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JAMA
JAMA. 2019 Jun 11; 321(22): 2175–2182.
Published online 2019 Jun 11. doi:10.1001/jama.2019.7234
PMCID: PMC6563557
PMID: 31184740
A Randomized Clinical Trial
Carles Subirà, MD,
1 Gonzalo Hernández, MD, PhD,2 Antònia Vázquez, MD, PhD,3 Raquel Rodríguez-García, MD,4 Alejandro González-Castro, MD,5 Carolina García, MD,6 Olga Rubio, MD, PhD,1,7 Lara Ventura, MD,1 Alexandra López, MD,8 Maria-Carmen de la Torre, MD, PhD,9 Elena Keough, MD,10 Vanesa Arauzo, MD,11 Cecilia Hermosa, MD,12 Carmen Sánchez, MD,13 Ana Tizón, MD,14 Eva Tenza, MD, PhD,15 César Laborda, MD,16 Sara Cabañes, MD,17 Victoria Lacueva, MD,18 Maria del Mar Fernández, MD, PhD,19 Anna Arnau, MSc, PhD,1 and Rafael Fernández, RMD, PhD1,7,20
Author information Article notes Copyright and License information PMC Disclaimer
See editorial "The importance of timing for the spontaneous breathing trial" in Ann Transl Med, volume 7, S210.
See editorial "More than just a screen to liberate from mechanical ventilation: treat to keep extubated?" in Ann Transl Med, volume 7, S338.
See editorial "Weaning off mechanical ventilation: much less an art, but not yet a science" in Ann Transl Med, volume 7, S353.
See "Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children" in JAMA, volume 327 onpage1555.
This article has been corrected. See JAMA. 2019 August 20; 322(7): 696.
See commentary "Revisiting, Reframing, and Casting a New Light on Liberation From Mechanical Ventilation." in JAMA, volume 321 onpage2167.
Associated Data
- Supplementary Materials
Key Points
Question
What is the effect of a less demanding (30 minutes of pressure support ventilation) vs a more demanding (2 hours of T-piece ventilation) spontaneous breathing trial on rates of successful extubation?
Findings
In this randomized clinical trial that included 1153 adults receiving mechanical ventilation, the proportion of patients successfully extubated was 82.3% among those who received 30 minutes of pressure support ventilation compared with 74% among those who received 2 hours of T-piece ventilation, a difference that was statistically significant.
Meaning
These findings support the use of a shorter, less demanding strategy of 30 minutes of pressure support ventilation for spontaneous breathing trials.
Abstract
Importance
Daily spontaneous breathing trials (SBTs) are the best approach to determine whether patients are ready for disconnection from mechanical ventilation, but mode and duration of SBT remain controversial.
Objective
To evaluate the effect of an SBT consisting of 30 minutes of pressure support ventilation (an approach that is less demanding for patients) vs an SBT consisting of 2 hours of T-piece ventilation (an approach that is more demanding for patients) on rates of successful extubation.
Design, Setting, and Participants
Randomized clinical trial conducted from January 2016 to April 2017 among 1153 adults deemed ready for weaning after at least 24 hours of mechanical ventilation at 18 intensive care units in Spain. Follow-up ended in July 2017.
Interventions
Patients were randomized to undergo a 2-hour T-piece SBT (n = 578) or a 30-minute SBT with 8-cm H2O pressure support ventilation (n = 557).
Main Outcome and Measures
The primary outcome was successful extubation (remaining free of mechanical ventilation 72 hours after first SBT). Secondary outcomes were reintubation among patients extubated after SBT; intensive care unit and hospital lengths of stay; and hospital and 90-day mortality.
Results
Among 1153 patients who were randomized (mean age, 62.2 [SD, 15.7] years; 428 [37.1%] women), 1018 (88.3%) completed the trial. Successful extubation occurred in 473 patients (82.3%) in the pressure support ventilation group and 428 patients (74.0%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13.0%; P = .001). Among secondary outcomes, for the pressure support ventilation group vs the T-piece group, respectively, reintubation was 11.1% vs 11.9% (difference, −0.8%; 95% CI, −4.8% to 3.1%; P = .63), median intensive care unit length of stay was 9 days vs 10 days (mean difference, −0.3 days; 95% CI, −1.7 to 1.1 days; P = .69), median hospital length of stay was 24 days vs 24 days (mean difference, 1.3 days; 95% CI, −2.2 to 4.9 days; P = .45), hospital mortality was 10.4% vs 14.9% (difference, −4.4%; 95% CI, −8.3% to −0.6%; P = .02), and 90-day mortality was 13.2% vs 17.3% (difference, −4.1% [95% CI, −8.2% to 0.01%; P = .04]; hazard ratio, 0.74 [95% CI, 0.55-0.99]).
Conclusions and Relevance
Among patients receiving mechanical ventilation, a spontaneous breathing trial consisting of 30 minutes of pressure support ventilation, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for spontaneous breathing trials.
Trial Registration
ClinicalTrials.gov Identifier: NCT02620358
This randomized trial compares the effect of 30-minute pressure support vs 2-hour T-piece ventilation strategies in spontaneous breathing trials on rate of successful extubation among patients who had been receiving mechanical ventilation for at least 24 hours.
Introduction
Among patients receiving mechanical ventilation, readiness for extubation and liberation from ventilatory support is evaluated with a spontaneous breathing trial (SBT).1 Daily screening of respiratory function by SBT is associated with a shorter duration of mechanical ventilation.2 After a successful SBT and extubation, 10% to 25% of patients require reintubation, and reintubation is associated with higher mortality.3,4
The most common modes of SBT are T-piece ventilation and pressure support ventilation (PSV), lasting between 30 minutes and 2 hours.5,6,7 There are no differences in the rate of successful extubation between 2-hour PSV and 2-hour T-piece ventilation,8 between T-piece ventilation for 30 minutes vs 2 hours,9 or between PSV for 30 minutes vs 2 hours.10 Although shorter SBTs are better tolerated, there is no evidence that they result in higher successful extubation rates.9,10 Some patients in whom a T-piece SBT failed might have been successfully extubated after a PSV SBT.11
A recent meta-analysis suggested that T-piece SBTs are the optimal method for evaluating weaning readiness.12 Nevertheless, another meta-analysis found that PSV resulted in higher rates of successful extubation than T-piece SBTs.13 Moreover, the latest American Thoracic Society guidelines for weaning recommend PSV SBTs with moderate-quality evidence.14 Thus, further investigation is needed to determine the best approach for SBTs.
This study hypothesized that less demanding SBTs could result in a higher rate of successful extubation without increasing the reintubation rate. To test this hypothesis, 2 weaning strategies were compared: an approach that is more demanding for patients (T-piece SBT for 2 hours) vs an approach that is less demanding for patients (8-cm H2O PSV for 30 minutes).
Methods
From January 2016 through April 2017, a multicenter randomized clinical trial was conducted in 18 Spanish intensive care units. The ethics committee of each hospital approved the study, and all patients or their relatives provided written informed consent. The study protocol is available in Supplement 1.
Patients aged 18 years or older undergoing mechanical ventilation for at least 24 hours who fulfilled the weaning criteria were eligible. The weaning criteria were (1) the resolution or improvement of the condition leading to intubation; (2) hemodynamic stability, defined as systolic blood pressure between 90 and 160 mm Hg and heart rate less than 140/min without vasopressors or with low doses of vasopressors; (3) Glasgow Coma Scale score of 13 or greater; (4) respiratory stability (oxygen saturation >90% with fraction of inspired oxygen [Fio2] ≤0.4, respiratory rate <35/min, spontaneous tidal volume >5 mL/kg, ratio of respiratory rate to tidal volume <100/min per liter, and maximal inspiratory pressure >15 cm H2O); and (5) noncopious secretions (<3 aspirations in the last 8 hours). Patients with tracheostomies or do-not-reintubate orders were excluded.
Randomization
Patients were randomized in a 1:1 ratio to one of the two weaning strategies by means of tables of computer-generated random numbers in blinded blocks of 4 patients for each center. A central administrator who was not involved in the analyses used an opaque envelope to allocate patients to receive one of the two treatments. The intervention was not blinded for the investigators or attending physicians.
Interventions
Patients randomized to undergo a highly demanding SBT underwent a 2-hour T-piece SBT; patients randomized to undergo a less demanding SBT underwent a 30-minute SBT with 8-cm H2O PSV and zero positive end-expiratory pressure; Fio2 remained unchanged from the mechanical ventilation period leading up to the SBT.
Before randomization, attending physicians had to decide on the extubation strategy (whether to reconnect the patient to the ventilator for 1 hour before extubation and whether to administer noninvasive ventilation or high-flow nasal cannula after extubation).
Patients who successfully completed the SBT were extubated. Arterial blood gas analysis was not required, but when it was done, the results were recorded. Physicians were also recommended to record dyspnea using the Borg Dyspnea Scale (score range, 0-10; 0 indicates no dyspnea and 10 indicates maximal dyspnea) at the beginning and at the end of SBTs and to ask patients about their confidence in their ability to sustain breathing without a ventilator.
Patients who did not tolerate the SBT were reconnected to a ventilator. Criteria for failure to tolerate the SBT were agitation, anxiety, low level of consciousness (Glasgow Coma Scale score <13), respiratory rate higher than 35/min and/or use of accessory muscles, oxygen saturation by pulse oximetry less than 90% with Fio2 higherthan 0.5, heart rate higher than 140/min or greater than a 20% increase from baseline, systolic blood pressure lower than 90 mm Hg, or development of arrhythmia. Additional SBTs were not protocolized, and mode and duration were left to the discretion of attending teams.
Respiratory failure within 72 hours of extubation was defined as the occurrence of at least 1 of the following: respiratory acidosis with pH lower than 7.32 and Paco2 higher than 45 mm Hg, oxygen saturation less than 90% with Fio2 higher than 0.5, respiratory rate higher than 35/min, low level of consciousness (Glasgow Coma Scale score <13), severe agitation, or clinical signs of respiratory fatigue. Treatment of postextubation respiratory failure was not protocolized. When noninvasive ventilation was used, duration, maximum inspiratory and expiratory pressures, and maximum Fio2 were recorded. When respiratory failure was treated with a high-flow nasal cannula, duration, maximum flow, and maximum Fio2 were recorded.
Patients needing reintubation within 72 hours were not randomized again for weaning, but the need for tracheostomy and the date of final liberation from mechanical ventilation were registered.
Outcomes
The primary outcome was successful extubation, defined as remaining free of invasive mechanical ventilation 72 hours after the first SBT.
Secondary outcomes were rate of reintubation among patients who were extubated after the SBT; intensive care unit and hospital lengths of stay; and hospital and 90-day mortality.
Exploratory outcomes were time to reintubation and reasons for reintubation, incidence of tracheostomy, and use of noninvasive ventilation and high-flow nasal cannula as prophylaxis against postextubation respiratory failure and to treat it.
Post hoc outcomes were intensive care unit mortality, Borg Dyspnea Scale score at the end of the SBT, patients’ confidence in their ability to breathe without the ventilator, and arterial blood analysis after successful SBT.
Statistical Analysis
Based on previous studies,8,9 a successful extubation rate of 75% and an absolute increase in successful extubation of 7% were expected. Thus, the required sample for an α=.05 and a power of 80% was estimated to be 540 patients in each group.
A prespecified interim analysis was performed when 500 patients were enrolled. The results showed a nonsignificant difference in primary outcome between groups. For this reason, the investigators decided to complete the estimated sample enrollment.
All patients were analyzed in the group to which they were randomized using the intention-to-treat principle, with no exclusion after randomization. Patients extubated outside of protocol were analyzed as having a failed SBT. No participants were excluded from main or secondary analyses because of missing or incomplete data. Reintubation was recorded only among patients who completed the trial.
Categorical variables are presented as absolute and relative frequencies. Continuous variables are summarized as medians and interquartile ranges (IQRs) for nonnormal distributions. The Mann-Whitney U was used for nonparametric continuous variables. To compare categorical variables, the χ2 test was used, except when expected frequencies in contingency tables were less than 5, in which case the Fisher exact test or the Monte Carlo method was used.
Time-to-event outcomes were analyzed with Kaplan-Meier curves and compared by log-rank test. For the time-to-event outcome of 72-hour successful extubation, deaths occurring before 72 hours were introduced in the survival analysis as censored data. Event or censored times for all patients were calculated from the time of randomization. Crude hazard ratios and 95% confidence intervals were calculated using a univariable Cox proportional regression model to estimate the effect size of randomization group. Proportionality of hazards was verified by examining Schoenfeld residual plots.
A post hoc random-effects multilevel logistic regression model was used to determine variables associated with 72-hour successful extubation, taking into account the effect of hospital. Patient characteristics that were associated with 72-hour successful extubation in the bivariable analysis were introduced in the random-effects multilevel logistic regression model as first-level variables and hospital as a second-level variable (random effect). Odds ratios (ORs) and median ORs with 95% confidence intervals were used to measure the association between each covariate and 72-hour successful extubation. The median OR is a measure of the variation between rates of 72-hour successful extubation at different hospitals that is unexplained by the modeled risk factors; it is defined as the median of the set of ORs that could be obtained by comparing 2 patients with identical patient-level characteristics from 2 randomly chosen hospitals. Covariates were introduced in the random-effects multilevel logistic regression model using a researcher-controlled backward exclusion strategy.
Post hoc analyses were performed for primary, secondary, exploratory, and post hoc outcomes among the following populations: patients extubated after the first SBT, patients extubated outside of protocol, patients treated per protocol, and several subgroups defined by baseline demographic characteristics. Effect sizes were evaluated by computing absolute risk differences with 95% confidence intervals for binary outcomes and differences in means with 95% confidence intervals for continuous outcomes. Figures were plotted for unadjusted risk ratios and 95% confidence intervals in the subgroup analysis by age; days of mechanical ventilation; Acute Physiology and Chronic Health Evaluation (APACHE) II score; chronic obstructive pulmonary disease (COPD); and medical, surgical, or trauma admission. No tests for interaction were conducted for the subgroup analyses.
A 2-sided α=.05 was considered statistically significant. Data were analyzed using SPSS version 22 (IBM Corp) and Stata version 14 (StataCorp). Subgroup analysis graphs were generated using R version 3.5.2 (R Foundation for Statistical Computing). There was no adjustment for multiple comparisons. Therefore, the results of the subgroup analyses and the analyses for secondary and exploratory outcomes should be interpreted as exploratory.
Results
Study Participants
Figure 1 shows participant flow through the trial. During the study period, 2649 patients received mechanical ventilation for at least 24 hours in the participating intensive care units; 1501 of these fulfilled the inclusion criteria, and 1153 were included in the study; 578 patients were randomized to undergo a 2-hour T-piece SBT and 575 patients were randomized to undergo a 30-minute SBT with 8-cm H2O PSV). The 2 groups were similar in age, sex, APACHE II score on admission, reason for intensive care unit admission, and length of mechanical ventilation before the SBT (Table 1). No patients were lost to follow-up.
Figure 1.
Flow of Participants in a Trial of Pressure Support vs T-Piece Ventilation Strategies for SBTs
SBT indicates spontaneous breathing trial.
Table 1.
Baseline Participant Characteristicsa
| Characteristics | 30-min PSV SBT (n = 575) | 2-h T-Piece SBT (n = 578) |
|---|---|---|
| Age, median (IQR), y | 65 (52-75) | 63 (53-73) |
| Sex | ||
| Men | 352 (61.2) | 373 (64.5) |
| Women | 223 (38.8) | 205 (35.5) |
| APACHE II score, median (IQR)b | 16 (11-22) | 16 (11-22) |
| Comorbidity | ||
| Cardiovascular disease | 146 (25.4) | 162 (28.0) |
| Diabetes mellitusc | 123 (22.0) | 147 (25.8) |
| Chronic obstructive pulmonary disease | 110 (19.1) | 118 (20.4) |
| Neurological disease | 107 (18.6) | 99 (17.1) |
| Cancer | 87 (15.1) | 94 (16.3) |
| Renal disease | 76 (13.2) | 68 (11.8) |
| Liver disease | 64 (11.1) | 63 (10.9) |
| Reason for admission | ||
| Medical, nonrespiratory | 215 (37.4) | 206 (35.6) |
| Medical, respiratory | 189 (32.9) | 190 (32.9) |
| Emergency surgery | 105 (18.3) | 113 (19.6) |
| Planned surgery | 35 (6.1) | 29 (5.0) |
| Trauma | 31 (5) | 40 (6.9) |
| Length of mechanical ventilation before SBT, median (IQR), d | 4 (2-8) | 4 (2-8) |
| Reconnection to ventilator before extubationd | 145 (25.2) | 158 (27.3) |
| Prophylactic noninvasive ventilation after extubationd | 51 (8.9) | 34 (5.9) |
| Prophylactic high-flow nasal cannula after extubationd | 91 (15.8) | 74 (12.8) |
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Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; IQR, interquartile range; PSV, pressure support ventilation; SBT, spontaneous breathing trial.
aData are expressed as No. (%) of participants unless otherwise indicated.
bData were missing for 8 patients in the 2-hour T-piece SBT group and for 15 patients in the 30-minute PSV SBT group.
cThe APACHE II score ranges from 0 to 71, with higher scores indicating higher mortality risk. A patient with a score of 16 has an estimated mortality risk of 25%.
dAttending physicians decided on the extubation strategy (reconnection to ventilator and prophylactic noninvasive ventilation or high-flow nasal cannula) prior to randomization.
Primary Outcome
Successful extubation, defined as remaining free of mechanical ventilation 72 hours after the SBT, occurred in 473 patients (82.3%) in the PSV group and 428 patients (74%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13%) (Table 2).
Table 2.
Primary, Secondary, Exploratory, and Post Hoc Outcomes of Patients Who Underwent a 2-Hour T-Piece SBT or a 30-Minute PSV SBTa
| Outcomes | 30-min PSV SBT (n = 575) | 2-h T-Piece SBT (n = 578) | Difference, PSV SBT Minus T-Piece SBT (95% CI)b | P Value |
|---|---|---|---|---|
| Primary Outcome | ||||
| Successful extubation, No. (%)c | 473 (82.3) | 428 (74.0) | 8.2 (3.4 to 13.0) | .001 |
| Secondary Outcomes | ||||
| Extubation after first SBT, No. (%) | 532 (92.5) | 486 (84.1) | 8.4 (4.7 to 12.1) | <.001 |
| Reintubation within 72 h, No. (%)d | 59 (11.1) | 58 (11.9) | −0.8 (−4.8 to 3.1) | .63 |
| ICU length of stay, median (IQR), d | 9 (5-17) | 10 (5-17) | −0.3 (−1.7 to 1.1) | .69 |
| Hospital length of stay, median (IQR), d | 24 (15-40) | 24 (15-39) | 1.3 (−2.2 to 4.9) | .45 |
| Hospital mortality, No. (%) | 60 (10.4) | 86 (14.9) | −4.4 (−8.3 to −0.6) | .02 |
| 90-Day mortality, No. (%) | 76 (13.2) | 100 (17.3) | −4.1 (−8.2 to 0.01) | .04 |
| Exploratory Outcome | ||||
| Tracheostomy, No. (%) | 41 (7.1) | 50 (8.7) | −1.5 (−4.6 to 1.6) | .38 |
| Post Hoc Outcome | ||||
| ICU mortality, No. (%) | 29 (5.0) | 38 (6.6) | −1.5 (−4.2 to 1.1) | .26 |
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Abbreviations: ICU, intensive care unit; IQR, interquartile range; PSV, pressure support ventilation; SBT, spontaneous breathing trial.
aNo patients were lost to follow-up.
bDifferences were calculated as absolute risk differences for successful extubation, extubated after first SBT, reintubation within 72 hours, mortality, and tracheostomy and as difference in means for length of stay.
cDefined as remaining free of mechanical ventilation for 72 hours after first SBT.
dAmong patients extubated after first SBT.
The Kaplan-Meier curves show a significant difference, with a higher successful extubation rate in the PSV group (hazard ratio, 1.54; 95% CI, 1.19-1.97; P < .001]) (Figure 2).
Figure 2.
Probability of Successful Extubation After First SBT in Each Group
PSV indicates pressure support ventilation; SBT, spontaneous breathing trial. Successful extubation was defined as remaining free of mechanical ventilation for 72 hours after first SBT.
Secondary Outcomes
After the first SBT, 486 patients (92.5%) undergoing the 30-minute PSV SBT and 532 patients (84.1%) undergoing the 2-hour T-piece SBT were extubated (difference, 8.4%; 95% CI, 4.7%-12.1%; P < .001). Reintubation within 72 hours occurred in 59 patients (11.1%) in the PSV group and in 58 patients (11.9%) in the T-piece group (difference, −0.8%; 95% CI, −4.8% to −3.1%; P = .63) (Table 2). The median intensive care unit length of stay was 9 days (IQR, 5-17) in the PSV group and 10 days (IQR, 5-17) in the T-piece group (mean difference, −0.3 days; 95% CI, −1.7 to 1.1 days; P = .69). The median hospital length of stay was 24 days (IQR, 15-40) in the PSV group and 24 days (IQR, 15-39) in the T-piece group (mean difference, 1.3 days; 95% CI, −2.2 to 4.9 days; P = .45). Hospital mortality rates were 10.4% (n = 60) in the PSV group and 14.9% (n = 86) in the T-piece group (difference, −4.4%; 95% CI, −8.3% to −0.6%; P = .02) (Table 2).
Mortality at 90 days was significantly lower in the PSV group (13.2%) compared with the T-piece group (17.3%) (difference, −4.1% [95% CI, −8.2% to 0.01%; P = .04]; hazard ratio, 0.74 [95% CI, 0.55-0.99]) (eFigure 1 in Supplement 2).
Exploratory Outcomes
In the T-piece group, 58 patients required reintubation, and in the PSV group, 59 patients required reintubation. The median time to reintubation was 23 hours (IQR, 9-45 hours) in the PSV group and 24.5 hours (IQR, 9.8-44 hours) in the T-piece group (mean difference, 0.53 hours; 95% CI, −7.2 to 8.3 hours). Reasons for reintubation were not significantly different in the 2 groups; excessive work of breathing was the most common in both groups, followed by inability to clear secretions and hypoxemia (Table 3). Four patients (3 in the T-piece group and 1 in the PSV group) had cardiac arrest within 72 hours after extubation.
Table 3.
Exploratory Outcomes: Reasons for Reintubation
| Outcomes | 30-min PSV SBT (n = 59) | 2-h T-Piece SBT (n = 58) | Difference, PSV SBT Minus T-Piece SBT (95% CI)a |
|---|---|---|---|
| Time to reintubation, median (IQR), h | 23.0 (9.0-45.0) | 24.5 (9.8-44.0) | 0.53 (−7.2 to 8.3) |
| Reasons for reintubation, No. (%)b | |||
| Excessive work of breathing | 23 (39.0) | 24 (41.4) | −2.4 (−20.2 to 15.4) |
| Difficulty managing secretions | 19 (32.2) | 18 (31.0) | 1.2 (−15.7 to 18.0) |
| Refractory hypoxemia | 14 (23.7) | 11 (19.0) | 4.8 (−10.1 to 19.6) |
| Level of consciousness | 6 (10.2) | 11 (19.0) | −8.7 (−21.5 to 3.9) |
| Airway obstruction | 6 (10.2) | 8 (13.8) | −3.6 (−15.4 to 8.1) |
| Surgery | 4 (6.8) | 4 (6.9) | −0.1 (−9.2 to 9.0) |
| Cardiac arrest | 1 (1.7) | 3 (5.1) | −3.4 (−10.0 to 3.1) |
| Agitation | 4 (6.8) | 3 (5.2) | 1.6 (−7.0 to 10.2) |
| Aspiration | 1 (1.7) | 3 (5.2) | −3.5 (−10.1 to 3.1) |
| Bradycardia (heart rate <50/min) | 0 | 1 (1.7) | −1.7 (−5.1 to 1.6) |
| Hemodynamic shock | 1 (1.7) | 1 (1.7) | −0.0 (−4.7 to 4.7) |
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Abbreviations: IQR, interquartile range; PSV, pressure support ventilation; SBT, spontaneous breathing trial.
aDifferences were calculated as absolute risk differences for reasons for reintubation and as difference in means for time to reintubation.
bPatients could have more than 1 reason for reintubation.
Among reintubated patients, tracheostomy was performed in 41 patients (7.1%) in the PSV group and in 50 patients (8.7%) in the T-piece group (difference, −1.5%; 95% CI, −4.6% to 1.6%) (Table 2).
Before randomization, physicians had to decide on an extubation strategy (standard oxygen, reconnection to the ventilator for a 1-hour rest after the SBT, and/or prophylactic noninvasive ventilation or high-flow nasal cannula after extubation). The use of each treatment was not significantly different in both groups (Table 1).
Postextubation respiratory failure occurred in 110 patients (20.7%) in the PSV group and in 103 patients (21.2%) in the T-piece group (difference, −0.5%; 95% CI, −5.5% to 4.5%). Among these 213 patients, 117 (11.4%) were reintubated. Respiratory failure was treated by noninvasive ventilation in 91 (42.7%) patients, and 36 (39.6%) of these patients were reintubated. Respiratory failure was treated by high-flow nasal cannula in 47 (22.1%) patients, and 20 (42.6%) of these patients were reintubated. The remaining 75 patients (35.2%) received standard oxygen, and 61 (81.3%) of these patients were reintubated.
Post Hoc Analysis
In patients extubated after the first SBT, the 72-hour successful extubation rate was not significantly different between groups (eTable 1 in Supplement 2).
The post hoc analysis showed that 29 patients (5%) in the PSV group and 38 patients (6.6%) in the T-piece group died in the intensive care unit (difference, −1.5%; 95% CI, −4.5% to 1.1%).
Multilevel logistic regression found a hospital-level random effect on successful extubation (median OR, 1.56; P < .001). After adjustment for this random effect, the effect of the PSV persisted (adjusted OR, 1.64; 95% CI, 1.23-2.20; P = .001). Other patient characteristics independently associated with 72-hour successful extubation were length of mechanical ventilation before SBT (adjusted OR, 0.96; 95% CI, 0.94-0.98; P < .001) and COPD (adjusted OR, 0.62; 95% CI, 0.44-0.87; P = .006). Multilevel logistic regression did not find an association between hospital and risk of reintubation (median OR, 1.19; P = .30). After adjustment for this random effect, reintubation in the PSV group was not significantly different than in the T-piece group (adjusted OR, 0.92; 95% CI, 0.62-1.35; P = .67). The only variable independently associated with reintubation was length of mechanical ventilation before SBT (adjusted OR, 1.04; 95% CI, 1.01-1.07; P = .03).
A total of 36 patients (3.1%) in whom the SBT failed were extubated, either because of physician decision or self-extubation during the SBT (eTable 2 in Supplement 2). The results of the per-protocol analysis were similar to those of the intention-to-treat analysis (eAppendix and eTable 3 in Supplement 2).
Subgroup analyses were generally consistent with the overall study findings (Figure 3; eFigures 2 and 3 in Supplement 2). eTables 4, 5, and 6 in Supplement 2 report post hoc analyses of Borg Dyspnea Scale scores at the end of the SBT, patients’ confidence in breathing without a ventilator, and blood gas analyses.
Figure 3.
Unadjusted Risk Ratios for Successful Extubation After First SBT in Predefined Subgroups
PSV indicates pressure support ventilation; SBT, spontaneous breathing trial; APACHE, Acute Physiology and Chronic Health Evaluation; COPD, chronic obstructive pulmonary disease. Successful extubation was defined as remaining free of mechanical ventilation for 72 hours after first SBT.
During the study, there were no severe adverse events attributable to the randomization group. The adverse events that occurred after extubation, such as difficulty managing secretions or excessive work of breathing, are inherent to critically ill patients.
Discussion
In this randomized trial of patients receiving mechanical ventilation, a 30-minute PSV-SBT resulted in a significantly higher rate of successful extubation than a 2-hour T-piece SBT without significantly increasing reintubation. The higher rate was related to more patients being extubated after the PSV-SBT, suggesting that a less demanding SBT better allows critically ill patients to demonstrated their ability to sustain breathing.
A recent meta-analysis concluded that breathing through a T piece requires the same amount of work as breathing after extubation, and the authors recommended that SBTs should be performed with T pieces because this approach better reflects the physiologic conditions after extubation.12 Supported by anecdotal reports, physicians may be concerned that some patients who breathe comfortably with low levels of PSV and/or positive end-expiratory pressure could develop respiratory failure immediately after extubation, which might even be followed by cardiac arrest.15 The results of this randomized trial designed to study extubation outcomes of opposing SBT strategies suggest that this concern may not be warranted. The current study found that the T-piece SBT was less well tolerated than the PSV SBT, although the work of breathing with the T piece may have been similar to breathing spontaneously. In patients who successfully completed the SBT, the reintubation rate was not significantly different in the 2 groups, and no imminent respiratory failure was observed after extubation from PSV. Moreover, the time to reintubation was about 24 hours in both groups, and the incidence of cardiac arrest was very low and even nominally higher in the T-piece group than in the PSV group.
Vallverdú et al16 showed that among patients in whom a 2-hour T-piece SBT failed, 64% of failures occurred in the first 30 minutes, 12% between 30 and 60 minutes, and 24% between 60 minutes and 2 hours. In a recent observational study including 352 patients who underwent an SBT with PSV, Liang et al17 sought to identify the characteristics of the 41 patients (11.6%) in whom a 120-minute SBT failed after successful completion of the first 30 minutes. Patients with SBT failures after 30 minutes were older, had more cardiopulmonary disease, had spent more time receiving mechanical ventilation before the SBT, and had undergone more previous SBTs. The authors suggested that patients with these characteristics might need a longer SBT to ensure that their ability to breathe is not overestimated. Nevertheless, it is unknown what the outcomes of these patients would have been if the SBT had been limited to 30 minutes. In the present study, the 30-minute PSV SBT was enough to check patients’ ability to breathe without increasing the rates of postextubation respiratory failure and reintubation.
Another finding related to tolerance of the 2 SBT approaches is that self-extubation during the SBT was more common in the T-piece group. Tolerance to SBTs in this trial may be compared with the studies in the late 1990s by Esteban et al8,9: patients’ tolerance to T-piece SBTs in the present study was better than in the first trial by Esteban et al (84% vs 78%) and similar to their second trial (84.6% vs 84.1%). Moreover, tolerance to the 30-minute T-piece SBT in the second trial by Esteban et al was worse than tolerance to the 30-minute PSV in the present study (87.7% vs 92.5%). However, patients in the studies by Esteban et al received longer mechanical ventilation before the SBT, and this could contribute to worse tolerance and a higher reintubation rate.
In a single-center study comparing a 2-hour T-piece SBT and a 2-hour PSV SBT, Matić et al18 found a higher rate of successful extubation with PSV than with a T piece (80% vs 73%), similar to the difference found in the present study despite a longer duration of the PSV SBT. This suggests that tolerance is not only about duration but also about the mode of SBT. Along the same lines, Ezingeard et al11 found that some patients who did not tolerate a T-piece SBT went on to tolerate a PSV SBT and had a reintubation rate similar to patients who underwent a PSV SBT without having attempted a T-piece SBT. Taken together with these studies, the results of the present study suggest that a T-piece SBT is not the best way to check a patient’s ability to breathe.
In this study, the reintubation rate was not significantly different between the 2 groups (about 11%), which is lower than the 17% in the first study by Esteban et al8 and similar to the 13% in their second study.9 Conversely, the reintubation rate was higher than in a study by Perren et al10 (9% for short SBTs and 4% for long SBTs), but that study’s single-center design and small sample size preclude direct comparison.
Logistic regression analysis showed that the 30-minute PSV SBT was associated with successful extubation, whereas longer duration of mechanical ventilation before the SBT as well as COPD were associated with extubation failure. However, only length of mechanical ventilation was significantly associated with reintubation. This result lends additional support to the idea that the concern that PSV SBTs increase risk of respiratory failure and reintubation may be exaggerated.
Hospital mortality and 90-day mortality were significantly higher in the T-piece group. This finding cannot be explained by the reintubation rate, days of mechanical ventilation after a failed SBT, APACHE II score at admission, or hospital length of stay, which were not significantly different between the 2 groups.
Limitations
This study has several limitations. First, prophylactic use of noninvasive ventilation and high-flow nasal cannula after extubation was not protocolized. In some cases, these approaches were routinely used based on recent studies, but in others, they were used only in patients with more comorbidities, such as heart failure or COPD, or more risk factors for extubation failure. For this reason, it is impossible to draw conclusions about the use of noninvasive ventilation and high-flow nasal cannula for postextubation respiratory failure.
Second, patients extubated outside of protocol, although few, could be expected to influence the main results, but the sensitivity analysis ruled out such bias (eTable 2 in Supplement 2).
Third, investigators and attending physicians were not blinded to treatment randomization group.
Conclusions
Among mechanically ventilated patients, an SBT consisting of 30 minutes of PSV, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for SBTs.
Notes
Supplement 1.
Trial Protocol
Click here for additional data file.(912K, pdf)
Supplement 2.
eTable 1. Primary, Secondary, Exploratory and Post Hoc Outcomes in Patients Extubated After the First Spontaneous Breathing Trial
eFigure 1. Probability of 90-Day Mortality According to Group Allocation
eTable 2. Primary, Secondary, Exploratory and Post Hoc Outcomes of Patients Who Underwent a Planned Extubation vs an Extubation Out-of-Protocol According to Group Allocation
eAppendix. Primary, Secondary, Exploratory and Post Hoc Outcomes, Per-Protocol Analysis
eTable 3. Primary, Secondary, Exploratory and Post Hoc Outcomes, Per-Protocol Analysis
eFigure 2. Unadjusted Risk Ratios (95%) for Patients Extubated After First SBT in Predefined Subgroups
eFigure 3. Unadjusted Risk Ratios (95%) for Reintubation in Predefined Subgroups
eTable 4. Patients’ Confidence in Their Ability to Breathe Without the Ventilator Among Patients Extubated After the First Spontaneous Breathing Trial
eTable 5. Borg Dyspnea Scale at the End of the Spontaneous Breathing Trial
eTable 6. Arterial Blood Analysis After Successful Spontaneous Breathing Trial
Click here for additional data file.(496K, pdf)
Supplement 3.
Data Sharing Statement
Click here for additional data file.(115K, pdf)
Notes
Section Editor: Derek C. Angus, MD, MPH,Associate Editor, JAMA (ude.cmpu@cdsugna).
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