Abstract
Rationale: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed.
Objectives: To analyze outcomes based on the new weaning classification in a cohort of mechanically ventilated patients.
Methods: Secondary analysis included 2,714 patients who were weaned and underwent scheduled extubation from a cohort of 4,968 adult patients mechanically ventilated for more than 12 hours.
Measurements and Main Results: Patients were classified according to a new weaning classification: 1,502 patients (55%) as simple weaning, 1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning. Variables associated with prolonged weaning (>7 d) were: severity at admission (odds ratio [OR] per unit of Simplified Acute Physiology Score II, 1.01; 95% confidence interval [CI], 1.001–1.02), duration of mechanical ventilation before first attempt of weaning (OR per day, 1.10; 95% CI, 1.06–1.13), chronic pulmonary disease other than chronic obstructive pulmonary disease (OR, 13.23; 95% CI, 3.44–51.05), pneumonia as the reason to start mechanical ventilation (OR, 1.82; 95% CI, 1.07–3.08), and level of positive end-expiratory pressure applied before weaning (OR per unit, 1.09; 95% CI, 1.04–1.14). The prolonged weaning group had a nonsignificant trend toward a higher rate of reintubation (P = 0.08), tracheostomy (P = 0.15), and significantly longer length of stay and higher mortality in the intensive care unit (OR for death, 1.97; 95% CI, 1.17–3.31). The adjusted probability of death remained constant until Day 7, at which point it increased to 12.1%.
Conclusions: Only patients who need more than 7 days for weaning have an increased mortality.
It has been estimated that 40% of the time that a patient spends on mechanical ventilation is devoted to the withdrawal from mechanical ventilation. However, there is little information about the relationship between duration of weaning and outcome.
Among patients who begin weaning, a weaning duration longer than 7 days identifies a subgroup of patients at increased risk for death.
The discontinuation of mechanical ventilation can be defined as the process of abruptly or gradually withdrawing ventilatory support and represents one of the most important issues in intensive care. It has been estimated that 40% of the time that a patient spends on mechanical ventilation is devoted to the withdrawal from mechanical ventilation (1). The understanding of the clinical reason for mechanical ventilation, the techniques used to identify patients capable of ventilator discontinuation, managing the interaction between weaning and sedation, and the ventilator management strategy may help minimize both complications and resource consumption during discontinuation of mechanical ventilation (2–4).
Weaning is a term often used to describe the ventilator discontinuation process by many consensus groups (3, 5) and will be a term used throughout the rest of this article. The European Respiratory Society, American Thoracic Society, European Society of Intensive Care Medicine, Society of Critical Care Medicine, and Societé de Réanimation de Langue Francaise recently convened an International Conference on weaning from mechanical ventilation. From this, a new weaning classification was proposed according to the difficulty and length of the weaning process. Weaning was categorized into three groups (simple, difficult, and prolonged weaning) (5). This classification was based on expert opinion rather than from rigorous analysis of a cohort of ventilated patients; hence, little is known about clinical outcomes and validity among these groups. This new weaning classification has been evaluated in clinical practice by only two small studies (6, 7). In both studies, only the prolonged weaning group was associated with increased mortality in the intensive care unit (ICU).
Our objectives were to describe a cohort of heterogeneous mechanically ventilated patients using this new weaning classification and to analyze the risk of death based on the duration of the weaning process. Some of the results of this study have been previously reported in the form of abstract (8).
In a prospective study, we enrolled consecutive patients who received mechanical ventilation for at least 12 hours after admission to one of 349 participating ICUs in 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 with a waiver of informed consent.
For the purpose of this secondary analysis we selected only the patients who were successfully weaned and underwent a scheduled extubation in the study ICU.
The following information was collected on each enrolled patient at baseline: demographic data (age, sex, height, and weight); Simplified Acute Physiology Score (SAPS II) at the time of admission to the ICU; day of initiating mechanical ventilation; the primary indications for mechanical ventilation, including acute on chronic pulmonary disease (chronic obstructive pulmonary disease [COPD], asthma, chronic pulmonary disease other than COPD); coma; neuromuscular disease; acute respiratory failure (acute respiratory distress syndrome [ARDS], postoperative, congestive heart failure, aspiration, pneumonia, sepsis, trauma, cardiac arrest, and other). The following variables were collected daily during ventilatory support until the first attempt of withdrawal of mechanical ventilation up to Day 28: ventilator settings (VT, respiratory rate, positive end-expiratory pressure [PEEP], peak pressure, plateau pressure), use of sedative, use of neuromuscular blockers, and complications arising during the course of the mechanical ventilation (ARDS, barotrauma, ventilator-associated pneumonia, sepsis, and multiorgan failure [cardiovascular, respiratory, renal, hepatic, and hematologic] defined as a score higher than 2 points in the Sequential Organ Failure Assessment). The onset of weaning was the time that the physician in charge considered the patient likely to resume and sustain spontaneous breathing after a patient met standard criteria for weaning readiness (9): improvement of the cause of respiratory failure, PaO2 to FIO2 ratio above 200, PEEP 5 cm H2O or less, and stable cardiovascular function. We noted the date weaning started, the method of weaning (daily spontaneous breathing trial [T-tube circuit, pressure support ventilation of 7 cm H2O, continuous positive airway pressure of 5 cm H2O, other mode] or gradual reduction of support [pressure support, synchronized intermittent mandatory ventilation with or without pressure support, other mode]), the date of extubation, the need for reintubation (and when it occurred), and the need for tracheostomy after a first extubation. The patients were prospectively followed for outcomes until hospital discharge.
To characterize patients according to the duration of withdrawal (weaning) from mechanical ventilation and identify predictors for difficult or prolonged weaning. For this purpose, patients were classified into one of three weaning groups as follows: simple weaning group, including patients who were extubated on the same day as their first attempt of withdrawal from mechanical ventilation; difficult weaning group, including patients who required up to 7 days to be extubated from the first attempt of withdrawal from mechanical ventilation; prolonged weaning group, including patients who required more than 7 days of weaning after the first attempt of withdrawal from mechanical ventilation.
To estimate if duration of weaning was independently associated with mortality after adjustment for other variables related to mortality.
Data are expressed as mean (SD), median (interquartile range), and proportions, as appropriate. Analysis of variance and Kruskall-Wallis H test were used to compare continuous variables, and chi-square test or Fisher exact test were used to compare proportions.
A multinomial logistic regression with backward stepwise selection was performed to estimate the variables associated with difficult or prolonged weaning, taking the easy weaning group as their reference. Variables with a P value less than 0.10 in the univariate analysis were entered in the multivariable analysis, including: age, SAPS II, body mass index, asthma, chronic pulmonary disease other than COPD, postoperative acute respiratory failure, pneumonia, sepsis, neuromuscular blockers, ventilatory settings (the highest PEEP and the lowest VT used during ventilatory support before the first attempt of withdrawal from mechanical ventilation), ARDS during mechanical ventilation, sepsis during mechanical ventilation, ventilator-associated pneumonia, cardiovascular failure, respiratory failure (with or without criteria for ARDS), renal failure, hepatic failure, hematologic failure, and duration of mechanical ventilation before first attempt of withdrawal from mechanical ventilation. A P value less than 0.05 was considered significant.
To estimate if duration of weaning was associated with mortality, we performed a logistic regression with backward stepwise selection to adjust for the following variables: age, SAPS II, reason to start mechanical ventilation, complications and organ dysfunctions developed during mechanical ventilation before start weaning, duration of mechanical ventilation before the weaning period, and duration of weaning entered using the new weaning classification as a dummy variable taking the simple weaning group as the reference.
Statistical analyses were performed with SPSS 17.0 statistical software (IBM Inc., Armonk, NY).
From the cohort of 4,968 mechanically ventilated patients, in this analysis we included the 2,714 patients who were weaned and underwent a scheduled extubation (Figure 1). Of these, 1,502 patients (55%) were classified as simple weaning, 1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning. The characteristics of each group are shown in Table 1.
Figure 1. Flow chart of exclusion–inclusion criteria for the analysis and mode of withdrawal from mechanical ventilation of included patients. ICU = intensive care unit.
[More] [Minimize]| Simple Weaning (N = 1,502) | Difficult Weaning (N = 1,058) | Prolonged Weaning (N = 154) | P Value | |
| Age, mean (SD), yr | 57 (18) | 59 (18) | 58 (16) | 0.008 |
| SAPS II, points, mean (SD) | 38 (16) | 42 (17) | 43 (16) | <0.001 |
| Female, n (%) | 599 (40) | 441 (42) | 74 (48) | 0.13 |
| Reason to start mechanical ventilation, n (%) | ||||
| COPD | 60 (4) | 53 (5) | 7 (4.5) | 0.47 |
| Asthma | 35 (2) | 7 (1) | 0 | 0.001 |
| Chronic pulmonary disease, non-COPD | 4 (0.3) | 16 (1.5) | 5 (3) | <0.001 |
| Coma | 269 (18) | 183 (17) | 32 (21) | 0.57 |
| Neuromuscular disease | 10 (1) | 16 (1.5) | 2 (1) | 0.11 |
| Acute respiratory failure | ||||
| ARDS | 24 (2) | 20 (2) | 4 (3) | 0.62 |
| Postoperative | 531 (35) | 268 (25) | 28 (18) | <0.001 |
| Congestive heart failure | 81 (5) | 63 (6) | 7 (4.5) | 0.71 |
| Pneumonia | 85 (6) | 116 (11) | 23 (15) | <0.001 |
| Sepsis | 79 (5) | 88 (8) | 14 (9) | 0.004 |
| Trauma | 101 (7) | 52 (5) | 11 (7) | 0.14 |
| Cardiac arrest | 59 (4) | 39 (4) | 6 (4) | 0.95 |
| Aspiration | 31 (2) | 34 (3) | 4 (3) | 0.19 |
| Other | 133 (9) | 103 (10) | 11 (7) | 0.51 |
| Management during mechanical ventilation | ||||
| VT, mean (SD), ml/kg predicted body weight | ||||
| Highest recorded daily | 10.1 (2.4) | 10.2 (2.5) | 10.1 (2.8) | 0.42 |
| Lowest recorded daily | 8.6 (2.0) | 8.5 (2.2) | 8.0 (2.6) | 0.01 |
| Highest daily PEEP, mean (SD), cm H2O | 6.3 (3.4) | 7.3 (3.9) | 8.4 (4.8) | <0.001 |
| Use of sedatives, n (%) | 1,064 (71) | 822 (78) | 123 (80) | <0.001 |
| Use of neuromuscular blockers, n (%) | 115 (8) | 95 (9) | 21 (14) | 0.03 |
| Complications over the course of mechanical ventilation, n (%) | ||||
| Barotrauma | 35 (2) | 38 (4) | 4 (3) | 0.16 |
| ARDS | 22 (1.5) | 38 (4) | 10 (6.5) | <0.001 |
| Sepsis | 70 (5) | 62 (6) | 17 (11) | 0.003 |
| Ventilator-associated pneumonia | 77 (5) | 87 (8) | 25 (16) | <0.001 |
| Cardiovascular failure | 513 (34) | 464 (44) | 86 (57) | <0.001 |
| Respiratory failure | 1,170 (78) | 880 (83) | 140 (91) | <0.001 |
| Renal failure | 277 (18) | 260 (25) | 47 (30.5) | 0.001 |
| Hepatic failure | 199 (13) | 181 (17) | 34 (22) | 0.001 |
| Hematologic failure | 318 (21) | 240 (23) | 44 (29) | 0.09 |
| Days of mechanical ventilation before first attempt of withdrawal from mechanical ventilation, median (IQR) | 3 (2, 4) | 4 (2, 7) | 5 (3, 8) | <0.001 |
Table 2 shows the methods of withdrawal from mechanical ventilation used in each group. A spontaneous breathing trial with T-piece was more commonly used in the simple weaning group than in other groups. In the difficult and prolonged weaning groups, a gradual reduction of pressure support was the preferred method for weaning.
| First Attempt | Weaning | ||||||
| Simple Weaning (N = 1,502) | Difficult Weaning (N = 1,058) | Prolonged Weaning (N = 154) | P Value | Difficult Weaning (N = 1,058) | Prolonged Weaning (N = 154) | P Value | |
| Spontaneous breathing trial, n (%) | 1,227 (82) | 495 (47) | 58 (38) | <0.001 | 312 (29.5) | 31 (20) | 0.02 |
| T-piece | 49 | 36 | 38 | 41 | 45 | ||
| CPAP | 27 | 38 | 33 | 36 | 35.5 | ||
| Pressure support < 8 cm H2O | 22 | 24 | 29 | 21.5 | 19 | ||
| Other | 2 | 2 | — | 2 | — | ||
| Gradual reduction of support, n (%) | 275 (18) | 563 (53) | 96 (62) | <0.001 | 746 (70.5) | 123 (80) | 0.02 |
| Pressure support | 62 | 67 | 71 | 67 | 72 | ||
| SIMV-PS | 24 | 24 | 25 | 24 | 24 | ||
| SIMV | 2 | 5 | 1 | 5 | 1 | ||
| Other | 12 | 4 | 3 | 4 | 2 | ||
The variables related to difficult and prolonged weaning are shown in Table 3, taking the simple weaning group as a reference. Patients with high severity of illness at admission to the ICU and those with chronic pulmonary disease other than COPD or pneumonia as the reason to start mechanical ventilation were more likely to have a difficult/prolonged weaning. Patients with postoperative acute respiratory failure were more likely to be easily weaned. A longer duration of mechanical ventilation before the start of weaning was associated with a longer duration of weaning. Last, the need to be ventilated with a high PEEP during active ventilatory support was also related to difficult/prolonged weaning.
| Difficult Weaning | Prolonged Weaning | |||
| OR (95% CI) | P Value | OR (95% CI) | P Value | |
| SAPS II, per unit | 1.013 (1.008–1.018) | <0.001 | 1.011 (1.001–1.022) | 0.031 |
| Days of mechanical ventilation before first attempt of withdrawal from mechanical ventilation, per day | 1.043 (1.018–1.068) | 0.001 | 1.096 (1.058–1.134) | <0.001 |
| Reason for mechanical ventilation | ||||
| Chronic pulmonary disease, non-COPD | 6.030 (1.990–18.266) | 0.020 | 13.259 (3.444–51.047) | <0.001 |
| Postoperative acute respiratory failure | 0.805 (0.667–0.971) | 0.023 | 0.633 (0.405–0.989) | 0.045 |
| Pneumonia | 1.601 (1.180–2.171) | 0.002 | 1.817 (1.073–3.078) | 0.026 |
| PEEP before first attempt of withdrawal from mechanical ventilation, per cm H2O | 1.057 (1.032–1.082) | <0.001 | 1.088 (1.044–1.135) | <0.001 |
Table 4 shows the comparison of outcomes for the three groups. According to the definitions of the classification of the European Consensus, there were significant differences (P < 0.001) noted in median (interquartile range) time of weaning between the three groups: 1 (1, 1) versus 3 (2, 4) versus 9 (8, 13) days in the simple, difficult, and prolonged groups, respectively.
| Simple Weaning (N = 1,502) | Difficult Weaning (N = 1,058) | Prolonged Weaning (N = 154) | P Value | |
| Reintubation, n (%) | 147 (10) | 177 (10) | 24 (16) | 0.08 |
| Tracheostomy,* n (%) | 88 (6) | 63 (6) | 15 (10) | 0.15 |
| Length of stay in the ICU, median (IQR) | 6 (3, 10) | 9 (6, 15) | 18 (14, 25) | <0.001 |
| Mortality in the ICU, n (%) | 101 (7) | 72 (7) | 20 (13) | 0.01 |
The prolonged weaning group had a nonsignificant trend toward higher rates of reintubation and tracheostomy compared with the simple and difficult groups. The prolonged weaning group also had a significantly longer length of stay and a higher observed ICU mortality rate compared with the other two groups (P < 0.001).
The overall ICU mortality of the included cohort was 7.1% (193 of 2,714 patients). After adjustment for other variables, only the prolonged weaning group was associated with a significantly (P = 0.01) higher mortality compared with the simple weaning group (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.17–3.31), whereas the mortality for the difficult weaning group had a similar mortality to the simple weaning group (OR, 0.89; 95% CI, 0.65–1.22). Figure 2 shows that the adjusted probability of death remained constant for any duration of weaning up to Day 7, after which point the risk of death appeared to increase.
Figure 2. Mean (SD) adjusted probability of death in the intensive care unit for each day of duration of withdrawal from mechanical ventilation.
[More] [Minimize]The main finding of our study is that, in our cohort of heterogeneous mechanically ventilated patients, duration of weaning longer than 7 days (corresponding to the prolonged weaning group in the European Consensus classification for weaning) had a significantly higher mortality than patients with simple weaning. Other findings of our study were: (1) patients with prolonged weaning represent a small proportion of ventilated patients reaching the weaning period; (2) the duration of mechanical ventilation before the start of weaning is associated with weaning outcome; (3) patients with chronic pulmonary disease, but not COPD, with neuromuscular disease or patients with pneumonia as the reason for initiating mechanical ventilation were more likely to have difficult or prolonged weaning; and (4) the level of PEEP necessary during ventilatory support was statistically associated with prolonged weaning.
The outcome of weaned patients classified based on the new classification (5) has been reported in two previous studies (6, 7). In a smaller study, Funk and colleagues (6) reported an increased hospital mortality in patients with prolonged weaning (32%) in comparison to those with simple weaning (13%) (OR, 4.89; 95% CI, 1.32–18.08). In agreement with Funk and colleagues, we found no difference in ICU mortality when comparing simple and difficult weaning. Therefore, weaning that is delayed but still successful within 1 week of onset does not adversely impact ICU survival. In fact, in our cohort weaning time did not appear to affect ICU mortality until the patient reached 7 days of weaning. We have identified several factors associated with prolonged/difficult weaning. One of the factors described is the duration of mechanical ventilation before the first attempt of spontaneous breathing. Previously, several studies had reported that finding. Esteban and colleagues (10) reported that the duration of ventilator support before weaning began was associated with weaning failure (relative rate of successful weaning per 1-day increment, 0.94; 95% CI, 0.90–0.98). Vallverdú and colleagues (11) found that the number of days receiving mechanical ventilation before the weaning trial was significantly higher in the weaning failure group than in the successful weaning group (12 ± 12 vs. 7 ± 7; P < 0.001). Increased length of time receiving mechanical ventilation before the first spontaneous breathing trial may identify a cohort with greater severity of initial injury and identify patients more likely to receive sedation, analgesia, and muscle paralysis.
The second variable associated with weaning outcome is the reason to start mechanical ventilation in the first place. We have previously shown that pneumonia as the reason to initiate mechanical ventilation was associated with increased risk for extubation failure (12). Our hypothesis is that these patients may not have fully cleared the microbial load from their pneumonia and therefore require a longer ventilatory support. Another reason associated with prolonged/difficult weaning was chronic pulmonary disease other than COPD. There is little published information on the outcome of mechanical ventilation and weaning of patients with a chronic pulmonary disease such as bronchiectasis or interstitial lung diseases. The reasons for the difficulty in weaning of these patients are likely similar to those described for patients with severe COPD: disturbances in different aspects of lung mechanics (13) or respiratory muscles (14). Patients with COPD are typically regarded as difficult to wean, but this was not observed in our study or in a previous epidemiological study (15). In contrast, Esteban and colleagues (10) found that 41% of patients with COPD failed the first attempt at spontaneous breathing. Also, Vallverdú and colleagues (11) showed that 61% of patients with COPD needed progressive withdrawal of mechanical ventilation. One of the possible explanations for these divergent results could be the method used during the spontaneous breathing trial. For example, in the presence of increased work of breathing due to auto-PEEP, weaning failure may be more likely with T-piece than with continuous positive airway pressure or pressure support with PEEP (13). In the current study, only 31% of patients with COPD had their spontaneous breathing trial conducted on a T-piece.
Last, we have shown that the level of PEEP applied over the course of ventilatory support was associated with a longer duration of weaning. This was a statistically significant difference, but at only 2 cm H2O it is of questionable clinical relevance. A possible biological explanation for this finding is that patients who required higher PEEP were patients with a higher incidence of ARDS, who required more sedation and more neuromuscular blocking. All these factors have been associated with difficult weaning. To our knowledge, previous studies have not evaluated the relationship between ventilatory settings during mechanical ventilation and the subsequent duration of weaning. In a recent metaanalysis of studies comparing higher PEEP versus lower PEEP in patients with acute lung injury (16), it is reported that median of days with unassisted breathing was similar in both groups (13 d in higher PEEP vs. 11 d in lower PEEP).
An interesting observation was that patients with difficult or prolonged weaning were more likely to be weaned with a gradual reduction of support. It could be argued that the use of gradual support may have contributed to more time on the ventilator and to an increased likelihood of complications, such as ventilator-associated pneumonia. In our study, a gradual reduction of pressure support was the most frequent method used in patients weaned with a gradual reduction of support. A systematic review of trials evaluating modes of weaning showed that only synchronized intermittent mandatory ventilation may lead to a longer duration of the weaning process than either T-piece or pressure support ventilation (17). We therefore believe that it is more likely a selection bias and an association that prolonged weaning patients received gradual reductions, rather than a causal effect. Also striking is the differential success rate on the first attempt of weaning with a spontaneous breathing trial (SBT) (69%) versus a gradual reduction (29%). Although patient selection bias may also play a role here, this may suggest that some patients could have been weaned more quickly if they had received an initial SBT.
Our study has several limitations. First, we were unable to get information about the implementation of specific weaning or sedation protocols, nor the exact duration or settings used for spontaneous breathing trials, which could have affected the weaning process and/or outcome (4, 18). Second, we did not analyze the influence of polyneuropathy associated with weaning time (19, 20). In this regard, we collected information about the use of sedative and muscular blocker medications, and we found that the difficult weaning group had a significantly higher use of those medications compared with the simple weaning group. Third, we have no information about the complications, including delirium, experienced over the weaning time. In our study, we found a nonsignificant higher rate of tracheostomy and reintubation in prolonged weaning compared with simple weaning and difficult weaning. Nevertheless, it could have been interesting to analyze complications over the course of weaning period that may be responsible for weaning failure (21).
In conclusion, among patients who begin weaning, a weaning duration longer than 7 days identifies a subgroup of patients at increased risk for death.
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*A complete list of members may be found before the beginning of the References.
Supported by CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain. N.D.F. is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). A.E. is supported by the Best Spanish Clinical Researcher, Lilly Award (Spain).
Author contributions: Coordination in the acquisition of data: A.A., C.A., M.G., N.N., K.R., V.T., P.D., Y.A., P.P., M.K., M.J., D.M. Study concept and design: O.P., F.F.-V., A.A., N.D.F., A.E. Analysis and interpretation of data: O. P., F.F.-V., C.F., A.A., N.D.F., S.K.E., C.A., A.E. Drafting of the manuscript: O.P., F.F.-V. Critical revision of manuscript: A.A., N.D.F., S.K.E., C.A., M.G., N.N., K.R., V.T., P.D., Y.A., P.P., M.K., M. J., D.M., A.E. Statistical expertise: O.P., C.F.
Originally Published in Press as DOI: 10.1164/rccm.201011-1887OC on May 26, 2011
Author disclosures
Ventila Group Collaborators
Argentina: Coordinators: Carlos Apezteguía (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 de Palermo, 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 de Mendoza, Godoy Cruz), 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 (IIM 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 Division) and Maureen O. Meade (McMaster University).
J. T. Granton (Toronto General Hospital), S. E. Lapinsky (Mount Sinai, 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).
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).
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).
England: Coordinator: Peter Nightingale (Wythenshawe Hospital, Manchester).
J. Hunter (Macclesfield District General Hospital, Macclesfield), J. Hunter (Rotherdam District General Hospital, Rotherdam), 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).
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 (Hôpital Henri Mondor, Créteil) and Arnaud Thille (Hôpital Henri Mondor, Créteil).
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), D.M. 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 J. Schlechtweg (Klinikum Bad Salzungen gGmbH), M. Quintel (Universitaetsklinikum der Georg-August-Universitaet Goettingen), E. 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), F. Ragalmuto (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), B. Eller (Staedt. Hellmig-Krankenhaus, Kamen), K. Schwarke (Evang. Krankenhaus Schwerte GmbH), J. Büttner (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), V. 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 J. 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: Dimitros 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: 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, Jesús María), J. Zevallos and S. Alcabes (Hospital Guillermo Almenara Irigoyen, La Victoria), 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, El Agustino), A. Cifuentes (Hospital de Emergencias José Casimiro Ulloa, Miraflores), 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. Charizosa (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 (La Rabta Tunis), M. Amamou and H. Thabet (CAMUR), 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 (Istanbul Medical Faculty, 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), H. Sungurtekin (Pamukkale University Medical Faculty).
United States: Coordinator: Antonio Anzueto (University of Texas Health Science Center, San Antonio, Texas).
A. C. Arroliga (Cleveland Clinic, Cleveland), O. Gajic and M. Ali (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), 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, C. Haas, and D. Fickle (University of Michigan Medical Center), Ch. Burger and L. Gambino (Mayo Clinic, Jacksonville), 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), R. D. Hite (Wake Forest Baptist Hospital Medical Center, Winston Salem), P. J. McShane and K. N. Olivier (Wilford Hall Medical Center, Texas), K. W. 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).
