How Is Mechanical Ventilation Employed in the Intensive Care Unit? An International Utilization Review ANDRÉS ESTEBAN, ANTONIO ANZUETO, INMACULADA ALÍA, FEDERICO GORDO, CARLOS APEZTEGUÍA, FERNANDO PÁLIZAS, DAVID CIDE, ROSANNE GOLDWASER, LUIS SOTO, GUILLERMO BUGEDO, CARLOS RODRIGO, JORGE PIMENTEL, GUILLERMO RAIMONDI, and MARTIN J. TOBIN for the Mechanical Ventilation International Study Group Hospital Universitario de Getafe, Madrid, Spain; University of Texas Health Science Center, San Antonio, Texas; Hospital Profesor Posadas, Buenos Aires, Argentina; Clínica Bazterrica, Buenos Aires, Argentina; Hospital Universitario Clementino Fraga Filho, Río de Janeiro, Brazil; Instituto Nacional de Enfermedades Respiratorias y Cirugía Torácica, Santiago, Chile; Pontificia Universidad Católica de Chile, Santiago, Chile; Asociación Española Primera de Socorros Mutuos, Montevideo, Uruguay; Hospital da Universidade, Coimbra, Portugal; F.L.E.N.I., Buenos Aires, Argentina; and Loyola University, Chicago; and Hines Veterans Affairs Hospital, Hines, Illinois
A 1-d point-prevalence study was performed with the aim of describing the characteristics of conventional mechanical ventilation in intensive care units ICUs from North America, South America, Spain, and Portugal. The study involved 412 medical-surgical ICUs and 1,638 patients receiving mechanical ventilation at the moment of the study. The main outcome measures were characterization of the indications for initiation of mechanical ventilation, the artificial airways used to deliver mechanical ventilation, the ventilator modes and settings, and the methods of weaning. The median age of the study patients was 61 yr, and the median duration of mechanical ventilation at the time of the study was 7 d. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic obstructive pulmonary disease (13%), coma (10%), and neuromuscular disorders (10%). Mechanical ventilation was delivered via an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1%. Ventilator modes consisted of assist/control ventilation in 47% of patients and 46% were ventilated with synchronized intermittent mandatory ventilation, pressure support, or the combination of both. The median tidal volume setting was 9 ml/kg in patients receiving assist/control and the median setting of pressure support was 18 cm H2O. Positive end-expiratory pressure was not employed in 31% of patients. Method of weaning varied considerably from country to country, and even within a country several methods were in use. We conclude that the primary indications for mechanical ventilation and the ventilator settings were remarkably similar across countries, but the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country.
The basic understanding of mechanical ventilation has advanced to a stage that randomized controlled trials can be undertaken to evaluate different ventilator strategies. Such trials usually consist of the comparison of a new treatment against conventional therapy. Given the diversity of ventilator modes and settings, however, it is difficult to know what constitutes “conventional mechanical ventilation.” The problem of defining conventional mechanical ventilation in arbitrary terms is highlighted by recent studies evaluating the efficacy of strategies designed to minimize ventilator-induced injury in patients with the acute respiratory distress syndrome (ARDS). In comparison with conventional ventilation, Amato and colleagues
(1) reported that a lung-protective ventilator strategy decreased mortality, whereas Stewart and colleagues (2) and Brochard and coworkers (3) did not observe a reduction in mortality with such a strategy. In these studies, patients in the conventional arm were ventilated with volume-cycled ventilation, but tidal volume was larger in the study of Amato and colleagues (1) (12 ml/kg of body weight) than in the studies of Stewart and colleagues (2) (10.1 to 10.8 ml/kg) and Brochard and coworkers (3) (9.9 to 10.7 ml/kg). Peak inspiratory pressure was specifically limited to 50 cm H2O in the conventional arm of the study of Stewart and colleagues (2) and to 60 cm H2O in the study of Brochard and coworkers (3). In contrast, peak inspiratory pressure was not limited in the study of Amato and colleagues; this lack of pressure limit in the conventional group combined with a larger tidal volume favor a beneficial outcome in the intervention arm. To be able to decide if some modification of ventilator management represents a true therapeutic advance, it is necessary to first define what is meant by conventional mechanical ventilation. In 1992, the Spanish Lung Failure Collaborative Group conducted a survey of the use of mechanical ventilation, specifically the indications, modes employed, and methods of weaning (4). The study involved 290 patients in 47 intensive care units (ICUs). Of patients admitted to ICUs in the study, 46% were receiving mechanical ventilation at the moment of the survey. Most patients were ventilated with assist/control (A/C) ventilation (55%) or synchronized intermittent mandatory ventilation (SIMV) (26%), and the following techniques were used for weaning: T-tube trials, 24%; SIMV, 18%; pressure support (PS), 15%; SIMV plus PS, 9%; or a combination of two or more methods in succession, 33%. Because the study was confined to Spain, it is difficult to know if the data are representative of the general use of mechanical ventilation. To better define the characteristics of conventional mechanical ventilation today, we undertook a study of ventilator use in North America, South America, Spain, and Portugal—the first large international study of its kind. The aims of this study were to define the indications for mechanical ventilation in an ICU setting, the characteristics of patients receiving mechanical ventilation, the use of available ventilator modes, settings, and artificial airways, and the methods employed for discontinuation of mechanical ventilation.
(Received in original form February 2, 1999 and in revised form September 22, 1999 )
Correspondence and requests for reprints should be addressed to Andrés Esteban, M.D., Ph.D., Unidad de Cuidados Intensivos, Hospital Universitario de Getafe, Carretera de Toledo Km 12,500, Getafe 28905, Madrid, Spain. Am J Respir Crit Care Med Vol 161. pp 1450–1458, 2000 Internet address: www.atsjournals.org
A prospective study was conducted in Argentina, Brazil, Chile, Spain, and Uruguay on November 27, 1996, and in Canada, Portugal, and the United States of America on January 15, 1997. The study was performed at 11:00 A.M. on the stated date and involved 412 ICUs. Before
Esteban, Anzueto, Alía, et al.: International Utilization Review on Mechanical Ventilation
the collection of data, the study protocol was reviewed and approved by Institutional Review Committees of each hospital. For an ICU to be included in the study, it had to possess six or more beds and at least 60% of the physicians had to have undergone ICU training and/or have more than 5 yr of experience in an ICU. Pediatric ICUs, postoperative recovery areas, and units that provide exclusive coronary care were excluded. To minimize a change in behavior as a result of being observed, only the investigator and research coordinator of a given ICU were aware that the study was about to be undertaken.
study was confined to patients who were receiving mechanical ventilation at 11:30 A.M. on the study date, and, consequently, patients undergoing a spontaneous breathing trial at that moment were excluded. Patients listed as undergoing spontaneous breathing trials were those who underwent a least one such trial in the preceding 24 h. 4. Physician questionnaire. One week after the study date, the physician who took care of patients included in the study completed another data sheet to indicate his or her preferred ventilator mode and preferred method of weaning. It was completed in anonymity and delivered to the investigator of each ICU in the study.
Each investigator and research coordinator was provided with a comprehensive manual describing data collection requirements and variable definitions. Each National Coordinator was able to answer questions regarding the process of data collection, and they collected questionnaires in their country after completion of the study. The forms were then sent to Spain, where data were entered in a computer program specifically designed for this study. Each questionnaire was checked by three study coordinators to identify omissions, and inconsistent data were corrected whenever possible. Information on each hospital, each study ICU, and each patient receiving ventilator support were collected on the data sheets. The information on the ICU and hospital included the number of beds in the hospital, number of beds in the ICU, number of patients in the ICU at the moment of the study, and number of patients receiving mechanical ventilation at that time. The following information was collected in each patient receiving mechanical ventilation at the moment of the study:
Results are expressed as mean ⫾ standard deviation, median with the first and third quartiles, or proportions with 95% confidence intervals. Continuous variables were compared by analysis of the variance (ANOVA) and qualitative variables were compared with the chisquare test. A difference was considered significant if the p value was less than 0.05.
1. Demographic data. The sex, age and weight of each patient, date of admission to the ICU, APACHE II score at the time of admission to the ICU, date of initiating mechanical ventilation, and mode of access to the patient’s airway, viz., orotracheal intubation, nasotracheal intubation, facial mask, or tracheostomy were recorded. If a patient had undergone a tracheostomy, the date of its performance was recorded. 2. Ventilator indications. The indication for the initiation of mechanical ventilation was selected from the following predefined list of categories. (1) Acute exacerbation of chronic respiratory failure, which described patients with obstructive and/or restrictive lung disease, requiring mechanical ventilation because of infection, bronchospasm, heart failure, or another acute episode. (2) Coma, which described patients requiring mechanical ventilation caused by loss of consciousness secondary to organic or metabolic conditions (hepatic encephalopathy, cerebral hemorrhage, etc.). (3) Neuromuscular disease, which described patients whose respiratory failure was due to impairment of the peripheral nerves, myoneural junction, muscle mass, etc. (4) Acute respiratory failure, which described patients without a preexisting obstructive or restrictive lung disease requiring mechanical ventilation because of respiratory failure. Whenever a patient had more than one indication for mechanical ventilation, the data collector recorded the reason judged dominant. The patients who fell in the category of acute respiratory failure were separated into the following subgroups: (1) acute respiratory distress syndrome (ARDS), defined according to the criteria of the American-European consensus conference (5); (2) postoperative state, consisting of patients who required the continuation of mechanical ventilation after surgery because of a serious underlying medical problem, advanced age or the high risk of the operative procedure; (3) acute pulmonary edema/congestive heart failure, consisting of patients with dyspnea, bilateral alveolar infiltrates, hypoxemia and evidence of cardiac disease or patients in cardiogenic shock; (4) aspiration, defined by visualization of gastric contents in the airways or in a tracheal aspirate; (5) pneumonia, defined by the development of a new alveolar infiltrate or worsening of previous alveolar infiltrates, accompanied by fever/hypothermia and leukocytosis/leukopenia; (6) sepsis/septic shock, defined by preestablished criteria (6); and (7) trauma, consisting of patients requiring mechanical ventilation because of injury to the thorax, abdomen, or head. 3. Ventilator data. In each patient, the ventilator mode and settings at the moment of the study were recorded. The patient was considered to be in a weaning phase when so judged by the responsible physician, and the method being used for weaning was recorded. The
RESULTS Demographic Data
In the 412 ICUs included into the study, 4,153 patients occupied beds at that time. The median ICU occupancy rate, calculated as the number of patients per number of beds in the ICU at the moment of the study, was 83% (25th and 75th percentiles: 63%, 100%). In the 1,638 patients receiving mechanical ventilation (39% of the total group), the median age was 61 yr (25th and 75th percentiles: 44, 71), and men predominated in every country (average, 60%) except Brazil (Table 1). The median APACHE II score on admission to the ICU was 19 (25th and 75th percentiles: 14, 25). At the time of the study, the median duration of ICU stay in the ventilator-supported patients was 8 d and the median duration of mechanical ventilation was 7 d; an exception was Portugal, where the median was 12 d. Indication for Mechanical Ventilation
Acute respiratory failure was the most frequent reason for the initiation of mechanical ventilation (Table 2), being the precipitating cause in 66% of the total study group; this indication was more common in North America (73%) than in Spain, Uruguay, Portugal, and Argentina (p ⬍ 0.01). ARDS accounted for 12% of patients in acute respiratory failure and 8% of the total study population. An acute exacerbation of chronic respiratory failure was the precipitating cause in 13%; in Portugal it accounted for 23% of patients (p ⬍ 0.001). Coma, which was the indication in 15% of the total study group, was the condition with the greatest variation among countries. In most countries, a neuromuscular disorder was the indication in less than 10% of patients. Artificial Airway
The access to the airway for delivery of mechanical ventilation at the moment of the study consisted of an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1% (Table 3). Of the endotracheal tubes, 96% were passed through the mouth and 4% through the nose. In patients who had undergone a tracheostomy, it was performed at a median of 11 d (25th and 75th percentiles: 5, 19) after intubation, and this elapsed time did not differ among countries. A tracheostomy was performed in 24% of patients. The frequency of tracheostomy varied significantly depending on the patient’s underlying condition and the time from initiation of mechanical ventilation. Over the initial 3 wk, a tracheostomy was performed more frequently in patients with neuromuscular disease (31.3%) than in those with COPD (14.8%, p ⬍
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TABLE 1 CHARACTERISTICS OF INTENSIVE CARE UNITS AND PATIENTS ACCORDING TO COUNTRY* USA/Canada ICUs, n Patients admitted Patients ventilated Occupancy, %† Ventilation, %† Age† APACHE II† Women, %‡ Days in ICU Days of ventilator support Days from intubation to tracheostomy
167 1,833 747 83 (67, 100) 40 (20, 60) 60 (45, 71) 19 (15, 25) 43 (39, 46) 8 (3, 19) 7 (3, 18) 12 (6, 18)
Spain 79 1,028 443 92 (82, 100) 39 (27, 60) 64 (46, 71) 19 (14, 25) 35 (30, 39) 8 (3, 16) 7 (3, 15) 12 (7, 20)
89 680 154 73 (50, 89) 17 (0, 33) 59 (40, 68) 17 (12, 24) 35 (28, 43) 6 (3, 12) 6 (2, 10) 8 (1, 20)
25 273 122 83 (71, 94) 47 (25, 50) 58 (38, 71) 19 (14, 26) 58 (49, 67) 8 (4, 18) 7 (3, 18) 8 (1, 15)
27 10 160 90 60 68 79 (50, 100) 100 (88, 100) 40 (20, 50) 75 (50, 76) 60 (39, 69) 66 (50, 73) 20 (12, 25) 19 (15, 26) 38 (26, 52) 37 (26, 49) 8 (4, 17) 13 (4, 46) 8 (3, 16) 12 (2, 47) 9 (0, 12) 14 (4, 33)
Uruguay 15 89 44 50 (47, 83) 45 (25, 86) 56 (43, 68) 17 (12, 21) 32 (19, 48) 7 (2, 15) 5 (2, 12) 9 (8, 17)
Total 412 4,153 1,638 83 (63, 100) 36 (17, 58) 61 (44, 71) 19 (14, 25) 40 (38, 43) 8 (3, 18) 7 (3, 17) 11 (5, 19)
* Age, APACHE II, and sex refer to patients receiving mechanical ventilation. Days in ICU and days in ventilator support refer to the duration of mechanical ventilation or length of ICU stay until the day of study. † Median (25th, 75th percentiles). ‡ Percentage (95% confidence interval).
0.05) or acute respiratory failure (9.1%, p ⬍ 0.001). After the third week, the proportion of patients with a tracheostomy did not differ among the diagnostic categories (Table 4).
tidal volume did not differ between patients with ARDS and those with other causes of acute respiratory failure receiving A/C (8.7 ⫾ 2.3 ml/kg versus 9.1 ⫾ 2.2 ml/kg). Positive end-expiratory pressure (PEEP) was not employed in 31% of patients (range: 16 to 50) (Figure 1). In those receiving PEEP, the median value was 5 cm H2O (25th and 75th percentiles: 5, 6), with no difference among countries (Table 6). A significantly higher level of PEEP was employed in patients with ARDS than in those with an acute exacerbation of chronic lung disease (8.0 ⫾ 3.4 versus 5.5 ⫾ 2.3 cm H2O, p ⬍ 0.05).
Ventilator Modes and Settings
Of the total group of ventilator-supported patients, 47% received assist/control (A/C) ventilation (Table 5), and this was the most common mode of ventilation in Argentina, Chile, and Spain. An almost equal proportion (46%) of the overall group were ventilated with synchronized intermittent mandatory ventilation (SIMV), pressure support (PS), or the combination of both. The use of SIMV on its own was infrequent in all countries, with the exception of Uruguay (20%), and overall it was 6%. In no country was PS alone the most frequently used mode, and overall it was employed in 15% patients. The combination of SIMV and PS showed considerable variation among countries, ranging from the 7% (Argentina) to 52% (Uruguay); in North America, this combination was used with the same frequency as A/C (34% in both instances). The median tidal volume setting was 9 ml/kg (25th and 75th percentiles: 8, 10) in patients receiving A/C. The median PS setting was 18 cm H2O (25th and 75th percentiles: 13, 23). The setting of tidal volume was remarkably constant among countries (Table 6), with little interquartile variation. The median level of PS was also similar among countries, although interquartile variation was considerable. In patients receiving A/C,
Methods of Weaning
Physicians considered 32% of the patients to be in a weaning phase at the moment of the study or during the preceding 24 h. Because the study was confined to patients actually receiving mechanical ventilation at 11:00 A.M. on the study day, patients undergoing a trial of spontaneous breathing with a T-tube setup or flow-by at that point in time were not included in the study. The methods varied considerably among the countries. Overall, the most frequent method of weaning was PS, used in 36% of the patients. The combination of SIMV and PS was used in 28% of the patients (Table 5), but varied considerably among countries, ranging from 3% of patients in Argentina to 47% in Uruguay. Use of some form of spontaneous breathing trial also varied considerably among countries.
TABLE 2 INDICATIONS FOR THE INITIATION OF MECHANICAL VENTILATION ACCORDING TO COUNTRY* USA/Canada Reason for MV COPD ARF Coma Neuromuscular Cause of ARF ARDS Postoperative Heart Failure Aspiration Pneumonia Sepsis Trauma Others
(n ⫽ 747 ) 16 (13, 18) 74 (70, 77) 7 (6, 9) 3 (2, 5) (n ⫽ 547) 9 (7, 12) 17 (14, 21) 13 (10, 16) 3 (1, 4) 13 (10, 16) 17 (14, 20) 13 (10, 16) 16 (13, 19)
(n ⫽ 443) 11 (8, 14) 64 (59, 68) 20 (17, 25) 4 (3, 7) (n ⫽ 283) 14 (10, 18) 13 (10, 18) 14 (11, 19) 2 (1, 5) 18 (13, 23) 12 (8, 16) 15 (12, 20) 11 (8, 15)
(n ⫽ 154 ) 10 (6, 16) 50 (42, 58) 32 (25, 40) 8 (5, 14) (n ⫽ 77) 18 (11, 29) 10 (5, 20) 16 (9, 26) 8 (3, 17) 17 (10, 27) 19 (12, 30) 3 (0, 10) 9 (4, 18)
(n ⫽ 122) 9 (5, 16) 66 (56, 74) 21 (15, 30) 4 (1, 10) (n ⫽ 80) 11 (6, 21) 5 (2, 13) 5 (2, 13) 8 (3, 16) 29 (20, 40) 16 (9, 27) 9 (4, 18) 16 (9, 27)
(n ⫽ 60) 10 (4, 21) 62 (48, 74) 15 (7, 27) 13 (6, 25) (n ⫽ 37 ) 32 (18, 50) 5 (1, 19) 5 (1, 19) 3 (0, 16) 19 (9, 36) 24 (12, 42) 8 (2, 23) 3 (0, 16)
(n ⫽ 68) 23 (14, 36) 47 (35, 59) 10 (5, 21) 19 (11, 31) (n ⫽ 32) 6 (1, 22) 28 (14, 47) 16 (6, 33) 3 (0, 18) 19 (8, 37) 12 (4, 30) 12 (4, 30) 3 (0, 18)
(n ⫽ 44 ) 5 (1, 17) 50 (35, 65) 43 (29, 59) 2 (0, 13) (n ⫽ 22) 14 (4, 36) 23 (9, 46) 4 (0, 25) 14 (4, 36) 23 (9, 46) 18 (6, 41) 4 (0, 25) —
(n ⫽ 1,638) 13 (11, 15) 66 (63, 68) 15 (13, 17) 5 (4, 6) (n ⫽ 1,078) 12 (10, 14) 15 (13, 17) 12 (10, 14) 3 (2, 5) 16 (14, 18) 16 (13, 18) 12 (10, 14) 13 (11, 15)
Definition of abbreviations: ARF ⫽ acute respiratory failure; MV ⫽ mechanical ventilation. * Results are shown as percentages with 95% confidence intervals shown in parentheses.
Esteban, Anzueto, Alía, et al.: International Utilization Review on Mechanical Ventilation TABLE 3 AIRWAY USED IN VENTILATED PATIENTS ACCORDING TO COUNTRY Chile
A total of 2,226 physicians completed the questionnaire. A/C was the preferred mode of 62%, but that percentage varied considerably among countries (Table 7). In general, the mode listed by physicians corresponded with the mode most frequently employed in a given country. The preferred methods for weaning were PS (34% of the respondents) and SIMV with or without PS (35% of the respondents).
DISCUSSION The primary indications for mechanical ventilation were remarkably similar across countries. In contrast, the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country. Of patients in the ICUs, an average of 39% were receiving mechanical ventilation, but the proportion varied considerably among countries. The variation may reflect differences in type of ICU, admission and discharge policies, and patient profiles. The ICUs were not selected randomly, and the identification of ICUs and also their voluntary participation may have produced a selection bias. It cannot be assumed that the studied ICUs are necessarily representative of a given country, and observed differences among countries must be interpreted with caution. The percentage of patients receiving mechanical ventilation would have been higher if patients receiving ventilation for a brief period of time had been enrolled in the study. When planning the study, we deliberately selected 11:00 A.M. to minimize the influence of patients receiving brief ventilator support after surgery on the overall study population. This aspect of study design may explain why postoperative patients constituted less than 10% of the total study population and that patients receiving short-term ventilator support (less than 24 h) accounted for only 18% of the study population. The average age of our patients was high: 25% of the ventilated patients were older than 71 yr of age. This finding was not confined to countries where the average age of the population is high. In recent published series of ventilator-supported patients, the mean age has been around 60 yr (2, 4, 7–10). The data suggest that advanced age did not preclude patients from being admitted to the ICU; indeed, it has been demonstrated
that the prognosis in elderly patients admitted to an ICU (11) or receiving mechanical ventilation (12) does not depend exclusively on age, but rather on the severity of the acute illness and the functional status. Men accounted for 60% of the patients receiving mechanical ventilation. Other investigators have also reported a higher proportion of men among patients receiving mechanical ventilation (2, 4, 7, 9, 10) or admitted to an ICU (13). Acute respiratory failure was the most frequent indication for mechanical ventilation, accounting for two thirds of patients in four countries and for half the patients in the other three countries. Among the subgroups of acute respiratory failure, ARDS accounted for 12% of ventilated patients. Because of the complex pulmonary pathophysiology in patients with ARDS and the many new modes of mechanical ventilation developed to deal with this problem, attempts have been made to obtain more precise information on the incidence of acute lung injury and ARDS. The reported incidence of ARDS ranges from 1.5 to 8 cases per 100,000 inhabitants (14–16). Of all 4,153 patients in ICUs on the day of our study, only 3% had ARDS—similar to the rates of 2 to 3% in two recent retrospective studies (17, 18). Patients with COPD accounted for 13% of all patients receiving mechanical ventilation, being the most common indication in North America and greater than any subcategory of acute respiratory failure in all countries. We cannot calculate the proportion of patients with COPD receiving mechanical ventilation since we do not know the total number admitted to ICUs at the time of the study. In control groups of recent prospective studies of noninvasive ventilation in patients with COPD, Brochard and colleagues (19) and Kramer and coworkers (20) reported intubation rates of 74 and 67%, respectively. These figures are much higher than the intubation rate of 35% reported by Connors and colleagues (21) in a study of 1,016 patients admitted to hospital with an acute exacerbation of COPD complicated by hypercapnia. The proportion of patients with COPD in our study is markedly higher than in the APACHE III data base (22), where only 1% of 17,440 unselected admissions to 42 ICUs received mechanical ventilation because of an acute exacerbation of COPD. The fact that medical ICUs accounted for only 10% of ICUs in the APACHE III
TABLE 4 PERCENTAGE OF PATIENTS WITH TRACHEOSTOMY ACCORDING TO THE INDICATION FOR MECHANICAL VENTILATION AND THE DURATION OF VENTILATOR SUPPORT* Duration of Mechanical Ventilation Indication for MV COPD ARF Neuromuscular
1 to 7 d 5/82 (6.1) 14/555 (2.5) 4/25 (16.0)
For definition of abbreviations, see Table 2. * Numbers within parentheses represent percentages.
8 to 14 d 8/36 (22.2) 29/203 (14.3) 4/14 (28.6)
15 to 21 d 8/24 (33.3) 35/101 (34.6) 8/12 (66.7)
⬎ 21 d 36/49 (73.5) 122/188 (64.9) 22/32 (68.7)
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TABLE 5 VENTILATOR MODES AND METHODS OF WEANING ACCORDING TO COUNTRY* USA/Canada Ventilation A/C SIMV PS SIMV ⫹ PS Others† Weaning PS‡ SIMV SIMV ⫹ PS Intermittent SB trials§ Daily SB trial§ Others¶
(n ⫽ 747 ) 34 (31, 38) 6 (4, 8) 18 (15, 21) 34 (31, 38) 7 (6, 10) (n ⫽ 274 ) 45 (39, 51) 5 (3, 9) 32 (26, 38) 6 (3, 9) 3 (1, 5) 9 (6, 14)
(n ⫽ 443) 62 (57, 66) 7 (1, 10) 11 (9, 15) 13 (11, 17) 6 (4, 9) (n ⫽ 108) 23 (16, 32) 1 (0, 6) 25 (17, 34) 39 (30, 49) 6 (3, 13) 5 (2, 11)
(n ⫽ 154) 68 (60, 75) 9 (5, 15) 10 (6, 16) 7 (4, 13) 6 (3, 11) (n ⫽ 39) 28 (15, 45) 13 (5, 28) 3 (0, 15) 33 (20, 50) 10 (3, 25) 13 (5, 28)
(n ⫽ 122) 40 (31, 49) 4 (1, 10) 10 (5, 17) 31 (23, 40) 15 (9, 23) (n ⫽ 39) 28 (16, 45) 3 (0, 15) 36 (22, 53) 8 (2, 22) 8 (2, 22) 18 (8, 34)
(n ⫽ 60) 72 (58, 82) 5 (1, 15) 5 (1, 15) 17 (9, 29) 2 (1, 10) (n ⫽ 9) 33 (9, 69) — 44 (15, 77) 22 (4, 60) — —
(n ⫽ 68) 44 (32, 57) — 34 (23, 46) 13 (7, 24) 9 (4, 19) (n ⫽ 32) 31 (17, 50) 6 (1, 22) 6 (1, 22) 37 (22, 56) — 19 (8, 37)
(n ⫽ 44 ) 25 (14, 41) 20 (10, 36) 2 (0, 13) 52 (37, 67) — (n ⫽ 19) 21 (7, 46) 16 (4, 40) 47 (25, 70) 10 (2, 34) — 5 (0, 28)
(n ⫽ 1,638) 47 (44, 49) 6 (5, 8) 15 (13, 16) 25 (23, 27) 7 (6, 9) (n ⫽ 520) 36 (32, 40) 5 (4, 8) 28 (24, 32) 17 (14, 21) 4 (3, 6) 9 (7, 12)
* Results are shown as percentage of ventilated patients with 95% confidence intervals shown in parentheses. † Other ventilator modes were pressure-control ventilation, biphasic positive airway pressure (BiPAP), inverse ratio ventilation, airway pressure release ventilation, and high-frequency ventilation. ‡ Pressure support included gradual reduction in pressure support (33%) or a period with a fixed level of 7 cm H2O (3%). § Spontaneous breating trials were performed with T-tube, CPAP, or flow-by. ¶ Other methods of weaning were: BIPAP or the combination of two or more methods.
data base (23) is probably responsible, at least in part, for the small number of patients with COPD in their study. Neuromuscular disease was the indication for mechanical ventilation in less than 8% of patients in all but two of the countries. Although patients with neuromuscular disease constitute a small proportion of all ICU patients, they account for a disproportionate amount of costs because their stay is usually prolonged. From the initiation of mechanical ventilation until the day of the study, the median duration of ventilator support was 16 d (25th, 75th percentiles: 5, 48) in patients with neuromuscular disease, compared with 10 d (25th, 75th percentiles: 3, 22) in patients with COPD (p ⬍ 0.01) and 7 d (25th, 75th percentiles: 3, 16) in patients receiving ventilation because of acute respiratory failure (p ⬍ 0.01). The incidence of tracheostomy varied with the underlying condition: 39% among patients with neuromuscular disease, 28% in patients with COPD, and 20% in patients with acute respiratory failure. These findings are quite similar to our previous report (4): of 290 patients receiving mechanical ventilation in Spanish hospitals, 47% of the patients with neuromuscular disease and 30% of the patients with COPD had a tracheostomy. In the present study, the proportion of patients with a tracheostomy varied according to elapsed time from initiation of mechanical ventilation. During the first 3 wk, tracheostomy was performed more frequently in patients with neuromuscular disease than in those with COPD or acute respiratory failure
(Table 3). These data give credence to the notion that physicians base the decision to perform a tracheostomy on the anticipated duration of mechanical ventilation (24). Of patients in the study, only 1% were receiving noninvasive mechanical ventilation. Since non-invasive ventilation is commonly delivered intermittently throughout the day, our number may underestimate the true use of this form of ventilator support. The selection of ventilator settings was remarkably similar among countries. Of patients ventilated with A/C, the median selected tidal volume was 9 ml/kg. Interestingly, in patients ventilated with PS, which does not permit a direct selection of volume, the achieved median tidal volume was similar (7 ml/ kg); respiratory rate was lower with A/C. Peak airway pressure was higher in patients ventilated with A/C mode than with PS (30 versus 19 cm H2O). Given the different flow-delivery systems with A/C and PS, this difference in peak pressure is expected. The setting of tidal volume has been somewhat arbitrary in nature, although from the early 1970s a setting of 10 to 15 ml/kg had become conventional (24, 25). Some investigators, however, reported tidal volumes of 20 to 24 ml/kg (26, 27). Of the patients receiving A/C in the present study, 63% (486/767) had a tidal volume of less than 10 ml/kg (the percentage in patients with ARDS [52/73, 71%] was similar to the total group). For more than a decade, there has been growing awareness of the potential for ventilator-induced injury, so
TABLE 6 VENTILATOR SETTINGS IN PATIENTS RECEIVING ASSIST-CONTROL VENTILATION OR PRESSURE SUPPORT VENTILATION ACCORDING TO COUNTRY* USA/Canada Assist Control Tidal volume, ml/kg Respiratory rate, breaths/min Peak pressure, cm H2O PSV Tidal volume, ml/kg Respiratory rate, breaths/min Peak pressure, cm H2O PEEP, cm H2O
(n ⫽ 256) 8 (7, 10) 16 (12, 20) 32 (27, 38) (n ⫽ 134) 6 (5, 8) 23 (20, 28) 18 (13, 23) 5 (5, 6)
(n ⫽ 273) 9 (8, 10) 16 (13, 18) 32 (25, 40) (n ⫽ 51) 9 (7, 9) 21 (17, 25) 19 (15, 25) 5 (5, 8)
(n ⫽ 105) 9 (8, 10) 14 (12, 17) 27 (20, 30) (n ⫽15) 8 (5, 10) 18 (16, 24) 18 (15, 22) 5 (5, 7)
(n ⫽ 49) 8 (7, 10) 18 (16, 24) 26 (22, 30) (n ⫽ 12) 7 (7, 10) 21 (17, 25) 21 (15, 26) 5 (4, 8)
(n ⫽ 42) 9 (8, 11) 18 (15, 20) 28 (20, 32) (n ⫽ 3) — — — 5 (4, 6)
(n ⫽ 30) 8 (7, 9) 20 (16, 20) 22 (20, 30) (n ⫽ 23) 7 (6, 9) 19 (16, 24) 20 (15, 26) 4 (4, 5)
(n ⫽ 11) 10 (9, 12) 14 (12, 18) 29 (22, 42) (n ⫽ 1) — — — 5 (4, 6)
(n ⫽ 767) 9 (8, 10) 16 (13, 20) 30 (25, 37) (n ⫽ 239) 7 (5, 9) 22 (18, 26) 19 (15, 25) 5 (5, 6)
* Values are shown as medians with 25th, 75th percentiles shown in parentheses. The values of PEEP were calculated for those patients receiving some level of PEEP irrespective of the employed ventilator mode.
Esteban, Anzueto, Alía, et al.: International Utilization Review on Mechanical Ventilation
Figure 1. Level of positive end-expiratory pressure used in the studied patients.
called volutrauma (28), which has culminated in the deliberate use of low tidal volumes—a strategy referred to a controlled hypoventilation or permissive hypercapnia (1–3, 29). Milberg and colleagues (30) reported a decrease in mortality in patients with ARDS from the early 1980s to the early 1990s, and opined that this might be due to the greater use of permissive hypercapnia. However, permissive hypercapnia was listed as being in use in only 2.3% of our entire cohort of patients and in only 7.8% of those with ARDS. Probably no aspect of mechanical ventilation has been the subject of such a voluminous literature as PEEP. Stemming from the initial favorable experience of Petty and Ashbaugh (31) extensive research has been undertaken to understand the mechanisms of its salutary actions and decide on the optimal level (32). The findings of the present study suggest that physicians make little effort in attempting to define the optimal level of PEEP for an individual patient, but instead write a generic order of “5 of PEEP,” as indicated by the median level of 5 cm H2O, and the narrow 25th and 75th percentiles (5, 6 cm H2O). The level of PEEP was similar in all countries, almost a third of patients (31%) were ventilated without PEEP, and only three patients were receiving a PEEP above 15 cm H2O. Despite the introduction of several new ventilator modes, A/C was used in 40 to 72% of patients in all countries, with the exceptions of North America and Uruguay. In a survey pub-
lished by Venus and colleagues in 1987 (33), 72% of physicians in the United States listed SIMV as their preferred ventilator mode. Ten years later, SIMV on its own was used in only 6% of patients receiving mechanical ventilation in North American ICUs, and the frequency of use differed little among countries. In North America, the use of a combination of SIMV and PS tied with A/C as the most commonly used mode; in Uruguay, this combination was used twice as often as any other modality. The popularity of the SIMV and PS combination is surprising, in that this modality has undergone little scrutiny (34). The clinical use of ventilator modes recently introduced, such as pressure-control, inverse-ratio ventilation, or airway pressure release ventilation, seems very limited, to judge by the present data and those we collected in Spanish ICUs 6 yr ago (4). The greatest diversity of practice among countries was in the method of weaning. For example, trials of spontaneous breathing were being used in 46% of the patients in Spain versus only 16% in North American patients, whereas the SIMV and PS combination was used in 66% of patients in Uruguay versus only 7% of patients in Portugal. The exclusion of patients undergoing a spontaneous breathing trial at 11:00 A.M. on the study date necessarily results in an underestimate of the frequency with which this weaning modality was employed. The SIMV plus PS combination was the second most frequently used method in the United States despite its being the only technique of weaning whose efficacy has not been adequately evaluated. Weaning is an aspect of mechanical ventilation that has been the subject of several randomized controlled trials. In preselected groups of difficult-to-wean patients, Brochard and colleagues (7) reported difference in the rate of successful weaning between patients weaned with PS and patients weaned with either SIMV or with a T-tube pooled together, whereas the Spanish Lung Failure Collaborative Group (8) found that a single daily trial of spontaneous breathing achieved a threefold and twofold increase in the rate of successful weaning compared with IMV and PS, respectively. More recently, Ely and colleagues (9) found that systematic measurement of predictive indices, including the frequencyto-tidal volume ratio (35), combined with spontaneous breathing trials (8) resulted in a greater than twofold increase in the rate of successful weaning than in a control group weaned with IMV or PS, and decreased the rate of reintubation and ICU costs. The demonstration of the superiority of spontaneous breathing trials by the Spanish Lung Failure Collaborative Group may account for the almost twofold increase in the use of this approach in Spain between 1992 (24%) (4) and 1997 (46%). In summary, the primary indications for mechanical ventilation were quite consistent from country to country. Although
TABLE 7 PHYSICIANS PREFERENCES FOR VENTILATOR MODES AND METHODS ACCORDING TO COUNTRY
Ventilator modes A/C SIMV PSV SIMV ⫹ PSV PCV Methods of weaning SIMV PSV SIMV ⫹ PSV Intermittent SB trials Daily SB trial
128 (32.5%) 55 (13.9%) 33 (8.4%) 163 (41.4%) 14 (3.5%)
481 (72.0%) 43 (6.4%) 25 (3.7%) 111 (16.6%) 3 (0.4%)
540 (82.6%) 41 (6.3%) 81 (12.4%) 40 (6.1%) 11 (1.7%)
76 (39.8%) 10 (5.2%) 6 (3.1%) 74 (39.3%) 24 (12.6%)
77 (70.0%) 8 (7.3%) 33 (30.0%) 25 (22.7%) —
13 (54.2%) 1 (4.2%) 8 (33.3%) 7 (29.2%) —
18 (14.6%) 14 (11.4%) — 90 (73.2%) 1 (0.8%)
1,333 (61.6%) 172 (7.9%) 87 (4.0%) 511 (23.6%) 53 (2.4%)
20 (5.1%) 163 (41.4%) 125 (31.7%) 36 (9.1%) 27 (6.8%)
21 (3.1%) 163 (23.9%) 176 (25.8%) 271 (39.7%) 50 (7.3%)
85 (12.8%) 70 (10.5%) 95 (14.3%) 352 (53.0%) 62 (9.3%)
8 (4.2%) 57 (29.8%) 96 (50.3%) 24 (12.6%) 6 (3.1%)
5 (4.6%) 14 (12.8%) 54 (49.5%) 31 (28.4%) 5 (4.6%)
— 11 (37.9%) 2 (6.7%) 12 (41.4%) 4 (13.8%)
11 (8.9%) 7 (5.6%) 80 (64.5%) 22 (17.7%) 4 (3.2%)
150 (6.8%) 485 (22.1%) 628 (28.6%) 748 (34.1%) 158 (7.2%)
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
greater variation was noted in the selection of ventilator modes, more than 90% of patients were ventilated with A/C or PS (alone or in conjunction with SIMV). Greater consistency was noted in the selection of tidal volumes, 7 to 10 ml/kg, and PEEP, which, if used at all, was usually 5 cm H2O. A striking feature was the infrequent use of certain modalities such as SIMV as a stand-alone mode, noninvasive ventilation, permissive hypercapnia, and other new modes of ventilation. In about one third of the patients, an attempt at weaning was being made at the time of the study. The techniques employed for weaning showed considerable variation from country to country, and even within a country several techniques were in use. The results suggest that findings from research on mechanical ventilation and weaning are incorporated into clinical practice at a very slow pace. In conclusion, the study provides a unique picture of the types of patients receiving mechanical ventilation in many different countries and the methods employed; the data should prove useful in the design of trials of newer ventilator modalities and in serving as a baseline against which future changes in ventilator techniques can be gauged. Acknowledgment : The writers are indebted to the study coordinators, clinical research associates, medicine residents, and pulmonary/critical care fellows who participated in the data collection of this study.
References 1. Amato, M. B., C. S. Barbas, D. M. Medeiros, R. B. Magaldi, G. P. Schettino, G. Lorenzi-Filho, R. A. Kairalla, D. Deheinzelin, C. Munoz, R. Oliveira, T. Y. Takagaki, and C. R. Carvalho. 1998. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N. Engl. J. Med. 338:347–354. 2. Stewart, T. E., M. O. Meade, D. J. Cook, J. T. Granton, R. V. Hodder, S. E. Lapinsky, C. D. Mazer, R. F. McLean, T. S. Rogovein, B. D. Schouten, T. R. Todd, and A. S. Slutsky. 1998. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N. Engl. J. Med. 338:355–361. 3. Brochard, L., F. Roudot-Thoraval, E. Roupie, C. Delclaux, J. Chastre, E. Fernandez-Mondéjar, E. Clémenti, J. Mancebo, P. Factor, D. Matamis, M. Ranieri, L. Blanch, G. Rodi, H. Mentec, D. Dreyfuss, M. Ferrer, C. Brun-Buisson, M. Tobin, and F. Lemaire. 1998. Tidal volume reduction in the adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 158:1831–1838. 4. Esteban, A., I. Alía, J. Ibañez, S. Benito, M. J. Tobin, and the Spanish Lung Failure Collaborative Group. 1994. Modes of mechanical ventilation and weaning: a national survey of Spanish hospitals. Chest 106: 1188–1193. 5. Bernard, G. R., A. Artigas, K. L. Brigham, J. Carlet, K. Falke, L. Hudson, M. Lamy, J. R. Legall, A. Morris, and R. Spragg. 1994. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am. J. Respir. Crit. Care Med. 149:818–824. 6. Bone, R. C., R. A. Balk, F. B. Cerra, R. P. Dellinger, A. M. Fein, W. A. Knaus, R. M. H. Schein, and W. J. Sibbald. 1992. ACCP/SCCM Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies is sepsis. Chest 101:1644–1655. 7. Brochard, L., A. Rauss, S. Benito, G. Conti, J. Mancebo, N. Rekik, A. Gasparetto, and F. Lemaire. 1994. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am. J. Respir. Crit. Care Med. 150:896–903. 8. Esteban, A., F. Frutos, M. J. Tobin, I. Alía, J. F. Solsona, I. Valverdú, R. Fernández, M. A. de la Cal, S. Benito, R. Tomás, et al. 1995. A comparison of four methods of weaning from mechanical ventilation. N. Engl. J. Med. 332:345–350. 9. Ely, E. W., A. M. Baker, D. P. Dunagan, H. L. Burke, A. C. Smith, P. T. Kelly, M. M. Johnson, R. W. Browder, D. L. Bowton, and E. F. Haponik. 1996. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N. Engl. J. Med. 335:1864–1869. 10. Esteban, A., I. Alía, F. Gordo, R. Fernández, J. F. Solsona, I. Vallverdú, S. Macías, J. M. Allegue, J. Blanco, D. Carriedo, M. Leon, M. A. de la Cal, F. Taboada, J. Gonzalez de Velasco, E. Palazon, F. Carrizosa, R. Tomas, J. Suarez, and R. S. Goldwasser. 1997. Extubation outcome af-
ter spontaneous breathing trials with T-tube or pressure support ventilation. Am. J. Respir. Crit. Care Med. 156:459–465. Knaus, W. A., D. P. Wagner, J. E. Zimmerman, and E. A. Draper. 1993. Variations in mortality and length of stay in intensive care units. Ann. Intern. Med. 118:753–761. Meinders, A. J., J. G. Van der Hoeven, and A. E. Meinders. 1996. The outcome of prolonged mechanical ventilation in elderly patients: are the efforts worthwhile? Age Ageing 25:353–356. Castillo-Lorente, E., R. Rivera-Fernandez, and G. Vazquez-Mata. 1997. Limitation of therapeutic activity in elderly critically ill patients. Crit. Care Med. 25:1643–1648. Villar, J., and A. S. Slutsky. 1989. The incidence of the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 140:814–816. Thomsen, G. E., and A. H. Morris. 1995. Incidence of the adult respiratory distress syndrome in the State of Utah. Am. J. Respir. Crit. Care Med. 152:965–971. Lewandowski, K., J. Metz, C. Deutschmann, H. Preiss, R. Kuhlen, A. Artigas, and K. J. Falke. 1995. Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany. Am. J. Respir. Crit. Care Med. 151:1121–1125. Knaus, W. A., X. Sun, R. Hakim, and D. P. Wagner. 1994. Evaluation of definitions for adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 150:311–317. Ferring, M., and J. L. Vincent. 1997. Is outcome from ARDS related to the severity of respiratory failure? Eur. Respir. J. 10:1297–1300. Brochard, L., J. Mancebo, M. Wysocki, F. Lofaso, G. Conti, A. Rauss, G. Simonneau, S. Benito, A. Gasparetto, F. Lemaire, D. Isabey, and A. Harf. 1995. Noninvasive ventilation for acute exacerbation of chronic obstructive pulmonary disease. N. Engl. J. Med. 333:817–822. Kramer, N., T. J. Meyer, J. Meharg, R. D. Cece, and N. S. Hill. 1995. Randomized prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am. J. Respir. Crit. Care Med. 151: 1799–1806. Connors, A. F., N. V. Dawson, C. Thomas, F. E. Harrell, N. Desbiens, W. J. Fulkerson, P. Kussin, P. Bellamy, L. Goldman, and W. A. Knaus. 1996. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. 154: 959–967. Seneff, M. G., D. P. Wagner, R. P. Wagner, J. E. Zimmerman, and W. A. Knaus. 1995. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. J.A.M.A. 274:1852–1857. Knaus, W. A., D. P. Wagner, E. A. Draper, J. E. Zimmerman, M. Bergner, P. G. Bastos, C. A. Sirio, D. J. Murphy, T. Lotring, A. Damiano, et al. 1991. The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100:1619–1636. Lutch, J. S., and J. F. Murray. 1972. Continuous positive pressure ventilation: effects of systemic oxygen transport and tissue oxygenation. Ann. Intern. Med. 76:193–202. Pontoppidan, H., B. Geffin, and E. Lowenstein. 1972. Acute respiratory failure in the adult. N. Engl. J. Med. 287:799–806. Falke, K. J., H. Pontoppidan, A. Kumar, D. Leith, B. Geffin, and M. B. Laver. 1972. Ventilation with end-expiratory pressure in acute lung disease. J. Clin. Invest. 51:2315–2323. Jardin, F., J. C. Farcot, L. Boisante, N. Curien, A. Margairaz, and J. P. Bourdarias. 1981. Influence of positive end-expiratory pressure on left ventricular performance. N. Engl. J. Med. 304:387–392. Dreyfuss, D., P. Soler, G. Basset, and G. Saumon. 1988. High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am. Rev. Respir. Dis. 137:1159–1164. Darioli, R., and C. Perret. 1984. Mechanical controlled hypoventilation in status asthmaticus. Am. Rev. Respir. Dis. 129:385–387. Milberg, J. A., D. R. Davis, K. P. Steinberg, and L. D. Hudson. 1995. Improved survival of patients with acute respiratory distress syndrome. J.A.M.A. 273:306–309. Petty, T. L., and D. G. Ashbaugh. 1971. The adult respiratory distress syndrome: clinical features, factors influencing prognosis and principles of management. Chest 60:273–279. Rossi, A., and M. V. Ranieri. 1994. Positive end-expiratory pressure. In M. J. Tobin, editor. Principles and Practice of Mechanical Ventilation. McGraw-Hill, New York. 259–303. Venus, B., R. A. Smith, and M. Mathru. 1987. National survey of methods and criteria used for weaning from mechanical ventilation. Crit. Care Med. 15:530–533. Leung, P., A. Jubran, and M. J. Tobin. 1997. Comparison of assisted ven-
Esteban, Anzueto, Alía, et al.: International Utilization Review on Mechanical Ventilation tilator modes on triggering, patient effort, and dyspnea. Am. J. Respir. Crit. Care Med. 155:1940–1948. 35. Yang, K. L., and M. J. Tobin. 1991. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N. Engl. J. Med. 324:1445–1450.
APPENDIX ARGENTINA: G. Murías (Clínica Bazterrica, Buenos Aires); C. Fuentes (Hosp. Regional Español, Bahía Blanca); D. Fainstein (Hosp. Privado del Sur, Bahía Blanca); D. Aimone (Policlínico del Vidrio, Don Bosco); P. Schoon (Hosp. Prof. Dr. Luis Güemes, Haedo); J. Spolidoro (Hosp. Dr. Diego Paroissien, Isidro Casanova); D. Drago (Hosp. Gob. Domingo Mercante, José C. Paz); O. Otero (Centro Oncológico de Excelencia, Gonnet); E. Estenssoro (Hosp. Escuela José de San Martín, La Plata); E. Turchetto (Hosp. Privado de la Comunidad, Mar del Plata); S. Gago (Clínica Modelo, Morón); M. Landa (Clínica Privada Regional, Necochea); M. Torreno (Sanatorio Modelo, Quilmes); C. Bevilacqua (Hosp. Privado San Juan de Dios, Ramos Mejía); H. Ferraro (Corporación Médica, San Martín); V. Mezzina (Hosp. Ramón Santamarina, Tandil); D. Ceraso (Clínica Independencia, Munro); G. Raimondi (FLENI, Buenos Aires); N. Wainsztein (Hosp. Privado Fundación Favaloro, Buenos Aires); P. Valdéz (Hosp. Dalmacio Vélez Sarsfield, Buenos Aires); C. Irrazábal (Hosp. de Clínicas José de San Martín, Buenos Aires); E. Capparelli (Hosp. Eva Perón, San Martín); A. Rodríguez (Hosp. Israelita, Buenos Aires); L. Glez Zambrano (Hosp. Italiano, Buenos Aires); O. Miseta (Hosp. Ignacio Priovano, Buenos Aires); F. Villarejo (Hosp. Prof. Dr. Alejandro Posadas, Haedo); G. Fdez. Cid (Hosp. E. Tornú, Buenos Aires); E. De Vito (Instituto Alfredo Lanari, Buenos Aires); E. Schiavi (Hosp. María Ferrer, Buenos Aires); H. Rguez Vivier (Clínica La Sagrada Familia, Buenos Aires); P. Pardo (Sanatorio de la Trinidad, Buenos Aires); C. Plaza (Sanatorio Julio Méndez, Buenos Aires); A. Raimondi (Sanatorio Mater Dei, Buenos Aires); C. Castro (Sanatorio San Patricio, Buenos Aires); O. López (Sanatorio Santa Isabel, Buenos Aires); D. Pérez Chada (Sanatorio Otamendi, Buenos Aires; O. Disanto (Sanatorio Frangioli, Resistencia); S. Filippus (Clínica del Valle, Comodoro Rivadavia); D. Schonfeld (Sanatorio de la Ciudad, Puerto Madryn); S. Sená (Sanatorio Trelew, Puerto Madryn); M. Pretel (Clínica Junín, Córdoba); J. Brunetto (Clínica Sucre, Córdoba); J. Leiva (Hosp. Córdoba, Córdoba); S. Ricci (Hosp. Municipal de Urgencias, Córdoba); R. Alasino (Hosp. Italiano, Córdoba); J. Vergottini (Hosp. Nacional de Clínicas, Córdoba); E. Romero (Hosp. Privado Centro Médico Córdoba); B. Vázquez (Hosp. San Roque, Córdoba); J. Balbi (Hosp. Tránsito Cáceres de Allende, Córdoba); E. Conci (Instituto Modelo de Cardiología, Córdoba); C. Galletti (Sanatorio Allende, Córdoba); J. Leiva (Hosp. Militar, Villa Revoll); L. Huespe (Hosp. Escuela José F. de San Martín, Corrientes); A. Piacenza (Instituto de Cardiología, Corrientes); L. De Rosa (Sanatorio Quintar, San Salvador de Jujuy); G. Elías (Clínica Peregrina, Godoy Cruz); H. Lamacchia (Hosp. El Carmen, Godoy Cruz); W. Vázquez (Hosp. Español, Godoy Cruz); J. Arroyo (Hosp. Italiano, Guaymallén); M. Santamarina (Hosp. Central, Mendoza); C. Martínez (Sanatorio Borati, Posadas); S. Cravetz (Sanatorio Nosiglia, Posadas); S. Lignieres (Sanatorio Asociación de Obras Sociales, Neuquén); A. Kraly (Hosp. Regional Castro Rendón, Neuquén); G. Zabert (Clínica Pasteur, Neuquén); R. Navarro (Policlínico, Neuquén); M. Delgado (Clínica Roca, General Roca); M. Cabana (Sanatorio Juan XXIII, General Roca); F. Baccaro (Hosp. Artémides Zatti, Viedma); A. Glez Roffo (Sanatorio El Carmen, Salta); M. Villar (Sanatorio Asociación de Obras Sociales, San Juan); R. Gimbernat (Instituto Médico, San Juan); M. Cafaro (Hosp. Regional, Rio Gallegos); G. García (Hosp. Clemente Alvárez, Rosario); A. Diez (Hosp. del Centenario, Rosario); R. Guidi (Hosp. Italiano Garibaldi, Rosario); J. Fara (Policlínico Ferroviario, Rosario); F. Martino (Sanatorio Reconquista, Reconquista); D. Sánchez (Sanatorio Julioo Corzo, Rosario) J. Baldi (Hosp. Regional, Río Grande); E. Solano (Hosp. Regional, Ushuaia); A. Stocki (Centro L. Lucero, Bahía Blanca); C. Stolzin (Hosp. Dr. Guillermo Rawson, San Juan); O. Yunk (Hosp. Español, Buenos Aires; P. Pardo (Sanatorio del Jockey Club, San Isidro); J. Berón (Hosp. Pablo Soria, San Salvador de Jujuy); D. Ceraso (Hosp. Dr. Juan A. Fernández, Buenos Aires). BRAZIL: I. A. de Oliveira Jr. (Hosp. Evangelico, Minas Gerais); R. Terzi (Hosp. de Clínicas da UNICAMP, Campi-
nas); W. Nakasato (Hosp. de Clínicas de Ipanema, Rio de Janeiro); F. Maceil (Hosp. Municipal Arthur Ribeiro de Saboya, Sao Paulo); M. Correia de Oliveira (Hosp. Agamenon Magalhaes, Recife); J. Hamilton (Irmandade da Santa Casa de Misericordia, Porto Alegre), J. S. Brauner (Hosp. de Clínicas, Porto Alegre); M. Knibel (Hosp. de Clínicas Mario Lioni, Duque de Caixas); S. L. B. Lopes (Santa Casa de Ribeirao Preto, Ribeirao Preto); C. Duarte (Hosp. Ana Costa, Santos); S. H. Prezzi (Hosp. Nossa Senhora da Conceiçao, Porto Alegre); R. Costa Filho (Hosp. Pró-Cardiaco, Rio de Janeiro); A. Guanaes (Hosp. Santo Amaro, Salvador de Bahía); J. Dias de Matos (Hosp. Governador Celso Ramos, Florianapolis); P. C. Silva Pereira de Souza (Hosp. de Clinicas de Niterol, Rio de Janeiro); S. Lobo (Hosp. de Base de Sao José de Rio Preto, Ribeirao Preto); E. Stefanini (Hosp. Sirio Libanés, Sao Paulo); N. Mozachi (Hosp. Universitario Evangélico, Curitiba); M. L. Toscano (Hosp. Municipal Miguel Couto, Rio de Janeiro); E. Gasparini (Hosp. Universitario Cassiano A. Moraes, Vitoria); J. L. Gomes do Amaral (Hosp. Sao Paulo da UNIFESP, Sao Paulo); J. R. Azevedo (Hosp. Sao Domingo, Sao Luiz); C. H. Ferrari (Case de Saúde Sao José, Duque de Caxias); R. Moritz (Hosp. Universitario Federal, Santa Catarina). CHILE: W. Gallardo (Hosp. Juan Noé, Arica); E. Chávez (Asistencia Pública, Santiago); E. Sáez (Hosp. Barros Luco Trudeau, Santiago); G. Núñez (Clínica Santa María, Santiago); M. Andresen (Hosp. Clínico Universidad Católica, Santiago); J. Castro (Hosp. Clínico Universidad de Chile, Santiago); J. P. Ilic (Mutual de Seguridad, Santiago); G. Arenas (Hosp. Parroquial San Bernardo, Santiago); J. Godoy (Hosp. Sótero del Río, Santiago); J. Mendoza (Hosp. San Juan de Dios, Santiago); G. Heiremans (Hosp. del Trabajador, Santiago); I. Caviédes (Clínica Alemana, Santiago); R. Altuzarra (Hosp. Dipreca, Santiago); S. Meza (Hosp. de Neurocirugía, Santiago); S. Gálvez (Hosp. Gustavo Fricke, Viña del Mar); E. Labarca (Hosp. Naval Almirante Nef, Viña del Mar); E. Fuenzalida (Hosp. de Rancagua, Rancagua); R. Silva (Hosp. de Talca, Talca); C. Ortega (Hosp. Grant Benavente, Concepción); P. Rioseco (Hosp. Las Higueras, Talcahuano); F. Saldías (Hospital de Valdivia, Valdivia); S. Micco (Hosp. Grant Benavente, Concepción); H. Díaz (Hosp. Las Higueras, Talcahuano); F. Saldias (Hosp. de Valdivia, Valdivia); L. Schölz (Hosp. de Osorno, Osorno); C. Rojas (Hosp. Llanchipal, Puerto Montt); E. Encalada (Hosp. C. Van Buren, Valparaiso); L. Soto G. (Hosp. de Coquimbo). PORTUGAL: E. Lafuente (Hosp. S. Da Oliveira, Guimaraes); M. Machado (Hosp. S. Marcos, Braga); F. Rua (Hosp. St. Antonio, Porto); P. Martins (Hosp. Universidade, Coimbra); J. Sa.cher (Hosp. S. José, Lisboa); E. Silva (Hosp. S. do Desterro, Lisboa); P. Freitas (Hosp. F. Fonseca, Amadora-Sintra); R. Moreno (Hosp. St. A. Capuchos, Lisboa); E. De Almeida (Hosp. García da Orta, Almada); R. Maul (Centro Hosp., Funchal); F. Faria (I.P.O., Porto). SPAIN: J. L. Cortés (Hosp. General, Albacete); R. de Pablo (Hosp. Universitario Príncipe de Asturias, Alcalá de Henares); B. Alvárez (Hosp. General, Alicante); R. Conejero (Hosp. Universitario de San Juan, Alicante); J. R. Vicente (Hosp. Torrecárdenas, Almería); A. Ramírez (Hosp. Ntra. Sra. de Sonsoles, Avila); A. Rivera (Hosp. San Agustín., Avilés); A. López (Hosp. Infanta Cristina, Badajoz); R. Tomás (Hosp. Germans Trias i Pujol, Badalona); J. R. Iruretagoyena (Hosp. de Cruces, Baracaldo); R. Anglés (Hosp. Vall d’Hebrón, Barcelona); A. Torres (Hosp. Clinic i Provincial, Barcelona); A. Vázquez (Hosp. del Mar, Barcelona); I. Vallverdú (Hosp. Sta. Cruz y San Pablo, Barcelona); L. Cabré (Hosp. de Barcelona, Barcelona); M. de Frutos (Hosp. Gral. Yagüe, Burgos), J. Gil (Hosp. Universitario de Puerto Real, Cádiz); J. M. Allegue (Hosp. Sta. Ma. del Rosell, Cartagena); T. Mut (Hosp. General, Castellón); J. Ortega (Hosp. Ntra. Sra. de Alarcos, Ciudad Real); J. M. Serrano (Hosp. Reina Sofia, Córdoba); J. M. Añón (Hosp. Virgen de la Luz, Cuenca); A. García (Hosp. Arquitecto Macide, El Ferrol); J. A. Rodríguez (Hosp. General del SVS, Elda); L. Yarritu (Hosp. de Galdakao, Vizcaya); A. Bonet (Hosp. Dr. Josep Trueta., Girona); F. Gordo (Hosp. Universitario, Getafe); M. Lacort (Hosp. de Cabueñes, Gijón); R. Ginestal (Hosp. General Universitario, Guadalajara); C. Homs (Hosp. General San Jorge, Huesca); L. Rucabado (Hosp. General, Jaen); A. Gil (Hosp. General, Jerez de la Frontera); F. Frutos (Hosp. Universitario de Canarias, La Laguna); J. García (Hosp. Juan Canalejo, La Coruña); R. Lorenzo (Hosp. Insular, Las Palmas); S. Ruiz-Santana (Hosp. Ntra Sra del Pino, Las Palmas); J. Súarez (Hosp. Severo Ochoa, Leganés); D. Carriedo (Hosp. Virgen Blanca, León); M. León (Hosp. Arnau de Villanova, Lleida); A. Moreno (Hosp. San
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Millán, Logroño); C. Martín (Hosp. de la Princesa, Madrid); J. E. Guerrero (Hosp. Gregorio Marañón, Madrid); L. Landín (Hosp. Ramón y Cajal., Madrid); R. Suárez (Hosp. Clínico San Carlos, Madrid); J. M. Rubio (Hosp. 12 de Octubre, Madrid); P. Saura (Centre Hospitalari, Manresa); P. Galdos (Hosp. de Móstoles, Móstoles); J. Gómez-Rubí (Hosp. Universitario Virgen de la Arrixaca, Murcia); E. L. Palazón (Hosp. General Universitario, Murcia); G. González (Hosp. Morales Meseguer, Murcia), F. Taboada (Hosp. Central de Asturias, Oviedo); J. López-Messa (Hosp. General Rio Carrión, Palencia); J. Ibañez (Hosp. Son Dureta, Palma de Mallorca); E. Maraví (Hosp. Virgen del Camino, Pamplona); J. P. Tirapu (Hosp. de Navarra, Pamplona); J. Maldonado (Hosp. de la Serranía, Ronda); R. Fernández (Hosp. Parc Taulí, Sabadell); V. Parra (Hosp. de Sagunto, Sagunto); G. Antona (Hosp. Virgen de la Vega, Salamanca); I. Mintegui (Hosp. Ntra Sra de Aránzazu, San Sebastian); M. Moya (Hosp. General de Cataluña, San Cugat del Vallés); P. Ugarte (Hosp. Marqués de Valdecilla, Santander); S. Macías (Hosp. General, Segovia); A. Lesmes (Hosp. Ntra Sra de Valme, Sevilla); A. García-Labatut (Hosp. General, Soria); F. Jara (Hosp. Mutua de Terrasa, Terrasa); P. Dorado (Hosp. Obispo Polanco, Teruel); A. Ayensa (Hosp. Virgen de la Salud, Toledo); J. Gudín (Hosp. Universitario La Fé, Valencia); J. Cuñat (Hosp. Clínico Universitario, Valencia); J. Blanco (Hosp. Río Ortega, Valladolid); J. Castañeda (Hosp. Universitario, Valladolid); A. Loma (Hosp. Txagorritxu, Vitoria); F. Artigas (Hosp. Miguel Servet, Zaragoza). URUGUAY: P. Amonte (Hosp. Evangélico, Montevideo); R. Benedetti (Sanatorio 2 CASMU, Montevideo); A. Deicas (Sanatorio 4 CASMU, Montevideo); H. Bagnulo (Hosp. Maciel, Montevideo); F. Villalba (CIMA España, Montevideo); M. Giangrossi (Médica Uruguaya, Montevideo); J. Terra (Hosp. Militar, Montevideo); C. Santos (Hosp. de Clínicas, Montevideo); L. Gallo (Cooperativa Médica, Canelones); J. Ongay (Asistencial Médica, Rivera); W. González (Camdel Minas, Rivera); C. Cunha (Comita, Tacuarembo); N. Bentancor (Hosp. de Paysandú, Paysandú); A. Soler (Comepa, Paysandú); M. Machado (Cooperativa Asistencial Médica Oeste Colonia); D. Casanyes (Sanatorio Rochense); A. Piedrabuena (Hosp. Regional de Salto); F. Descalzi (Instituto Nacional de Enfermedades Respiratorias y Cirugía Torácica, Santiago). USA/CANADA: E. Abraham (University of Colorado Health Science Center, Denver, CO); S. M. Aguayo (Emory University/VA Medical Center, Decatur, GA); R. K. Albert (University of Colorado Health Science Center, Denver, CO); T. K. Aldrich (Montefiore Medical Center, Bronx, NY); D. Angus (University of Pittsburgh Medical Center, Pittsburgh, PA); C. Arroliga (Cleveland Clinic Foundation, Cleveland, OH); R. M. Aris (University of North Carolina School of Medicine, Chapel Hill, NC); F. M. Azrieli (Jacoby Medical Center, Bronx, NY); R. A. Balk (Rush-Presbyterian-St. Lukes Medical Center, Chicago, IL); R. P. Baughman (University of Cincinnati, Cincinnati, OH); J. F. Beamis (Lahey Clinic, Burlington, MA); S. A. Blosser (Milton S. Hershey Medical Center, Hershey, PA); D. J. Bower (Emory University/VA Medical Center, Decatur, GA); J. Bradley (William Beaumont Army Medical Center, El Paso, TX); W. A. Broughton (University of South Alabama, Mobile, AL); C. D. Burger (Mayo Clinic, Jacksonville, FL); S. C. Campbell (VA Medical Center, Tucson, AZ); R. J. Cassiari (Pul-
monary Consultants, Orange, CA); V. J. Cardenas (University of Texas Medical Branch, Galveston, TX); B. R. Celli (St. Elizabeth Medical Center, Boston, MA); G. E. D’Alonzo (Temple University School of Medicine, Philadelphia, PA); A. Davies (Baylor College of Medicine, Houston, TX); S. D. Derdak (Willford Hall Medical Center, Lackland, TX); P. Dicpinigaitis (Montefiore Medical Center, Bronx, NY); T. A. Dillard (Madigan Army Medical Center, Tacoma, WA); R. Ph. Dillinger (Rush-Presbyterian-St. Lukes Medical Center, Chicago, IL); T. M. Fitzpatrick (Walter Reed Army Medical Center, Washington DC); P. A. Flume (Medical University of South Carolina, Charleston, SC); G. B. Hayes (St. Elizabeth Medical Center, Boston, MA); J. E. Heffner (Medical University of South Carolina, Charleston, SC); N. S. Hill (Rhode Island Hospital, Providence, RI); R. D. Hubmayr (Mayo Clinic, Rochester, MN); S. Idell (University of Texas Health Center, Tyler, TX); D. H. Ingbar (Unversity of Minnesota, Minneapolis, MN); A. Jubran (E. Hines VA Hospital/Loyola University, Hines, IL); R. M. Kacmarek (Harvard Medical School, Boston, MA); J. I. Kennedy (University of Alabama Medical Center, Birmingham, AL); B. P. Krieger (Mt. Sinai Medical Center, Miami Beach, FL); K. Kutty (The Medical College of Wisconsin, Milwaukee, WI); V. Kvetan (Montefiori Medical Center, Bronx, NY); H. Levy (University of New Mexico, Alburquerque, NM); N. R. MacIntyre (Duke University Medical Center, Durham, NC); M. J. Mador (SUNY Buffalo/VA Medical Center, Buffalo, NY); M. G. Marin (UMDNJ-New Jersey Medical School, Newark, NJ); T. W. Marcy (University of Vermont School of Medicine, Burlington, VT); M. A. Matthay (University of California, San Francisco, CA); Z. Mohsenifar (Cedars Sinai Medical Center, Los Angeles, CA); A. Nahum (St. Paul-Ramsey Medical Center, St. Paul, MN); B. M. S. Niedermann (Winthrop University, Mineola, NY); D. R. Ouellette (Brooke Army Medical Center, Fort Sam, Houston, TX); R. C. Perkins (University of Texas Health Science Center, Tyler, TX); S. K. Pingleton (Kansas University Medical Center, Kansas City, KS); M. R. Pinsky (University of Pittsburgh Medical Center, Pittsburgh, PA); C. Piquette (University of Nebraska Medical Center, Omaha, NE); D. Roberts (University of Mannitoba, Winnipeg, MB); W. Rodriguez (VA Medical Center, San Juan, PR); J. D. Sandham (Foothills Hospital, Calgary, Canada); J. San Pedro (Lousiana State University Medical Center, Shreveport, LA); C. N. Sessler (Medical College of Virginia, Richmond, VA); J. B. Silman (Pulmonary Associates, Kerrville, TX); C. Strange (Medical University of South Carolina, Charleston, SC); M. R. Suchyta (LDS Hospital, Salt Lake City, UT); J. I. Sznajder (The University of Illinois, Chicago, IL); D. E. Taylor (University of Texas Health Science Center, Houston, TX); A. V. Thomas, Jr. (Howard University Hospital, Washington DC); J. Varon (University of Texas Health Science Center, Houston, TX); J. M. Walsh (Loyola University Medical Center, Maywood, IL); I. M. Weisman (William Beaumont Army Medical Center, El Paso, TX); G. E. Westney (Morehouse School of Medicine, Atlanta, GA); H. P. Wiedemann (Cleveland Clinic Foundation, Cleveland, OH); S. Wright (Lung Specialists, Phoenix, AZ); R. G. Wunderink (Mid-South Pulmonary and Critical Care Research Foundation, Memphis, TN); K. R. Young, Jr. (University of Alabama, Birmingham, AL).