Evolution of Mechanical Ventilation in Response to Clinical Research

Evolution of Mechanical Ventilation in Response to Clinical Research

Andrés Esteban MD, PhD (1); Niall D. Ferguson MD, MSc (2); Maureen O. Meade MD, MSc (3); Fernando Frutos-Vivar MD (1); Carlos Apezteguia MD (4); Laurent Brochard MD (5); Konstantinos Raymondos MD (6); Nicolas Nin, MD (1); Javier

Hurtado MD (7); Vinko Tomicic MD (8); Marco González MD (9); José Elizalde MD (10); Peter Nightingale MD (11); Fekri Abroug MD (12); Paolo Pelosi MD (13); Yaseen Arabi MD (14); Rui Moreno MD (15); Manuel Jibaja MD (16); Gabriel

D’Empaire MD (17), Fredi Sandi MD (18); Dimitros Matamis MD (19); Ana María Montañez MD (20); and Antonio Anzueto MD (21) for the VENTILA Group.

1. Hospital Universitario de Getafe, Madrid, Spain. CIBER Enfermedades respiratorias. 2. Interdepartmental Division of Critical Care Medicine, and Department of Medicine, Division of

Respirology, University Health Network, University of Toronto, Toronto, Canada 3. Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada 4. Hospital Profesor A.Posadas, El Palomar, Buenos Aires, Argentina 5. AP-HP, Centre hospitalier Albert-Chenvier - Henri Mondor, INSERM U 841, Université Paris 12 6. Medizinische Hochschule, Hannover, Germany 7. Hospital de Clínicas, Montevideo, Uruguay 8. Clínica Alemana de Santiago, Chile 9. Clínica Medellín y Universidad Pontificia Bolivariana, Medellín, Colombia 10. Hospital ABC, México DF, México 11. Wythenshawe Hospital, Manchester, United Kingdom 12. Fattouma Bourguiba Monastir, Tunicia 13. Ospedale di Circolo, Universita’ degli Studi dell’Insubria, Varese, Italy 14. King Fahad National Guard Hospital, Riyadh, Saudi Arabia 15. Hospital de Santo António dos Capuchos, Lisboa, Portugal 16. Hospital Militar de Quito, Ecuador 17. Hospital de Clínicas, Caracas, Venezuela 18. Hospital Obrero Número 1, La Paz, Bolivia 19. Papageorgiou General Hospital, Thessaloniki, Greece

AJRCCM Articles in Press. Published on October 25, 2007 as doi:10.1164/rccm.200706-893OC

Copyright (C) 2007 by the American Thoracic Society.

20. Sociedad Peruana de Medicina Intensiva 21. South Texas Veterans Health Care System and University of Texas Health Science Center, San

Antonio, Texas, USA (AA) Corresponding author:Andres Esteban, MD, PhD Intensive Care Unit Hospital Universitario de Getafe Carretera de Toledo Km 12,500 28905-Getafe, Madrid, Spain Phone: 34-916834982 Fax: 34-916832095 E-mail: [email protected] Funding support: This study was supported by Red GIRA (G03/063) and Red RESPIRA (C03/11) from Instituto de Salud Carlos III, Spain. The study sponsor had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. Financial Disclosures: All authors have nothing to declare. Short running title: Evolution of Mechanical Ventilation Description number: 5Word count: 3479 At a Glance CommentaryScientific Knowledge on the Subject:

There is little information about the translation of the results of randomized trials on mechanical ventilation to clinical practice. What This Study Adds to the Field:

In this first analysis of the application of results from randomized controlled trials on mechanical ventilation practice, we have observed a strong concordance of predicted and observed practice changes, suggesting that clinical research is indeed driving changes in clinical practice. This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org

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ABSTRACTWord count: 248 Rationale: Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice. Objective: To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort. Methods: Prospective international observational cohort study, with a nested comparative study carried out in 349 intensive care units in 23 countries. We enrolled 4968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1675 patients) that also participated in the 1998 cohort (1383 patients). Measurements and main results: In 2004 compared with 1998, the use of non-invasive ventilation increased (11.1 versus 4.4%; p<0.001). Among patients with acute respiratory distress syndrome tidal volumes decreased (7.4 versus 9.1 ml/kg; p<0.001) and positive end-expiratory pressure levels increased slightly (8.7 versus 7.7 cm of water; p=0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 versus 62%; p<0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 versus 11%; p<0.001). Observed practice confirmed 10 of our 11 practice-change hypotheses. Conclusion: The strong concordance of predicted and observed practice changes suggests that randomized trials results have advanced mechanical ventilation practices internationally. Key Words: Mechanical ventilation, mortality, acute respiratory distress syndrome, non-invasive positive pressure ventilation, weaning

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Introduction

Implementation of known effective therapies is an important target in the provision of quality healthcare.1-3 Meanwhile, delays in the translation of knowledge from clinical research to clinical practice are ubiquitous,4-5 and the practice of critical care medicine is no exception to this trend.6-10

An international prospective observational study of mechanical ventilation practices conducted in 1998 included 5183 consecutive eligible patients from 20 countries.11 Our goals were to provide detailed natural history and prognostic data, to evaluate practice variability, and to generate ‘usual care’ benchmarks for both clinicians and clinical investigators in the field of mechanical ventilation. Among other important observations, we found that patients continue to spend on average 40% of their duration of mechanical in the process of weaning, and that the overall rate of mortality in the intensive care unit (ICU) was high (31%; 95% confidence interval: 29 to 32%).11

From a global perspective, the potential benefit of interventions shown to improve survival associated with mechanical ventilation will be large. The past decade has witnessed the conduct of numerous randomized trials related to reducing need for mechanical ventilation (e.g., non-invasive ventilation trials), reducing the duration of mechanical ventilation (e.g., weaning and extubation studies), and improving safety of mechanical ventilation (e.g., trials of lung-protective ventilation in acute respiratory distress syndrome [ARDS]). The impact of this body of research on clinical practice is unknown; moreover, the current relevance of 1998 data is diminishing.11-12

We therefore conducted a second international observational study of mechanically ventilated patients using methodology similar to the original study. The objectives of this study were to: (1) describe current mechanical ventilation practices; (2) compare current results with those of the 1998 cohort study; and (3) judge the concordance of practice change (or lack thereof) with interval reports of randomized trials. Some of the results of this study have been previously reported in the form of abstracts13-15.

Methods

Observational Study

In a prospective utilization review, we enrolled consecutive patients who received mechanical ventilation for at least 12 hours after admission to one of 349 participating ICUs within 23 participating countries. Beginning March 1, 2004, we enrolled patients over a 1-month period at each center, and followed each patient for the duration of mechanical ventilation, up to 28 days. Only the investigative team members at each site were aware of the purpose and the precise timing of the study. The research ethics board of each participating institution approved the study protocol.

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We followed the methodology of the original study.11 We collected demographic and baseline data at ICU admission, and then recorded ventilator settings, gas exchange variables, ICU discharge, or day 28, whichever came first. We recorded method(s) and duration of weaning, and the need for reintubation or tracheostomy. As in the original study, we calculated the duration of weaning from the first day a patient met standard criteria for weaning readiness (improvement in the cause of respiratory failure; PaO2/FiO2 > 200 mm Hg; positive end-expiratory pressure (PEEP) ≤ 5 cm of water; and no need for vasoactive drugs), to the time of successful extubation (lasting at least 48 hours); patients were classified as ‘difficult to wean’ if they failed their first spontaneous breathing trial. We recorded vital status at hospital discharge.

Literature Review

We sought to identify all randomized controlled trials and systematic reviews evaluating the impact of ventilation techniques on outcomes of importance to patients that were likely to have influenced practice on several continents. We systematically searched the top 5 general medical journals (according to 2003 impact factor: New England Journal of Medicine, Journal of the American Medical Association, Lancet, Annals of Internal

Medicine, British Medical Journal), and the top 5 general critical care journals (American Journal of Respiratory

and Critical Care Medicine, Critical Care Medicine, Intensive Care Medicine, Chest, Critical Care). We searched for studies published over the 6 years preceding the first cohort (1992-1997), and in the 6-year interval between the 2 cohorts (1998-2003), reasoning that adoption of research findings into clinical practice may take several years.16 We searched MEDLINE using a sensitive strategy for identifying randomized controlled trials, 17,18 and a combination of MeSH headings and text words to identify relevant interventions (full search strategy available in the online supplement). One investigator (NDF) hand-searched reference lists of included trials and systematic reviews to identify any further studies.

Two investigators (NDF, MOM) independently applied the following criteria to select publications relevant to this study: (1) randomized controlled trial or systematic review of randomized controlled trials (study design); (2) adult patients with acute or acute-on-chronic respiratory failure (study population); (3) non-invasive positive-pressure ventilation, ventilator weaning technique, ventilation mode, lung-protective ventilation (including tidal volume or positive end-expiratory pressure interventions), prone position, or tracheostomy, (study intervention); and (4) outcomes of importance to patients (including mortality, intubation, reintubation, duration of ventilation or length of hospital stay). Agreement between the 2 investigators for study inclusion was excellent (chance-corrected agreement, kappa = 0.97, 95% confidence interval 0.91 to 1.0) and any differences were resolved by consensus. These 2 investigators independently abstracted study data and quality indicators for each included

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paper, and resolved disagreements by consensus. Tables summarizing the key characteristics and findings of each of the 48 primary studies, excluding systematic reviews and meta-analyses, that ultimately met our inclusion criteria are available in an online appendix to this article.

Generation of Practice-Change Hypotheses

Blinded to the results from the 2004 cohort, we derived summary statements for the major findings related to each intervention. Using these summary statements, 2 investigators (NDF, MOM) independently generated hypotheses regarding how clinical practice might have changed between 1998 and 2004 if these research findings were widely implemented (see online supplement). We only considered hypotheses that we could test using the data in both cohorts. In resolving differences, we based our consensus practice-change hypotheses exclusively upon the summary data (or lack thereof). The resultant practice-change hypotheses, therefore, do not necessarily reflect our personal beliefs or practices, and are not intended as recommendations for clinical care.

Statistical analysis

Data are expressed as means (standard deviation), medians (interquartile range) and proportions as appropriate. For comparisons between the 2004 and 1998 cohorts we considered only data from ICUs that participated in both studies. Student’s t or Mann Whitney U tests were used to compare continuous variables and chi-squared tests were used for categorical variables. We rejected the null hypothesis of no difference between cohorts at a nominal significance level of 0.05. Statistical analyses were conducted using SPPS 13.0 (SPSS Inc, Chicago, Ill).

Results

Table 1 shows the 11 practice-change hypotheses developed from the systematic review of the literature (see online supplement).

General Characteristics & Outcomes

The majority of the 349 ICUs were medical-surgical (239; 69%); 55 units were medical (16%), 48 units were surgical (48; 14%), and 7 units were neurological (2%); 107 (31%) had also contributed patients to the 1998 study. During the 1-month study period 19,505 patients were admitted to a study ICU and 4968 (25%) received mechanical ventilation for more than 12 hours. 1675 (34%) patients were admitted to an ICU that participated in both cohort studies. Table 2 summarizes the patient characteristics and main outcomes from both cohorts.

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Non-invasive Positive Pressure Ventilation

As predicted, the use of non-invasive ventilation was significantly greater in the 2004 cohort, approximately doubling both for acute exacerbations of chronic obstructive pulmonary disease and other causes of acute respiratory failure (Table 3). The median duration of non-invasive ventilation decreased [2 (2-4) versus 3 (2-6) days; p=0.03], though neither the need for intubation nor the mortality among these patients changed significantly (Table 3).

Acute Respiratory Distress Syndrome

We identified a total of 333 patients with acute respiratory distress syndrome who were admitted to one of the ICUs participating in both studies: 135 patients in 1998 and 198 patients in 2004 (Table 4). Tidal volumes over the first week of ARDS were significantly lower in 2004 (Table 4); fewer patients received a tidal volume above 10 ml/kg (7.5 versus 29.6%; p<0.001) and more had tidal volumes below 6 ml/kg actual body weight (19.6 versus 4.4%; p<0.001). A strategy of pressure/volume limitation was applied significantly more commonly in 2004 than in 1998 (Table 4). PEEP levels in the first week increased (Table 4); use of PEEP greater than 10 cm of water increased (40 versus 28%; p<0.001), while use of levels less than 5 cm of water was unchanged (22 versus 26%; p=0.42). Inspiratory pressures were slightly lower in 2004 (Table 4).

Volume assist-control remained the most common ventilator mode used in ARDS and the use of pressure control mode did not increase. For each 1000 days of ARDS, volume assist-control mode was used in 548 days in 1998 and 504 days in 2004 (p = 0.19) and pressure controlled ventilation in 244 days and 202 days, respectively (p = 0.05). We observed a decrease in the use of prone position, being employed at any time in 7% versus 13% of patients in 1998 (p=0.04).

Outcomes for the ARDS patients are displayed in Table 4. Intensive care unit mortality remained above 50% and was not significantly lower compared with the 1998 cohort.

Weaning mechanical ventilation

Table 5 summarizes the characteristics and outcomes of the 1649 patients who underwent a planned extubation. There was a trend towards an increase in the use of spontaneous breathing trials to evaluate extubation readiness (58% in 1998 versus 62% in 2004; p = 0.09), and the percentage of patients extubated after successfully completing their only attempt of spontaneous breathing increased significantly (62% versus 77%; p< 0.001). T-piece was the most common initial method for spontaneous breathing trials, (76% in 1998 versus 71% in 2004; p = 0.07), but trials using low levels of pressure support trended upward over time (10% versus 14%; p=0.06). Among patients not extubated after the first attempt of spontaneous breathing, the median duration of

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weaning was similar in the two cohorts (Table 5), but methods for gradual withdrawal differed. We observed significant reductions in the use of synchronized intermittent mandatory ventilation (11% versus 1.6%; p<0.001) and synchronized intermittent mandatory ventilation with pressure support (26% versus 15%; p<0.001), and a concomitant increase in the use of the pressure support weaning (19% versus 55%; p<0.001). Again among those patients who were not extubated after their first trial of spontaneous breathing, the use of daily spontaneous breathing trials as a weaning method, with T-piece, continuous positive airway pressure or low levels of pressure support, decreased from 39% in 1998 to 27.7% in 2004 (p < 0.001).

Excluding patients admitted to ICU with a tracheostomy tube in situ, 151 patients in 1998 and 206 patients in 2004 received a tracheostomy during their course of ventilation. The rate [12.5% (2004) versus 11% (1998); p=0.19] and median (interquartile range) timing of tracheostomy [2004: 11 (7, 15) versus 1998: 12 (7-17) days; p=0.10] did not change.

Discussion

The main finding of this study is the high degree of concordance between observed changes in mechanical ventilation practice and changes predicted from reports of randomized controlled trials; however, we were not able to detect significant differences in clinical outcomes. The results of this international utilization review may also serve as a current benchmark on the usual care and outcomes of patients requiring mechanical ventilation for acute respiratory failure. We developed 11 practice-change hypotheses, 7 of which predicted a change in practice, the others predicting no change and serving in a way as negative controls. Ten of our hypotheses were borne out when we compared patients admitted to those ICUs that participated in both the 1998 and 2004 cohort studies. The use of non-invasive positive pressure ventilation doubled the use of lower tidal volumes in acute respiratory distress syndrome increased, more patients were promptly extubated after a first attempt of spontaneous breathing, and fewer patients were weaned using synchronized intermittent mandatory ventilation. Meanwhile, as predicted there was only a minimal increase in applied positive end-expiratory pressure, no increase in the use of pressure control ventilation, and no change in the use or timing of tracheostomy. Though we predicted no change in the use of prone ventilation for acute respiratory distress syndrome, there was a statistically significant reduction.

Despite these positive changes in mechanical ventilation practices, clinical outcomes did not improve significantly between 1998 and 2004. We can speculate on a number of reasons as to why we arrived at this seemingly inconsistent and disappointing result. First, however, we must point out that in this utilization review, detecting differences in clinical outcomes was not the primary outcome; consistent with our chosen methodology,

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examining change (or lack of change) in clinical practice was our main objective. This type of before-after international observational study is methodologically ideal for describing changes in usual practice, but it is clearly not the design of choice for studying the effects of these changes on patient outcomes, and therefore our results should not be taken to overturn those of prior randomized controlled trials. We believe that we should still look to results of randomized trials in mechanical ventilation to help guide us towards what we should be doing, meanwhile studies like ours inform us of what we are doing.

Some of the reasons for a lack of improvement in outcomes may therefore be related to study design and are applicable across all patient groups. These include the possibility that differences in ICU admission patterns over time led to a patient population with a higher risk of worse outcomes in the 2004 cohort. In addition, although overall practice change may have moved in the right direction along a continuous spectrum (for example in reducing tidal volume in ARDS), it is possible that the magnitude of this change was insufficient to effect the same changes seen in prior trials. Importantly, we must recognize that our study is underpowered to detect clinically important reductions in mortality (again, this was not our primary outcome), especially in the smaller subpopulations where the strongest randomized trial evidence for mortality benefit exists. It is encouraging to note however, that numerically, if not statistically significantly, ICU mortality rates were 5-6% lower in 2004 among the noninvasive ventilation and ARDS subgroups, and in the overall population hospital mortality was indeed statistically significantly lower in 2004.

We note that coincident with a doubling in the use of noninvasive ventilation in subgroups with the strongest support from clinical trial data (COPD and congestive heart failure) we have observed a 50% reduction in the overall numbers of patients in the ICU whose primary reason for mechanical ventilation was COPD or heart failure. We speculate that this may be a result of increased uptake and successful use of noninvasive ventilation in these patients outside the ICU (in the emergency room, recovery room, hospital ward, etc.), which in turn could have created a form of selection bias, whereby patients with a poor clinical evolution were admitted to the ICU for ongoing ventilatory support. Finally, in the noninvasive ventilation group and to an even greater extent in the group with ARDS, prior randomized trials were appropriately conducted in populations that were carefully selected to a maximize treatment effects. For example, in the ARDS Network study of low tidal volume ventilation, only 12% of all screened acute lung injury patients were actually enrolled in the trial, with many being excluded because of co-morbidities that would limit the efficacy of lung-protective ventilation in reducing mortality19. In contrast, our observational study included all patients that were identified by their physicians as having ARDS. The presence of this dilution of effect (i.e. a lack of selection in inclusion) is supported by the fact that outcomes observed in our study in 2004 were uniformly worse than those reported in clinical trials. Acute respiratory distress

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syndrome mortality was 56% compared with 30% or less reported in ARDS Network clinical trials 20-22, and the failure rate for non-invasive ventilation (need for intubation) was 35% compared with trial values 15-30%. 23-26

Little is known about knowledge translation in the intensive care unit, both in terms of the scope of the problem and the best way to study and overcome potential barriers.6,7 Implementing research findings in the ICU may be very different from an outpatient primary care setting, with many issues needing to be addressed at a system level, rather than influencing the opinion or behavior of individual physicians. Considerations such as the specialist nature of ICU practice, the fact that many ICU clinicians are focused on ventilatory care, and the relatively small number of positive clinical trials available to guide clinical practice, all may have contributed to our positive findings.

On the other hand, it is possible to ask whether the degree of practice change that we observed is sufficient. This is an extremely difficult question to answer, and certainly one that needs further study. The situation for general strategies of mechanical ventilation in the intensive care unit is much more complex than, for example, the situation of drug prescription for a defined disease. In the case of mechanical ventilation, change generally involves a shift in practice along a spectrum in the application of a common technique, rather than the introduction of a new drug. Moreover, the generalizability of oftentimes single-center studies results to heterogeneous intensive care unit populations contrasts with the generalisability of results from multiple multicenter trials to a more homogeneous population, as in studies of acute myocardial infarction. All of these factors may influence clinicians’ choices regarding the implementation of new evidence.27,28 As noted above, however, it is possible that an insufficient degree of practice change contributed to our inability to detect significant reductions in ICU mortality over time. Overall, however, we are unable to comment with certainty on the adequacy of observed clinical practice change, only on the direction of this change.

Upon reading our results with respect to weaning and liberation from mechanical ventilation, one might initially question how it was possible for us to detect an increase use of spontaneous breathing trials to identify extubation readiness while simultaneously documenting a reduction in the use of spontaneous breathing trials as a weaning method. This seemingly paradoxical result is explained by the fact that we, like many clinicians, made a sharp distinction between detecting readiness to liberate from the ventilator and true weaning. The increased use of spontaneous breathing trials to identify extubation readiness refers to the former, and reflects the fact that more patients underwent a trial to detect extubation readiness after meeting standard ‘readiness to wean’ criteria

(improvement in the cause of respiratory failure, PaO2/FiO2 > 200 mm Hg, PEEP ≤ 5 cm of water, and stable

cardiovascular function with no vasoactive drugs). The majority (77%) of these patients was successfully extubated after this first trial and did not need any true weaning. In contrast the reduction in the use of

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spontaneous breathing trials as a method for weaning refers only to patients who had already failed their first trial and had thus demonstrated their need for weaning. In this situation we saw an increase in the use of gradual reductions in pressure support, and a moderate decrease in the use of daily spontaneous breathing trials as weaning methods (along with a marked reduction in the use of synchronized intermittent mandatory ventilation).

To our knowledge, this is the first study to analyze the evolution of mechanical ventilation practices over time among such a large and diverse group of patients with respiratory failure. Additional strengths of this study include the fact that the study populations under comparison were reasonably homogeneous, the rigorous approach to identifying relevant literature, and the development of practice-change hypotheses prior to any knowledge of the results of the second cohort study. In an effort to limit sampling bias, our nested cohort study compared only patients admitted to intensive care units that participated in both studies. Limitations of our study include the fact that we did not collect information to describe the process by which practice changed, for example some of the study intensive care units may have implemented guidelines related to the topics we evaluated in our study. As discussed above, we are unable to judge whether or not the degree of practice change we observed was appropriate. Finally, for management of the acute respiratory distress syndrome, we are only able to comment on practice change among patients who have been identified by clinicians as having this condition. Previous work suggests that acute respiratory distress syndrome is under-recognized by clinicians, 29 and we acknowledge that it is possible that a number of patients with this entity did not receive treatment according to the current evidence. In conclusion, our results provide a description of the current usual care and outcomes of mechanically ventilated patients across several countries and continents. As indicated by the concordance of predicted and observed practice changes, our study demonstrates that in the field of respiratory failure and mechanical ventilation the translation of clinical research to clinical practice is happening. Significant reductions in ICU mortality were not demonstrated; several potential mechanisms for this finding exist.

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Table 1 – Practice-Change Hypotheses (1998 vs. 2004)

Non-invasive positive pressure ventilation

• Increased use of non-invasive positive pressure ventilation for chronic obstructive pulmonary disease exacerbations

• Increased use of non-invasive positive pressure ventilation for acute hypoxemic respiratory failure

Acute respiratory distress syndrome

• Decreased tidal volumes

• Minimal increase in levels of positive end-expiratory pressure

• No change in the use of pressure controlled modes

• No change in the use of prone position

Weaning from mechanical ventilation

• Increased use of pressure support vs. T-piece in spontaneous breathing trials

• Increased use of spontaneous breathing trials to assess extubation readiness

• Decreased use of synchronized intermittent mandatory ventilation as a method for gradually reducing ventilatory support

• Increased use of pressure support as a method for gradually reducing ventilatory support

• No significant change in tracheostomy use or timing

Table 2– General Characteristics and Outcomes of the Cohorts

Patients from ICUs participating in both cohorts

1998 Cohort

2004 Cohort

1998 2004 p value

N = 5183 N = 4968 N = 1383 N = 1675

Age, mean (SD), years 59 (17) 59 (17) 59 (18) 58 (18) 0.13

Female sex, N (%) 1985 (39%) 1967 (40%) 521 (38%) 682 (41%) 0.13

Simplified Acute Physiology Score II, mean (SD), points

44 (17) 42 (18) 44 (17) 43 (18) 0.05

Medical problem, N (%) 3428 (66%) 2921 (59%) 917 (66%) 1138 (68%) 0.26

Main reason for mechanical ventilation#, N (%)

Chronic obstructive pulmonary disease 522 (10%) 267 (5%) 133 (10%) 109 (7%) 0.002

Asthma 79 (2%) 63 (1%) 13 (1%) 29 (2%) 0.06

Other chronic lung disease 60 (1%) 85 (2%) 11 (1%) 29 (2%) 0.02

Coma 864 (17%) 938 (19%) 303 (22%) 401 (24%) 0.18

Neuromuscular disease 94 (2%) 58 (1%) 26 (2%) 24 (1%) 0.33

Acute respiratory failure

Postoperative 1080 (21%) 1053 (21%) 259 (19%) 213 (13%) <0.001

Pneumonia 721 (14%) 528 (11%) 183 (13%) 198 (12%) 0.24

Sepsis 458 (9%) 449 (9%) 123 (9%) 169 (10%) 0.26

Acute respiratory distress syndrome 231 (5%) 148 (3%) 67 (5%) 62 (4%) 0.12

Congestive heart failure 539 (10%) 285 (6%) 152 (11%) 103 (6%) <0.001

Cardiac arrest 100 (2%) 239 (5%) 31 (2%) 91 (5%) <0.001

Trauma 407 (8%) 284 (6%) 99 (7%) 68 (4%) <0.001

Aspiration 129 (3%) 139 (3%) 24 (2%) 41 (2%) 0.17

Other cause of acute respiratory failure

367 (7%) 432 (9%) 79 (6%) 138 (8%) 0.007

Days of mechanical ventilation*, median (interquartile range)

3 (2, 7) 4 (2, 8) 4 (2, 7) 4 (2, 8) 0.002

Days of weaning*, median (interquartile range) 2 (1, 4) 1 (1, 2) 2 (1, 3) 1 (1, 3) <0.001

Days of intubation, median (interquartile range) 4 (2, 8) 4 (2, 8) 4 (2, 8) 5 (2, 9) 0.32

Reintubation†, N (%) 424 / 3037

(14%) 320 / 2859

(11%) 136 / 797

(17%) 113 / 908

(12%) 0.004

After planned extubation, % 350 / 2858

(12%) 279 / 2724

(10%) 127 / 780

(16%) 105 / 869

(12%) 0.01

After unplanned extubation, % 74 / 179 (41%)

41 / 135 (30%)

9 / 17 (53%)

8 / 39 (20%)

0.01

Length of stay in ICU, days, median (interquartile range)

7 (4, 14) 8 (4, 15) 8 (4, 14) 8 (4,15) 0.91

Length of stay in hospital, days, median (interquartile range)

16 (9, 29) 17 (9, 31) 18 (9, 32) 17 (9, 32) 0.57

ICU mortality, N (%) [95% confidence interval]

1590 (31%)

[29 – 32]

1533 (31%)

[29 – 32]

481 (35%)

[32 – 37]

560 (33%)

[31 – 36] 0.43

Hospital mortality§, N (%) [95% confidence interval]

1876 / 4718 (40%)

[38 – 41]

1759 / 4757 (37%)

[35 – 38]

581 / 1282 (45%)

[43– 48]

636 / 1567 (41%)

[38– 48] 0.01

# Because of rounding, percentages may not total 100. In 1998 more than one cause of acute respiratory failure per patient was permitted *Days of ventilation and weaning are mutually exclusive †Includes patients reintubated after either accidental or deliberate extubation § Patients whose status at discharge from hospital was unknown were not included in the calculation

Table 3 – Characteristics and outcomes of patients receiving non-invasive positive pressure ventilation

1998 Cohort

N = 61 2004 Cohort

N = 186 p

value

Age, mean (SD), years 64 (14) 62 (17) 0.45

Simplified Acute Physiology Score II, mean (SD) (points) 39 (14) 36 (15) 0.18

Use by reason for initiation of ventilation, N (%)

Chronic obstructive pulmonary disease 22/133(17%) 48/109(44%) <0.001

Asthma 1/13 (8%) 9 / 29 (31%) 0.21

Acute respiratory failure 35 / 897 (4%) 109/1083(10%) <0.001

Gas exchange

Prior to non-invasive ventilation

pH, mean (SD) 7.31 (0.09) 7.32 (0.10) 0.73

PaCO2, mean (SD), mmHg 58 (23) 53 (22) 0.23

Ratio PaO2 to FiO2, mean (SD) 172 (83) 175 (90) 0.84

Need for intubation, N. (%) 19 (31%) 65 (35%) 0.59

Intensive care unit mortality among all non-invasive positive pressure ventilation patients

18 / 61 (30%) 44 / 186 (24%) 0.36

Mortality in failed non-invasive ventilation, N (%) 9 / 19 (47%) 31 / 65 (47%) 0.98

Mortality in successful non-invasive ventilation, N (%) 9 / 42 (21%) 13 / 121(10%) 0.08

Table 4 - Characteristics and outcomes of patients with acute respiratory distress syndrome

1998 Cohort

N = 135 2004 Cohort

N = 198 p

value

Age, mean (SD), years 64 (14) 62 (17) 0.45

Simplified Acute Physiology Score II, mean (SD), points 39 (14) 36 (15) 0.18

Reason for initiation of ventilation when not acute respiratory distress syndrome*, N, %

N=68 N=136

Chronic obstructive pulmonary disease 3 (4%) 3 (2%) 0.40

Pneumonia 17 (25%) 38 (28%) 0.65

Postoperative 9 (13%) 7 (5%) 0.04

Sepsis 9 (13%) 24 (18%) 0.42

Trauma 13 (12%) 11 (8%) 0.39

Aspiration 2 (3%) 10 (7%) 0.21

Ventilator settings in the first week of acute respiratory distress syndrome

Tidal volume, ml/kg actual body weight

Higher, median (SD) 10 (9, 11) 8 (7, 10) <0.001

Lower, median (SD) 8 (7, 9) 6 (5, 8) <0.001

Positive end-expiratory pressure¶, cm of water

Higher, median (interquartile range) 10 (8, 12) 12 (8, 15) <0.001

Lower, median (interquartile range) 5 (0, 8) 5 (0, 8) 0.66

Peak pressure, cm of water

Higher, median (interquartile range) 39 (34, 45) 37 (31, 42) 0.004

Lower, median (interquartile range) 29 (26, 33) 26 (21, 31) <0.001

Plateau pressure#, cm of water

Higher, median (interquartile range) 29 (24, 32) 29 (24, 32) 0.68

Lower, median (interquartile range) 22 (22, 28) 23 (18, 26) 0.11

Use of a pressure/volume limitation strategy‡

Days of utilization per 1000 ARDS-days 206 548 <0.001

Percentage of the days fulfilling ARDS criteria, mean (SD) 27 (40) 54 (43) <0.001

Duration of intubation, median (interquartile range), days 8 (5,15) 10(5,16) 0.27

Length of stay in the intensive care unit, median (interquartile range), days

12 (7, 23) 14 (7, 21) 0.54

Intensive care unit mortality, N (%) 82 (61%) 111(56%) 0.39

Hospital mortality§, N (%) 87/126(69%) 117/185(63%) 0.29

* Reason for initiation of ventilation is applicable to patients who developed ARDS over the course of mechanical ventilation. ¶ On the first day with criteria of acute respiratory distress syndrome 16% of patients in 1998 and 11% in 2004 were ventilated with zero positive end-expiratory pressure (PEEP). # Plateau pressure was available in 90 patients in 1998 and in 144 patients in 2004. Ventilator settings (tidal volume and end-expiratory positive pressure) in these patients were similar to patients who plateau pressure was not available. ‡ Pressure/Volume Limitation strategy was arbitrarily defined as tidal volume less than 6 ml per kg actual body weight, or volume tidal less than 8 ml/kg actual body weight and plateau pressure or peak inspiratory pressure less than 30 cm of water. § Patients whose status at discharge from hospital was unknown were not included in the calculation

Table 5 – Characteristics and outcomes of patients who underwent planned extubation

1998 Cohort

N=780 2004 Cohort

N=869 p

value

Age, mean (SD), years 58 (19) 56 (18) 0.02

Simplified Acute Physiology Score II, mean (SD), points

42 (16) 40 (17) 0.08

Main reason for mechanical ventilation, N (%)

Chronic obstructive pulmonary disease 85 (11%) 53 (6%) <0.001

Asthma 10 (1%) 18 (2%) 0.21

Other chronic pulmonary disease 3 (0.4%) 7 (1%) 0.27

Coma 154 (20%) 221 (25%) 0.006

Neuromuscular disease 11 (1%) 12 (1%) 0.96

Acute respiratory failure:

Postoperative 178 (23%) 163 (19%) 0.04

Pneumonia 85 (11%) 87 (10%) 0.56

Sepsis 50 (6%) 72 (8%) 0.15

Acute respiratory distress syndrome 22 (3%) 24 (3%) 0.94

Congestive heart failure 96 (12%) 51 (6%) <0.001

Cardiac arrest 14 (2%) 37 (4%) 0.004

Trauma 59 (8%) 37 (4%) 0.004

Aspiration 16 (2%) 15 (2%) 0.63

Other cause 52 (7%) 72 (8%) 0.21

Days of mechanical ventilation prior to weaning, median (interquartile range)

3 (2,6) 4 (2,7) 0.004

Days of weaning in difficult-to-wean patients median (interquartile range)*

3 (2, 5) 3 (2, 4) 0.94

Time devoted to weaning, median (interquartile range), % of total ventilation time

50 (28, 67)

40 (25, 50)

<0.001

Reintubation within 48 hours, N (%) 127 (16.3) 105 (12.1) 0.01

* ‘Difficult-to-wean’ patients were those who failed their first spontaneous breathing trial

The VENTILA group members include (in italic letter the ICUs participating in both studies): Argentina: Coordinators: Carlos Apezteguia (Hospital Prof. A. Posadas, El Palomar, Buenos Aires) and Pablo Desmery (Sanatorio Mitre, Buenos Aires). A. Sarasino and D. Ceraso (Hospital Dr. Juan A. Fernández, Buenos Aires), D. Pezzola and F.Villarejo (Hospital

Prof. A. Posadas, El Palomar), C. Cozzani and M. Torres Boden (Hospital Dr. C. Argerich, Buenos Aires), C. Santos and E. Capparelli (Hospital Eva Perón, San Martín), M. Tavella and C. Irrazábal (Hospital de Clínicas José

de San Martín, Buenos Aires), L. Cardonnet and A. Diez (Hospital Provincial del Centenario, Rosario), A. Giannelli and L. Vargas (Policlínico de Neuquén), M. Bustamante (Hospital Héroes de Malvinas, Merlo), E. Turchetto (Hospital Privado de la Comunidad, Mar del Plata), J. Teves and O. Elefante (Hospital Oscar Alende, Mar del Plata), C. Sola and J. Mele (Hospital Dr. José Penna, Bahía Blanca), V. Sciuto and P. Grana (Hospital Provincial de Neuquén), G. Jannello and R. Valentini (CEMIC, Buenos Aires), S. Ilutovich (Sanatorio Mitre, Buenos Aires), L. Huespe Gardel (Hospital Escuela José F. de San Martín, Corrientes), J. Scapellato and E. Orsini (Hospital F. Santojanni, Buenos Aires), G. Agüero and Á. Sánchez (Policlínico Regional J. Perón, Mercedes), R. Fernández and L. Villalobos Castañeda (Hospital Italiano, Buenos Aires), F. González and E.Estenssoro (Hospital General

San Martín, La Plata), S. Lasdica (Hospital Privado del Sur, Bahía Blanca), A. Gómez and J. Scapellato (Clínica de la Esperanza, Buenos Aires), P. Pratesi (Hospital Universitario Austral, Pilar), M. Blasco and F. Villarejo (Clínica Olivos, Olivos), G. Olarte and C. Bevilacqua (Clínica Modelo de Morón / Hospital San Juan de Dios, R.Mejía), M. Quinteros (Sanatorio San Lucas, San Isidro), P. Ripoll (Clínica La Sagrada Familia, Buenos Aires), S. Filippus (Clínica del Valle, Comodoro Rivadavia), F. Guzman Díaz and M.Deheza (Hospital B. Rivadavia, Buenos Aires), E. García and J. Arrieta (Hospital Regional de Comodoro Rivadavia), P. Pardo and J. Neira (Sanatorio de

la Trinidad, Buenos Aires), J. Núñez and F. Pálizas (Clínica Bazterrica, Buenos Aires), A. Ciccolini and G.Murias (Sanatorio Santa Isabel, Buenos Aires), W. Vázquez and M. Grilli (Hospital Español, Mendoza), F. Chertcoff and E. Soloaga (Hospital Británico, Buenos Aires), D. Vargas and J. Berón (Hospital Pablo Soria, San Salvador de

Jujuy), A. Maceira and P. Schoon (Hospital Prof. Luis Güemes, Haedo), D. Pina (Sanatorio Franchín, Buenos Aires), E. Sobrino and A.Raimondi (Sanatorio Mater Dei, Buenos Aires), E. De Vito (Instituto Alfredo Lanari,

Buenos Aires). Belgium: M. Malbrain (Ziekenhuis Netwerk, Antwerpen) Bolivia: Coordinator: Freddy Sandi Lora (Hospital obrero N° 1, La Paz)

A. Lavandez and C. Alfaro (Complejo Hospitalario Viedma, La Paz), J. Guerra (Instituto gastroenterológico boliviano japonés, Santa Cruz). Canada: Coordinators Niall D. Ferguson (Toronto Hospital Western) and Maureen O. Meade (McMaster University) J.T. Granton (Toronto General Hospital), S. E. Lapinsky (Mount Sinai Hospital, Toronto), J. Meyer (St. Joseph´s

Hospital, Toronto), D.C. Scales (St. Michael´s Hospital, Toronto), R.A. Fowler (Sunnybrook Health Sciences

Centre, Toronto), B. Kashin (William Osler Health Centre, Brampton, Ontario), D. J. Cook (St. Joseph's Healthcare). Chile: Coordinator: Vinko Tomicic (Clínica Alemana de Santiago) L.Soto (Instituto Nacional del Tórax, Santiago), C. Romero (Hospital Clínico Pontificia Universidad Católica,

Santiago), M.Teresa Caballero and L. Chiang (Hospital naval almirante NEF), E. Poch (Instituto de Neurocirugía), J. Canteros Gatica (Hospital Curico), H. Ugarte (Hospital de Coquimbo), M. Calvo, C. Vargas and M.Yacsich. (Hospital Regional de Valdivia), E. Tobar (Hospital Clínico de la Universidad de Chile, Santiago), J. G. Urra (Clínica Alemana de Temuco) Colombia: Coordinator Marco A. González (Clínica Medellín y Universidad Pontificia Bolivariana, Medellín) A. Guerra (Hospital General de Medellín and Clínica SOMA, Medellín), C. Cadavid (Hospital Pablo Tobón Uribe,

Medellín), R. Panesso (Clínica Las Américas, Medellín), M.Granados (Clínica Valle del Lilli, Cali), C. Dueñas (Hospital Bocagrande, Cartagena), F. Molina (Clínica Bolivariana, Medellín), R. Camargo (Clínica General del Norte de Barranquilla), G. Ortiz (Hospital de Santa Clara, Bogotá), M. Gómez (Hospital de San José). Ecuador: Coordinator: Manuel Jibaja (Hospital Militar de Quito)G. Paredes and E. Bazantes (Hospital Enrique Garcés, Quito), P. Jiménez (Hospital Carlos Andrade Martín,

Quito), J. Vergara and L. González (Hospital Luis Vernaza Valdez, Guayaquil) France: Coordinators Laurent Brochard (Centre hospitalier Albert-Chenvier - Henri Mondor, Paris) and Arnaud Thille (Centre hospitalier Albert-Chenvier - Henri Mondor, Paris). L. Mallet (Centre Hospitalier D’Auch), P. Andrivet (Centre Médico-Chirurgical de Bligny, Bris-sous-Forges), O. Peyrouset (Hôpital Ambroise Paré, Boulogne Billancourt), I. Mohammedi (Hôpital Edouard Herriot, Lyon), E.

Guerot (Hôpital Européen Georges Pompidou , Paris), N. Deye (Hôpital Lariboisière, Paris), S. Monsel and F. Bouvet (Hôpital Pitié Salpétrière, Paris), M. Darmon (Hôpital Saint Louis, Paris), M. Fartoukh and A. Harb (Hôpital

Tenon, Paris), N. Anguel (Hôpital de Bicêtre, Kremlin-Bicêtre). Germany: Coordinator: Konstantinos Raymondos (Medizinische Hochschule Hannover) A. Nowak, T. Pahlitzsch and K. F. Rothe (Krankenhaus Dresden-Friedrichstadt), M. Ragaller and T. Koch (Universitaetsklinikum Carl Gustav Carus Dresden), G. Sterzel (Kreiskrankenhaus Loebau, Ebersbach), R. Wittich (Carl-Thiem-Klinikum Cottbus gGmbH), K. Rudolph and J. Raumanns (St. Elisabeth gGmbH Leipzig), U. Grueneisen and F. Stupacher (Bundeswehrkrankenhaus Leipzig), H. Bromber, G. Leonhardt and J. Soukup (Universitaetsklinikum der Martin-Luther-Universitaet Halle-Wittenberg), C. Wuttke (Krankenhaus St. Elisabeth und St. Barbara Halle, Saale), M. Holler (Staedtisches Krankenhaus Martha-Maria Halle-Doelau gGmbH), J. Haberkorn (Georgius-Agricola-Klinikum Zeitz), P. Jehle (Paul-Gerhard-Stiftung, Lutherstadt Wittenberg), B. Albrecht (Zeisigwaldkliniken Bethanien Chemnitz), Klut (Kreiskrankenhaus Rochlitz), H. J. Hartung (Vivantes Krankenhaus am Urban, Berlin-Kreuzberg), H. Gerlach (Vivantes-Klinikum Neukoelln, Berlin), T. Henneberg, S. Weber-Carstens, K. Haid, and C. Melzer-Gartzke, M. Oppert (Charité Universitaetsklinikum, Campus Virchow, Berlin), M. Reffenberg (Lungenklinik Heckeshorn, Berlin), Ch. Werel and A. Kopietz (Klinikum Barnim GmbH, Werner Forßmann Krankenhaus, Eberswalde), T. Nippraschk and D. Hoffmeister (Ruppiner Klinikum GmbH, Neuruppin), M. Schneider (Dietrich-Bonhoeffer-Klinikum-Neubrandenburg), D. A. Vagts and G. Noeldge-Schomburg (Medizinische Fakultaet der Universitaet Rostock), G. Savinski and T. Kloess (Allgemeines Krankenhaus Harburg, Hamburg), C. Frenkel, D. Yakisan, H. Schroeder and C. Daniels (Staedtisches Klinikum Lueneburg), B. Sedemund-Adib (Universitaetsklinikum Schleswig Holstein - Campus Luebeck), S. Krueper (Klinikum Hannover Nordstadt), J. Ahrens, U. Molitoris and K. Johanning (Medizinische Hochschule Hannover), D. Korth and W. Seitz (Kreiskrankenhaus Hameln), J. Kleideiter and P. Palomino (Staedtische Kliniken Bielefeld gGmbH), A. Lunkeit and Schlechtweg (Klinikum Bad Salzungen gGmbH), M. Quintel (Universitaetsklinikum der Georg-August-Universitaet Goettingen), Schild and C.P. Criée (Evangelisches Krankenhaus Goettingen-Weende e.V., Bovenden-Lenglern), M. Bund (Albert-Schweitzer-Krankenhaus Northeim), M. Hundt, U. Schulze and J. Kolle (Kreiskrankenhaus Charlottenstift, Stadtoldendorf), J. Offensand, S. Youssef, and J.P. Juvana (Klinikum Salzgitter GMBH), W. Seyde (Staedtisches Klinikum Wolfenbuettel), T. Luecke and A. Gruener (Universitaetsklinikum Mannheim), E. Calzia (Universitaetsklinikum fur Anasthesiologie, Ulm), J. Heine, M. Borth, U. von Leitner and M. Hoffmann (Dr. Herbert-Nieper-Krankenhaus-Goslar), W. Brandt (Universitaetsklinikum Magdeburg), A. Keller and S. Scieszka (Krankenhaus Neuwerk, Moenchengladbach), E. Schroeder and F. L. Deres (Kreiskrankenhaus

Dormagen), M. Burrichter, T. Bernhardt and W. Wilhelm (St.-Marien-Hospital, Luenen), M. Beiderlinden (Universitaetklinikum Essen), H. Steiniger and V. Weißkopf (Ruhrlandklinik, Essen), H. Militzer (Evangelisches und Johanniter Klinikum, Dinslaken), K. Eicker and F. Hinder (Universitaetsklinikum Muenster), C. Weilbach and M. Raab (St. Josefs-Stift Cloppenburg), Ragaymutu (Kliniken der Stadt Koeln Krankenhaus Holweide), T. Moellhoff and K. Tsompanidis (Katholische Stiftung Marienhospital Aachen), D. Henzler and R. Kuhlen (Universitaetsklinikum Aachen), H. Wrigge, C. Putensen and F. L. Dumoulin (Universitaetsklinikum Bonn), M. Foedisch and J. Busch (Evangelisches Waldkrankenhaus Bad Godesberg gGmbH, Bonn), W. Theelen (St. Johannes-Krankenhaus Troisdorf), A. Deller (Krankenhaus der Barmherzigen Brueder, Trier), W. Baier (St. Nikolaus-Stiftshospital GmbH, Andernach), Eller (Staedt. Hellmig-Krankenhaus, Kamen), K. Schwarke (Evang. Krankenhaus Schwerte GmbH), Buettner (Evangelisches Krankenhaus Elisabethenstift gGmbH, Darmstadt), K. P. Wresch and K. Steidel (St.-Vincentius-Krankenhaus Speyer), J. F. Meyer (Universitaetsklinikum der Ruprecht-Karls-Universitaet Heidelberg), M. Layer (Thoraxklinik Heidelberg gGmbH), G. Meinhardt (Robert-Bosch-Krankenhaus, Stuttgart), J. Fritschi and P. Zaar (Ermstalklinik Staedtisches Krankenhaus Sindelfingen), H. P. Stegbauer (Kreiskrankenhaus Leonberg), Tumbass and S. Hahn (Ermstalklinik Bad Urach), H. Mende, M. Fischer, J. Martin and A. Assmann (Klinik am Eichert Goeppingen), V. Schoeffel, K. van Deyk and S. Seyboth (Stadtklinik Baden-Baden), H. Kerger and Ernst (Evangelisches Diakoniekrankenhaus, Freiburg), H. F. Ginz (Kreiskrankenhaus Loerrach), F. Brettner (Krankenhaus der Barmherzigen Brueder, Muenchen), O. Karg (ASKLEPIOS Fachkliniken Muenchen-Gauting), M. Glaser and T. P. Zucker (Klinikum Traunstein), J. Jahn and A. Schneider (Fachkliniken Wangen), M. Burkert (Bundeswehrkrankenhaus Ulm), H. Kuenzig and T. Bein (Klinikum der Universitaet Regensburg), A. Speicher (Krankenhaus der Barmherzigen Brueder, Regensburg), J. Brederlau, E. Kaufmann, F. Schuster and C. Soellmann (Universitaetsklinik Wuerzburg), S. Frenzel and L. Pfeiffer (Unstrut-Hainich Kreiskrankenhaus Muehlhausen), S. Weber-Carstens, K. Haid, C. Melzer-Gartzke, C. von Heymann and B. Temmesfeld (Charité Universitaetsklinikum, Campus Mitte, Berlin).

Greece: Coordinator: Dimitrios Matamis (Papageorgiou General Hospital, Thessaloniki). H. Mouloudi (Ippokration General Hospital, Athens) Italy: Coordinator: Paolo Pelosi (Ospedale di Circolo di Varese) A.Pesenti and N. Rossi (Ospedale San Gerardo, Monza), D. Chiumello and L. Gattinoni (Ospedale Maggiore

Policlinico, Milano), P. Severgnini (Ospedale di Circolo di Varese), R. Fumagalli and A. Nikiforov (Ospedali Riuniti di Bergamo), S.Grasso (Ospedale di Venere, Bari).

Mexico: Coordinator: José Elizalde (Hospital ABC, México DF)P. Cerda (Centro Médico de las Américas, Mérida), R. Mercado (Hospital Universitario de Monterrey), J.Albe Castañón (Instituto mexicano del seguro social HECMNS XXI, México DF). Netherlands: Michael Kuiper (Medical Center Leeuwarden)P.H.M. Egbers and M. Koopmans (Medical Center Leeuwarden)

Peru: Coordinator: Ana María Montañez M. Contardo, J. Cerna and R.Roldán (Hospital Edgardo Rebagliati Martins, Lima), J.Zevallos and S.Alcabes (Hospital Guillermo Almenara Irigoyen, Lima), C.Salcedo and D.Bruzone (Hospital Nacional Daniel Alcides Carrión, Callao), J.Quiñones (Hospital de Emergencias Grau, Lima), M.Suárez Lazo (Hospital Nacional Hipólito Unanue, Lima), A.Cifuentes (Hospital de Emergencias José Casimiro Ulloa, Lima), M.Mayorga (Clínica San Pablo, Lima). Portugal: Coordinator: Rui Moreno (Hospital de Santo António dos Capuchos, Lisboa) P.Casanova (Hospitais da Universidade de Coimbra), R. Matos and A.L. Jardim (Hospital de Santo António dos Capuchos, UCIP, Lisboa), A. Godinho (Hospital dos SAMS, UCI, Lisboa), P. Póvoa (Hospital São Francisco Xavier, UCIM, Lisboa), P. Coutinho (Centro Hospitalar de Coimbra), L. Reis (Hospital de São José, Unidade de Urgência Médica, Lisboa). Saudi Arabia: Coordinator: Yaseen Arabi (King Fahad National Guard Hospital) N.Abouchala (King Faisal Hospital), F. Hameed (King Khalid National Guard Hospital) Spain: Coordinators: Nicolas Nin and Eva Tejerina (Hospital Universitario de Getafe). F. Gordo (Fundación Hospital de Alcorcón), R. Fernandez (Complejo Hospitalario Parc Taulí, Sabadell), R. de Pablo (Hospital Universitario Príncipe de Asturias, Alcalá de Henares), J. Ibañez (Hospital Son Dureta, Palma de

Mallorca), E. Fernández Mondejar (Hospital Virgen de las Nieves, Granada), F. del Nogal (Hospital Severo

Ochoa, Leganés), F. Taboada (Hospital Central de Asturias, Oviedo), A. García Jiménez (Hospital Arquitecto

Marcide, El Ferrol), Ll. Cabré and J. Morillas (Hospital de Barcelona-SCIAS), S. Macias (Hospital General de

Segovia), R. de Celis (Hospital de Galdakao), J. M.Añón (Hospital Virgen de la Luz, Cuenca),P. Ugarte (Hospital

Marqués de Valdecilla, Santander), T. Mut (Hospital de la Plana, Vila-Real), J. Diarte (Complejo Hospitalario de

Ciudad Real), V. Sagredo (Hospital Clínico de Salamanca), M. Valledor (Hospital San Agustín, Avilés), G.González and L. Rodríguez (Hospital Morales Meseguer, Murcia), V.Parra and E. Gómez (Hospital de

Sagunto), F. Jara (Hospital Mutua de Terrassa), J.M. Quiroga (Hospital de Cabueñes, Gijón), L. Arnaiz (Hospital

Clínico Universitario de San Carlos, Madrid), Á. Ayensa (Hospital Virgen de la Salud, Toledo), F. Suárez Sippman (Fundación Jiménez Díaz), F. Carrizosa (Hospital General de Jerez de la Frontera), J. A. Rodríguez Sarría (Hospital de Elda), C. Homs (Hospital San Jorge, Huesca), A. Díaz Lamas (Hospital Cristal Piñor, Ourense), M. León (Hospital Arnau de Vilanova, Lleida), J. Allegue (Hospital Nuestra Señora del Rosell, Cartagena), M.Ruano (Hospital La Fe, Valencia). Tunisia: Coordinator: Fekri Abroug (Fattouma Bourguiba, Monastir) M.Besbes, J. Ben Khelil, K. Belkhouja and K. BenRomdhane (Hospital Abderrahmane Mami, Ariana), S. Ben Lakhal, S. Abdellatif and K. Bousselmi (Hospital Rabta, Tunis), M.Amamou and H.Thabet (CAMUR, Tunis), L. Besbes and N. Nciri (Fattouma Bourguiba, Monastir), M.Bouaziz, H. Kallel and M. Bahloul (Habib Bourguiba Sfax), S. ElAtrous, S.Merghli and M. Feki Hassen (Tahar Sfar Mahdia). Turkey: Coordinator: Nahit Cakar (Dokuz Eylun University, Istanbul). R. Iscimen (Uludag University School of Medicine, Bursa), M. Kyzylkaya (College of medicine, Ataturk University, Erzurum), B. Yelken (Osmangazi University, Eskisemir), I. Kati (Medical Faculty of Yuzuncu Yil University, Van) , T. Guldem (Haydarpasa Numune Teaching and Research Hospital, Istambul), U. Koca (Dokuz Eylun University, Istanbul), M.Cicek (Inonu University of Medical Faculty, Malatya). United Kingdom: Coordinator: Peter Nightingale (Wythenshawe Hospital, Manchester) J. Hunter (Macclesfield District General Hospital, Macclesfield), J. Hunter (Rotherham District General Hospital,

Rotherham), S. Mousdale (Blackburn Royal Infimary, Blackburn), J. Harper (Royal Liverpool University Hospital,

Liverpool), A. Conn (Wansbeck General Hospital, Ashington), D. Higgins (Southend Hospital, Westcliffe-on-Sea), D.Jayson (Southport & Formby District General Hospital, Southport), D. Hawkins (North Staffordshire Hospital,

Stoke on Trent). United States: Coordinator: Antonio Anzueto (University of Texas Health Science Center, San Antonio, Texas)

A.C. Arroliga (Cleveland Clinic, Cleveland), O. Gajic, Ch. Burger and L. Gambino (Mayo Clinic, Rochester), D. Ost, A.Fein, A. Kyprianou, L. Shulman and S. Chang (North Shore University Hospital, New York), J.S. Steingrub, M.A. Tidswell and K. Kozikowski (Baystate Medical Center, Springfield), C.A. Piquette and L.Morrow (Creighton University Medical Center, Nebraska), P.Scheinberg and J.Green (Saint Joseph’s Hospital, Atlanta), L.Penogreen and K. Kannady (Georgia State University Kennestone), M. Moss, M. Mealer, and R.D. Restrepo (Grady Hospital Georgia, Atlanta), H.E. Fessler, R. Brower, D. Hager and A. Scully (John Hopkins University Hospital, Baltimore), J. Beamis, D.E. Craven and W. Miner (Lahey Clinic Medical Center, Burlington), S. Blosser, K. Miller, L.Cornman and J.Breidinger (Penn State Hershey Medical Center, Hershey), J.T. Huggins and Ch.Strange (Medical University of South Carolina, Charleston), N.S. Hill and L.Lawler (Tufts-New England Medical Center, Boston), M. Rembert (Newark Beth Israel Medical Center, Newark), H.K. Donnelly, J.D. D’Amico, R.G. Wunderink, N.Queseda and J. Topin (Northwestern Memorial Home Health University, Chicago), G.T. Kinasewitz and G.L. Lee (University of Oklahoma Health Sciences Center, Oklahoma City), J.Walls and V. Zimmer (Presbyterian Healthcare, Charlotte), A.X. Freire (Regional Medical Center, Memphis), C. Steven and L. Caskey (Louisiana State University Health Sciences Center, Shreveport), R. Dhand and L.A. Despins (University Hospital and Clinics MU Healthcare, Columbia), R.Hyzy, R.E. Dechert,Carl Haas, D. Fickle (University of Michigan Medical Center), D. Marks and S. Benslimane (University of Texas Health Science Center, San Antonio), V.J. Cardenas Jr. (University of Texas Medical Branch Galveston), M.J. Wing and P.Krumpe (VA Sierra Nevada Health Care System, Reno), J. Truwit and M. Marshall (University of Virginia Health System, Charlottesville), D.L. Herr (Washington Hospital Center, Washington DC), RD Hite (Wake Forest Baptist Hospital Medical Center, Winston Salem), PJ McShane and KN Olivier (Wilford Hall Medical Center, Texas), KW Presberg (Froedtert & Medical College, Milwaukee).

Uruguay: Coordinator: Javier Hurtado (Cudam Sanatorio Colón, Sanatorio IMPASA and Hospital de Clínicas, Montevideo) M. Borde, E.Echavarría, S. Gómez and M. Berón (Hospital Maciel, Montevideo), F. Villalba (Sanatorio Casa de Galicia, Montevideo), I. Porras (Sanatorio CASMU 2, Montevideo), P. Cardinal, C. Surraco and V. Navarrete (Sanatorio CASMU 4, Montevideo), F. Rodríguez and J.C. Bagattini (Hospital Británico, Montevideo), R. Garrido (Hospital Evangélico and Sanatorio IMPASA, Montevideo), S. Infanzón and J. Caraballo (Hospital Militar and CTI-SMI, Montevideo), C. Santos and A. García (Hospital de Clínicas, Montevideo), R. Cal (CTI-SMI, Montevideo), G. Pittini and J. Cabrera (Centro Nacional de Quemados, Montevideo), F. Bazzano and F. Domínguez (Hospital

Pasteur, Colonia), P. Alzugaray, D. González and M.Machado (Sanatorio CAMOC, Carmelo), F.Torres (Sanatorio Mautone and Asistencial Medica de Maldonado, Maldonado), S. Mareque, M. Korintan, F.Mora, E. Altieri, E. Gianoni, C. Fregosi, A. Crossi, G. Larrarte (Sanatorio CAAMS, Soriano), O. Pereira (Sanatorio COMTA, Tacuarembó), J. Baraibar (Hospital Regional de Tacuarembó), A. Soler (Sanatorio COMEPA, Paysandú), M. Rodríguez Verde (Hospital Paysandú), M. Díaz (Hospital de Salto and Sanatorio Uruguay, Salto), J. Martínez Ramos (Sanatorio Uruguay, Salto), I. Iturralde, W. González and E. Cubas (Sanatorio CAMDEL, Minas), A. Cataldo (Sanatorio CAMEDUR, Durazno), O. Rocha (Sanatorio GREMEDA, Artigas), A.Deicas (Sanatorio CASMU 2 and Sanatorio CASMU 4) Venezuela: Coordinator Gabriel D’Empaire (Hospital de Clínicas, Caracas). R. Zerpa (Hospital Militar de Caracas), M. Narvez (Hospital Domingo Luciani, Caracas), F.Pérez (Hospital de

Clínicas, Caracas), J. España (Hospital Universitario de Caracas).

Online Data Supplement

Evolution of Mechanical Ventilation in Response to Clinical Research

Andrés Esteban MD, PhD; Niall D. Ferguson MD, MSc; Maureen O. Meade MD, MSc; Fernando

Frutos-Vivar MD; Carlos Apezteguia MD; Laurent Brochard MD; Konstantinos Raymondos MD;

Nicolas Nin, MD; Javier Hurtado MD; Vinko Tomicic MD; Marco González MD; José Elizalde MD;

Peter Nightingale MD; Fekri Abroug MD; Paolo Pelosi MD; Yaseen Arabi MD; Rui Moreno MD;

Manuel Jibaja MD; Gabriel D’Empaire MD, Fredi Sandi MD; Dimitros Matamis MD; Ana María

Montañez MD; and Antonio Anzueto MD for the VENTILA Group.

Search strategy

1 randomized controlled trial.pt. (196305)2 controlled clinical trial.pt. (67398)3 randomized controlled trials/ (35450)4 random allocation/ (52127)5 double-blind method/ (79937)6 single-blind method/ (8605)7 or/1-6 (333323)8 animal/ not human/ (2824174)9 7 not 8 (315139)32 "new england journal of medicine".jn. (47704)33 jama.jn. (50756)34 lancet.jn. (98229)35 annals of internal medicine.jn. (20124)36 bmj.jn. (36653)37 "american journal of respiratory & critical care medicine".jn. (7076)38 critical care medicine.jn. (10719)39 intensive care medicine.jn. (5028)40 chest.jn. (24758)52 Positive-Pressure Respiration/ or Ventilators, Mechanical/ or Respiration, Artificial/ (37179)53 critical care london.jn. (379)54 or/32-40 (301047)55 53 or 54 (301426)61 peep.tw. (2700)62 tidal volume/ (5385)63 VENTILATOR WEANING/ (1540)64 TRACHEOSTOMY/ (2857)65 or/61-64 (12001)66 65 or 52 (44457)67 55 and 9 and 66 (822)68 limit 67 to yr=1992-2003 (659)

Figure E1 – Flow chart of the literature review

MEDLINE literature search forrandomized

controlled trialsand systematic reviews in 10 key

Excluded byabstract

Retrieved for detailed full-text review

Total articles = 78Did not meet inclusion

criteria• Not human (2)

• Not age > 18 (3)• Not randomized

controlled trialor systematic review (8)

Additional articlesidentified

from reference lists ofreview

Met Inclusion CriteriaTotal articles = 55

(48 randomized controlled

Table E1 – Non-invasive positive pressure ventilation randomized controlled trials (1992-2003)

Mortality (%) † Reintubation (%) † Length of stay †Author

(ref.)

year

C NTarget

population

Intervention

A

Intervention

B

Quality

notes* A Bp-

valueA B p-value A B

p-

value

Bott E1

19933 60 COPD NIV Usual care Cc, E 10.0‡ 3.0‡ 0.106 - - -

9

days

9

days-

Brochard E2

19955 85 COPD NIV Usual care - 9.3 28.6 0.02A 25.6 73.8 <0.001A

23

days

35

days0.02

Kramer E3

19952 31 COPD NIV Usual care Cc 6.3 13.3 - 31.3 73.3 0.05A

20.4

days

18.8

days-

Celikel E4

19981 30 COPD NIV Usual care Cr 0 6.7 - - - -

11.7

days

14.6

days<0.05A

Plant E5

200014 236 COPD NIV Usual care - 10.2 20.3 0.05A 15.3 27.1 0.02A - - -

Wysocki E6

19951 41 ARF NIV Usual care Cc 33.3‡ 50.0‡ 0.46 61.9 70.0 0.88

17

days

25

days0.16

Word E7

19981 27 ARF NIV Usual care - 25.0 0 0.123 43.8 45.5 0.71

17.4

days

9.1

days0.941

Confalonieri

E8

1999

3 56 ARF NIV Usual care Cr 25.0 21.4 - 21.4 50.0 0.03A1.8

days

6.0

days0.04A

Martin E9

20001 61 ARF NIV Usual care Cc, Ci 15.6‡ 34.5‡ 0.21 28.1 58.6 0.002A

5

days

6

days0.77

Ferrer E10

20033 105 ARF NIV Usual care CC, Ci 17.6‡ 38.9‡ 0.53 25.5 51.9 0.01A

9.6

days

11.3

days0.11

* Quality Notes: papers were assessed for adequacy of randomization (R); concealment (Cc); equality at baseline (E); cointervention

management (Ci); minimal crossover (Cr); follow-up (F); and intention-to-treat analysis (I). Only categories with concerns for

adequacy are indicated (i.e. if a category is not listed in the table it was judged to be adequate).

† Statistically significant results are presented in bold face and the superior treatment arm (A vs. B) is indicated by a superscript letter

next to the p-values; primary outcomes are underlined

‡ Indicates intensive care unit mortality – hospital mortality is presented otherwise

Other abbreviations: C = number of centres; N = number of patients; COPD = chronic obstructive pulmonary disease; ARF = acute

respiratory failure; NIV = non-invasive ventilation; CPAP = continuous positive airway pressure

Table E2 – Lung protection randomized controlled trials (1992-2003)

Mortality (%) †Duration of

ventilation †Author(ref.)

yearC N

Target

population

Intervention

A

Intervention

B

Quality

notes*A B p-value A B

p-

value

Amato E21

19952 28 ALI/ARDS

Lower tidal

volume +

High

PEEP +

Recruitment

maneuvers

Conventional

ventilationCc 33.3‡ 53.8‡ 0.45 - - -

Amato E22

1998 §2 53 ALI/ARDS

Lower tidal

volume +

High

PEEP +

Recruitment

Conventional

ventilation- 37.9‡ 70.8‡ <0.001A - - -

maneuvers

Ranieri E23

19992 37 ALI/ARDS

Lower tidal

volume +

High

PEEP +

Recruitment

maneuvers

Conventional

ventilationCi, I 38.0 58.0 0.19

12

Daysll

4

Daysll

<0.01A

Brochard

E24

1998

25 112 ALI/ARDSLower tidal

volume

Conventional

ventilation- 46.6 37.9 0.38

23.1

days

21.4

days0.88

Stewart E25

19988 120 ALI/ARDS

Lower tidal

volume

Conventional

ventilation- 50.0 46.7 0.72

16.6

days

9.7

days0.2

Brower E26

19994 52 ALI/ARDS

Lower tidal

volume

Conventional

ventilation- 50.0‡ 46.2‡ - - - -

ARDSnet E27

200010 861 ALI/ARDS

Lower tidal

volume

Conventional

ventilation- 31.0 40.0 0.007A

12

days

10

days0.007A




† Statistically significant results are presented in bold face and the superior treatment arm (A vs. B) is indicated by a superscript

letter next to the p-values; primary outcomes are underlined

§ This trial was a continuation of the Amato 1995 study


ll Ventilator free days at day 28

Other abbreviations: C = number of centres; N = number of patients; ALI = acute lung injury; ARDS = acute respiratory distress

syndrome; PEEP = positive end-expiratory pressure;

Table E3 – Ventilator mode and prone randomized controlled trials (1992-2003)

Mortality (%) †Duration of

ventilation †Author(ref.)

YearC N

Target

population

Intervention

A

Intervention

B

Quality

notes*A B

p-

valueA B

p-

value

Rappaport

E28

1994

1 30 ARF PCV

Volume

cycled

ventilation

E; Ci;

Cr; I56.3‡ 63.6‡ - - - -

Esteban E29

200012 79 ALI/ARDS PCV

Volume

cycled

ventilation

E 51.4 78.6 0.02A21

days

25

days0.46

Putensen

E30

2001

1 30

Ventilated

severe

trauma

APRV

PCV for 3

days and then

APRV

Cc; Ci;

Cr; F; I20.0‡ 26.7‡ -

15

days

21

days0.032A

Derdak E31 13 148 ALI/ARDS HFOV Conventional Cc 37.3‡ 52.1‡ 0.102 22 21 -

2002 ventilation days days

Gattinoni

E32

2001

28 304 ALI/ARDSProne

positionUsual care Ci 50.7‡ 48.0‡ - - - -

Staudinger

E33

2001

1 26 ALI/ARDSProne

positionRotating bed Cc 58.3 64.3 - - - -

Watanabe

E34

2002

1 16 ARFProne

positionUsual care Cc, Ci - - -

11.6

days

14

days0.003A




† Statistically significant results are presented in bold face and the superior treatment arm (A vs. B) is indicated by a superscript

letter next to the p-values; primary outcomes are underlined


Other abbreviations: C = number of centres; N = number of patients; ALI = acute lung injury; ARDS = acute respiratory distress

syndrome; ARF = acute respiratory failure; PCV = pressure control ventilation; APRV = airway pressure release ventilation; HFOV =

high-frequency oscillatory ventilation

Table E4 – Weaning randomized controlled trials (1992-2003)

Mortality (%) † Reintubation (%) †Duration of ventilation or

weaning †Author(ref.)

yearC N

Target

population

Intervention

A

Intervention

B

Quality

notes

* A Bp-

valueA B

p-

valueA B p-value

Strickland

E35

1993

1 15Ready to

wean

Weaning

protocol

Physician

weaningCi;F; I 77.8%‡ 33.3%‡ -

Ely E36

19961 300

Ventilated

patients

RT weaning

protocol

Physician

weaningCr 37.6 39.7 0.63 3.4 7.9 0.08

4.5

days

6

days0.003A

Kollef E37

19974 357

Ventilated

patients

Weaning

protocol

Physician

weaningCi 22.3 23.6 0.779 12.8 10.1 0.417

35

hours

44

hours0.057

Marelich E38

20001 335

Ready to

wean

Weaning

protocol

Physician

weaningCi, Cr 10.2 5.9 0.146 9.0 5.9 0.28

2.8

days

5.2

days<0.001A

Namen E39

20011 100

Ventilated

neurosurgery

RT weaning

protocolUsual care Cc, Cr 40.8 31.4 0.325 20.4 11.8 0.239 6.0 6.0 0.387

Brochard

E40

1994

3 109Ready to

wean

A: T-piece

B: SIMV

C: PS

-

A:22.9

B:23.3

C:12.9

-

A:5.7

B:11.6

C:3.2

-

A:42.9 hours

B:41.9 hours

C:22.6 hours

0.05C

Jouniaeux

E41

1994

1 19COPD

ventilated

SIMV + PS

weaning

SIMV

weaningCc, I - - - 0 22.2 -

4.2

days

5.3

days0.06

Esteban E42

199514 130

Ready to

wean

A: SIMV

B: PS

C: Multiple daily SBT

D: Once daily SBT

- - - -

A:13.8

B:18.9

C:15.2

D:22.6

-

A:5 days

B:4 days

C:3 days

D:3 days

See

below §

Esteban E43

199727 484

Ready to

weanT-piece SBT PS 7 SBT - - - - 18.8 18.5 0.94 - - -

Esteban E44

199930 526

Ready to

wean30-min SBT

120-min

SBT- 18.9 18.4 0.96 13.5 13.4 0.91

10

days

12

days0.005A

Perren E45

20021 98

Ready to

wean30-min SBT

120-min

SBTCi 19.6 17.3 0.97 8.7 3.8 -

6.0

days7.0 0.2

Nava E46

19983 50

COPD

ventilated

Extubate to

NIVPS weaning - 8.0 28.0 0.009A - - -

10.2

days

16.6

days0.021A

Girault E47

19991 33

COPD

ventilated

Extubate to

NIVPS weaning Cc, Ci 0 12.5 -

4.6

days

7.7

days0.004A

Ferrer E48

20032 43

Ready to

wean

Extubate to

NIVDaily SBT Cc 9.5ll 40.9ll 0.045A 14.3 27.3 0.457

9.5

days

20.1

days

0.03A††




† Statistically significant results are presented in bold face and the superior treatment arm is indicated by a superscript letter next to

the p-values; primary outcomes are underlined

‡ Indicates in this study successful weaning

§ Odds ratios (95% confidence interval) for successful weaning and extubation: 2.83 (1.36-5.89) D vs. A, p=0.006; 2.05 (1.04-4.04)

D vs. B, p=0.04

ll Indicates intensive care unit mortality – hospital mortality is presented otherwise

Other abbreviations: C = number of centres; N = number of patients; SIMV = synchronized intermittent mandatory ventilation; PS =

pressure support; SBT = spontaneous breathing trial; NIV = non-invasive ventilation; RT = respiratory therapist.

Table E5 - Summary Statements by Intervention

Noninvasive positive pressure ventilation

1992-1997 1998-2003

• In chronic obstructive

pulmonary disease, non-

invasive positive pressure

ventilation reduced intubation

and mortality (3 randomized

controlled trials, 1 review)

• In chronic obstructive pulmonary

disease, non-invasive positive

pressure ventilation reduced

intubation and mortality (2

randomized controlled trials, 3

reviews)

• In acute coronary syndromes,

non-invasive positive pressure

ventilation may cause harm (1

randomized controlled trial)

• In acute coronary syndromes, non-


ventilation was safe, may reduce

intubation (2 randomized

controlled trials)

• For other causes of acute

respiratory failure, non-


ventilation did not reduce

intubation or mortality (1


• For other causes of acute

respiratory failure, non-invasive

positive pressure ventilation

reduced intubation, may reduce

mortality (7 randomized controlled

trials)

Acute respiratory distress syndrome

1992-1997 1998-2003

• No randomized controlled trial

data on low tidal volumes,

airway pressures

• Restricting tidal volumes and

airway pressures had inconsistent

survival effects among 3 small

randomized controlled trials and 1

large positive randomized

controlled trial

• Combining low tidal pressures

and volumes, high positive

end-expiratory pressure (PEEP)

and recruitment maneuvers

may improve survival (1


• Combining low tidal pressures and

volumes, high positive end-

expiratory pressure (PEEP) and

recruitment maneuvers may

improve survival (2 randomized

controlled trials)

• Pressure control mode did not

significantly improve mortality

(1 randomized controlled trial)

• Pressure control mode improved

mortality, but this was confounded

by baseline differences (1



data on prone positioning

• Prone positioning did not improve

mortality in acute lung injury (2

randomized controlled trials)


data on high frequency

oscillation

• High-frequency oscillatory

ventilation showed a trend toward

lower mortality (1 randomized

controlled trial)

Weaning from mechanical ventilation

1992-1997 1998-2003

• Protocol-directed weaning

safely reduced duration of

ventilation (3 randomized

controlled trials)

• Protocol-directed weaning safely

reduced duration of ventilation (1

randomized controlled trial, 1

review); results may vary with

specific populations and protocols

(1 randomized controlled trial, 1

review)

• Spontaneous breathing trials

using T-piece and low-level

pressure support achieved

similar rates of reintubation (1


• Spontaneous breathing trials of 30

vs. 120 minutes duration achieved

similar rates of reintubation (2


• T-piece or pressure support

mode weaned patients more

quickly than synchronized

intermittent mandatory

ventilation (2 randomized

controlled trial)

• T-piece or pressure support modes

weaned patients more quickly than

synchronized intermittent

mandatory ventilation (1 review)


data on weaning with non-


• For patients with chronic

obstructive pulmonary disease,

extubation to non-invasive positive

ventilation pressure ventilation reduced

ventilation time and mortality (3

randomized controlled trials)


data on tracheostomy benefits

or timing

• No randomized controlled trial data

on tracheostomy benefits or

timing.

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Evolution of Mechanical Ventilation in Response to Clinical Research

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