HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meade, M. Articles by Cook, D. J. Search for Related Content PubMed PubMed Citation Articles by Meade, M. Articles by Cook, D. J.

Introduction to a Series of Systematic Reviews of Weaning From Mechanical Ventilation^*

^* From the Departments of Medicine (Drs. Meade, Guyatt, and Cook) and Clinical Epidemiology & Biostatistics (Mss. Griffith and Booker), McMaster University, Hamilton, Ontario, Canada; and the Department of Respiratory Therapy (Ms. Randall), St. Joseph’s Hospital, Hamilton, Ontario Canada.

Correspondence to: D.J. Cook, MD, McMaster University, Faculty of Health Sciences Center, Department of Clinical Epidemiology & Biostatistics, 1200 Main St West, Hamilton L8N 3Z5, Ontario, Canada; e-mail: debcook{at}mcmaster.ca

Key Words: mechanical ventilation • meta-analysis • methodology • systematic reviews • weaning

	Introduction

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
Why is weaning important? Over 90% of critically ill patients require mechanical ventilation, and 40% of the time the patient is receiving mechanical ventilation is spent in the process of weaning from it.¹ Meanwhile, there are several concerns associated with prolonged mechanical ventilation. For patients, these concerns include heightened morbidity (including ventilator-associated pneumonia,^{2 3 4} ventilator-associated lung injury ^{5 6 7} ), and increased mortality^{8 9} ). Additionally, even if patients are recovering from their acute illness, as long as they remain dependent on mechanical ventilation, they generally remain in the ICU. In the context of widespread and unceasing ICU bed shortages, this is a problematic situation. Finally, challenges to health-care organizations include the additional resource consumption incurred when patients receive mechanical ventilation, such as increased nursing, need for a respiratory therapist, and equipment costs.

It follows that weaning patients from mechanical ventilation should occur as quickly as possible. However, rapid weaning has its own potential problems. Reducing mechanical support too quickly may result in fatigue or cardiovascular instability, either of which may ultimately delay the weaning process. Premature extubation, leading to reintubation, is associated with the increased risk of pneumonia and with increased mortality.¹⁰

Because patients receiving mechanical ventilation incur significant morbidity, mortality, and costs, and because both premature weaning as well as delayed weaning can cause harm, weaning that is both expeditious and safe is highly desirable. Our objectives were to determine what we can learn from clinical studies of when and how weaning should begin, proceed, and end, and to summarize this literature for critical-care clinicians.

	Reviews of the Weaning Literature

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
We conducted the majority of this work under the auspices of the Agency for Health Care Policy and Research (AHCPR [recently renamed the Agency for Healthcare Research and Quality]), a subsidiary of the US Department of Health and Human Services. Contributors to this document include the members of the McMaster University Evidence-Based Practice Center, members of the American College of Chest Physicians’ Expert Panel on Weaning from Mechanical Ventilation, and an assembly of international experts in the field of mechanical ventilation who served as peer reviewers for the final report to AHCPR.

Our task for this CHEST supplement was to review all randomized trials and the clinically most applicable observational studies that could guide clinicians in weaning patients from mechanical ventilation. Conceptually, we were interested in any critically ill patients receiving mechanical ventilation, in any strategies that were designed to facilitate weaning and extubation, in predictors of weaning and extubation in heterogeneous ICU patients, in populations with COPD, and in patients who had undergone cardiac surgery. Our target populations included adult and pediatric patients who were receiving mechanical ventilation and had either an endotracheal tube or a tracheostomy tube.

We excluded studies of highly specific populations (for example, patients with spinal cord injury or obstructive sleep apnea) and studies in neonates (since many studies in this population have been published as Cochrane Collaboration reviews). The clinical settings relevant to our review include ICUs, intermediate-care units, and postanesthesia recovery rooms. We excluded studies of home ventilation for children or adults and those using chronic ventilation settings. With respect to weaning interventions, we included any ventilation, or weaning strategy or intervention (eg, mode, method, procedure, protocol, timing, operator, computer, tracheostomy, noninvasive ventilation modes, adjunctive holistic aids, and other miscellaneous approaches), that were geared to facilitate weaning and/or extubation. We excluded articles with a focus on mechanical ventilation strategies for short-term care (eg, lung protective ventilation strategies) and interventions the influence of which on the duration of ventilation has already been summarized in a recent systematic review (eg, sedation in the ICU or optimal timing of tracheotomy). Trials in which at least 20% of patients were eliminated from the analysis after randomization were excluded. We excluded costs due to insufficient reporting of economic outcomes and their poor generalizability. In addition, we reviewed predictors of weaning and/or extubation success, and predictors of the duration of mechanical ventilation in cardiac surgery and COPD patients. We omitted studies predicting terminal weaning for the purposes of the withdrawal of life support. Finally, we analyzed a broad range of clinical outcomes, although we excluded studies that reported only physiologic outcomes.

	Identifying Relevant Studies

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
To identify relevant studies, we searched MEDLINE, Excerpta Medica Database (EMBASE), Health Services Technology Administration and Research, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Controlled Trials Registry, and the Cochrane Data Base of Systematic Reviews from 1971 to 1998. We also examined reference lists and personal files, and we hand searched the journal Respiratory Care. We did not explicitly search for unpublished literature. We retrieved all articles that either of two reviewers of the titles and abstracts considered to be possibly eligible. The same two reviewers examined the full text and made final decisions regarding eligibility based on the inclusion and exclusion criteria described above.

Our database search for relevant articles yielded a total of 5,653 citations of which 927 proved potentially eligible on the basis of reviewing the title and abstract. We were able to obtain hard copies of 924 of these articles. We included a total of 154 studies after comprehensive review of the full article. The absolute agreement between the two observers for determining eligibility for articles was 0.89, and the for agreement was 0.68.

	Abstracting and Summarizing Data

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
Our goal was to be as systematic as possible, not only in the identification and selection of studies, but in the abstraction and summarization of the data. To achieve this goal, we developed general forms to abstract data from all studies and forms that were specific to randomized trials, nonrandomized controlled studies, and studies of weaning predictors. We developed an implementation manual and trained five respiratory therapists and five intensivists to abstract data related to study characteristics, methodological quality, and results using duplicate independent reviews. Quantitative data were abstracted using several metrics. We pooled results across randomized trials and across studies of weaning predictors only when our assessment of the patients, interventions, and outcomes suggested that pooling was legitimate. Additional details specific to each clinical question are reported in brief in subsequent reviews in this series.

	Strengths and Weaknesses of Our Systematic Reviews

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
The limitations of any review can be categorized into those relating to the review methods themselves and those related to the primary studies included in the review. We addressed the strengths and limitations of the primary studies (ie, randomized trials, nonrandomized controlled trials, observational studies, and qualitative studies) in the individual sections of this supplement. We will now critically appraise this report according to the review methodology we employed.

The strengths of our systematic reviews include efforts to define focused clinical questions and to identify explicit eligibility criteria for each question. Our eligibility criteria invariably specified the population of interest, the intervention or exposure, the outcome, and the methodology. As we have described, the scope of our searching was broad and involved five large databases. The use of EMBASE maximized the possibility of identifying relevant European literature to avoid a language bias in this review, and we included French, Italian, Spanish, Japanese, and Russian studies. Searching EMBASE, Health Services Technology Administration and Research, and CINAHL maximized the chances of finding relevant studies in nursing and respiratory therapy journals to avoid a biased selection of research in medical journals. We also hand-searched Respiratory Care, even though that journal is indexed on CINAHL, since we have previously found that many research reports are poorly indexed in bibliographic databases. We used the most current randomized trial registry from the Cochrane Library, as well as citation reviews, our personal files, and author contacts. Thus, our searching strategy was comprehensive and minimized language bias and discipline bias. We did not, however, search extensively for unpublished studies, and our results may therefore be subject to publication bias.

We critiqued each study in this report, providing clinical characteristics and methodological details in the text and associated tables. Given the diversity of the objectives, designs, populations, interventions, predictors, and outcomes of these studies, we did not use a universal quantitative scoring system to assess validity but chose instead a more explicit component approach to quality assessment that was adapted to each research question and study design. We used critical appraisal questions for most studies taken from the Users’ Guides to the Medical Literature series published in the Journal of the American Medical Association. Due to space constraints, some design features of the studies that we reviewed are not reported in these systematic reviews but are available on request.

Because reviews are retrospective exercises and are prone to systematic and random error, we conducted several steps in this systematic review in duplicate, including the following: (1) citation review from the bibliographic databases; (2) assessment of relevance based on the full text of each article; (3) assessment of methodological quality; (4) abstraction of clinical characteristics and results; and (5) statistical analysis. Steps 3 and 4 involved critical-care physicians and respiratory therapists trained in research methods. Our core research team members interpreted and synthesized the findings in duplicate. We were as careful as possible conducting the review, but we identified and remediated errors at each step in our process. Since our reviews were completed, several additional relevant studies have been published, which are not included in the ensuing articles for this CHEST supplement.

	Our Results

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
Our key findings may confirm many clinical impressions, but may challenge others. We have tried to be explicit about the evidence and to separate the evidence from our inferences. We trust that our summaries of the evidence will allow others, with different perspectives, to draw their own inferences.

The issue of the optimal start of weaning is confounded by alternative definitions of weaning. One reasonable conceptualization is weaning beginning with the onset of mechanical ventilation. The research to date suggests that the best answer to "when to start weaning" is to develop a protocol implemented by nurses and respiratory therapists that begins testing for the opportunity to reduce support very soon after intubation and reduces support at every opportunity. Differences in clinicians’ intuitive threshold for the reduction or discontinuation of ventilatory support appear to have a greater impact on the failure of spontaneous breathing trials, or on reintubation, than do modes of weaning. When clinicians set a high threshold, many patients who could tolerate weaning continue to receive mechanical ventilatory support longer than is necessary.

As to the modes and methods of weaning, for stepwise reductions in mechanical ventilatory support, pressure support mode or multiple daily t-piece trials may be superior to intermittent mandatory ventilation. For trials of unassisted breathing, low levels of pressure support may be beneficial to overcome the resistance of the ventilator circuit. There may be substantial benefits to early extubation and the institution of noninvasive positive-pressure ventilation (NPPV) for patients who are alert, cooperative, and ready to breathe without an artificial airway. However, like others,¹¹ we conclude that the manner in which the mode of weaning is applied may have a greater effect on the likelihood of weaning than the mode itself.

Following cardiac surgery, a variety of anesthetic interventions and ICU protocols facilitate early extubation. The attendant reduction in ICU stay is generally modest, complications are very rare, and thus, a substantial benefit is not well-established.

We found that most theoretically plausible predictors of weaning and extubation success have no predictive power. Those with some predictive power include the rapid shallow breathing index, which has been most intensively studied, as well as the ratio of mouth occlusion pressure measured 0.1 s after the onset of inspiratory effort at P0.1 impedance to maximal inspiratory pressure and the CROP (compliance, rate, oxygenation, and pressure) index. However, these are relatively weak predictors of weaning success. We found that tests are rarely useful in increasing the probability of weaning success, although on occasion, they can lead to moderate reductions in the probability of success. The reason that weaning predictors were found to perform poorly is probably because physicians have already considered the results when they select patients for study.

	Future Research Directions

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 
These systematic reviews led to several suggestions for future research directions in weaning patients from mechanical ventilation.

1. Examination of alternative weaning strategies should enroll more homogeneous groups than in most prior studies, clearly separating those patients whose likely period of additional ventilation is a few hours from those whose likely period is a few days. Examples of homogeneous populations for targeting in future studies include patients with COPD exacerbations and postoperative cardiac surgery patients.
   
2. In the setting of a high threshold for extubation associated with low failure rates, randomized trials of thousands of patients would be needed to demonstrate the differences between techniques, and sample sizes of tens of thousands would be needed to demonstrate differences in the complications rates of failed extubation. Investigators should establish plausible event rates before embarking on randomized clinical trials.
   
3. Studies are needed to elucidate the tradeoff between decreasing the duration of mechanical ventilation and increasing the reintubation rates associated with a low weaning threshold. For example, what reduction in the duration of time on a ventilator would warrant an increase in reintubation rates from 5 to 10%? This work should attend to the important consequences of prolonged ventilation and reintubation, including nosocomial pneumonia, cardiac morbidity, and death.
   
4. Future research should examine the potential for NPPV to reduce the duration of intubation and total mechanical ventilation support. Useful studies would explore the optimal timing and management of NPPV for weaning purposes, including the postextubation application of NPPV targeted at patients at high risk of extubation failure.
   
5. Additional randomized trials of weaning protocols implemented by respiratory therapists and nurses should be launched. These trials should evaluate the impact of different protocols in different types of patients and in ICUs with different organizational structures (eg, open vs closed units and teaching vs community hospitals). The impact of protocols on ICU and hospital lengths of stay and costs are important considerations.
   
6. A more fruitful line of investigation than further research seeking powerful predictors of successful weaning or extubation might be randomized trials building on the protocol studies already published. Such trials could test multifaceted, multidisciplinary weaning programs addressing both pulmonary and nonpulmonary influences on weaning that may decrease the duration of mechanical ventilation without substantially increasing the rates of failed extubation and other complications.
   
7. Finally, health services research is needed to evaluate whether clinicians are applying the results of the most promising studies appropriately, and what the consequences of this application are in the real world. Individual practitioners, multidisciplinary teams, and institutional infrastructures should be tested to determine the best ways to put into practice what we already know about optimal methods to wean patients from mechanical ventilation.
   

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.¹²

	Acknowledgements

 
We thank Ann Mckibbon for her expert librarian skills and database searching, and Bruce Weaver, Stephen Walter, and Robin Roberts for their statistical advice. The peer reviewers for this AHCPR Report provided insightful advice, and we thank Suzanne Burns, Wes Ely, Scott Epstein, Jesse Hall, John Heffner, Dean Hess, Rolf Hubmayer, Robert Kacmarek, Neil McIntyre, Peter Pronovost, and Peer Review Editor Patricia Houston. Our appreciation is extended to Heiner Bucher, Toshi Fukuoka, Luz Letelier, and Marco Ranieri for the translation of non-English-language articles. We are grateful to several individuals for their administrative help during the preparation of these reviews, including Anne Snider, Alejandro Jadad, Marlene Taylor, Deborah Maddock, Karen Burns, and Laurel Raftery. Finally, we would like to acknowledge our advisors Arthur Slutsky and Anne Perry, as well as Sydney Parker and Ed Dellert of the American College of Chest Physicians.

	Footnotes

 
Abbreviations: AHCPR = Agency for Health Care Policy and Research; CINAHL = Cumulative Index to Nursing and Allied Health Literature; EMBASE = Excerpta Medica Database; NPPV = noninvasive positive-pressure ventilation

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

TOP Introduction Reviews of the Weaning... Identifying Relevant Studies Abstracting and Summarizing Data Strengths and Weaknesses of... Our Results Future Research Directions References

 

1. Esteban, A, Alia, I, Ibanez, J, et al (1994) Modes of mechanical ventilation and weaning: a national survey of Spanish hospitals; the Spanish Lung Failure Collaborative Group. Chest 106,1188-1193[Abstract/Free Full Text]
2. Cook, DJ, Walters, S, Brun-Buisson, C, et al (1998) Ventilator-associated pneumonia: incidence and risk factors: the Canadian Critical Care Trials Group. Ann Intern Med 129,433-440[Abstract/Free Full Text]
3. Vincent, J, Bihari, D, Suter, PM, et al (1995) The prevalence of nosocomial infection in intensive care units in Europe (EPIC). JAMA 274,639-644[Abstract]
4. Papazian, L, Bregeon, F, Thirion, X, et al (1996) Effect of ventilator-associated pneumonia on mortality and morbidity. Am J Respir Crit Care Med 154,91-97[Abstract]
5. Meade, MO, Cook, DJ (1995) The etiology, consequences and prevention of barotrauma: a critical review of the literature. Clin Intensive Care 6,166-173[Medline]
6. Slutsky, AS, Tremblay, LN (1998) Multiple system organ failure: is mechanical ventilation a contributing factor? Am J Respir Crit Care Med 157,1721-1725[Free Full Text]
7. Meade, MO, Cook, DJ, Kernerman, P, et al (1997) How to use articles about harm: the relationship between high tidal volumes, ventilating pressures, and ventilator-induced lung injury. Crit Care Med 25,1915-1922[CrossRef][ISI][Medline]
8. Fagon, JY, Chastre, J, Vuagnat, A, et al (1996) Nosocomial pneumonia and mortality among patients in intensive care units. JAMA 275,866-869[Abstract]
9. Ely, EW, Baker, AM, Evans, GW, et al (1999) The prognostic significance of passing a daily screen of weaning parameters. Intensive Care Med 25,581-587[CrossRef][ISI][Medline]
10. Esteban, A, Alia, I, Gordo, F, et al (1997) Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation: the Spanish Lung Failure Collaborative Group [published erratum appears in Am J Respir Crit Care Med, 1997; 156:2028] Am J Respir Crit Care Med 156,459-465[Abstract/Free Full Text]
11. Butler, R, Keenan, SP, Inman, KJ, et al (1999) Is there a preferred technique for weaning the difficult-to-wean patient? A systematic review of the literature. Crit Care Med 27,2331-2336[CrossRef][ISI][Medline]
12. Criteria for weaning from mechanical ventilation. Evidence Report/Technology Assessment No. 23 from the Agency for Healthcare Research and Quality: AHRQ Publication No. 01-E010

This article has been cited by other articles:

				S. E. McLean, L. A. Jensen, D. G. Schroeder, N. R. T. Gibney, and N. M. Skjodt Improving Adherence to a Mechanical Ventilation Weaning Protocol for Critically Ill Adults: Outcomes After an Implementation Program Am. J. Crit. Care., May 1, 2006; 15(3): 299 - 309. [Abstract] [Full Text] [PDF]

				S. K. Hanneman Weaning From Short-term Mechanical Ventilation Crit. Care Nurse, February 1, 2004; 24(1): 70 - 73. [Full Text] [PDF]

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meade, M. Articles by Cook, D. J. Search for Related Content PubMed PubMed Citation Articles by Meade, M. Articles by Cook, D. J.