable clinicians to 1997;43:372-84.
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Proc AMIA Symp 1999;251-5. Accepted: 08 November 2010

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RESEARCH

ventilator output to the patient’s needs with closed

Incomplete outcome data addressed

initiated spontaneous breathing trials, 32 36 and one used

Free from selective reporting

titrated respiratory rate and pressure support. 10 Six stu-

used a stepwise reduction in positive end expiratory

with extubation. 33 34 Kollef et al implemented the proto- Marelich 200018 + + + + + +

page 6 of 14 BMJ | ONLINE FIRST | bmj.com

Weaning protocol Usual care

Total (95% CI) 942 931 100 -0.29 (-0.50 to -0.09)

Weaning protocol Usual care

Total (95% CI) 942 931 100 -0.29 (-0.50 to -0.09)

Intensive care unit

Weaning protocol Usual care

page 10 of 14 BMJ | ONLINE FIRST | bmj.com

Weaning protocol Usual care

Weaning protocol Usual care

evidence emerges and in response to feedback, and the Cochrane Library

BMJ | ONLINE FIRST | bmj.com page 13 of 14

page 14 of 14 BMJ | ONLINE FIRST | bmj.com

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