Comparison of Two Methods for Weaning Patients with Chronic Obstructive Pulmonary Disease Requiring Mechanical Ventilation for More Than 15 Days

Comparison of Two Methods for Weaning Patients with Chronic Obstructive Pulmonary Disease Requiring Mechanical Ventilation for More Than 15 Days MICHELE VITACCA, ANDREA VIANELLO, DANIELE COLOMBO, ENRICO CLINI, ROBERTO PORTA, LUCA BIANCHI, GIOVANNA ARCARO, GIOVANNI VITALE, ENRICO GUFFANTI, ALBINO LO COCO, and NICOLINO AMBROSINO Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Gussago, Lung Function Unit, Gussago, Italy; Ospedale Civile, Padova, Italy; INRCA Casatenovo, Italy; and Ospedale Civico, Palermo, Italy We designed a prospective multicenter randomized controlled study in three long-term weaning units (LWU) to evaluate which protocol, inspiratory pressure support ventilation (PSV) or spontaneous breathing trials (SB), is more effective in weaning patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in both groups). No significant difference was found in weaning success rate (73% versus 77% in the PSV and SB group, respectively), mortality rate (11.5% versus 7.6%), duration of ventilatory assistance (181 161 versus 130 106 h), LWU (33 12 versus 35 19 d), or total hospital stay. The results of these defined protocols were retrospectively compared with an uncontrolled clinical practice in weaning historical control patients. The overall 30-d weaning success rate was significantly greater (87% versus 70%) and the time spent under mechanical ventilation by survived and weaned patients was shorter in the patients in the study than in historical control patients (103 144 versus 170 127 h). The LWU and hospital stays were also significantly shorter (27 12 versus 38 18 and 38 17 versus 47 18 d). Spontaneous breathing trials and decreasing levels of PSV are equally effective in difficult-to-wean patients with COPD. The application of a well-defined protocol, independent of the mode used, may result in better outcomes than uncontrolled clinical practice. Endotracheal intubation and mechanical ventilation are often needed in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure who may undergo difficulties in the weaning process and related need of tracheostomy. A recent review of the literature (1) of patients in general intensive care units (ICUs) (a minority with COPD) was unable to identify a superior weaning technique among the three most popular modes (T-piece, synchronized intermittent mandatory ventilation [SIMV], or pressure support ventilation [PSV]) (2, 3). Furthermore recent trials have demonstrated that simply introducing a protocol or guideline for the weaning process leads to a decrease in weaning time independent of the mode used (4, 5). Similar studies have not been performed in a long-term weaning unit (LWU) setting yet, nor have studies been specifically dedicated to patients with COPD. These patients are (Received in original form August 29, 2000 and in revised form November 27, 2000) Correspondence and requests for reprints should be addressed to Michele Vitacca, M.D., Fondazione S. Maugeri IRCCS, Istituto Scientifico di Gussago, Via Pinidolo 23, 25064 Gussago (BS) Italy. E-mail: mvitacca@fsm.it This article has on online data supplement, which is accessible from this issue s tabel of contents online at www.atsjournals.org Am J Respir Crit Care Med Vol 164. pp 225 230, 2001 Internet address: www.atsjournals.org characterized by a different response to ventilator disconnection and weaning compared with patients in acute settings. Therefore results of studies performed in the acute setting in patients without COPD cannot be applied to difficult-to-wean patients with COPD. A better knowledge of the best weaning modality could help improve the general management of such patients and, ultimately, lead to a greater rate of discontinuation of mechanical ventilation and closure of the tracheostomy with reduced need of home ventilation and reduced human and financial costs (6). Therefore, we designed a prospective, randomized multicenter study to identify which modality (if any), spontaneous breathing (SB) trials or decreasing levels of PSV, is superior in weaning tracheostomized patients with COPD requiring mechanical ventilation for more than 15 d. As a secondary end point, we also performed a retrospective comparison with historical control patients to determine whether a well-defined protocol, independent of the mode used, is more effective than uncontrolled clinical practice in weaning. METHODS Patients We studied 75 consecutive tracheostomized difficult-to-wean patients with COPD (7), mechanically ventilated for at least 15 d (range 15 39) and transferred from 24 ICUs of other hospitals to three longterm weaning units (LWUs). Retrospective study. Fifty-five prospectively studied patients from one LWU (Gussago) were retrospectively compared with 62 patients admitted to the same LWU in the 2 yr preceding the study. In this LWU, those patients had undergone an uncontrolled clinical practice of weaning (4, 5). Comparability parameters were location, age, ideal body weight (IBW), arterial blood gases under mechanical ventilation, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (8) within 24 h of admission to the LWU. Measurements The following data were recorded at admission: anthropometrics, activity of daily life (ADL) scale (9), and location prior to ICU admission; number of hospitalizations in the year before the study and referral; ICU length of stay; APACHE II score; and presence of pneumonia at admission to the LWU. Lung function data in the last stable state before ICU admission or assessed at discharge from the LWU and maximal inspiratory pressure (MIP) during the first 5 min of the T-piece trial (10) were also recorded. Breathing pattern (tidal volume [VT], respiratory frequency [fr]) and minute ventilation ( V E) under mechanical ventilation were monitored through the ventilator display. Protocol Before the T-piece trial, medical therapy was optimized, and patients airway secretions were frequently suctioned. The patients were ventilated with an inspiratory pressure support (19 3 cm H 2 O) adjusted

226 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 164 2001 to achieve ph 7.35, arterial oxygen saturation (Sa O2 ) 92%, fr 10 and 25 breaths/min, and inspiratory oxygen fraction (FI O2 ) 0.4. An external positive end-expiratory pressure (PEEP) 6 cm H 2 O (4 1 cm H 2 O) was added when intrinsic PEEP (PEEP i ) was suspected on a clinical basis. T-piece trial. Patients were eligible to T-piece trial if they fulfilled the conditions previously reported (4, 11): the T-piece trial was considered unsuccessful if during 48 h of SB, the patient showed any sign of poor tolerance (4, 11). Randomization. All patients failing the T-piece trial were randomly assigned to receive PSV or SB trials according to modified protocols by Brochard and coworkers (3) with the ventilator set to require the lowest patient effort to initiate a mechanical ventilator breath. For the purposes of the study, patients of both groups were considered as successfully weaned when able to tolerate at least 48 consecutive h of SB. Patients completing all the levels of either the PSV or SB trial (2), but showing poor tolerance to SB within 48 h of ventilator disconnection, were reconnected to the ventilator for at least 8 consecutive h. Thereafter, the protocol was reinstituted starting from the lowest tolerated level of PSV or from the longest tolerated duration of SB. Weaning Outcomes The following parameters were recorded and compared in the two groups and, in the retrospective study, in the study population and the historical control patients: initial T-piece trial success rate, 10- and 30-d weaning success rate, time of weaning, LWU, and hospital length of stay. Failure was a patient who died or who still needed mechanical ventilation after at least 30 consecutive days of weaning protocol. Statistical Analysis Statistical analysis, as well as other additional METHODS sections, is shown in the online data supplement to this article at www.atsjournals.org. RESULTS Prospective Study During the study period 114 patients were admitted to the three LWUs. Thirty-seven patients (15 with postcardiosurgical sequelae, 9 neuromuscular, 9 neurological, and 4 with acute respiratory distress syndrome [ARDS]) did not have COPD. Two patients with COPD were excluded from the study due to concomitant cancer. Randomization. Twenty-three of the 75 eligible patients (31%) had a successful early T-piece trial and were excluded from randomization. Fifty-two (69%) patients failed the T-piece trial after a mean time of 290 452 min (median: 120 min, range: 15 2145 min) and were randomly assigned to either the PSV or SB group (26 patients in each group). Figure 1 shows the trial profile. The anthropometric, functional, and clinical characteristics of the two groups can be accessed in the Journal s online repository. There were no significant differences in anthropometrics, lung function in stable state, clinical severity at admission, breathing pattern, V E, and arterial blood gases under mechanical ventilation at randomization and MIP at the T-piece trial. As shown in Table 1, the two groups were not different as to location, ADL, hospitalizations in the year preceding ICU admission, and length of ICU stay before LWU admission. Comorbidities were present in 13 patients in the PSV and 15 in the SB group. In the PSV group, the pathologies were pneumonia (5 patients), arterial hypertension (10), arrhythmia (2), congestive heart failure (1), and diabetes (5). In the SB group, the pathologies were pneumonia (2), arterial hypertension (11), arrhythmia (1), congestive heart failure (2), and diabetes (7). Differences were not significant. Figure 1. Patient distribution. Outcomes. Figure 2 shows the percentage of patients who were unable to be weaned from mechanical ventilation (i.e., patients who died and patients who failed to be weaned after 30 d) in both modes of weaning. No significant differences TABLE 1. CLINICAL STATUS PRIOR TO ICU ADMISSION* Location prior to ICU, patients, n Home 26 26 Length of ICU stay before LWU 25 9 27 17 admission, d Length of ICU stay before LWU admission, patients, n Days 1 7 0 0 8 15 2 0 16 23 14 13 24 31 6 4 32 4 9 ADL, patients, n Level of disability None 3 2 Moderate 14 12 Severe 9 12 Year hospital admissions before ICU, patients, n Admissions, n 0 7 8 1 8 10 2 6 4 2 5 4 Definition of abbreviations: ADL activity of daily life; ICU intensive care unit; LWU long-term weaning unit; PSV pressure support ventilation; SB spontaneous breathing. * Data are mean SD. No difference was significant. PSV SB

Vitacca, Vianello, Colombo, et al.: Weaning COPD Patients Requiring Mechanical Ventilation 227 Figure 2. Kaplan Meier curves of probability of remaining under mechanical ventilation for patients survived and weaned performing the fixed protocol (solid circles) or having undergone uncontrolled clinical practice (open circles). Differences were significant (p 0.0001). were found between the groups either at 10 d (probability of remaining under mechanical ventilation 35% and 31% for the PSV and SB groups, respectively) or at 30 d (27% versus 23%) after the start of the protocol. Although patients in the PSV group weaned and survived, and spent more hours on mechanical ventilation than those in the SB group (181 161 versus 130 106 h, respectively), the difference was not significant. The two groups showed similar LWU (33 12 versus 35 19 d for the PSV and SB groups, respectively) and total hospital stay (49 27 versus 50 32 d). None of the 39 successful patients from the combined groups needed reinstitution of mechanical ventilation after the final 48 h. Three of 26 patients (11.5%) from the PSV group and two patients (7.6%) from the SB group died within the first 30 d of protocol application. All deaths were due to multiple organ failure and were not considered related to prolonged mechanical ventilation. Four patients in each group failed attempts at weaning and therefore were discharged home with long-term invasive mechanical ventilation. Three of these eight patients died in the 3 mo following hospital discharge. Five of the 39 (13%) subjects from both groups who survived and were weaned died in the 3 mo following hospital discharge. In 45 of the overall 62 weaned patients (72%), tracheostomy was closed before hospital discharge. Table 2 shows the anthropometric, clinical, and physiological characteristics of the patients from the PSV and SB groups combined according to weaning success or failure. Patients failing weaning underwent more hospitalizations in the year before ICU admission, had a greater limitation in ADL, spent more time in the referring ICUs, and had lower inspiratory muscle strength during the initial T-piece trial. Stepwise discriminant analysis showed that hospitalizations in the preceding year, MIP, severity of airway obstruction (FEV 1 /FVC) in a stable state, days spent in the general ICU, and IBW, in that order, separated weaned patients from those not weaned. Complications. New pneumonias were diagnosed in three patients in the PSV group and in two patients in the SB group; new arrhythmias were found in three patients in the PSV group and three patients in the SB group; agitation needing low dose sedative (benzodiazepine, morphine) was found in seven patients in the PSV group and three patients in the SB group. Differences were not significant. Retrospective Study As shown in Table 3, the 55 eligible patients and the 62 historical control patients from the Gussago LWU were not different as to comparable parameters and severity of airway obstruction in a stable state, ADL, yearly hospital admissions before ICU, breathing pattern, minute ventilation, and heart rate under ventilatory assistance. Figure 3 shows the retrospective comparison of the percentage of patients who were unable to be weaned from mechanical ventilation (deaths and failure to be weaned after 30 d) with and without the use of a prefixed weaning protocol including the initial T-piece trial. The overall 30-d weaning success rate (probability of remaining under mechanical ventilation 87% versus 70%, respectively, p 0.01) was greater and the time spent under mechanical ventilation by survived and weaned patients was shorter (103 144 versus 170 127 h, p 0.0001) in the patients in the study than in the historical controls. The LWU (27 12 versus 38 18 d) and hospital TABLE 2. CHARACTERISTICS OF PATIENTS IN STUDY ACCORDING TO WEANING SUCCESS OR FAILURE* Success Failure p Value Patients, n, % 39 (75%) 13 (25%) Time of T-piece failure, min 343 505 115 93 0.11 Age, yr 71 5 74 5 0.57 IBW, % 91 11 85 11 0.14 FEV 1, % pred 33 8 23 5 0.15 FVC, % pred 43 10 34 9 0.54 Pre-ICU year hospitalization, n 1.5 0.7 2.8 0.7 0.005 ADL, n patients (%) None 4 (10) 0 (0) 0.17 Moderate 24 (63) 2 (15) 0.001 Severe 11 (27) 11 (85) 0.001 ICU stay before LWU, d 23 6 35 24 0.03 APACHE II 16 4 18 4 0.69 Pa O2 /FI O2 217 65 219 62 0.38 Pa, mm CO 2 Hg 55 10 55 11 0.10 V E, L/min 8 3 6 2 0.65 fr/vt 84 60 0.32 MIP, cm H 2 O 37 11 26 7 0.005 Pneumonia, n patients (%) 8 (20) 4 (31) 0.32 Arrythmia, n patients (%) 8 (20) 1 (8) 0.29 Agitation, n patients (%) 7 (18) 3 (23) 0.68 Definition of abbreviations: ADL activity of daily life; APACHE Acute Physiology and Chronic Health Evaluation; FI O2 fraction of inspired oxygen; fr respiratory frequency; IBW ideal body weight; ICU intensive care unit; LWU long-term weaning unit; MIP maximal inspiratory pressure; V E minute ventilation; VT tidal volume. * Data are mean SD. Historical data or assessed at hospital discharge. Recorded at admission. Recorded under mechanical ventilation at randomization. Assessed during the first 5 min of T-piece trial.

228 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 164 2001 Figure 3. Kaplan Meier curves of probability of mechanical ventilation for the 52 randomized patients according to the two techniques studied. There was no significant difference between the two groups (solid circles, PSV group; open circles, SB group). (38 17 vs 47 18 d) stays were also shorter in the patients weaned with the fixed protocol in the study than in the historical control patients. DISCUSSION Our study shows that spontaneous breathing trials and decreasing levels of inspiratory pressure support are equally effective in weaning tracheostomized patients with COPD undergoing mechanical ventilation for more than 15 d. By means of an historical comparison, this study also shows that the application of a well-defined protocol, independent of the mode used, is associated with greater weaning success rate, shorter time under mechanical ventilation, and shorter LWU and hospital stay than uncontrolled clinical practice. It is estimated that 1% to 5% of mechanically ventilated patients repeatedly fail attempts at weaning from mechanical ventilation and face a substantial risk of becoming chronic ventilator-dependent patients who cannot sustain SB for more than a few hours (6). This proportion increases to as much as 31% to 56% in some LWUs where difficult-to-wean patients are located (6, 12). Studies of predictors, protocols, and specific weaning strategies have been largely confined to patients intubated for short periods of time (2 4, 13). A recent review of the literature (1) on weaning techniques used in intubated patients with different etiologies (a minority with COPD) admitted to general ICUs was unable to identify a superior weaning technique between the two modalities used in our study (namely SB trials and reducing levels of inspiratory pressure support) (2, 3). Similar studies have not been performed yet in an LWU setting, nor have studies been specifically dedicated to patients with COPD. These patients are considered to be the most difficult to wean from the ventilator (3). The major mechanism underlying the need for prolonged mechanical ventilation in patients with COPD has been reported to be the association between abnormal lung mechanics, in particular PEEP i, lung resistances, and reduced pressure-generating capacity of the inspiratory muscles because of pulmonary hyperinflation (14). Data from the general ICUs in patients with acute respiratory failure from etiologies other than COPD cannot be extrapolated to patients with COPD requiring prolonged mechanical ventilation in an LWU. Our study is the first to evaluate the effectiveness of the most popular modalities of weaning patients with COPD undergoing prolonged mechanical ventilation (more than 15 d). Despite the small sample size, our study seems to confirm findings reported in acute patients (2, 3) and in difficult-to-wean patients with COPD. Recent trials performed on general populations of ICU patients (only a minority with COPD) (4, 5, 15) have demonstrated that simply introducing a protocol or guideline to the weaning process leads to a decrease in weaning time, independent of the mode used. The results of our retrospective comparison suggest that the application of a fixed weaning proto- TABLE 3. ANTHROPOMETRIC, CLINICAL, AND FUNCTIONAL CHARACTERISTICS OF PATIENTS IN THE RETROSPECTIVE STUDY Prospective Group Retrospective Group p Value Subjects, n 55 62 Age, yr 71 5 73 5 0.58 IBW, %* 90 10 91 5 0.55 APACHE II 15 3 16 3 0.08 ph 7.40 0.04 7.41 0.05 0.60 Pa, mm CO 2 Hg 54 9 56 8.9 0.25 Pa O2 /FI O2 225 48 214 74 0.23 FEV 1 /FVC,%* 47 8 48 9 0.38 ADL, n (%) of patients None 3 (5) 6 (10) 0.39 Moderate 27 (50) 30 (49) 0.40 Severe 25 (45) 25 (41) 0.69 Year hospital admissions before ICU, n (%) of patients 0 6 (11) 11 (18) 0.40 1 27 (49) 24 (39) 0.50 2 8 (15) 7 (12) 0.68 2 14 (25) 19 (31) 0.46 ICU stay before LWU admission, d 23 17 26 9 0.11 fr breaths/min 20 6 21 4 0.11 VT, ml 396 149 400 100 0.50 V E, L/min 8.1 2.5 8.6 1.4 0.16 Heart rate, beats/min 96 18 99 16 0.26 MIP, cm H 2 O 38 10 32 6.6 0.01 Definition of abbreviations: ADL activity of daily life; APACHE Acute Physiology and Chronic Health Evaluation; FI O2 fraction of inspired oxygen; fr respiratory frequency; IBW ideal body weight; ICU intensive care unit; LWU long-term weaning unit; MIP maximal inspiratory pressure; V E minute ventilation; VT tidal volume. * Historical data (53% and 55% for prospective and retrospective groups, respectively) or assessed at hospital discharge under tracheostomy (47% and 45% for prospective and retrospective groups, respectively). At admission to LWU. Under mechanical ventilation within 24 h of admission to LWU. During the first minutes of T-piece trial.

Vitacca, Vianello, Colombo, et al.: Weaning COPD Patients Requiring Mechanical Ventilation 229 col, in the conditions and in the patients of this study, may increase the weaning success rate and reduce the time spent under mechanical ventilation in patients with COPD ventilated for more than 15 d. These results must be considered with caution. Although there was no change in staffing or in attitude of staff over time, an effect of time differences between the two weaning periods rather than the protocol itself cannot be excluded, and further randomized, prospective studies must confirm our results. Reducing the proportion of ventilator-dependent patients to be discharged with home mechanical ventilation and their LWU stay might have relevant social and economic consequences. Another important result of our study is that 31% of tracheostomized patients with COPD referred to an LWU for prolonged weaning may be disconnected from the ventilator after an early T-piece trial without any need for a further weaning process. In the acute setting, Saura and coworkers (15) reported that following the implementation of a weaning protocol, there was a greater number of patients extubated without any weaning technique; that is, the initial SB trial was the most important factor. Thus, at least in the conditions of our study, an early T-piece trial should be recommended in these difficult-to-wean patients with COPD (16). Although a recent ICU study suggests that a 30-min weaning trial may be as good as a longer 120-min trial in predicting successful weaning (17), another study on a large population pointed out that short trials bear a high risk of reintubation rate (13). Our data demonstrate that this short time cannot be extrapolated to tracheostomized patients with COPD: in fact our patients from both groups failed the T-piece trial after a period of apparent stability longer than reported in studies in an acute setting (13, 17). At variance with studies in the ICU (18, 19), Purro and coworkers (14), in LWU patients similar to ours, did not find any significant change in breathing pattern, neuromuscular drive, inspiratory muscle strength, lung mechanics, PEEP i, and lung resistances between the beginning and the end of the SB trial, independent of weaning success. However, they found a progressive increase in Pa CO2 at the end of the SB period indicating that the SB pattern was not efficient in terms of CO 2 elimination and that the ventilatory pump was not coping with the metabolic demand (20). This may be confirmed by the fact that in our study MIP was lower in the unweanable patients than in those successfully weaned. Similar results had also been found by Nava and coworkers (21). Fourteen or 21 d is commonly considered the time limit to judge a patient as difficult to wean and to perform tracheostomy in the ICU (1). Patients considered unweanable require intensive nursing (22), physiotherapy, counseling, and nutritional and psychological support before being judged as ventilator-dependent patients and discharged home under mechanical ventilation. Dasgupta and coworkers (23) showed that 60% of the patients considered unweanable at the time of ICU discharge regained respiratory autonomy after a relatively short (mean: 17 d) stay in a specialized respiratory care unit. Our study confirms and extends those data in that more than 80% of patients with COPD admitted to an LWU for prolonged weaning may be restored to SB after a mean time of 28 11 d of LWU stay. This is a success rate superior to that previously reported (24, 25). Nevertheless, in our LWUs, weaning success rates at 10 and 30 d of all eligible 75 patients were not significantly different (77% and 83%, respectively), the success rate at 30 d increasing by only 6%. Whether this difference makes it worthwhile to prolong the weaning attempts to 30 d with related greater costs and LWU stay remains to be evaluated by specific studies on a greater number of patients. Limitations of the Study Our results are limited by the small sample size, which might have influenced the lack of statistical differences between the two interventions (assuming clinically relevant a 20% difference in the rate of weaning between SB and PSV, for a Type I error 0.05 and for a Type II error 0.20, the required sample size for a two-tailed comparison would be 90 subjects for each group). Nevertheless, our results showed the complete absence of any trends for a difference, and, therefore, we can speculate that it is unlikely that a significant difference would emerge, even with substantially larger numbers. A potential influence of the specific weaning protocol on the rates of weaning success on the first days cannot be ruled out. Indeed limitations on the number of reductions in PSV level or length of SB trials per day might have resulted in more similar rates of weaning. Nevertheless, although this may have affected the initial portions of the Kaplan Meier curves, it should not have influenced 30-d weaning rates. In conclusion, we have shown that in difficult-to-wean patients with COPD spontaneous breathing trials and decreasing levels of inspiratory pressure support are equally effective in weaning success rate and weaning time. With the limitations of an historical comparison, we have also shown that a welldefined protocol, independent of the modality used, was associated with a better outcome than uncontrolled clinical practice previously performed in the LWU. Nevertheless, further randomized, prospective studies on a larger number of patients are required to confirm our results. Acknowledgment: The authors thank Prof. Laurent Brochard for useful discussion and comments. References 1. Butler R, Keenan SP, Inman KJ, Sibbald WJ, Block G. Is there a preferred technique for weaning the difficult-to-wean patient? A systematic review of the literature. Crit Care Med 1999;27:2331 2336. 2. Esteban A, Frutos F, Tobin M, Alia I, Solsona J, Valverdu I, Fernandez R, De La Cal MA, Benito S, Tomas R, Carriedo D, Macias S, Blanco J. A comparison of four methods of weaning from mechanical ventilation. N Engl J Med 1995;332:345 350. 3. Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994;150:896 903. 4. Ely EW, Baker AM, Dunagan DP, Burke HR, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect of the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864 1869. 5. Kollef MH, Shapiro SD, Silver P, St John RE, Printice D, Sauer S, Ahrens TS, Shannon W, Baker-Clinkscale D. A randomized controlled trial of protocol directed versus physician directed weaning from mechanical ventilation. Crit Care Med 1997;25:567 574. 6. Celli BR. Home mechanical ventilation. In: Tobin MJ, editor. Principles and practice of mechanical ventilation, 1st ed. New York: McGraw- Hill; 1994. p. 619 629. 7. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152(Suppl):S77 S120. 8. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Apache II: a severity of disease classification system. Crit Care Med 1985;13:818 829. 9. Katz S, Ford AB, Moskowitz RV, Jackson A, Jaffe MW. Studies of illness in the aged the index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963;185:914 919. 10. Black L, Hyatt R. Maximal airway pressures: normal values and relationship to age and sex. Am Rev Respir Dis 1969;99:696 702. 11. Tobin MJ, Alex CG. Discontinuation of mechanical ventilation. In: Tobin MJ, editor. Principles and practice of mechanical ventilation, 1st ed. New York: McGraw-Hill; 1994. p. 1177 1206. 12. Scheinhorn D, Chao DC, Stearn-Hassenpflug M, La Bree LD, Heltsley DJ. Post-ICU mechanical ventilation: treatment of 1123 patients at a regional weaning center. Chest 1997;111:1654 1659.

230 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 164 2001 13. Vallverdù I, Calaf M, Subirana M, Net A, Benito S, Mancebo J. Clinical characteristics, respiratory functional parameters and outcome of a two-hour T-piece-trial in patients weaning from mechanical ventilation. Am J Respir Crit Care Med 1998;158:1855 1862. 14. Purro A, Appendini L, De Gaetano A, Gudjonsdottir M, Donner CF, Rossi A. Physiologic determinants of ventilator dependence in longterm mechanically ventilated patients. Am J Respir Crit Care Med 2000;161:1115 1123. 15. Saura P, Blanch L, Mestre J, Vallés J, Artigas A, Fernandez R. Clinical consequences of the implementation of a weaning protocol. Intensive Care Med 1996;22:1052 1056. 16. Esteban A, Alia I. Clinical management of weaning from mechanical ventilation. Intensive Care Med 1998;24:999 1008. 17. Esteban A, Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, Blanch L, Bonet A, Vazquez A, Pablo RD, Torres A, Cal M, Macias S. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Am J Respir Crit Care Med 1999;159: 512 518. 18. Yang K, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991;324:1445 1450. 19. Jubran A, Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 1997;155:906 915. 20. Stroetz RW, Hubmayr RD. Tidal volume maintenance during weaning with pressure support. Am J Respir Crit Care Med 1995;152:1034 1040 21. 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 d. Eur Respir J 1994;7:1645 1652. 22. Vitacca M, Clini E, Porta R, Ambrosino N. Preliminary results on nursing workload in a dedicated weaning centre. Intensive Care Med 2000; 26:796 799. 23. Dasgupta A, Rice R, Mascha E, Litaker D, Stoller JK. Four year experiance with a unit for long term ventilation (respiratory special unit) at the Cleveland Clinic Foundation. Chest 1999;116:447 455. 24. Scheinhorn DJ, Hassenpflug M, Artinia BM, Libree L, Catlin J. Predictors of weaning after 6 weeks of mechanical ventilation. Chest 1995; 107:500 505. 25. Menzies R, Gibbons W, Goldberg P. Determinant of weaning and survival among patients with COPD who require mechanical ventilation for acute respiratory failure. Chest 1989;95:398 405.