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ORIGINAL ARTICLE

Effort to Breathe with Various Spontaneous Breathing

Trial Techniques
A Physiologic Meta-analysis
Michael C. Sklar1,2, Karen Burns2,3, Nuttapol Rittayamai4, Ashley Lanys2, Michela Rauseo2,5, Lu Chen2, Martin Dres2,6,
Guang-Qiang Chen2,7, Ewan C. Goligher3,8, Neill K. J. Adhikari3,9, Laurent Brochard2,3, and Jan O. Friedrich2,3
1
Department of Anesthesiology and 3Interdepartmental Division of Critical Care Medicine, University of Toronto, Ontario,
Canada; 2Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada; 4Department of
Medicine, Division of Respiratory Diseases and Tuberculosis, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok,
Thailand; 5Department of Anaesthesia and Intensive Care, University of Foggia, Foggia, Italy; 6Sorbonne Universités, UPMC Univ Paris
06, INSERM, UMRS_1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France; 7Department of Critical Care
Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 8Division of Respirology, Department of Medicine,
University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada; and 9Department of Critical Care Medicine, Sunnybrook
Health Sciences Centre, Toronto, Ontario, Canada
ORCID ID: 0000-0002-7512-1865 (L.C.).

Abstract (ratio of means [RoM], 0.70; 95% confidence interval [CI],

Rationale: Spontaneous breathing trials (SBTs) are designed to
simulate conditions after extubation, and it is essential to understand
the physiologic impact of different methods.
Objectives: We conducted a systematic review and pooled measures
reflecting patient respiratory effort among studies comparing SBT
methods in a meta-analysis.
Methods: We searched Medline, Excerpta Medica Database, and Web
of Science from inception to January 2016 to identify randomized and
nonrandomized clinical trials reporting physiologic measurements of
respiratory effort (pressure–time product) or work of breathing during at
least two SBT techniques. Secondary outcomes included the rapid shallow
breathing index (RSBI), and effort measured before and after extubation.
The quality of physiologic measurement and research design was
appraised for each study. Outcomes were analyzed using ratio of means.
Measurements and Main Results: Among 4,138 citations,
16 studies (n = 239) were included. Compared with T-piece,
pressure support ventilation significantly reduced work by 30%
0.57–0.86), effort by 30% (RoM, 0.70; 95% CI, 0.60–0.82), and RSBI
by 20% (RoM, 0.80; 95% CI, 0.75–0.86). Continuous positive airway
pressure had significantly lower pressure-time product by 18%
(RoM, 0.82; 95% CI, 0.68–0.999) compared with T-piece, and
reduced RSBI by 16% (RoM, 0.84; 95% CI, 0.74–0.95). Studies
comparing SBTs with the postextubation period demonstrated
that pressure support induced significantly lower effort and RSBI;
T-piece reduced effort, but not the work, compared with
postextubation. Work, effort, and RSBI measured while
intubated on the ventilator with continuous positive airway
pressure of 0 cm H2O were no different than extubation.
Conclusions: Pressure support reduces respiratory effort compared
with T-piece. Continuous positive airway pressure of 0 cm H2O
and T-piece more accurately reflect the physiologic conditions after
extubation.
Keywords: mechanical ventilation; weaning; work of breathing;
pressure time product

( Received in original form July 1, 2016; accepted in final form October 19, 2016 )
Author Contributions: M.C.S. developed study design, performed data abstraction and analysis, and wrote the manuscript. K.B. and E.C.G. developed study
design, reviewed the manuscript, and were responsible for final approval of the manuscript. N.R., A.L., M.R., M.D., and G.-Q.C. developed study design and
performed data abstraction and analysis. L.C. developed study design, performed data abstraction and analysis, and developed physiologic quality criteria.
N.K.J.A. and L.B. developed study design, reviewed the manuscript, developed physiologic quality criteria, and were responsible for final approval of the
manuscript. J.O.F. developed study design, reviewed the manuscript, performed statistical analysis, and was responsible for final approval of the manuscript.
Correspondence and requests for reprints should be addressed to Laurent Brochard, M.D., 209 Victoria Street, Room 4-080, Toronto, ON M5B 1T8 Canada.
E-mail: brochardl@smh.ca
This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org
Am J Respir Crit Care Med Vol 195, Iss 11, pp 1477–1485, Jun 1, 2017
Copyright © 2017 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.201607-1338OC on October 21, 2016
Internet address: www.atsjournals.org

Sklar, Burns, Rittayamai, et al.: Physiologic Measures of Respiratory Effort during SBTs 1477

At a Glance Commentary
Scientific Knowledge on the
Subject: Clinical studies of various
spontaneous breathing trial (SBT)
techniques have not demonstrated
differences in clinical endpoints of
weaning success, intubation rates,
pneumonia, length of intensive care
unit stay, or mortality. A better
understanding of the physiologic
impact of different SBT techniques
might help clinicians to select the SBT
technique for an individual patient.
What This Study Adds to the
Field: SBT techniques are associated
with significantly different levels of
patient respiratory effort. Pressure
support significantly reduces work of
breathing and pressure–time product
compared with other SBTs, but T-piece
and being on the ventilator with zero
pressure support or positive end-
expiratory pressure represent similar
respiratory physiology compared with
postextubation values.
Mechanical ventilation is often required
in patients with critical illness, but after
recovery from the acute illness, several
problems can impair the successful
separation of the patient from the ventilator (1).
A spontaneous breathing trial (SBT) is
most often performed to assess the ability
of a patient to sustain spontaneous
breathing when extubated. Several methods
are used to conduct so-called SBTs that
differ in the amount and type of support
provided in inspiration and expiration (see
the online supplement) supposedly to
compensate part of the equipment. SBTs
with low ventilatory support include
pressure support ventilation (PSV) usually
up to 5–7 cm H2O with or without
positive end-expiratory pressure (PEEP),
continuous positive airway pressure
(CPAP) alone (i.e., no inspiratory pressure
support), or automatic tube compensation.
T-piece trials provide no ventilatory
support. Similarly, spontaneous breathing
on the ventilator with PSV and/or CPAP all
set at 0 cmH20 also provides no ventilatory
support.
How these different SBT methods affect
respiratory physiology (2–4) and the SBT
type that most closely mimics extubation
1478 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 11 | June 1 2017
conditions have been debated (2, 4).
Bedside measurements of respiratory effort
including the work of breathing (WOB) (5),
the pressure time product (PTP) (6), or
surrogates for effort, such as airway
occlusion pressure at 100 milliseconds
(P0.1) (7), the rapid shallow breathing index
(RSBI) (8), and diaphragmatic electrical
activity (9), may inform identification of
preferred SBT techniques (see the online
supplement).
Physiologic studies of patient effort
under various SBT methods have been
performed (10–16) but the results have
not been taken into account in guidelines
or recommendations (17), and ongoing
controversies on this topic are reflected by a
diversity of practices. Understanding the
physiologic effects of different SBT methods
is highly relevant to selecting the optimal
SBT method, because the relationship
between SBT methods and clinical outcomes
is highly confounded by competing clinical
issues. Indeed, the decision to extubate
incorporates assessment of the ability to
clear secretions and to keep the airway
protected, general trends of physiologic
parameters, goals of care, level of
consciousness, and by organizational factors.
These factors confound the relationship
between SBT results and clinical outcomes,
but do not affect the relationship between
SBT results and physiologic parameters
(i.e., WOB and inspiratory effort). Therefore,
it is important to separate the physiologic
outcomes from clinical outcomes to
correctly interpret the breadth of data.
Furthermore, extubation failure is rare,
making it difficult to have clinical studies
powered sufficiently to test the influence
of different techniques on extubation
outcome (18, 19).
To summarize and disseminate the
physiologic data, we conducted a systematic
review and meta-analysis of previously
published physiologic studies. Meta-analysis
summarizes a large amount of physiologic
research conducted over several decades
into Forest plots for visual analysis. In
addition, meta-analysis features strong
methodologic characteristics: (1) it
incorporates a systematic search of trials;
(2) the weighting of the trials is model-
based (not arbitrary); and (3) there is a way
to properly assess publication bias.
We conducted a systematic review of
the literature to determine the impact of SBT
technique on inspiratory effort in critically
ill patients.
ORIGINAL ARTICLE
Methods
A complete version of the methods is
presented in the online supplement.
Search Strategy
We systematically searched electronic
databases including Medline (1946 to Week 5
of 2016), Excerpta Medica Database (1947
to Week 5 of 2016), and Web of Science
Conference Proceedings (inception to
January 2016) for articles and abstracts of
randomized controlled trials (RCTs) and
nonrandomized studies comparing at
least two SBT techniques that reported a
physiologic measure evaluating WOB or the
PTP, or a surrogate. We also searched the
bibliographies of included studies and review
articles. In addition, we searched a clinical
trials registry (http://clinicaltrials.gov) for
unpublished and ongoing studies evaluating
physiologic parameters during SBTs and
hand searched conference proceedings from
five conferences (American College of Chest
Physicians, European Society of Intensive
Care Medicine, American Thoracic Society,
International Symposium on Intensive Care
and Emergency Medicine, and the Society of
Critical Care Medicine) from 2010 to June
2015. No language restrictions were applied.
Inclusion and Noninclusion Criteria
We included RCTs or nonrandomized
studies if at least two adult (.18 yr) patients
underwent at least two different SBT
methods and authors reported at least one of
our primary outcomes of WOB or PTP. Our
secondary outcomes included P0.1, electrical
activity of the diaphragm (see online
supplement), and the RSBI. In addition, we
included studies reporting on at least one
physiologic outcome (WOB or PTP) if it was
measured before and after extubation. We
excluded studies evaluating SBT methods in
patients with tracheotomy and in patients
receiving noninvasive ventilation.
Data Analysis
All SBTs using PSV with settings greater
than 0 cm H2O were combined into a single
group (PSV SBT), regardless of applied
PEEP, the level of which was not always
specified. When reported, we combined
groups of patients attached to the ventilator
on PSV or CPAP set at 0 cm H2O
(PSV0/CPAP0). Primary and secondary
continuous outcomes were pooled
comparing alternative SBT methods and
ORIGINAL ARTICLE
preextubation and postextubation
measurements using ratio of means (RoM),
as described previously (20). Trial results
were pooled with RoM using the generic
inverse variance weighting method in
Review Manager (RevMan version 5.2;
Cochrane Collaboration, Oxford, UK) as
previously described (20) with a two-sided
significance level of 0.05.
Results
Search Results
We identified 4,138 unique citations
(Figure 1). We reviewed the full text of
35 studies to ascertain eligibility. Of these,
15 studies met our inclusion criteria. One
additional study was identified (21) and
retrieved by a senior author (L.B.). In total,
16 studies (239 patients) were included in
this systematic review (Table 1). We did not
identify any trial on clinicaltrials.gov.
Characteristics of Included Studies
We identified one parallel group RCT (22),
eight randomized crossover studies (2, 3,
21, 23–27), and seven nonrandomized
crossover studies involving sequential
interventions applied in a nonrandom
order (4, 28–33). One crossover RCT
(n = 9 patients) included exclusively patients
Identification
Records identified through
database searching
(n = 4,138)
Screening
Records after duplicates removed
(n = 35)
Eligibility
Full-text articles assessed for
eligibility
(n = 35)
Included
Studies included in systematic
review
(n = 16)
Figure 1. PRISMA flow diagram of the study selection process. PRISMA = Preferred Reporting Items
for Systematic Reviews and Meta-Analyses; SBT = spontaneous breathing trial.
Sklar, Burns, Rittayamai, et al.: Physiologic Measures of Respiratory Effort during SBTs
with chronic obstructive pulmonary disease
(25), another enrolled 20 patients with
hypoxemic respiratory failure (3), and the
remaining involved patients with mixed
respiratory failure (2, 21, 23, 24, 26, 27).
Three randomized crossover studies (3, 24, 25)
and three nonrandomized crossover
studies involving sequential interventions
(31–33) compared more than two SBT
methods. Six studies had an intervention
group in which patients were connected to
the ventilator with either PSV or CPAP set
at 0 cm H2O (PSV0/CPAP0) (21, 24, 25, 28,
29, 31). Six studies provided physiologic
measurements preextubation and
postextubation (3, 4, 21, 28, 29, 31). For two
studies (2, 21), we combined two PSV SBTs
into a single group for analysis (i.e., PSV 7
with and without PEEP were combined to
make a single group for each study).
Quality Assessment
Methodologic risk of bias. The parallel
group RCT (22) was deemed to be of
unclear risk of bias because it was
unblinded. Two of the eight randomized
crossover trials (2, 3, 21, 23–27) were
deemed at high risk of bias because they
included patients who developed
respiratory distress postextubation (3, 21).
Two randomized crossover trials (26, 27)
# records excluded
(n = 4,103)
# records excluded
(n = 20)
Pediatric patient population (< 18): 2
Weaning study: 6
Tracheostomy patients: 3
Inaccessible articles: 2
No primary outcome reported: 4
Only 1 SBT technique without
extubation: 2
Use of noninvasive ventilation: 1
# manuscripts under
review at time the
search was performed
(n = 1)
published in abstract form only were
categorized as unclear risk of bias. Two more
studies were graded as unclear risk of bias
because a washout time was not provided
(24, 25) and the final randomized crossover
study was graded as unclear risk of bias
because details pertaining to the recording
of outcomes was not explicit (23). The seven
nonrandomized studies (4, 28–33) were all
deemed high risk under the treatment order
category because of nonrandomization. Two
of the seven studies were deemed overall
high risk of bias because one study had no
washout period (30) and one study included
patients who failed extubation (29). The
remaining five nonrandomized studies (4, 28,
31–33) were considered unclear risk of bias
(see Table E1 in the online supplement).
Physiologic risk of bias. All studies
used either Campbell diagram or Bicore
pulmonary monitor. Also, all but three studies
were deemed to be at low risk of physiologic
bias because they measured and accounted
for intrinsic PEEP (PEEPi), separately
measured chest wall compliance, and
included the Baydur maneuver (34). The
remaining three studies (3, 22, 23) did
not measure or account for chest wall
compliance (one also failed to report a
Baydur maneuver) and were deemed to be
high risk of physiologic bias (see Table E2)
(3). A specific sensitivity analysis was
therefore performed without these low or
unclear physiologic quality studies.
Effect of Interventions
Primary Outcomes
Compared with T-piece (Figures 2 and 3),
PSV SBTs were associated with 30% lower
WOB (RoM, 0.70; 95% confidence interval
[CI], 0.57–0.86; 10 studies; n = 142 patients)
and PTP (RoM, 0.70; 95% CI, 0.60–0.82;
nine studies; n = 129 patients). PSV SBTs
compared with CPAP SBTs (Figure 2; see
Figure E1) showed similar WOB (RoM,
0.91; 95% CI, 0.70–1.18; n = 154 patients)
and PTP (RoM, 0.96; 95% CI, 0.79–1.18;
n = 156 patients). CPAP (Figure 2; see
Figure E2) compared with T-piece showed
nonsignificantly lower WOB (RoM, 0.87;
95% CI, 0.74–1.02; n = 136 patients) but
18% lower PTP, which was statistically
significant (RoM, 0.82; 95% CI, 0.68–0.999;
P = 0.049; n = 78 patients) (see Table E3).
Similarly, compared with
PSV0/CPAP0, PSV SBTs showed 49%
lower WOB (RoM, 0.51; 95% CI, 0.42–0.62;
1479
 ORIGINAL ARTICLE

Table 1. Characteristics of the Studies Included in Systematic Review with SBT Type, Sample Size, and Outcome Data

SBT Duration
Reference Patients SBT Modalities (min) Outcomes

Randomized parallel group trials

Koh et al. 2000 (22) n = 22 per arm; PSV8 vs. TP 30 (PSV), WOB, PTP, P0.1, f/Vt
mixed 60 (TP)
Randomized crossover trials
Cabello et al. 2010 (2) n = 14; mixed PSV7 1 PEEP5 vs. PSV7 1 PEEP0 vs. TP 60 WOB, PTP, f/ Vt
Mehta et al. 2000 (3) n = 20; hypoxemic PSV5 vs. CPAP5 vs. TP vs. extubation 15 WOB, PTP, P0.1, f/ Vt
Ferreira et al. 2012 (26) n = 7; ND PSV5 1 PEEP5 vs. NAVA 1 PEEP5 30 Eadi
Ferreira et al. 2014 (27) n = 17; ND PSV5 1 PEEP5 vs. NAVA 1 PEEP5 ND Eadi
Kuhlen et al. 2003 (23) n = 12; mixed PSV7 1 PEEP7 vs. ATC vs. TP 30 WOB, PTP, P0.1, f/ Vt
Sassoon et al. 1991 (24) n = 10; mixed PSV5 vs. CPAP5 vs. CPAP0 vs. TP 30 PTP, f/ Vt
Sassoon et al. 1992 (25) n = 9; mixed PSV5 vs. CPAP8 vs. CPAP0 15 WOB
Mahul et al. 2016 (21) n = 17; obese, PSV7 1 PEEP7 vs. PSV0 1 PEEP7 vs. 15 WOB, PTP, f/ Vt
mixed PSV 7 1 ZEEP vs. PSV 0 1 ZEEP vs.
TP vs. extubation
Nonrandomized crossover studies
Straus et al. 1998 (4) n = 14; mixed TP vs. extubation 60 WOB, f/ Vt
Muttini et al. 2015 (30) n = 18; mixed CPAP vs. NAVA 15–30 (CPAP) Eadi
20 (NAVA)
Brochard et al. 1991 (28) n = 11; mixed PSV4 vs. PSV0 vs. TP vs. extubation 30 WOB, f/ Vt
Ishaaya et al. 1995 (29) n = 8; mixed PSV6 vs. PSV0 vs. TP vs. extubation 2 WOB, PTP, f/ Vt
Nathan et al. 1993 (31) n = 7; mixed PSV7 vs. CPAP0 vs. TP vs. extubation ND WOB, PTP, f/ Vt
Petros et al. 1993 (32) n = 8; mixed PSV10 vs. PSV5 vs. CPAP5 vs. TP 30 WOB, PTP, P0.1, f/ Vt
Patel et al. 1996 (33) n = 23; mixed PSV5 vs. CPAP5 6 demand valve vs. TP 5 WOB, PTP, f/ Vt

Definition of abbreviations: ATC = automatic tube compensation; CPAP = continuous positive airway pressure; Eadi = electrical activity of the diaphragm
(mV); f/ Vt = respiratory rate/tidal volume (breaths/min*L21, rapid shallow breathing index); NAVA = neurally adjusted ventillatory assist; ND = not described;
P0.1 = airway pressure drop in 100 ms (cm H2O); PEEP = positive end-expiratory pressure; PSV = pressure support ventilation; PTP = pressure time
product (cm H2O*s*min21); SBT = spontaneous breathing trial; TP = T-piece; WOB = work of breathing (units J/L); ZEEP = zero end-expiratory pressure.
For Cabello et al. (2), we combined the PSV7/PEEP5 and PSV7/ZEEP groups with weighted means and SD into a single group for analysis. Similarly, for
Mahul et al. (21), we combined the PSV7/PEEP7 and PSV7/ZEEP groups into a single group with weighted means and SD for analysis. In the study by
Patel et al. (33), the CPAP with demand valve group was not analyzed.

n = 52 patients) and 42% lower PTP (RoM,
0.58; 95% CI, 0.40–0.83; n = 42 patients)
(Figures 2 and 4), and CPAP SBTs also
showed lower WOB (RoM, 0.77; 95% CI,
0.61–0.97; n = 26 patients) and PTP (RoM,
0.74; 95% CI, 0.65–0.84; n = 27 patients)
(Figure 2; see Figure E3) but by a lesser
amount than PSV. In contrast, T-piece
showed similar WOB (RoM, 1.09; 95% CI,
0.96–1.24; n = 43 patients) and PTP (RoM,
1.06; 95% CI, 0.86–1.31; n = 42 patients)
compared with PSV0/CPAP0 (Figure 2; see
Figure E4). However, it should be noted that
each of these pooled results of PSV0/CPAP0
patients were based on a small number of
studies (2–5) enrolling small numbers of
patients (n = 26–52 patients) (Figures 2 and 4;
see Figures E3 and E4, Table E3).
Secondary Outcomes
RSBI. Compared with T-piece (Figure 2; see
Figure E5), RSBI for PSV SBTs was 20%
lower (RoM, 0.80; 95% CI, 0.75–0.86; n = 154
patients) and CPAP SBTs 16% lower (RoM,
0.84; 95% CI, 0.74–0.95; n = 55 patients).
PSV SBTs also exhibited 12% lower RSBI
compared with PSV0/CPAP0 (RoM, 0.88;
95% CI, 0.80–0.97; n = 53 patients), but
similar RSBI compared with CPAP SBTs
(RoM, 0.95; 95% CI, 0.84–1.07; n = 55
patients) and automatic tube compensation
SBTs (RoM, 0.81; 95% CI, 0.68–1.05; n = 12
patients) (Figure 2; see Figure E5). CPAP
SBTs also showed similar RSBI compared
with PSV0/CPAP0 (RoM, 0.87; 95% CI,
0.73–1.05; n = 27 patients) (Figure 2; see
Figure E5). Compared with T-piece, RSBI for
PSV0/CPAP0 was 10% lower (RoM, 0.90;
95% CI, 0.82–0.98; n = 53 patients), but RSBI
for automatic tube compensation SBTs was
no different (RoM, 0.84; 95% CI, 0.68–1.05;
n = 12 patients) (see Figure E5, Table E3).
Effort before and after extubation.
Compared with extubation, PSV SBTs
showed 46% lower WOB (RoM, 0.54; 95%
CI, 0.38–0.78; n = 63 patients), 49% lower
PTP (RoM, 0.51; 95% CI, 0.44–0.59; n = 52
patients), and 23% lower RSBI (RoM, 0.77;
95% CI, 0.69–0.86; n = 63 patients) (Figures
2 and 5). Compared with extubation, CPAP
SBTs also showed 25% lower WOB (RoM,
0.75; 95% CI, 0.64–0.87; n = 37 patients),
32% lower PTP (RoM, 0.68; 95% CI,
0.60–0.78; n = 37 patients), and 22% lower
RSBI (RoM, 0.78; 95% CI, 0.71–0.86; n = 37
patients) (Figure 2; see Figure E8). For
T-piece compared with extubation, there was
only a 23% lower PTP (RoM, 0.77; 95% CI,
0.64–0.94; n = 52 patients) but no lower
WOB (RoM, 0.86; 95% CI, 0.72–1.02; n = 77
patients) or RSBI (RoM, 0.97; 95% CI,
0.88–1.08; n = 77 patients) (Figures 2 and 6).
PSV0/CPAP0 showed similar WOB (RoM,
0.99; 95% CI, 0.84–1.17; n = 43 patients) and
PTP (RoM, 0.95; 95% CI, 0.83–1.08; n = 32
patients) compared with extubation
(Figure 2; see Figure E9, Table E3).
Sensitivity Analysis
We performed a sensitivity analysis by
removing the three studies deemed at high
or unclear risk of physiologic bias (see Table
E2) (3, 22, 23). The online supplement
provides details of pooled results.
Discussion
This is the first systematic review
characterizing the physiologic variables

1480 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 11 | June 1 2017
ORIGINAL ARTICLE

1.4 Measurement
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Figure 2. Line plot showing ratio of means with 95% confidence intervals for work of breathing, pressure time product, and rapid shallow breathing index
on the y-axis, among different spontaneous breathing trial comparisons as displayed on the x-axis. CI = confidence interval; CPAP = continuous positive
airway pressure; PSV = pressure support ventilation; PTP = pressure–time product; RSBI = rapid shallow breathing index; WOB = work of breathing.

related to breathing effort during different The WOB and PTP seemed to vary T-piece and extubation with respect to
SBT methods in 16 studies enrolling in a dose–response relationship as the RSBI, PSV, or CPAP of 0 cm H2 O.
239 patients. This review demonstrates ventilator support decreased from PSV to Although described during T-piece, the
that specific SBT methods are associated CPAP to T-piece and zero support as RSBI is often measured during all SBT
with large and significant differences illustrated in Figure 2. Mechanical methods. Similar to the changes in WOB
in physiologic parameters of patient ventilation acts to “off-load” the and PTP there is a graded decrease in the
respiratory effort based on esophageal respiratory muscles; as the amount of RSBI with greater ventilator support during
pressure measurements and use of the support provided by the given SBT SBTs. Patients had similar RSBIs whether
Campbell diagram. In particular, PSV modality increases, respiratory muscle connected to a T-piece or after removal
and CPAP reduced effort compared workload decreases (35, 36). Given that of the endotracheal tube, suggesting that
with T-piece trials and zero support a trial of spontaneous breathing is the respiratory load (including airway
ventilation. PSV and CPAP trials were intended mimic physiologic conditions resistance) is similar between the two
comparable. Compared with extubation, after extubation, our results suggest that conditions.
PSV and CPAP significantly decreased PSV0/CPAP0 and T-piece trials best Low levels of ventilator support are
all measures of respiratory effort. T-piece mimic those conditions and are therefore sometimes advocated during SBTs to
led to similar WOB compared with the optimal methods for evaluating overcome the artificial resistance introduced
conditions after extubation; it seemed weaning readiness. Inspiratory effort was by the endotracheal tube and/or the
to slightly reduce the PTP compared lower during T-piece trials compared ventilator circuit; consequently, such SBT
with extubation, but this latter finding with postextubation conditions, but after methods would in theory better simulate
was not confirmed in a sensitivity restricting the analysis to studies at low postextubation conditions. Our findings,
analysis. Similarly, WOB and PTP risk of physiologic measurement bias, and previous physiologic studies (4),
after extubation were no different from the difference in PTP was no longer seriously challenge this approach. We
values obtained during zero ventilatory statistically significant. There was no assume that endotracheal tube sizes in these
support SBTs. significant statistical difference between studies were adapted to the patients’ height

Sklar, Burns, Rittayamai, et al.: Physiologic Measures of Respiratory Effort during SBTs 1481
 ORIGINAL ARTICLE

Favors PSV Favors T-Piece Ratio of Means Ratio of Means

Study or Subgroup Total Total Weight IV, Random, 95% CI IV, Random, 95% CI
WOB
*R-Cabello 2010 14 14 0.1% 0.50 [0.00, 323.07]
*R-Koh 2000 22 22 14.3% 0.54 [0.48, 0.61]
*R-Kuhlen 2003 12 12 11.1% 0.64 [0.47, 0.87]
*R-Mahul 2016 17 17 12.5% 0.57 [0.45, 0.72]
*R-Mehta 2000 20 20 11.8% 0.88 [0.67, 1.16]
NR-Brochard 1991 11 11 10.7% 0.88 [0.63, 1.23]
NR-Ishaaya 1995 8 8 8.7% 0.40 [0.25, 0.63]
NR-Nathan 1993 7 7 9.0% 0.61 [0.39, 0.93]
NR-Patel 1996 23 23 11.8% 0.84 [0.63, 1.10]
NR-Petros 1993 8 8 10.0% 1.32 [0.91, 1.92]
Subtotal (95% CI) 142 142 100.0% 0.70 [0.57, 0.86]
Heterogeneity. Tau2 = 0.07; Chi2 = 40.59, df = 9 (P < 0.00001); I2 = 78%
Test for overall effect: Z = 3.42 (P = 0.0006)

PTP
*R-Cabello 2010 14 14 3.2% 0.47 [0.22, 1.03]
*R-Koh 2000 22 22 15.2% 0.59 [0.51, 0.68]
*R-Mahul 2016 17 17 12.4% 0.53 [0.42, 0.67]
*R-Mehta 2000 20 20 12.4% 0.89 [0.70, 1.12]
*R-Sassoon 1991 10 10 14.7% 0.72 [0.61, 0.84]
NR-Ishaaya 1995 8 8 7.5% 0.63 [0.41, 0.96]
NR-Nathan 1993 7 7 11.8% 0.59 [0.46, 0.77]
NR-Patel 1996 23 23 13.0% 0.86 [0.69, 1.07]
NR-Petros 1993 8 8 9.7% 1.12 [0.80, 1.56]
Subtotal (95% CI) 129 129 100.0% 0.70 [0.60, 0.82]
Heterogeneity. Tau2 = 0.04; Chi2 = 29.23, df = 8 (P = 0.0003); I2 = 73%
Test for overall effect: Z = 4.43 (P < 0.00001)

0.5 0.7 1 1.5 2

Favors PSV Favors T-Piece
Test for subgroup differences: Chi2 = 0.00, df = 1 (P = 0.98), I2 = 0%
Figure 3. Forrest plot comparing pressure support ventilation (PSV) with T-piece for work of breathing (WOB) and pressure time product (PTP). Pooled
results for WOB and PTP. Arrowheads reflect confidence intervals beyond the scale of the figure. *R = randomized studies. CI = confidence interval;
df = degrees of freedom; IV = inverse variance; NR = nonrandomized studies.

and sex, and we cannot address the effect of Brochard and coworkers (28) and Straus and T-piece is a “challenging” physiologic test.
disproportionally small endotracheal tubes, coworkers (4), respiratory effort was not Indeed, none of the studies reported a
placed for specific reasons (e.g., upper different between extubation and T-piece. decrease in WOB or PTP after extubation.
airway obstruction). In the studies by These findings contradict the notion that Persistent high respiratory effort after

PSV PSV0/CPAP0 Ratio of Means Ratio of Means

Study or Subgroup Total Total Weight IV, Random, 95%CI IV, Random, 95% CI
WOB
*R-Mahul 2016 17 17 38.9% 0.57 [0.45, 0.72]
*R-Sassoon 1992 9 9 12.7% 0.61 [0.36, 1.01]
NR-Brochard 1991 11 11 12.7% 0.61 [0.36, 1.01]
NR-Ishaaya 1995 8 8 14.6% 0.33 [0.21, 0.53]
NR-Nathan 1993 7 7 21.1% 0.45 [0.31, 0.66]
Subtotal (95% CI) 52 52 100.0% 0.51 [0.42, 0.62]
Heterogeneity. Tau2 = 0.01; Chi2 = 5.15, df = 4 (P = 0.27); I2 = 22%
Test for overall effect: Z = 6.74 (P < 0.00001)
PTP
*R-Mahul 2016 17 17 26.2% 0.51 [0.40, 0.65]
*R-Sassoon 1991 10 10 27.8% 0.88 [0.75, 1.03]
NR-Ishaaya 1995 8 8 20.9% 0.50 [0.33, 0.77]
NR-Nathan 1993 7 7 25.2% 0.46 [0.35, 0.60]
Subtotal (95% CI) 42 42 100.0% 0.58 [0.40, 0.83]
Heterogeneity. Tau2 = 0.12; Chi2 = 25.55, df = 3 (P < 0.0001); I2 = 88%
Test for overall effect: Z = 2.95 (P = 0.003)

0.5 0.7 1 1.5 2

Test for subgroup differences: Chi2 = 0.34, df = 1 (P = 0.56), I2 = 0% Favors PSV Favors PSV0/CPAP0
Figure 4. Forrest plot comparing pressure support ventilation (PSV) with no support on the ventilator group (PSV0/CPAP 0 cm H2O) for work of breathing (WOB)
and pressure time product (PTP). Pooled results for WOB and PTP. Arrowheads reflect confidence intervals beyond the scale of the figure. *R = randomized
studies. CI = confidence interval; CPAP = continuous positive airway pressure; df = degrees of freedom; IV = inverse variance; NR = nonrandomized studies.

1482 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 11 | June 1 2017
ORIGINAL ARTICLE

PSV Extubation Ratio of Means Ratio of Means

Study or Subgroup Total Total Weight IV, Random, 95% CI IV, Random, 95% CI
WOB
*R-Mahul 2016 17 17 22.4% 0.57 [0.45, 0.72]
*R-Mehta 2000 20 20 21.2% 0.64 [0.48, 0.86]
NR-Brochard 1991 11 11 19.5% 1.03 [0.71, 1.49]
NR-Ishaaya 1995 8 8 17.8% 0.27 [0.17, 0.42]
NR-Nathan 1993 7 7 19.1% 0.44 [0.29, 0.65]
Subtotal (95% CI) 63 63 100.0% 0.54 [0.38, 0.78]
Heterogeneity. Tau2 = 0.13; Chi2 = 22.80, df = 4 (P = 0.0001); I2 = 82%
Test for overall effect: Z = 3.33 (P = 0.0009)
PTP
*R-Mahul 2016 17 17 30.5% 0.50 [0.38, 0.65]
*R-Mehta 2000 20 20 30.5% 0.57 [0.44, 0.75]
NR-Ishaaya 1995 8 8 12.4% 0.42 [0.27, 0.64]
NR-Nathan 1993 7 7 26.6% 0.51 [0.38, 0.68]
Subtotal (95% CI) 52 52 100.0% 0.51 [0.44, 0.59]
Heterogeneity. Tau2 = 0.00; Chi2 = 1.58, df = 3 (P = 0.66); I2 = 0%
Test for overall effect: Z = 8.69 (P < 0.00001)
f/ Vt
*R-Mahul 2016 17 17 27.2% 0.84 [0.67, 1.04]
*R-Mehta 2000 20 20 32.9% 0.74 [0.61, 0.90]
NR-Brochard 1991 11 11 19.5% 0.83 [0.64, 1.07]
NR-Ishaaya 1995 8 8 10.2% 0.68 [0.48, 0.97]
NR-Nathan 1993 7 7 10.2% 0.67 [0.47, 0.95]
Subtotal (95% CI) 63 63 100.0% 0.77 [0.69, 0.86]
Heterogeneity. Tau2 = 0.00; Chi2 = 2.02, df = 4 (P = 0.73); I2 = 0%
Test for overall effect: Z = 4.60 (P < 0.00001)

0.5 0.7 1 1.5 2

Favors PSV Favors Extubation
Test for subgroup differences: Chi2 = 19.08, df = 2 (P < 0.0001), I2 = 89.5%
Figure 5. Forrest plot comparing pressure support ventilation with extubation for work of breathing (WOB), pressure time product (PTP), and rapid shallow
breathing index (f/ Vt). Pooled results for WOB, PTP, and f/Vt. Arrowheads reflect confidence intervals beyond the scale of the figure. *R = randomized
studies. CI = confidence interval; df = degrees of freedom; IV = inverse variance; NR = nonrandomized studies; PSV = pressure support ventilation.

extubation may result from several possible
mechanisms including upper airway edema
or inflammation (4, 29, 31) or the worsening
of respiratory mechanics after extubation
as suggested by the development of
postextubation respiratory distress.
Preextubation and postextubation effort
levels are very consistent despite the fact that
measuring WOB and PTP in extubated
patients can be challenging, requiring the use
of a face mask or mouthpiece.
Although not the focus of this review,
cardiopulmonary interactions are
important determinants of the outcome
of ventilator weaning. By adding PSV
or CPAP, an SBT could mask cardiac
failure during the SBT and lead to
postextubation cardiogenic pulmonary
edema in patients with poor left
ventricular function (37).
Our study has several strengths and
weaknesses. We included all identified
studies in critically ill patients, which met
broad inclusion criteria, thereby enhancing
generalizability. We used a rigorous
methodologic quality assessment and
introduced criteria for physiologic quality.
Not surprisingly, for technically challenging
physiologic studies, many of the trials
included are small, with few RCTs, and high
heterogeneity in terms of quality. Studies
also varied in the implementation of similar
ventilation techniques; for example, in
studies of PSV, the pressure ranged from
5 to 7 cm H2O and many did not specify
whether PEEP was also used as well.
Because of the small numbers of included
RCTs for each comparison, we decided,
however, to pool all PSV trials, regardless of
the level of PSV or use of PEEP. We used a
similar approach when considering studies
of different levels of CPAP and studies
of PSV or CPAP 0 cm H2O, which we
considered to be clinically similar
conditions, respectively.
Heterogeneity was relatively high
(I2 typically .70%) for nearly all pooled
results. Moreover, most comparisons
included few studies and patients and
lack of differences could be caused by
insufficient statistical power because of
small numbers or high heterogeneity (e.g.,
the automatic tube compensation versus
T-piece comparison included only two
studies with contradictory results).
Furthermore, comparisons with lower
heterogeneity, mainly the PSV0/CPAP0
versus T-piece, and extubation
comparisons that demonstrated no
difference in physiologic outcomes may
have been underpowered in sample
size to show true differences. Although
smaller differences (e.g., in the range of
10%), may exist, they may be of limited
clinical impact.
Another potential limitation is
the applicability of our results to the
contemporary intensive care unit setting.
Many of the studies included in the
analysis were published more than
10 years ago, and there has since been a
focus on early weaning and extubation.
Notwithstanding, some recent studies
have reported similar findings (38). It is
also possible that patients selected for

Sklar, Burns, Rittayamai, et al.: Physiologic Measures of Respiratory Effort during SBTs 1483
 ORIGINAL ARTICLE

T-Piece Extubation Ratio of Means Ratio of Means

Study or Subgroup Total Total Weight IV, Random, 95% CI IV, Random, 95% CI
WOB
*R-Mahul 2016 17 17 20.8% 1.01 [0.84, 1.20]
*R-Mehta 2000 20 20 16.0% 0.73 [0.56, 0.97]
NR-Brochard 1991 11 11 11.9% 1.16 [0.80, 1.69]
NR-Ishaaya 1995 8 8 19.8% 0.67 [0.55, 0.82]
NR-Nathan 1993 7 7 10.6% 0.71 [0.47, 1.07]
NR-Straus 1998 14 14 20.8% 0.96 [0.81, 1.15]
Subtotal (95% CI) 77 77 100.0% 0.86 [0.72, 1.02]
Heterogeneity. Tau2 = 0.03; Chi2 = 15.34, df = 5 (P = 0.009); I2 = 67%
Test for overall effect: Z = 1.74 (P = 0.08)
PTP
*R-Mahul 2016 17 17 28.7% 0.94 [0.77, 1.15]
*R-Mehta 2000 20 20 23.8% 0.64 [0.50, 0.83]
NR-Ishaaya 1995 8 8 25.3% 0.67 [0.53, 0.85]
NR-Nathan 1993 7 7 22.3% 0.86 [0.65, 1.13]
Subtotal (95% CI) 52 52 100.0% 0.77 [0.64, 0.94]
Heterogeneity. Tau2 = 0.02; Chi2 = 7.80, df = 3 (P = 0.05); I2 = 62%
Test for overall effect: Z = 2.62 (P = 0.009)
f/ Vt
*R-Mahul 2016 17 17 26.1% 1.07 [0.88, 1.30]
*R-Mehta 2000 20 20 26.1% 0.90 [0.74, 1.10]
NR-Brochard 1991 11 11 10.2% 1.05 [0.77, 1.44]
NR-Ishaaya 1995 8 8 8.0% 0.78 [0.55, 1.11]
NR-Nathan 1993 7 7 8.0% 0.88 [0.62, 1.25]
NR-Straus 1998 14 14 21.6% 1.03 [0.83, 1.28]
Subtotal (95% CI) 77 77 100.0% 0.97 [0.88, 1.08]
Heterogeneity. Tau2 = 0.00; Chi2 = 3.84, df = 5 (P = 0.57); I2 = 0%
Test for overall effect: Z = 0.53 (P = 0.60)

0.5 0.7 1 1.5 2

Favors T-Piece Favors Extubation
Test for subgroup differences: Chi2 = 4.94, df = 2 (P = 0.08), I2 = 59.5%
Figure 6. Forrest plot comparing T-piece with extubation for work of breathing (WOB), pressure time product (PTP), and rapid shallow breathing
index (f/ Vt). Pooled results for WOB, PTP, and f/Vt. *R = randomized studies. CI = confidence interval; df = degrees of freedom; IV = inverse variance;
NR = nonrandomized studies.

physiologic measures may not be fully
representative of general intensive care
unit patients at risk of extubation failure.
Perhaps 20–30% of patients are difficult
to wean (38) and so these physiologic
measurements may be more appropriately
performed in this small subset of
intensive care unit patients. There is
ongoing work to identify this at-risk
group of patients (39).
Our review focuses on physiologic
outcomes under different SBT modalities.
It is important to distinguish the
physiologic outcomes from the clinical
outcomes, which may or may not be
aligned for a variety of reasons. Primarily,
the medical decision for extubation is a
complex process involving not only the
result of the patient’s SBT, but other
clinical and organizational factors and
is based on the subjective decision of
the clinician. Given that the extubation
decision-making process is complex, we
believe that it is important to separate the
physiologic outcomes from the clinical
outcomes to correctly interpret the clinical
studies and another study is ongoing to
separately analyze the clinical outcomes.
When including physiologic studies in
meta-analysis, it is important to consider
both study design and physiologic risk of
bias. For instance, the technique used to
measure patient WOB in the studies by
Brochard and coworkers (28) and Straus
and coworkers (4) used a Campbell
diagram for this calculation, which may be
considered the gold standard for WOB
measurements because it includes PEEPi in
the total WOB calculation. However, both
of these studies suffer from methodologic
bias as described previously.
An appropriate wash out time is an
important consideration when interpreting
the results of physiologic crossover trials.
We defined an appropriate wash out time
as 10 minutes for return of ventilatory
variables to baseline conditions. This was
based on the observation that the respiratory
control center adapts to changes very
rapidly (40) and that esophageal pressure
swings are close to their maximal values in
less than 10 minutes (5).
Conclusions
This review demonstrates that patient
respiratory effort, assessed by precise
physiologic measures, is markedly affected
by various SBT techniques. Among SBT
types, PSV reduces respiratory effort
compared with T-piece trials, and both
PSV0/CPAP0 and T-piece seem to more
accurately reflect the physiologic conditions
of extubation. Although the strength of
our conclusions is tempered by a limited
number of studies, small number of patients
within each study, and some clinical and
methodologic heterogeneity of the included
studies, the results seem consistent. n
Author disclosures are available with the text
of this article at www.atsjournals.org.

1484 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 11 | June 1 2017
ORIGINAL ARTICLE
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