American Journal of Respiratory and Critical Care Medicine

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.

Objectives: To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort.

Methods: A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 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 (1,675 patients) that also participated in the 1998 cohort (1,383 patients).

Measurements and Main Results: In 2004 compared with 1998, the use of noninvasive ventilation increased (11.1 vs. 4.4%, P < 0.001). Among patients with acute respiratory distress syndrome, tidal volumes decreased (7.4 vs. 9.1 ml/kg, P < 0.001) and positive end-expiratory pressure levels increased slightly (8.7 vs. 7.7 cm H2O, P = 0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 vs. 62%, P < 0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 vs. 11%, P < 0.001). Observations confirmed 10 of our 11 practice-change hypotheses.

Conclusions: The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally.

Scientific Knowledge on the Subject

There is little information about the influence of clinical trials on clinical practice in the field of the mechanical ventilation.

What This Study Adds to the Field

The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally.

Implementation of known effective therapies is an important target in the provision of quality health care (13). 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 (610).

An international, prospective, observational study of mechanical ventilation practices conducted in 1998 included 5,183 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 ventilation in the process of weaning, and that the overall rate of mortality in the intensive care unit (ICU) was high (31%; 95% confidence interval, 29–32%) (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 the need for mechanical ventilation (e.g., noninvasive 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 as follows: (1) to describe current mechanical ventilation practices, (2) to compare current results with those of the 1998 cohort study, and (3) to 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 abstracts (1315).

Observational Study

In a prospective utilization review, we enrolled consecutive patients who received mechanical ventilation for at least 12 hours after admission to 1 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.

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 H2O, and no need for vasoactive drugs), to the time of successful extubation (lasting at least 48 h); 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 five 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 five 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 two 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 (N.D.F.) hand-searched reference lists of included trials and systematic reviews to identify any further studies.

Two investigators (N.D.F., M.O.M.) 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) noninvasive positive-pressure ventilation, ventilator weaning technique, ventilation mode, lung-protective ventilation (including tidal volume or PEEP 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 two investigators for study inclusion was excellent (chance-corrected agreement, κ = 0.97; 95% confidence interval, 0.91–1.0) and any differences were resolved by consensus. These two investigators independently abstracted study data and quality indicators for each included 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 supplement 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, two investigators (N.D.F., M.O.M.) independently generated hypotheses regarding how clinical practice might have changed between 1998 and 2004 if these research findings were widely implemented (see the 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 on 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 (SD), 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 version 13.0 (SPSS, Inc., Chicago, IL).

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


Noninvasive positive-pressure ventilation
 • Increased use of noninvasive positive-pressure ventilation for chronic obstructive pulmonary disease exacerbations
 • Increased use of noninvasive 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 versus 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

General Characteristics and 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 4,968 (25%) received mechanical ventilation for more than 12 hours. A total of 1,675 (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.


Patients from ICUs Participating in Both Cohorts
1998 Cohort2004 Cohort19982004

(n = 5,183)
(n = 4,968)
(n = 1,383)
(n = 1,675)
P Value
Age, mean (SD), yr59 (17)59 (17)59 (18)58 (18)0.13
Female sex, n (%)1,985 (39)1,967 (40)521 (38)682 (41)0.13
Simplified Acute Physiology Score II, mean (SD), points44 (17)42 (18)44 (17)43 (18)0.05
Medical problem, n (%)3,428 (66)2,921 (59)917 (66)1,138 (68)0.26
Main reason for mechanical ventilation,* n (%)
 COPD522 (10)267 (5)133 (10)109 (7)0.002
 Asthma79 (2)63 (1)13 (1)29 (2)0.06
 Other chronic lung disease60 (1)85 (2)11 (1)29 (2)0.02
 Coma864 (17)938 (19)303 (22)401 (24)0.18
 Neuromuscular disease94 (2)58 (1)26 (2)24 (1)0.33
 Acute respiratory failure
  Postoperative1,080 (21)1,053 (21)259 (19)213 (13)<0.001
  Pneumonia721 (14)528 (11)183 (13)198 (12)0.24
  Sepsis458 (9)449 (9)123 (9)169 (10)0.26
  ARDS231 (5)148 (3)67 (5)62 (4)0.12
  Congestive heart failure539 (10)285 (6)152 (11)103 (6)<0.001
  Cardiac arrest100 (2)239 (5)31 (2)91 (5)<0.001
  Trauma407 (8)284 (6)99 (7)68 (4)<0.001
  Aspiration129 (3)139 (3)24 (2)41 (2)0.17
  Other cause of acute respiratory failure367 (7)432 (9)79 (6)138 (8)0.007
Days of mechanical ventilation, median (IQR)3 (2, 7)4 (2, 8)4 (2, 7)4 (2, 8)0.002
Days of weaning, median (IQR)2 (1, 4)1 (1, 2)2 (1, 3)1 (1, 3)<0.001
Days of intubation, median (IQR)4 (2, 8)4 (2, 8)4 (2, 8)5 (2, 9)0.32
Reintubation, n (%)424/3,037 (14)320/2,859 (11)136/797 (17)113/908 (12)0.004
 After planned extubation, %350/2,858 (12)279/2,724 (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, d, median (IQR)7 (4, 14)8 (4, 15)8 (4, 14)8 (4,15)0.91
Length of stay in hospital, d, median (IQR)16 (9, 29)17 (9, 31)18 (9, 32)17 (9, 32)0.57
ICU mortality, n (%) (95% CI)1,590 (31) (29–32)1,533 (31) (29–32)481 (35) (32–37)560 (33) (31–36)0.43
Hospital mortality§, n (%) (95% CI)
1,876/4,718 (40) (38–41)
1,759/4,757 (37) (35–38)
581/1,282 (45) (43–48)
636/1,567 (41) (38–48)

Definition of abbreviations: ARDS = acute respiratory distress syndrome; CI = confidence interval; COPD = chronic obstructive pulmonary disease; ICU = intensive care unit; IQR = interquartile range.

*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.

Noninvasive Positive-Pressure Ventilation

As predicted, the use of noninvasive ventilation was significantly greater in the 2004 cohort, approximately doubling for both acute exacerbations of chronic obstructive pulmonary disease (COPD) and other causes of acute respiratory failure (Table 3). The median duration of noninvasive ventilation decreased (2 [2–4] vs 3. [2–6] d, P = 0.03], although neither the need for intubation nor the mortality among these patients changed significantly (Table 3).


1998 Cohort

2004 Cohort

(n = 61)
(n = 186)
P Value
Age, mean (SD), yr64 (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 (%)
 COPD22/133 (17)48/109 (44)<0.001
 Asthma1/13 (8)9/29 (31)0.21
 Acute respiratory failure35/897 (4)109/1,083 (10)<0.001
Gas exchange
 Prior to noninvasive ventilation
  pH, mean (SD)7.31 (0.09)7.32 (0.10)0.73
  PaCO2, mean (SD), mm Hg58 (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
ICU mortality among all noninvasive positive-pressure ventilation patients18/61 (30)44/186 (24)0.36
 Mortality in failed noninvasive ventilation, n (%)9/19 (47)31/65 (47)0.98
 Mortality in successful noninvasive ventilation, n (%)
9/42 (21)
13/121 (10)

Definition of abbreviations: COPD = chronic obstructive pulmonary disease; ICU = intensive care unit.


We identified a total of 333 patients with ARDS 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 vs. 29.6%, P < 0.001) and more had tidal volumes below 6 ml/kg actual body weight (19.6 vs. 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 H2O increased (40 vs. 28%, P < 0.001), whereas use of levels less than 5 cm H2O was unchanged (22 vs. 26%, P = 0.42). Inspiratory pressures were slightly lower in 2004 (Table 4).


1998 Cohort

2004 Cohort

(n = 135)
(n = 198)
P Value
Age, mean (SD), yr64 (14)62 (17)0.45
Simplified Acute Physiology Score II, mean (SD), points39 (14)36 (15)0.18
Reason for initiation of ventilation when not ARDS,* n (%)(n = 68)(n = 136)
 COPD3 (4)3 (2)0.40
 Pneumonia17 (25)38 (28)0.65
 Postoperative9 (13)7 (5)0.04
 Sepsis9 (13)24 (18)0.42
 Trauma13 (12)11 (8)0.39
 Aspiration2 (3)10 (7)0.21
Ventilator settings in the first week of ARDS
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
PEEP, cm H2O
 Higher, median (IQR)10 (8, 12)12 (8, 15)<0.001
 Lower, median (IQR)5 (0, 8)5 (0, 8)0.66
Peak pressure, cm H2O
 Higher, median (IQR)39 (34, 45)37 (31, 42)0.004
 Lower, median (IQR)29 (26, 33)26 (21, 31)<0.001
Plateau pressure, cm H2O
 Higher, median (IQR)29 (24, 32)29 (24, 32)0.68
 Lower, median (IQR)22 (22, 28)23 (18, 26)0.11
Use of a pressure/volume limitation strategy§
 Days of utilization per 1,000 ARDS-days206548<0.001
 Percentage of the days fulfilling ARDS criteria, mean (SD)27 (40)54 (43)<0.001
Duration of intubation, median (IQR), days8 (5, 15)10(5,16)0.27
Length of stay in the ICU, median (IQR), d12 (7, 23)14 (7, 21)0.54
ICU mortality, n (%)82 (61)111 (56)0.39
Hospital mortality, n (%)
87/126 (69)

Definition of abbreviations: ARDS = acute respiratory distress syndrome; CI = confidence interval; COPD = chronic obstructive pulmonary disease; ICU = intensive care unit; IQR = interquartile range; PEEP = positive end-expiratory pressure.

*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 ARDS, 16% of patients in 1998 and 11% in 2004 were ventilated with zero 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 whose 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 H2O.

Patients whose status at discharge from hospital was unknown were not included in the calculation.

Volume assist-control remained the most common ventilator mode used in ARDS and the use of pressure-control mode did not increase. For each 1,000 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 and 202 days, respectively (P = 0.05). We observed a decrease in the use of prone position, which was used, at any time, in 7 versus 13% of patients in 1998 (P = 0.04).

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

Weaning from Mechanical Ventilation

Table 5 summarizes the characteristics and outcomes of the 1,649 patients who underwent a planned extubation. There was a trend toward an increase in the use of spontaneous breathing trials to evaluate extubation readiness (58% in 1998 vs. 62% in 2004; p = 0.09), and the percentage of patients extubated after successfully completing their only attempt of spontaneous breathing increased significantly (62 vs. 77%, P < 0.001). Use of a T-piece was the most common initial method for spontaneous breathing trials (76% in 1998 vs. 71% in 2004, P = 0.07), but trials using low levels of pressure support trended upward over time (10 vs. 14%, P = 0.06). Among patients not extubated after the first attempt of spontaneous breathing, the median duration of 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 vs. 1.6%, P < 0.001) and synchronized intermittent mandatory ventilation with pressure support (26 vs. 15%, P < 0.001), and a concomitant increase in the use of the pressure support weaning (19 vs. 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).


1998 Cohort

2004 Cohort

(n = 780)
(n = 869)
P Value
Age, mean (SD), yr58 (19)56 (18)0.02
Simplified Acute Physiology Score II, mean (SD), points42 (16)40 (17)0.08
Main reason for mechanical ventilation, n (%)
 COPD85 (11)53 (6%)<0.001
 Asthma10 (1)18 (2%)0.21
 Other chronic pulmonary disease3 (0.4)7 (1%)0.27
 Coma154 (20)221 (25%)0.006
 Neuromuscular disease11 (1)12 (1%)0.96
 Acute respiratory failure
  Postoperative178 (23%)163 (19%)0.04
  Pneumonia85 (11%)87 (10%)0.56
  Sepsis50 (6%)72 (8%)0.15
  ARDS22 (3%)24 (3%)0.94
  Congestive heart failure96 (12%)51 (6%)<0.001
  Cardiac arrest14 (2%)37 (4%)0.004
  Trauma59 (8%)37 (4%)0.004
  Aspiration16 (2%)15 (2%)0.63
  Other cause52 (7%)72 (8%)0.21
Days of mechanical ventilation prior to weaning, median (IQR)3 (2,6)4 (2,7)0.004
Days of weaning in difficult-to-wean patients median (IQR)*3 (2, 5)3 (2, 4)0.94
Time devoted to weaning, median (IQR), % of total ventilation time50 (28, 67)40 (25, 50)<0.001
Reintubation within 48 h, n (%)
127 (16.3)
105 (12.1)

Definition of abbreviations: ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; IQR = interquartile range.

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

Excluding patients admitted to the 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] vs. 11% [1998], P = 0.19) and median (interquartile range) timing of tracheostomy (2004, 11 [7–15] vs., 1998, 12 [7–17] d; P = 0.10) did not change.

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 noninvasive positive-pressure ventilation doubled, the use of lower tidal volumes in ARDS 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 PEEP, no increase in the use of pressure-control ventilation, and no change in the use or timing of tracheostomy. Although we predicted no change in the use of prone ventilation for ARDS, 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, 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 toward 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 (e.g., 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 (e.g., in the emergency room, recovery room, hospital ward), 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 (Acute Respiratory Distress Syndrome) Network study of low tidal volume ventilation, only 12% of all screened patients with acute lung injury were actually enrolled in the trial, with many being excluded because of comorbidities that would limit the efficacy of lung-protective ventilation in reducing mortality (19). 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. ARDS mortality was 56% compared with 30% or less reported in ARDS Network clinical trials (2022), and the failure rate for noninvasive ventilation (need for intubation) was 35% compared with trial values of 15–30% (2326).

Little is known about knowledge translation in the ICU, 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 ICU 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 study results to heterogeneous ICU populations contrasts with the generalizability 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 (10, 27). 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.

On 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 increased 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 H2O, and stable cardiovascular function with no vasoactive drugs). The majority (77%) of these patients were successfully extubated after this first trial and did not need any true weaning. In contrast, the reduction in the use of 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 following: the reasonably homogeneous study populations under comparison, the rigorous approach to identifying relevant literature, and the development of practice-change hypotheses before 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 ICUs 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 ICUs 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 ARDS, 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 ARDS is underrecognized by clinicians (28), 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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Correspondence and requests for reprints should be addressed to Andrés Esteban, M.D., Ph.D., Intensive Care Unit, Hospital Universitario de Getafe, Carretera de Toledo Km 12,500, 28905 Getafe, Madrid, Spain. E-mail:


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