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Journal of Critical Care (2006) 21, 185 – 192

Predictors of extubation failure in patients with chronic


obstructive pulmonary disease
Laurent Robriquet MDa,*, Hugues Georges MDb, Olivier Leroy MDb,
Patrick Devos MDc, Thibaut D’escrivan MDb, Benoit Guery MDb
a
Service de Réanimation Polyvalente, Centre Hospitalier Universitaire de Lille, 59000 Lille, France
b
Service de Réanimation Médicale et Maladies Infectieuses, Université de Lille,
Centre Hospitalier de Tourcoing, 59200 Tourcoing, France
c
Department of Biostatistics, Centre Hospitalier Universitaire de Lille, 59000 Lille, France

Keywords:
Abstract Few studies have focused on extubation outcome in patients with chronic obstructive
Chronic obstructive
pulmonary disease (COPD) requiring mechanical ventilation (MV). We conducted a study using
pulmonary disease;
prospectively collected data in a cohort of patients with COPD requiring invasive MV to identify
Extubation;
variables associated with extubation failure. Use of noninvasive or invasive MV within 48 hours after
Mechanical ventilation
extubation was defined as extubation failure. A total of 148 patients with COPD were studied.
Extubation failure occurred in 35% of studied patients. Using multiple regression analysis, independent
predictors of extubation failure were physiologic abnormalities measured by Simplified Acute
Physiology Score II above 35 on intensive care unit (ICU) admission (odds ratio [OR], 3.88; 95%
confidence interval [CI], 1.65-9.12), home noninvasive MV (OR, 12.99; 95% CI, 2.86-58.89), and
sterile endotracheal aspirations on the day of extubation were predictors of success (OR, 0.23; 95% CI,
0.10-0.52). Despite high rate of extubation failure, survival to ICU discharge was 91% of the studied
population. Extubation failure in patients with COPD remains high despite a successful spontaneous
breathing on T piece. Simplified Acute Physiology Score II at ICU admission, home noninvasive MV,
and isolated pathogens on quantitative cultures of tracheobronchial secretions within 72 hours preceding
extubation were predictors of extubation failure in the study population.
D 2006 Elsevier Inc. All rights reserved.

1. Introduction extubation and occurs in 2% to 25% of patients [1].


Extubation failure prolongs MV duration and intensive care
Extubation is the ultimate goal of weaning from invasive unit (ICU) and hospital length of stay [2]. Discontinuing
mechanical ventilation (MV). Regardless of the different MV constitutes a major clinical challenge more particularly
weaning strategies used, extubation failure is defined by the in patients with chronic obstructive pulmonary disease
necessity of reintubation within 24 to 48 hours of planned (COPD) in whom respiratory weakness and diaphragmatic
dysfunction may occur [3]. In these patients, the rate of
weaning failure is higher and ranges from 35% to 67%
* Corresponding author. Tel.: +33 3 20 69 44 30; fax: +33 3 20 69 44 39. [4,5]. However, few studies have focused on predisposing
E-mail address: lrobriquet@invivo.edu (L. Robriquet). factors of extubation failure, especially in patients with

0883-9441/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcrc.2005.08.007
186 L. Robriquet et al.

COPD succeeding a trial of spontaneous breathing on For each studied patient, only the first episode of
T piece (SBT) after disconnection from the ventilator. We extubation was analyzed. Extubation outcome was classi-
conducted a study in a cohort of patients with COPD fied as either success or failure. Successful extubation
requiring invasive MV to determine predisposing factors of occurred when patients could spontaneously breathe with-
extubation failure. out invasive or noninvasive MV for at least 48 hours after
extubation. After extubation, MV was considered again
when one of the following parameters was present:
2. Materials and methods decreased consciousness, respiratory muscle failure, cardiac
failure, upper airway obstruction, hypoventilation with
2.1. Study population respiratory acidosis (pH b7.25 with Paco2 N55 mm Hg),
and major pulse oxymetry desaturation (SaO2 b85% during
We conducted a retrospective study using prospectively
breathing with an Fio2 z0.5). Noninvasive MV was
collected data in a 16-bed university-affiliated ICU. From
attempted when there was no cardiac failure or impaired
January 1996 to May 2002, all patients with a history of
consciousness. Reintubation was instituted directly for
COPD requiring invasive MV were eligible. The diagnosis
patients with cardiac failure and decreased consciousness
of COPD was determined according to the American
and if noninvasive MV did not improve clinical signs of
Thoracic Society criteria [6].
increased respiratory work in the other patients.
2.2. Extubation procedure
2.3. Data collection
During the study period, all patients were extubated
following a standardized procedure; SBT trial was initiated All the following characteristics were collected: age,
when the following criteria were present: an improvement sex, and severity of illness. Severity of illness was assessed
in or resolution of the underlying cause of acute respiratory using Simplified Acute Physiology Score II (SAPS II) [9].
failure; adequate oxygenation (eg, Pao2/fraction of inspired Surgical procedure just before ICU admission was reported,
oxygen [Fio2] N150; requiring positive end-expiratory and postoperative patients were defined as planned surgery
pressure V8 cm H2O; Fio2 V0.5) and pH (eg, z7.35); patients or emergency surgery patients. Among medical
hemodynamic stability; and full level of consciousness, patients, cause of acute respiratory failure was noted. Use
cessation of all sedative agents, ability to initiate an of home noninvasive ventilation or home oxygen therapy
inspiratory effort, and effective cough strength on com- was recorded. The occurrence of previous intubation was
mand. Pao2/Fio2 ratio could be inferior to 150 in patients also noted. The following data were also recorded before
with severe chronic hypoxemia. Respiratory frequency, extubation: duration of invasive MV, duration of PSV, use
heart rate, systolic blood pressure, and arterial oxygen and duration of intravenous sedation (benzodiazepines and/
saturation measured by pulse oxymetry were recorded or opioids), and neuromuscular blocking agents (NBAs):
every 15 minutes during the SBT trial [7]. Trial of SBT
failed if patients developed respiratory frequency above
Table 1 Characteristics of the 148 studied patients during
35 breaths per minute, arterial oxygen saturation below ICU stay
90%, heart rate above 140 beats per minute, systolic blood
Variables Patients (n = 148)
pressure above 180 or below 90 mm Hg, or change in
mental status. When no sign of these defined criteria Demographics
occurred during 30 to 60 minutes of SBT, patients were Male sex 117 (79%)
extubated and received supplemental oxygen by face mask Age (y) 68.4 F 10.2
Home oxygen 37 (25%)
to obtain arterial oxygen saturation above 90%. If
Home noninvasive ventilation 13 (8.7%)
respiratory distress occurred during SBT trial, MV was Previous MV 21 (14.2%)
reinstituted, and reversible causes of weaning failure were Diagnosis at admission
then investigated [8]. In this group, pressure support Acute exacerbation 83 (56.1%)
ventilation (PSV) was attempted when signs of respiratory Pneumonia 36 (24.3%)
distress disappeared. The level of PSV, comprised between Emergency surgery 9 (6.1%)
8 and 20 cm H2O, was determined to achieve adequate Planned surgery 6 (4%)
minute ventilation (minute ventilation between 5 L/min and Other 20 (14%)
12 L/min), respiratory rate between 12 and 20 per minute, ICU stay
and no sign of respiratory distress. A positive end- SAPS II on ICU admission 38.6 F 10.9
expiratory pressure of 5 cm H2O was systematically added. Duration of MV before first 7.1 F 5.2
extubation attempt (d)
If PSV was not tolerated by the patient, assist-control
Deaths 13 (9%)
ventilation was used. Subsequent SBT trials were next
Data are presented as n (%) or mean F SD. Among medical patients,
assayed every day if patients met the preceding defined
many diagnoses at admission were possible.
criteria for extubation attempts.
Predictors of extubation failure in patients with COPD 187

use of sedation was considered positive when sedative Table 3 Patients characteristics on the day of extubation
drugs were used more than 24 hours. One single
Variables Extubation Extubation P
administration of NBA was considered as a positive use
success (n = 96) failure (n = 52)
of the drug.
Data collected on the day of extubation were SAPS II, SAPS II 28.3 F 6.9 29.8 F 5.4 .19
DSAPS II 8.3 F 8.7 12.4 F 8.9 .008
difference between SAPS II on ICU admission and on the
Temperature (8C) 37.4 F 0.5 37.5 F 0.6 .43
day of extubation, axillary temperature (maximum temper-
pH 7.42 F 0.05 7.42 F 0.06 .47
ature within 24 hours preceding extubation), biochemical Pao2/Fio2 283 F 80.6 274 F 71.9 .54
tests (serum creatinine, blood urea nitrogen, calcium, Paco2 (mm Hg) 42.8 F 6.9 45.9 F 9.4 .04
phosphorus, and albumin level), arterial blood gases and Serum creatinine 9.3 F 4.1 9.1 F 5.2 .79
Pao2/Fio2 on MV before SBT trial, hemoglobin level, and (mg/L)
use of antimicrobial agents. Blood urea 0.56 F 0.31 0.58 F 0.33 .67
Culture of endotracheal aspirates (EA) performed within nitrogen (g/L)
72 hours preceding extubation was also recorded. Quanti- Hemoglobin 10.9 F 1.6 10.9 F 1.5 .87
tative cultures of tracheobronchial secretions were per- level (mg/L)
formed twice a week and not systematically on the day of Calcium (mg/L) 83.7 F 6.8 83.5 F 6.1 .82
Phosphorus (mg/L) 29.6 F 10.0 29.3 F 8.5 .89
extubation. Quantitative cultures of EA were considered
Serum albumin (g/L) 24.3 F 5.2 21.8 F 4.4 .01
positive at the threshold of 105 CFU/mL. In cases where Antibiotics 61 (64%) 32 (57%) .68
more than 1 pathogen was present on EA cultures, the Steroids 48 (50%) 28 (54%) .65
pathogen with the highest bacterial load was taken Intravenous 44 (43.4%) 27 (50%) .47
into account. bronchodilatators
Institution of new therapeutic modalities within the Data are presented as n (%) or mean F SD. DSAPS II indicates the
48 hours after extubation was recorded: inotropic drugs, intra- difference between SAPS II on ICU admission and SAPS II on the day
venous bronchodilatators (b-adrenergic agonists), cortico- of extubation.
steroids, diuretics, intravenous nitroglycerin, and antibiotics.
2.4. Statistical analysis
Descriptive analysis (frequencies for categorical data,
Table 2 Patient characteristics on ICU admission and during mean, SD, and box plot for numerical variables) was
ICU stay before extubation performed according to 2 groups, successful and failed
Variables Extubation Extubation P extubations. Categorical variables were compared using v 2
success (n = 96) failure (n = 52) test or Fisher exact test when v 2 was not appropriate.
Baseline characteristics Continuous variables were compared using Student t test.
Age (y) 67.3 F 10.9 70.2 F 8.5 .09 Differences between groups were considered to be signif-
SAPS II 36.6 F 10.9 42.2 F 10.3 .003 icant for variables yielding P V. 05. Some continuous
Sex (male/female) 80/16 37/15 .08 variables were categorized into classes by selecting the best
Home oxygen 21 (22%) 16 (31%) .23 cutoffs (receiver operating characteristic curve analysis,
Home noninvasive 3 (3%) 10 (19%) .001 maximization of the v 2). All variables attaining an a value
MV
of .05 were included in a multiple logistic regression
Previous MV 13 (14%) 8 (15%) .75
analysis model with a stepwise selection of variables. All
Diagnosis at admission
Acute exacerbation 53 (55%) 30 (58%) .77 statistical analyses were performed using the SAS Software
Pneumonia 21 (22%) 15 (29%) .34 version 8.2.
Emergency surgery 7 (7%) 2 (4%) .4
Planned surgery 6 (6%) 0 .06
Others 13 (14%) 7 (13%) .98 3. Results
ICU stay
Duration of MV (d) 6.5 F 5.5 8.1 F 4.5 .07 One hundred forty-eight patients with COPD with a first
Use of sedation 82 (85%) 46 (88%) .6 extubation attempt were included during the study period.
Duration of sedative 3.96 F 3.75 4.47 F 2.76 .32 Characteristics of these patients during ICU stay are reported
drugs (n = 128) (d) on Table 1. Successful extubation was achieved for
Use of NBA 5 (5%) 2 (4%) .52 96 patients (65%). Noninvasive MV was instituted in
Use of PSV 76 (79%) 41 (79%) .96 25 patients. Among the 52 patients with extubation failure,
Duration of PSV 3.2 F 2.9 3.4 F 2.9 .7 invasive MV was directly instituted in 27 patients. Post-
(n = 117) (d)
extubation noninvasive MV was performed in 25 patients
Data are presented as n (%) or mean F SD. Among medical patients, and allowed to avoid reintubation in 17 patients, whereas the
many diagnoses at admission were possible.
remaining 8 patients had to be reintubated. Causes of acute
188 L. Robriquet et al.

Table 4 Characteristics of EA cultures results and anti-


Unsuccessful extubation after MV, in the general
microbial chemotherapy in the studied population population, occurs in up to 20% of patients within 24 to
72 hours of planned extubation [1,2]. The higher rate of
Extubation Extubation P
extubation failure in our study is explained by the studied
success failure
(n = 96) (n = 52) population and by our definition of extubation failure:
institution of noninvasive MV in patients developing acute
Positive EA (n) 22 (23%) 25 (48%) .001
respiratory failure after extubation was considered as failure.
Isolated pathogens .42
Pseudomonas aeruginosa 9 11
Esteban et al [10] showed, in a recent study, that
Staphylococcus aureus 7 4 noninvasive MV does not reduce mortality or the need for
Streptococcus pneumoniae 0 1 reintubation among patients exhibiting respiratory failure
Enteric gram-negative bacilli 3 4 after extubation. However, despite our high rate of
Haemophilus influenzae 0 3 extubation failure, mortality (9% of our patients) remained
Other species 3 2 similar to other studies. Seneff et al [11] reported an ICU
Antibiotics on the 61 32 .25 mortality of 9.4% in a cohort of 362 patients COPD
day of extubation requiring ICU admission. Another study of 180 patients
Data are presented as n (%). with COPD admitted to an ICU for acute respiratory failure
showed an inhospital mortality rate of 15% [12]. This low
mortality despite a high rate of reintubation is explained by
respiratory failure after extubation were respiratory muscle
the success of a second or a third episode of extubation and
failure caused by abundant respiratory secretions (n = 14),
the realization of a tracheotomy, allowing for some patients
cardiac failure (n = 2), upper airway obstruction (n = 2),
to be discharged from ICU.
hypoventilation with respiratory acidosis (n = 18), and
The severity of illness on ICU admission has a strong
hypoxemic respiratory failure (n = 16).
influence on extubation outcome. In our study, we measured
3.1. Univariate analysis initial severity of illness by the SAPS II prognostic system
and found that a SAPS II above 35 on ICU admission was
Predisposing factors of extubation failure during ICU associated with extubation failure. Severity of illness on
stay or on the day of extubation are, respectively, reported admission measured by scoring systems has already been
on Tables 2 and 3. highlighted by several authors, resulting in a longer duration
Fifty-seven EAs were positive. Isolation of pathogens of MV and then difficulties in weaning [13-15].
was associated with a significant increase of extubation Home noninvasive ventilation concerned 8.7% of our
failure (Table 4). Nevertheless, no specific species were studied population. The rate of extubation failure was higher
associated with failure. for these patients. Home noninvasive ventilation is generally
New therapeutics were instituted after 23 extubation used in stable hypercapnic patients with COPD even if it is
procedures and were not more frequent in the failed not assessed by published guidelines [16,17]. Thus, home
extubation group (10 new treatments in the failed group noninvasive ventilation suggests more severe underlying
vs 13 in the successful group, P = .36). functional respiratory disorders. Some studies assessed that
use of noninvasive MV improved weaning in patients with
3.2. Multivariate analysis COPD who failed an SBT trial [18,19]. In patients using
Stepwise logistic regression independently isolated 3 home noninvasive ventilation, systematic institution of
predisposing factors of extubation failure: SAPS II on ICU noninvasive MV just after extubation could be started.
admission above 35 noninvasive ventilation at home, and Another important data from our study is that isolation of
positive EA (Table 5). pathogens on EA is a significant predisposing factor for
extubation failure. In COPD mechanically ventilated
patients, it is difficult to know if presence of pathogens
4. Discussion
Table 5 Multiple logistic regression analysis of variables
To our knowledge, our study has included the most predictive of extubation failure
important number of patients with COPD to assess
Predictor variables Adjusted 95% confidence P
predisposing factors of extubation failure. The main find- odds ratio interval
ings of this study are that extubation failure occurs in 35%
Home noninvasive 12.99 2.86-58.89 .0009
of patients with COPD, despite achievement of a successful
ventilation
SBT trial allowing extubation, and that using logistic SAPS II N35 on 3.88 1.65-9.12 .001
regression analysis, predisposing factors to extubation ICU admission
failure are the existence of home noninvasive MV, SAPS Sterile EA on the 0.23 0.10-0.52 .0005
II on ICU admission above 35, and a positive culture of EA day of extubation
within 72 hours preceding extubation.
Predictors of extubation failure in patients with COPD 189

means bronchial colonization, reflecting severity of under- substantial risk for extubation failure, patients with COPD
lying chronic respiratory insufficiency or bronchial infec- requiring invasive MV have a realistic chance of surviving
tion. In patients with severe COPD, there is a correlation to ICU discharge.
between deterioration of lung function and bacteria isolated
from tracheobronchial secretions [20,21]. Nouira et al [22]
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Commentary SBT was commenced. If a patient passed an SBT, then the
information was relayed to the physician and a decision
regarding extubation was made. Patients in the SBT
Commentary: Extubating patients with chronic protocol arm had 1.5 fewer days of mechanical ventilation
obstructive pulmonary disease: Transitioning from and had a 5% lower reintubation rate than patients treated
art to science with standard care. Accordingly, protocols involving SBTs
have been recommended as a means of deciding who is safe
The decision to extubate a patient is one of the most to extubate.
challenging decisions facing intensivists. In many critical Unfortunately, despite rigorous adherence to a weaning
care units, this decision is based more on intuition and protocol, 4% to 20% of patients will still require reintuba-
personal experience than on clinical evidence or scientific tion [6]. Factors affecting reintubation include inadequate
rationale. This leads to a wide variation in practice patterns respiratory muscle capacity, cardiac ischemia, upper airway
and large differences in the duration of mechanical obstruction, and ineffective clearance of respiratory secre-
ventilation [1]. However, the absence of evidence-based tions [8]. Specialized tests have been developed in an
practice is certainly not caused by a lack of importance attempt to predict who might fail extubation after passing an
regarding this decision. Leaving a patient intubated for too SBT, but none has been adequately validated to support
long can have grave consequences, predisposing the patient widespread use [8]. Tests to predict airway patency, such as
to ventilator-associated pneumonia and increasing his or her the cuff-leak test, have been inconsistent in predicting
intensive care unit length of stay [2]. Alternatively, postextubation stridor [9,10]. Similarly, methods to assess
extubating a patient too soon will frequently lead to the adequacy of cough or the ability to protect one’s airway
reintubation, an act associated with greater morbidity and have met with conflicting results [8]. Consequently, there is
mortality [3-5]. no widely accepted and effective test to predict extubation
Reintubating a patient in the first 48 to 72 hours failure once weaning has been achieved.
postextubation has been termed extubation failure and is Patients with chronic obstructive pulmonary disease
expected to occur in 4% to 20% of patients [6]. Numerous (COPD) are particularly prone to extubation failure because
studies have shown that extubation failure is associated with of their compromised respiratory mechanics and their
a higher morbidity and mortality [3-5]. The increased propensity to develop abundant secretions. Patients with
mortality may relate to a greater underlying severity of COPD have an increased load as a result of greater amounts
illness in the patient that fails extubation. Alternatively, it of intrinsic positive end-expiratory pressure, chest wall
may be associated with the complications of reintubation, abnormalities, and increased airway resistance [11]. In
such as aspiration pneumonia. Lastly, the excess morbidity addition, hyperinflation forces patients with COPD to
may be attributable to the stress of the events occurring breathe on the steeper portion of the pressure volume curve,

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