To assess the efficacy of noninvasive ventilation (NIV) in patients with persistent weaning failure, we conducted a prospective, randomized, controlled trial in 43 mechanically ventilated patients who had failed a weaning trial for 3 consecutive days. This trial was stopped after a planned interim analysis. Patients were randomly extubated, receiving NIV (n = 21), or remained intubated following a conventional-weaning approach consisting of daily weaning attempts (n = 22). Compared with the conventional-weaning group, the noninvasive-ventilation group had shorter periods of invasive ventilation (through tracheal intubation) (9.5 ± 8.3 vs. 20.1 ± 13.1 days, p = 0.003) and intensive care unit (ICU) (14.1 ± 9.2 vs. 25.0 ± 12.5 days, p = 0.002) and hospital stays (27.8 ± 14.6 vs. 40.8 ± 21.4 days, p = 0.026), less need for tracheotomy to withdraw ventilation (1, 5% vs. 13, 59%, p < 0.001), lower incidence of nosocomial pneumonia (5, 24% vs. 13, 59%, p = 0.042) and septic shock (2, 10% vs. 9, 41%, p = 0.045), and increased ICU (19, 90% vs. 13, 59%, p = 0.045) and 90-day survival (p = 0.044). The conventional-weaning approach was an independent risk factor of decreased ICU (odds ratio: 6.6; p = 0.035) and 90-day survival (odds ratio: 3.5; p = 0.018). Earlier extubation with NIV results in shorter mechanical ventilation and length of stay, less need for tracheotomy, lower incidence of complications, and improved survival in these patients.
Invasive mechanical ventilation is associated with an increased risk of nosocomial pneumonia and mortality (1–4). Prolonged mechanical ventilation, a major risk factor for nosocomial pneumonia (5, 6), may be a consequence of persistent weaning failure (7) and is associated with an increased morbidity and mortality, especially in patients with chronic respiratory failure (8).
Noninvasive ventilation (NIV) facilitates early extubation and improves the outcome of selected patients with an exacerbation of chronic obstructive pulmonary disease (COPD) and weaning failure (9). In patients with acute-on-chronic respiratory failure, failing one single weaning attempt, the use of NIV resulted in a mild reduction of the duration of endotracheal mechanical ventilation but no improvement in outcome (10). Despite this evidence, the efficacy of NIV in patients with persistent weaning failure, a frequent clinical situation in mechanically ventilated patients with chronic respiratory disorders, has not been assessed as yet.
We postulated that in patients with persistent weaning failure, earlier extubation, taking advantage of NIV, would reduce the period of invasive ventilation as the primary end-point variable, hence decreasing the incidence of complications associated with prolonged mechanical ventilation and improving survival. Accordingly, we conducted a prospective, randomized clinical trial to assess the efficacy of this strategy compared with the conventional-weaning approach.
Some of the results of this study have been reported previously in abstract form (11).
(For more details, see the online supplement.)
A prospective, randomized controlled study was conducted in two centers. Intubated patients who met criteria to proceed in the weaning attempt (see criteria in the online supplement) but had failed a spontaneous breathing trial for 3 consecutive days were considered eligible for the study. The exclusion criteria were (1) facial or cranial trauma or surgery, (2) recent gastric or esophageal surgery, (3) tracheotomy, (4) active upper gastrointestinal bleeding, (5) excessive amount of respiratory secretions, and (6) lack of co-operation. The study was approved by the Ethics Committee of the two institutions, and written informed consent was obtained in all cases.
Weaning attempts consisted of once-daily spontaneous breathing trials with a T-piece. If no signs of spontaneous breathing trial failure appeared within 2 hours (see criteria in the online supplement), patients were extubated and were not eligible for the study. Alternatively, if signs of spontaneous breathing trial failure appeared during this period, patients were reconnected to the ventilator. Patients in whom the spontaneous breathing trial failed during 3 consecutive days were randomly allocated, using a computer-generated table for each center either for (1) extubation and NIV treatment (NIV group) or (2) reconnection to the ventilator and once-daily weaning attempts (conventional-weaning group).
NIV (BiPAP Vision; Respironics Inc., Murrysville, PA) using the S/T mode was continuously delivered immediately after extubation, at least during the first 24 hours after extubation. Then, NIV was gradually withdrawn if patients tolerated spontaneous breathing until they could permanently sustain spontaneous breathing. A face mask was used as the first choice, but a nasal mask was optionally used if patients did not tolerate the face mask.
Patients were reconnected to the ventilator and daily spontaneous breathing trials were performed until patients could be extubated (12, 13). When needed, low doses of sedatives or opioids were used between the spontaneous breathing trials to manage anxiety or pain and to avoid fighting against the ventilator. The weaning process was interrupted—and full sedation reinstituted—if complications that significantly worsened patients' clinical conditions occurred and resumed if these complications were solved.
Reintubation criteria were predefined: respiratory or cardiac arrest, respiratory pauses with loss of consciousness or gasping for air, psychomotor agitation inadequately controlled by sedation, massive aspiration, persistent inability to remove respiratory secretions, heart rate below 50/minute with loss of alertness, and hemodynamic instability without response to fluids and vasoactive drugs. To avoid reintubation, NIV was initiated in the conventional-weaning group if other minor criteria of spontaneous breathing failure occurred (14). Tracheotomy was performed if patients were unable to clear or remove their secretions or if there was prolonged mechanical ventilation without positive evolution of the weaning process (15).
Data from patients were recorded and patients' follow-up was extended to 90 days after randomization. Successful weaning was defined as the ability to sustain spontaneous breathing at least for 3 consecutive days. Extubation failure was defined as reintubation within 72 hours after extubation.
Clinical diagnosis of nosocomial pneumonia (16), septic shock (17), and multiple organ failure (18) were defined by criteria published previously (see criteria in the online supplement).
The primary end-point variable was to decrease the duration of invasive ventilation, defined as positive pressure ventilation delivered through orotracheal intubation or tracheotomy, in the NIV group. Initial calculations revealed a required sample size of 42 subjects in each group, with the duration of invasive ventilation to be reduced by 6 days (9). We planned an interim analysis after inclusion of 50% of the estimated patients, using an α curtailment (p < 0.005) to correct the analysis.
Qualitative or categorical variables were compared with the χ2 test or Fisher's exact test. Quantitative continuous variables were compared using the unpaired Student's t test or the Mann–Whitney nonparametric test. The Kaplan–Meier estimate-of-survival curve was used to determine the cumulative probability of successful weaning and 90-day survival; curves between the two groups were compared using the log-rank test. The level of significance was set in all tests at 0.05 (all two-tailed).
Univariate and multivariate analyses of intensive care unit (ICU) survival were performed using logistic regression with a conditional stepwise forward model.
Univariate analyses of 90-day survival were performed with the Kaplan–Meier estimate-of-survival curve. Multivariate analyses of this type of survival were performed with Cox proportional hazard regression. To correct collinearity in all multivariate analyses, a conditional stepwise forward model was chosen (pin < 0.05). Adjusted odds ratios and 95% confidence intervals were computed for variables independently associated with survival.
The planned interim analysis after inclusion of 50% of the estimated patients revealed a significant reduction of the duration of invasive ventilation in the NIV group (p = 0.003). Therefore, the study was stopped, in such a way that 43 consecutive patients were included during a 24-month period (Figure 1)
: 21 patients were allocated to the NIV group and 22 patients to the conventional-weaning group. General clinical characteristics of patients at randomization are summarized in Table 1NIV Group | Conventional-Weaning | ||
---|---|---|---|
(n = 21) | Group (n = 22) | p Value | |
Age, yr | 70.3 ± 7.5 | 71.0 ± 7.2 | 0.767 |
Sex, M/F | 13/8 | 17/5 | 0.444 |
Current or former smoker, n (%) | 13 (62) | 17 (77) | 0.444 |
Current or former alcohol abuse, n (%) | 4 (19) | 2 (9) | 0.412 |
APACHE-II on admission | 17.8 ± 4.6 | 18.5 ± 3.9 | 0.589 |
Duration of ICU stay, d | 7.3 ± 2.8 | 7.5 ± 3.9 | 0.801 |
Duration of mechanical ventilation, d | 7.1 ± 2.8 | 7.0 ± 3.4 | 0.959 |
Number of comorbidities per patient | 1.8 ± 0.9 | 1.8 ± 0.9 | 0.894 |
White blood cells, ×109/L | 12.1 ± 4.3 | 12.4 ± 3.0 | 0.794 |
Hematocrit, L/L | 0.38 ± 0.07 | 0.35 ± 0.05 | 0.170 |
Patients with chronic pulmonary disorders, n (%) | 16 (76) | 17 (77) | 1.000 |
Causes of mechanical ventilation, n | 0.545 | ||
Exacerbation of chronic pulmonary disorders | 10 | 9 | |
Congestive heart failure | 4 | 5 | |
Community-acquired pneumonia | 2 | 4 | |
Hospital-acquired pneumonia | 1 | 1 | |
Postoperative respiratory failure | – | 2 | |
Acute lung injury | 1 | 1 | |
Thoracic trauma | 1 | – | |
Hemoptisis | 1 | – | |
Cardiac arrest | 1 | – |
The physiologic parameters of patients on the day of randomization are summarized in Table 2
Mechanical Ventilation | Spontaneous Breathing Trial | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
NIV Group | Conventional-Weaning | NIV Group | Conventional-Weaning | |||||||
(n = 21) | Group (n = 22) | p Value | (n = 21) | Group (n = 22) | p Value | |||||
f, min−1 | 19.2 ± 5.6 | 17.4 ± 5.2 | 0.300 | 31.0 ± 5.2 | 28.7 ± 8.0 | 0.276 | ||||
VT, L | 0.46 ± 0.13 | 0.50 ± 0.11 | 0.271 | 0.27 ± 0.08 | 0.32 ± 0.12 | 0.184 | ||||
f/VT ratio | – | – | – | 122 ± 42 | 108 ± 58 | 0.378 | ||||
Heart rate, min−1 | 97 ± 16 | 97 ± 12 | 0.840 | 109 ± 15 | 108 ± 17 | 0.791 | ||||
Mean blood pressure, mm Hg | 89 ± 13 | 85 ± 14 | 0.312 | 104 ± 20 | 97 ± 20 | 0.255 | ||||
Arterial pH | 7.42 ± 0.05 | 7.41 ± 0.05 | 0.740 | 7.37 ± 0.06 | 7.38 ± 0.07 | 0.708 | ||||
PaCO2, mm Hg | 45.6 ± 10.6 | 47.0 ± 6.7 | 0.609 | 53.6 ± 16.2 | 51.9 ± 12.2 | 0.688 | ||||
PaO2, mm Hg | 95 ± 30 | 86 ± 18 | 0.207 | 66 ± 21 | 70 ± 17 | 0.510 | ||||
PaO2/FIO2 | 259 ± 81 | 226 ± 58 | 0.129 | 172 ± 57 | 171 ± 44 | 0.948 |
Weaning results and length of stay are summarized in Table 3
NIV Group | Conventional-Weaning | ||
---|---|---|---|
(n = 21) | Group (n = 22) | p Value | |
Duration of invasive ventilation, d | 9.5 ± 8.3 | 20.1 ± 13.1 | 0.003 |
Total period of ventilatory support*, d | 11.4 ± 8.0 | 20.1 ± 13.1 | 0.012 |
ICU stay, d | 14.1 ± 9.2 | 25.0 ± 12.5 | 0.002 |
Hospital stay, d | 27.8 ± 14.6 | 40.8 ± 21.4 | 0.026 |
Reintubation, n (%) | 3 (14) | 6 (27) | 0.457 |
Main causes of reintubation, n | |||
Severe persistent hypoxemia | 1 | 3 | |
Severe dyspnea | – | 2 | |
Inability to manage secretions | 2 | – | |
Hemodynamic instability | – | 1 | |
Tracheotomy, n (%) | 1 (5) | 13 (59) | <0.001 |
ICU survival, n (%) | 19 (90) | 13 (59) | 0.045 |
Causes of death within 90 d after entry in the study | |||
Septic shock/MOF | 1 | 9 | |
Refractory hypoxemia | 1 | 2 | |
Cardiac arrest | 2 | 1 | |
Pneumothorax | – | 1 | |
Stroke | 1 | – | |
Pulmonary embolism | 1 | – |
The probability of weaning success was significantly higher in the NIV group (p = 0.002), as shown in Figure 2
. There were no significant differences in the incidence of reintubation between the two groups. In the conventional-weaning group, the use of NIV within 72 hours after extubation avoided reintubation in one patient. One patient from the NIV group and 13 patients from the conventional-weaning group needed tracheotomy to facilitate weaning, with differences that were significant (p < 0.001). In the whole population, tracheotomy was performed after 18 ± 4 days (range, 11–23 days) of mechanical ventilation.The number of patients with serious complications diagnosed after entry into the study, as shown in Table 4
NIV Group | Conventional-Weaning | ||
---|---|---|---|
(n = 21) | Group (n = 22) | p Value | |
Total number of patients | 5 | 16 | 0.004 |
Nosocomial pneumonia | 5 | 13 | 0.042 |
Catheter-related sepsis | – | 2 | – |
Sacrum-infected ulcer | – | 1 | – |
Urinary tract infection | – | 1 | – |
Chest wall abscess | – | 1 | – |
Gastrointestinal bleeding | 1 | – | – |
Pneumothorax | – | 1 | – |
Septic shock | 2 | 9 | 0.045 |
Compared with patients weaned conventionally, survival in the ICU (p = 0.045) was higher in the NIV group (Table 3). Likewise, the cumulative survival probability after 90 days of randomization, as shown in Figure 3
, was higher in the latter group (p = 0.044). The causes of death within 90 days of randomization are summarized in Table 3.The univariate and multivariate analyses of survival are summarized in Table 5
Adjusted Odds Ratio | 95% CI | p Value | Adjusted Odds Ratio | 95% CI | p Value | |
---|---|---|---|---|---|---|
Decreased ICU survival | Univariate analysis | Multivariate analysis | ||||
Conventional-weaning approach | 6.6 | 1.2–35.6 | 0.029 | 6.6 | 1.1–38.8 | 0.035 |
Age > 70 yr | 5.8 | 1.1–31.3 | 0.041 | – | – | NS |
Decreased 90-d survival | Univariate analysis | Multivariate analysis | ||||
Conventional-weaning approach | – | – | 0.044 | 3.5 | 1.2–9.6 | 0.018 |
Age > 70 yr | – | – | 0.012 | 5.1 | 1.7–15.0 | 0.003 |
PaCO2 during spontaneous breathing > 45 mm Hg | – | – | 0.018 | 5.8 | 1.8–18.7 | 0.003 |
In patients with persistent weaning failure, earlier extubation with NIV decreased the duration of ventilatory support, length of stay, incidence of nosocomial pneumonia and septic shock, and improved survival, compared with patients following a conventional-weaning approach.
The strongest evidence that NIV prevents endotracheal intubation and reduces complications and mortality is shown in patients with severe exacerbations of chronic obstructive pulmonary disease with hypercapnic respiratory failure and respiratory acidosis (14, 19–21). Moreover, in these patients with severe community-acquired pneumonia, NIV helped to avoid intubation and to improve survival (22). By contrast, significant debate still exists concerning the precise indications for NIV in patients with acute nonhypercapnic respiratory failure. One study has demonstrated that NIV is an adequate alternative means to conventional invasive ventilation in such patients (23), and more recently, that it prevents endotracheal intubation in selected groups of patients with cardiogenic pulmonary edema (24), immunosuppression (25, 26), and acute respiratory failure after lung resection (27).
There is less evidence supporting the efficacy of NIV during weaning. Shortened weaning and avoidance of reintubation are promising uses of NIV (28). The application of NIV during weaning was performed in a selected group of patients with chronic obstructive pulmonary disease who failed a spontaneous breathing trial after early recovery from an acute exacerbation (9). In this randomized controlled trial, NIV facilitated extubation within 48 hours after intubation, decreasing the period of ventilatory support, the ICU stay, and the incidence of nosocomial pneumonia, as well as increasing survival. Another randomized controlled trial in patients with acute-on-chronic respiratory failure after a single weaning trial failure (10) showed that NIV facilitated a modest reduction of the invasive-ventilation period, without significant changes in total duration of ventilation, ICU stay, incidence of complications, and survival. Conversely, a recent study showed no benefit from the addition of NIV to standard medical therapy in patients who develop postextubation respiratory distress (29).
The efficacy of NIV in patients with persistent weaning failure had not been assessed yet in randomized fashion. Persistent weaning failure is not an infrequent clinical situation in mechanically ventilated patients, especially those with chronic respiratory disorders. It is associated with prolonged mechanical ventilation (7) and increased morbidity and mortality (8), as shown by the more prolonged duration of mechanical ventilation and length of stay in patients from the conventional-weaning group of the present study, compared with previous trials (9, 10). Accordingly, all measures to reduce the weaning period are welcome.
The present trial stopped after the planned interim analysis showed a significant reduction of the duration of invasive ventilation in the NIV group, in accordance with the predefined stopping rule. We chose this period instead of total duration of ventilation because intubation, and not ventilatory support, is the main determinant of increased risk of complications. This decision was reinforced by the decreased incidence of serious complications in this group, the need for tracheotomy, and the ICU stay, which were all related with poor outcome. The excellent tolerance of NIV without any sedation in this subset of patients and the potential hazards derived from the need for sedation in patients still intubated in the conventional-weaning group (30) were additional reasons for stopping the trial.
Because patients with unsuccessful weaning are likely to develop a rapid and shallow breathing pattern (31), the ability of NIV to improve hypoxemia and hypercapnia by correcting such an abnormal breathing pattern (32) might explain the benefits of NIV in these patients. Despite earlier extubation in the NIV group, the incidence of reintubation, a potentially hazardous complication associated with increased morbidity and mortality (33, 34), was approximately half of the conventional-weaning group, although these differences were not significant. Moreover, the use of NIV resulted in a great reduction for the need to perform a tracheotomy to facilitate weaning. The presence of a tracheotomy for prolonged periods, even when patients are already breathing spontaneously, increases the period of artificial airway, and, therefore, susceptibility of patients to further acquire respiratory infections. In addition, these patients often need nasogastric intubation for enteral feeding. This is associated with increased incidence of gastroesophageal reflux and aspiration to the airways (35–37), a major risk factor for nosocomial pneumonia (5).
The time course of delivery may be relevant in the clinical efficacy of NIV. Similar to the study of Nava and coworkers (9), NIV in the present study was continuously delivered immediately after extubation for as much time as possible. Both studies showed marked improvement of outcome variables in patients who received NIV. By contrast, Girault and coworkers (10) used intermittent periods of NIV separated by scheduled periods of spontaneous breathing after extubation. This latter study did not show any significant differences in the incidence of complications and outcome among patients with and without NIV.
Prolonged invasive ventilation, as shown in the conventional-weaning group, is associated with a high incidence of nosocomial pneumonia (5, 6). It is of interest to note that the reported episodes of nosocomial pneumonia were late-onset (> 5 days of mechanical ventilation) (38). These types of pneumonia have higher mortality compared with early-onset ones. Consequently, the use of NIV to shorten the duration of invasive ventilation and to prevent late-onset pneumonias is of great benefit for the patient in terms of morbidity and mortality. In addition, and similar to other series of ventilated patients (9, 39, 40), the most frequent cause of death in this study was septic shock/multiple organ failure due to nosocomial pneumonia. A recent publication showed a slightly higher ICU mortality rate (above 50%) in patients ventilated for 20 days for clinical conditions similar to patients from our trial, not substantially different than our control group (41%) (41). Therefore, shortening such a prolonged period of invasive ventilation with the approach used in the NIV group without further complications in the majority of patients may explain the improved survival in this group. Moreover, the use of NIV was the only independent factor at the time of weaning to predict an increased ICU survival. Following this weaning approach may result in an important reduction in hospital costs as well because of the marked decrease of morbidity and the length of ICU and hospital stays. In addition, the use of NIV was also associated with improved outcome through a 90-day follow-up period. Other factors, such as advanced age and the development of hypercapnia during the spontaneous breathing trial, were good predictors of decreased 90-day survival.
To our knowledge, this is the first study to identify the development of hypercapnia during a failed spontaneous breathing trial as a marker of poor prognosis. This factor appears to be an accurate indicator of clinical deterioration after recovery of a life-threatening episode of respiratory failure. The detection of hypercapnia during persistently failed weaning attempts should alert physicians to start measures, such as noninvasive ventilatory support, to avert the poor outcome associated with this arterial blood gas finding.
Two potential limitations have to be taken into account when analyzing the differences between the two groups. First, although not specifically monitored, patients from the conventional-weaning group received more sedation than those in the NIV group; this limitation is inherent to the design of the study and difficult to solve in future trials because intubated patients often need more sedation than patients receiving NIV (20). Second, the two groups followed different weaning regimens after inclusion in the study, i.e., the gradual withdrawal of NIV versus once-daily T-piece trials until patients tolerated spontaneous breathing. Another potential limitation of this type of open clinical trials is the difficulty for a correct blinding of the investigators that might lead to possible bias. Despite the fact that we predefined the criteria for all relevant interventions and clinical decisions to be made by the attending physicians, as well as the outcome variables, this bias could not be entirely controlled.
In conclusion, NIV is effective to shorten the period of invasive ventilation in patients with persistent weaning failure, and, in consequence, to decrease the incidence of nosocomially acquired infections, mortality, and other outcome parameters such as length of ICU and hospital stays.
The authors wish to thank Antonio Alarcon for his technical expertise and the nursing staff of the two intensive care units for their cooperation in the development of this study.
1. | Torres A, Aznar R, Gatell JM, Jiménez P, González J, Ferrer A, Celis R, Rodriguez-Roisin R. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990;142:523–528. |
2. | Ibrahim EH, Tracy L, Hill C, Fraser VJ, Kollef MH. The occurrence of ventilator-associated pneumonia in a community hospital: risk factors and clinical outcomes. Chest 2001;120:555–561. |
3. | Bercault N, Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med 2001;29:2303–2309. |
4. | Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002;165:867–903. |
5. | Celis R, Torres A, Gatell JM, Almela M, Rodriguez-Roisin R, Agustí-Vidal A. Nosocomial pneumonia: a multivariate analysis of risk and prognosis. Chest 1988;93:318–324. |
6. | Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M. Supine body position is a risk factor of nosocomial pneumonia in mechanically ventilated patients: a randomised clinical trial. Lancet 1999;354:1851–1858. |
7. | Esteban A, Alia I, Ibańez J, Benito S, Tobin MJ. Modes of mechanical ventilation and weaning: a national survey of Spanish hospitals: The Spanish Lung Failure Collaborative Group. Chest 1994;106:1188–1193. |
8. | Nava S, Rubini F, Zanotti E, Ambrosino N, Bruschi C, Vitacca M, Fracchia C, Rampulla C. Survival and prediction of successful ventilator weaning in COPD patients requiring mechanical ventilation for more than 21 days. Eur Respir J 1994;7:1645–1652. |
9. | Nava S, Ambrosino N, Clini E, Prato M, Orlando G, Vitacca M, Brigada P, Fracchia C, Rubini F. Noninvasive mechanical ventilation in the weaning of patients with respiration failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med 1998;128:721–728. |
10. | Girault C, Daudenthun I, Chevron V, Tamion F, Leroy J, Bonmarchand G. Noninvasive ventilation as a systematic extubation and weaning technique in acute-on-chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med 1999;160:86–92. |
11. | Ferrer M, Arancibia F, Esquinas A, Maldonado A, Bauer TT, Gonzalez G, Carrillo A, Rodriguez-Roisin R, Torres A. Noninvasive ventilation for persistent weaning failure [abstract]. Am J Respir Crit Care Med 2000;161:A262. |
12. | Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864–1869. |
13. | Esteban A, Alía I. Clinical management of weaning from mechanical ventilation. Intensive Care Med 1998;24:999–1008. |
14. | Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995;333:817–822. |
15. | Kollef MH, Ahrens TS, Shannon W. Clinical predictors and outcomes for patients requiring tracheostomy in the intensive care unit. Crit Care Med 1999;27:1714–1720. |
16. | Woodhead MA, Torres A. Definition and classification of community-acquired and nosocomial pneumonias. In: Torres A, Woodhead M, editors. Pneumonia. Sheffield: European Respiratory Society Journals Ltd.; 1997. p. 1–12. |
17. | Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RMH, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: The ACCP/SCCM Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644–1655. |
18. | Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Prognosis in acute organ-system failure. Ann Surg 1985;202:685–693. |
19. | Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000;355:1931–1935. |
20. | Mehta S, Hill NS. Noninvasive ventilation. Am J Respir Crit Care Med 2001;163:540–577. |
21. | Peter JV, Moran JL, Phillips-Hughes J, Warn D. Noninvasive ventilation in acute respiratory failure: a meta-analysis update. Crit Care Med 2002;30:555–562. |
22. | Confalonieri M, Potena A, Carbone G, Della Porta R, Tolley E, Meduri G. Acute respiratory failure in patients with severe community-acquired pneumonia: a prospective randomized evaluation of noninvasive ventilation. Am J Respir Crit Care Med 1999;160:1585–1591. |
23. | Antonelli M, Conti G, Rocco M, Bufi M, Deblasi RA, Vivino G, Gasparetto A, Meduri GU. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998;339:429–435. |
24. | Masip J, Betbese AJ, Paez J, Vecilla F, Cañizares R, Padro J, Paz MA, de Otero J, Ballus J. Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial. Lancet 2000;356:2126–2132. |
25. | Antonelli M, Conti G, Bufi M, Costa MG, Lappa A, Rocco M, Gasparetto A, Meduri GU. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation. JAMA 2000;283:235–241. |
26. | Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-Benissan G, Dupon M, Reiffers J, Cardinaud JP. Noninvasive ventilation in immunosupressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 2001;344:481–487. |
27. | Auriant I, Jallot A, Hervé P, Cerrina J, Le Roy Ladurie F, Lamet Fournier J, Lescot B, Parquin F. Noninvasive ventilation reduces mortality in acute respiratory failure following lung resection. Am J Respir Crit Care Med 2001;164:1231–1235. |
28. | International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001;163:283–291. |
29. | Keenan SP, Powers C, McCormack DG, Block G. Noninvasive positive-pressure ventilation for postextubation respiratory distress: a randomized controlled trial. JAMA 2002;287:3238–3244. |
30. | Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342:1471–1477. |
31. | Tobin MJ, Perez W, Guenther SM, Semmes BJ, Mador MJ, Allen SJ, Lodato RF, Dantzker DR. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 1986;134:1111–1118. |
32. | Diaz O, Iglesia R, Ferrer M, Zavala E, Santos C, Wagner PD, Roca J, Rodriguez-Roisin R. Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:1840–1845. |
33. | Torres A, Gatell JM, Aznar E, El-Ebiary M, Puig de la Bellacasa J, González J, Ferrer M, Rodriguez-Roisin R. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med 1995;152:137–141. |
34. | Epstein SK, Ciubotaru RL, Wong J. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186–192. |
35. | Torres A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A, Lomeña F, Rodriguez-Roisin R. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992;116:540–543. |
36. | Orozco-Levi M, Torres A, Ferrer M, Piera C, El-Ebiary M, Puig de la Bellacasa, Rodriguez-Roisin R. Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Am J Respir Crit Care Med 1995;152:1387–1390. |
37. | Ferrer M, Bauer TT, Torres A, Hernández C, Piera C. Gastro-esophageal reflux and microaspiration to lower airways in intubated patients: impact of nasogastric tube size. Ann Intern Med 1999;130:991–994. |
38. | American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: a consensus statement. Am J Respir Crit Care Med 1995;153:1711–1725. |
39. | Ferring M, Vincent JL. Is outcome from ARDS related to the severity of respiratory failure? Eur Respir J 1997;10:1297–1300. |
40. | Estenssoro E, Dubin A, Laffaire E, Canales H, Saenz G, Moseinco M, Pozo M, Gomez A, Baredes N, Jannello G, et al. Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome. Crit Care Med 2002;30:2450–2456. |
41. | Esteban A, Anzueto A, Frutos F, Alia I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguia C, Nightingale P, et al. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 2002;287:345–355. |