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Indian Pediatr 2010;47: 307-308 |
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Post-Extubation Stridor: The Call for
Objectivity |
Robinder G Khemani
Department of Anesthesiology and Critical Care,
University of Southern California Keck School of Medicine, Children’s
Hospital Los Angeles, USA.
Email: [email protected]
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In this issue of Indian Pediatrics,
Sinha, et al.(1) have reported the results of a single center
randomized controlled trial evaluating aerosolized L-epinephrine vs
budesonide for the treatment of post-extubation stridor. While the
benefits of intravenous corticosteroids on post-extubation stridor are
still unclear(2), the authors propose inhaled steroids may provide similar
action to intravenous steroids, with fewer side effects.
They included all recently extubated children with a
stridor score ³4,
based on a stridor scale identical to the Westley Croup Scale(3). While no
specific exclusion criteria were listed, the 134 children categorized as
"excluded" appear to simply not meet inclusion criteria. An appropriate
block randomization strategy was implemented to ensure equal distribution
of those with pre-existing airway disease. The study was not blinded,
neither for assessment of outcome nor for analysis. Patients were
randomized to receive either 1000µg of budesonide or 0.25 mL of 1%
epinephrine. The primary outcome measure was "extubation failure," defined
as a stridor score remaining
³4,
re-nebulization, or reintubation within 24 hours of extubation. The study
was designed to detect a reduction in "failure rate" from 40% to 10%, a
30% absolute risk reduction, or a 75% relative risk reduction.
Overall there was no difference between budesonide and
epinephrine on the primary outcome measure. While the median 2 hour
stridor score was lower for those that received epinephrine compared to
budesonide, this was not adjusted for multiple comparisons with repeated
measures ANOVA, although the methods describe the intention to do this.
While both drugs were similar in efficacy, adverse effects, and onset of
action, the authors conclude epinephrine demonstrates a more sustained
effect because the stridor score at 2 hours was lower. However, this trend
is not evident by looking at the scores as a function of time, and without
adjustment for multiple comparisons, this may be a result of chance. To
their credit, they report this may not be clinically significant.
Regardless of the therapy, over 50% of patients had a
stridor score ³4
within the first 24 hours of treatment, with close to 40% requiring rescue
nebulization with epinephrine (both groups), and over 20% requiring re-intubation.
The overall incidence of "post-extubation stridor" was 31.6%. While the
authors should be congratulated for attempting to attack a common and
difficult problem in pediatric critical care, this study highlights the
challenges surrounding post-extubation stridor. While stridor scales have
been used to assess upper airway obstruction severity, they have never
been validated against objective measures of upper airway obstruction such
as spirometry(4), and have inconsistent inter-observer variability(5-7).
The authors do not describe how many investigators evaluated stridor
severity with the corresponding inter-observer reliability of the stridor
scale or the internal validity of the scale if a single investigator was
used. This is particularly important because the score was used both for
inclusion criteria and for the assessment of outcome. While baseline "stridor
scores" were similar between groups, there is only one element of this
score which is specific to upper airway obstruction (inspiratory stridor),
which carries less weight than other, less specific elements of the score.
As such, this score will be elevated if children have residual
respiratory, neuromuscular or neurologic disease. The use of a spontaneous
breathing trial prior to extubation could have further elucidated these
potential contributions. The uncertainty and variability of the stridor
scale is particularly important in this study because the investigators
assessing outcome were not blinded to the intervention, which could
introduce bias.
While the incidence of post-extubation stridor (31.6%)
was reported as similar to other studies, the cited studies are now 18
years old. More recent estimates reveal with careful consideration of tube
size, the incidence of stridor is closer to 15%(7,8). This difference can
partially be explained by the inclusion of children with underlying airway
anomalies (10%). It may also be explained by the lack of objectivity and
the variability of definitions of post-extubation stridor.
The study was largely underpowered, as a 30% absolute
or 75% relative risk reduction is well above what most would consider
clinically significant. However, there was no trend for benefit, so it is
unlikely that a significant difference between treatments in the first
hour was missed. Moreover, all patients who received "re-nebulization
(40%)," received racemic epinephrine at a median of 90 (60-240) minutes in
the budesonide group. Therefore the stridor scores after 60 minutes are
difficult to interpret because 40% of the patients in the budesonide group
subsequently received racemic epinephrine.
Finally, regardless of the treatment arm, approximately
half of the patients did not respond to either therapy. As the authors
suggest, the underlying etiology could contribute to this variability, but
it is also reflects the imprecision of the evaluation of post-extubation
stridor. If we are to move forward with studies on post-extubation stridor,
we must have a reliable and reproducible objective outcome measure. This
may include using spirometry and esophageal manometry to demonstrate flow
limitation. Without this, we will not be able to identify risk factors for
extubation failure from upper airway obstruction, or determine the
benefits of potential therapeutics such as racemic epinephrine, inhaled or
intravenous steroids, heliox, or non invasive positive pressure
ventilation.
Funding: None.
Competing interests: None stated.
References
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L-epinephrine vs budesonide for post-extubation stridor: A randomized
controlled trial. Indian Pediatr 2010; 47: 317-322.
2. Khemani RG, Randolph A, Markovitz B. Corticosteroids
for the prevention and treatment of post-extubation stridor in neonates,
children and adults. Update of Cochrane Database Syst Rev 2008; 2:
CD001000. Cochrane Database Syst Rev 2009; 3: CD001000.
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epinephrine by IPPB for the treatment of croup: a double-blind study. Am J
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