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* From the Departments of Medicine (Dr. Ely), Vanderbilt University School of Medicine, Nashville, TN; the John Hopkins University School of Medicine (Dr. Haponik), Baltimore, MD; Barnes-Jewish Medical Center and Washington University School of Medicine (Dr. Kollef), St. Louis, MO; the Cleveland Clinic Foundation (Dr. Stoller), Cleveland, OH; and the Evidence-Based Practice Center (Drs. Meade, Cook, and Guyatt), McMaster University, Hamilton, Ontario, Canada. This research was supported by National Institutes of Health grant No. AG01023-01A1 (EWE) and a Beeson Scholarship from the American Federation for Aging Research (EWE).
Correspondence to: E. Wesley Ely, MD, MPH, FCCP, Division of Allergy/Pulmonary/Critical Care Medicine, Center For Health Services Research, Sixth Floor Medical Center East, Vanderbilt University Medical Center, Nashville, TN 37232-8300; e-mail: wes.ely{at}mcmail.vanderbilt.edu
| Abstract |
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Key Words: analgesics artificial respiration clinical protocols critical care ICU mechanical ventilation outcomes respiratory insufficiency respiratory therapy sedation sedatives ventilator weaning
| Introduction |
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The McMaster University Evidence-Based Practice Center has conducted a comprehensive review of the literature regarding weaning to address key questions posed by the Agency for Health Care Policy and Research (AHCPR).1 To create this 380-page document, which reviewed approximately 1,000 articles from 1971 to 2000, the authors chose 154 articles for final review and evaluation. Among the many aspects of weaning reviewed by the McMaster-AHCPR investigators, the strongest conclusions were drawn in regard to the development and implementation of ventilator weaning protocols and the use of nonphysician HCPs (eg, respiratory-care practitioners [RCPs] and nurses) in the ICUs to enhance patients liberation from MV.
| Materials and Methods |
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Eligibility Criteria
We included all studies of adult patients who were receiving MV
that compared weaning conducted according to an explicit protocol
to the traditional, physician-directed approach. We included
randomized trials, or controlled nonrandomized studies. We excluded
studies that reported physiologic outcomes exclusively.
Search for Relevant Studies
To identify relevant studies, we searched MEDLINE, EMBASE,
HEALTHStar, CINAHL, the Cochrane Controlled Trials Registry, and the
Cochrane Data Base of Systematic Reviews from 1971 to September 1999,
and we examined the reference lists of all included articles for other
potentially relevant citations.
Data Abstraction and Assessment of Methodological Quality
Five respiratory therapists and five intensivists participated
in data abstraction and in rating the methodological quality of all
eligible randomized trials or nonrandomized controlled cohort studies
that addressed treatment issues. One of the investigators rechecked the
final data abstraction. The methodological features of randomized
trials that we abstracted included the following: the method of
randomization and whether randomization was concealed; the extent to
which groups were similar with respect to important prognostic factors;
whether investigators conducted an intention-to-treat analysis; whether
patients, clinicians, and those assessing outcome were blind to
allocation; the extent to which the groups received similar
cointerventions; and reporting of the reasons for study withdrawal. For
nonrandomized controlled clinical trials, we considered the extent to
which groups were similar with respect to important prognostic factors,
whether the investigators adjusted for differences in prognostic
factors, and the extent to which the groups received similar
cointerventions.
Statistical Analysis
We abstracted or, when necessary, calculated effect sizes in
terms of relative risks (RRs) and associated 95% confidence intervals
(CIs) for binary outcomes and mean differences and 95% CIs for
continuous variables.
| Results |
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Ely and colleagues9 reported a two-step protocol that was driven by nurses and RCPs incorporating daily screening followed by a spontaneous breathing trial (SBT). Although the 151 patients who were managed in the medical and coronary ICUs and were in the intervention group had a higher severity of illness than the 149 control patients, they were removed from the ventilator 1.5 days earlier, had 2 fewer days of weaning, had 50% fewer complications related to the ventilator, and had mean ICU costs of care that were lower by more than $5,000 lower per patient.9 These investigators studied patients whose median durations of MV were 4.5 and 6 days, respectively, in the protocol-directed and physician-directed groups. The RR of successful extubation in the protocol-directed group was 2.13 (95% CI, 1.55 to 2.92; p < 0.001), indicating that MV was successfully discontinued sooner in the protocol-directed group than in the control group. The largest separation between groups was at approximately 5 days, and differences disappeared by about 15 days. Patients in the physician-directed group spent a day longer in the ICUs and 1.5 days longer in the hospital. Neither of these differences reached statistical significance.
Kollef and colleagues11 conducted their study in four ICUs using three different weaning protocols that had been developed and tested by the ICU staff prior to the start of the study. Despite the large sample size, the power of their study to detect differences in key end points was limited by the fact that most patients spent a relatively short period of time on the ventilator. In the protocol-directed and physician-directed groups, 25% of the patients were extubated by 15 and 21 h, respectively, 50% were extubated by 35 and 44 h, respectively, and 75% were extubated by 114 and 209 h, respectively. Only 12% and 17%, respectively, of the patients spent > 7 days on the ventilator. Survival and regression analyses suggested a difference that favored patients in the protocol group. Simple analyses also favored the protocol-directed group, but they failed to reach statistical significance (Table 2) .
In a more recent investigation that included 335 patients (approximately 50% surgical, and predominantly trauma), Marelich and colleagues12 showed in an RCT that the use of a weaning protocol incorporating multiple daily SBT assessments shortened the median duration of MV from 124 to 68 h (p = 0.001). Investigators censored patients in the protocol group for whom attending physicians violated the protocol, potentially excluding from the analysis patients who were destined to wean more slowly from ventilation. This may overestimate the reported benefit of the weaning protocol with respect to the duration of ventilation; thus, these results are potentially misleading.
In addition to these RCTs, 11 non-RCTs have examined the impact of, largely, respiratory therapist-directed or nursing-directed weaning compared to physician-directed weaning on weaning outcomes in critically ill patients (Tables 3 4 4A ).13 14 15 16 17 18 19 20 21 These studies, conducted in a variety of populations, are generally much larger than the corresponding RCTs but are more prone to bias, given their observational design (Table 3) . The results of these nonrandomized studies are generally consistent with the results of the RCTs, demonstrating statistically significant reductions or trends toward reductions in the duration of MV and ICU length of stay. Protocol-based weaning was associated with other favorable process-of-care outcomes such as fewer arterial blood gas analyses. Mortality and reintubation rates did not appear to differ between the experimental and control groups. Complications of protocol-based weaning were not reported.
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| Discussion |
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Recommendation 1: Based on evidence from randomized trials, we recommend that nonphysician HCPs be included in the development and utilization of respiratory-care protocols (not confined to liberation from MV).
Weaning Protocols
The McMaster evidence-based AHCPR report on weaning1
concluded that there is strong evidence that weaning protocols can,
under some circumstances, decrease the length of time that a patient
spends on the ventilator. These protocols may be organized and led by
physician opinion leaders, then implemented on a daily basis by
nonphysician HCPs. A major transition in thought regarding weaning
began in 1994 and 1995, when it was demonstrated for the first time in
RCTs,8
32
that one modality of weaning might be superior
to another if it was executed in a specified fashion. However, these
data did not establish that a weaning protocol was superior to the
standard of care, which was the individual physicians best
management.33
Now, the results of three randomized
trials,9
11
12
including 992 patients, suggest that
protocols can, at least under some circumstances, result in important
decreases in the duration of MV. The implementation of nurse-driven or
RCP-driven weaning protocols, regardless of the specific weaning mode
employed, can significantly expedite safe liberation from
MV.1
31
That three RCTs using appreciably different protocols have all demonstrated statistically significant reductions in the time spent receiving MV (although the magnitude of the difference between groups varied substantially) suggests that it is the protocols (and the culture change that these protocols represent) that effect the benefit, rather than any specific modality of weaning. The current data do not support the use of any one protocol (although some guidelines are offered below), and the selection of an appropriate protocol is best left to multidisciplinary teams at individual institutions. Importantly, each institution must endorse the fiscal commitment and the staffing modifications that are necessary for developing and implementing a multidisciplinary weaning protocol team of dedicated HCPs.34 While institutions should embrace collaborative weaning efforts35 and should customize protocols to local practices, several important general concepts may ease the process of implementation and may enhance success, and these are reviewed in multiple sections below.
Recommendation 2: Based on evidence from RCTs, we recommend that ICU clinicians utilize protocols for liberating patients from MV in order to safely reduce the duration of MV.
SBTs
Given the low negative predictive value of most weaning parameters
(ie, the available parameters predict weaning failure
poorly),3
36
37
it appears most prudent to conduct daily
assessments of the patients ability to breathe
spontaneously.8
9
11
32
Clinicians should have a low
threshold to perform such a trial. Yet, in a recent international
utilization review38
of the actual weaning practices of
412 medical and surgical ICUs in 1,638 patients receiving MV, only 20%
of patients were weaned using some form of SBT, and in the United
States, SBTs were incorporated into weaning in < 10% of all patients
studied. Patients chosen for SBTs should be in hemodynamically stable
condition, and their condition should be improving with regard to the
underlying cause of respiratory failure. SBTs can be performed safely
by nonphysician HCPs using a T-piece, continuous positive airway
pressure without pressure support, or with pressure support up to 7 cm
H2O, and for durations of 30 min to 2
h.6
8
9
11
32
34
39
40
The monitored assessment of
spontaneous breathing should be conducted at least once daily (with the
head of the bed elevated and after notifying the patient of
the start of the SBT) and should be integrated with other major events
in the patients daily care, including the cessation or temporary
reduction in delivery of sedation and analgesia
medications.41
There are emerging data about the utility
of noninvasive positive-pressure ventilation to facilitate weaning and
to avoid reintubation,42
43
44
45
as well as ongoing
multicenter trials that are studying protocols using this modality of
respiratory support for weaning patients from MV.
Recommendation 3: Based on evidence from randomized trials, we recommend at least once daily SBTs to identify patients who are ready for liberation from the ventilator.
Recommendations for Patients Who Are "Not-Yet-Ready" for
Liberation
When a patient does not demonstrate readiness for liberation
from the mechanical ventilator, but is improving as indicated by
lessening support requirements, the clinician is faced with a decision
about how to wean MV support. In randomized trials, both Esteban et
al8
and Brochard et al32
employed a screening
process whereby patients were enrolled into the trials only if they
failed to demonstrate readiness via an SBT. In these studies, either
once-daily SBTs or pressure support ventilation were both superior to
intermittent mandatory ventilation alone. Reported differences in the
superiority of SBTs vs pressure support ventilation have been
attributed to variations in the management protocols. The value of
differing modes depends on thresholds for initiating, progressing
through, and terminating weaning. Unfortunately, these thresholds
involve more than objective data and appear to be related to physician
judgment.1
Therefore, based on evidence from these
investigations, we can offer the following recommendations.
Recommendation 4: When patients fail an SBT, we recommend the following assessments and interventions, based on varying levels of evidence:
Extubation Decisions
The clinical trials6
8
9
11
32
discussed above
each outlined a rigid extubation protocol or, alternatively, an
approach that incorporated the clinicians judgment and preferences
for the timing of extubation. Despite the care and rigor with which a
team of HCPs evaluates their patients abilities to be liberated from
MV, some patients will require reintubation,5
48
which
carries an estimated 8-fold higher odds ratio for nosocomial
pneumonia49
and a 6-fold to 12-fold increased mortality
risk.4
6
39
50
Reported reintubation rates range from 4 to
20% for different ICU populations4
5
6
8
9
32
34
51
and
may be as high as 33% in patients with mental status changes and
neurologic impairment.48
The optimal rate of reintubation
is not known but likely rests between 5% and 15% in
non-neurologically impaired patients.
One important cause of reintubation is self-extubation or accidental extubation of patients who are inadequately sedated and/or restrained. However, self-extubation also can occur in patients who are ready to be liberated from the ventilator. For instance, approximately 50% of patients who self-extubate do not require reintubation.50 52 53 54 55 This fact should further motivate physicians to adopt proactive protocols directed toward earlier extubation. In fact, two investigations have shown an associated reduction in reintubation rates by incorporating a protocol driven by nonphysician HCPs.9 56
Recommendation 5: Based on the sum of evidence from randomized trials and observational studies, we recommend that when patients have passed an SBT, clinicians seriously consider prompt extubation.
Sedation and Analgesia
When other key features in the management of patients receiving
MV, such as sedation and analgesia, are protocolized and managed by
nonphysician HCPs, further reductions in the time spent receiving MV
can be realized. Standardizing the delivery of sedatives and analgesics
is the most recent development in the area of protocolization and
weaning from MV. One RCT, using a nursing-implemented protocol
to manage the delivery of sedation, showed a reduction in the duration
of MV by 2 days (p = 0.008), decreased length of stay in the ICU by 2
days (p < 0.0001), and a lower tracheostomy rate among the
treatment group (6% vs 13%; p = 0.04).41
In
another recently published RCT57
among 128 patients
receiving MV in an ICU, those in whom sedation was maintained at a
lighter level (via daily interruption of their sedative infusion) spent
2 days less receiving MV (p = 0.004) and 3 days less in the ICU
(p = 0.02) than did patients in whom infusions were not interrupted.
In addition, the pharmacoeconomic impact of guidelines for analgesia,
sedation, and neuromuscular blockade appear to be favorable and have
received more attention in the medical literature
recently.58
In summary, these studies have demonstrated
the important interactions between the delivery of psychoactive
medications and the expeditious weaning from MV. However,
considering the nearly universal use of these agents in patients
receiving MV and the relative paucity of controlled investigations in
this area,59
further study is required before detailed and
specific methods of protocolization can be recommended. For example,
studies to date have monitored only the arousal component of
consciousness and have tracked relatively few adverse events, none of
which included patients distress during awakening, recollections of
discomfort after their stay in the ICU, delirium, or persistent
neuropsychological outcomes. Emerging work in the area of the
content of consciousness (eg, delirium) is
revealing important interactions between the development of delirium
and outcomes including the duration of the hospital stay, as well as
long-term neuropsychological outcomes.60
61
62
Recommendation 6: Based on evidence from randomized trials for the delivery of psychoactive medications, we recommend the consideration of protocols that include daily cessation and targeted sedation goals to reduce the duration of MV and of the length of stay in the ICU.
Implementation of Protocols
Both the level of institutional commitment to improving clinical
outcomes and the health-care teams leadership, persistence, and
consistency in the implementation of protocols will determine the
ultimate success of any management protocol. Protocolized care has been
advocated in many facets of medicine, but relinquishing control of the
patients management often creates resentment and frustration on the
part of physicians. Even when research clearly supports a change in
approach, it is very difficult to get physicians to alter their
practice and management styles.63
Certain physicians may
have a low "readiness to change," and these professionals
may require either motivational interventions or consultation with
respected opinion leaders.64
65
Negative reactions to
protocols may be reasonable under some circumstances, since protocols
have the potential to do harm. Important considerations that may
facilitate behavioral changes include interactive education, timely and
specific feedback, participation by physicians in the effort to
change, administrative interventions, and even financial incentives and
penalties.63
Through a staged implementation process,
using periodic reinforcement of all participants in ventilator
management and the close monitoring of compliance with the protocol,
large-scale implementation within major medical centers is
possible.34
Protocol implementation (and acceptance) is
potentially less complicated in smaller, self-contained units with
fewer staff and more direct communication channels. Tips for the
implementation of weaning protocols and for avoiding barriers to
success, which were derived from the study of > 15,000 patient-days
of MV over nearly 2 years of implementation,65
are
presented in Table 6 . The effective implementation of protocols requires adequate staffing,
and it has been shown that if staffing is reduced below certain
thresholds, clinical outcomes may be jeopardized.66
67
Indeed, in the specific context of liberation from MV, reductions in
nurse-to-patient ratios have been associated with a prolonged duration
of MV.68
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Recommendation 7: We recommend the consideration of the following strategies for weaning protocols: development using an evidence-based approach by a multidisciplinary team; and implementation using effective behavior-changing strategies such as interactive education, opinion leaders, reminders, audit, and feedback.
In summary, this evidence-based review suggests that protocols driven by nonphysician HCPs to manage the weaning and liberation of patients from MV can reduce the time that patients spend receiving MV. We have developed seven key recommendations to synthesize this information for those attempting to design a weaning protocol. We also have discussed key general issues to aid in protocol implementation. Acknowledging the important nuances in protocols that should be dictated by specific patient populations and institutional preferences, the following two steps in any successful weaning attempt derived from recent RCTs9 11 12 41 57 bear repeating: step A should involve minimizing or temporarily discontinuing sedation and analgesia enough to observe patient awakening; and step B should involve an assessment of the patients ability to spontaneously breathe.
The data included in this systematic review and a more comprehensive discussion of the original articles are included in an Evidence Report of the Agency for Healthcare Research and Quality.75
| Footnotes |
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This article is based on work performed by the McMaster University Evidence-based Practice Center, under contract to the Agency for Healthcare Research and Quality (Contract No. 290-97-0017), Rockville, MD.
| References |
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