Abstract:
Reintubation in the pediatric intensive care unit (PICU) increases
morbidity, mortality, and the overall cost of care. Post-extubation
airway obstruction (PEAO) is a potentially predictable cause of
extubation failure and may be prevented by the use of corticosteroids.
Defining which patients are most at risk for the development of POAE as
well as the optimal dose and timing of corticosteroids for prevention is
critical. We review the current literature regarding the use of
corticosteroids surrounding extubation in the PICU and discuss the
implications that a clear algorithm for identification and treatment of
these patients would have in the care of critically ill children.
The unanticipated need for reintubation in the pediatric intensive care
unit (PICU) is associated with significant increases in morbidity,
mortality, and cost of care.1 While patients may
require reintubation for a multitude of reasons, post-extubation airway
obstruction (PEAO) secondary to laryngeal edema is one that may be both
predictable and modifiable.2 Laryngeal edema can occur
from pressure or irritation by an endotracheal tube resulting in stridor
or obstruction after extubation.1 While this
complication occurs in all PICUs, the incidence is highest in low- and
middle-income countries due to the presence of unique risk factors.
These risk factors include circumstances surrounding intubation itself,
such as a higher number of intubations occurring outside of the PICU, as
well as patient factors such as malnutrition.2Post-extubation edema is also more commonly symptomatic in children due
to differences in airway anatomy including looser submucosal connective
tissue that allows fluid to accumulate and a less expandable cricoid
cartilage ring with a smaller trachea diameter. In theory, the
anti-inflammatory effect of corticosteroids may decrease the amount of
local laryngeal inflammation and decrease edema. Several studies have
demonstrated that the incidence of PEAO can be decreased by pretreatment
with dexamethasone.1 However, across these studies,
there has been significant dosing variation. Adverse effects associated
with high-dose corticosteroid use include hyperglycemia, hypertension,
immune suppression and secondary infection, and gastrointestinal
bleeding. These risks warrant further investigating what the optimal
dose of steroids may be to prevent life-threatening PEAO in children
while minimizing the risk of side effects.
In this issue of Pediatric Pulmonology , Parajuli et al. evaluate
the difference between low-dose (LD; 0.25 mg/kg/dose) and high-dose (HD;
0.5 mg/kg/dose) dexamethasone pretreatment in reducing the risk of PEAO
in pediatric patients. Their work follows an initial study from the same
institution that showed HD dexamethasone pretreatment reduced the risk
and severity of PEAO and need for reintubation.2 In
this randomized, open-label, non-inferiority trial, the authors report
no difference in risk for reintubation due to airway obstruction between
the two groups. This is in line with the findings of a recent study in
adults that showed no difference between LD (5 mg) and HD (10 mg)
dexamethasone in preventing PEAO in at risk patients in
Taiwan.3 Unfortunately, Parajuli et al. were unable to
enroll sufficient participants to achieve the desired study power due to
self-acknowledged time and logistical constraints. As a result, this
study was not adequately powered to prove the non-inferiority of LD
versus HD. Of note, in this particular institution the standard is to
use dexamethasone pretreatment prior to extubation for every patient
intubated for greater than 48 hours. The authors note that this is due
to unique factors among their patient population that increase their
risk of PEAO, that include a large proportion of patients intubated in
an uncontrolled setting outside of an PICU, prolonged periods of time
intubated outside of the PICU or receiving hand ventilation, and a large
percentage of patients with malnutrition and hypoalbuminemia at time of
extubation.
The use of prophylactic corticosteroids prior to extubation is not
universal among all PICUs and practice varies broadly with regard not
only to dosing regimen but also the identification of at-risk
patients.4 There are a number of known risk factors
for the development of laryngeal edema and post-extubation stridor
including upper airway infection, inappropriately large endotracheal
tube size or high cuff pressure, traumatic intubation including multiple
attempts, prolonged period of intubation, and excessive tube mobility
due to improper fixation or patient fighting against the endotracheal
tube. Despite these known risk factors, there is no clear system for
delineating which patients may benefit from corticosteroid pretreatment
prior to extubation.5 The air leak test is often
employed in an effort to determine which patients are at high risk for
post-extubation stridor and extubation failure. There is significant
variability in how this test is performed and what qualifies as a
positive test. Additionally, it has been shown neither to be very
sensitive nor specific.6 A more promising clinical
tool is the novel use of ultrasound to measure laryngeal air column
width with the endotracheal cuff inflated versus deflated. When compared
with the air leak test in one pediatric study, ultrasound was found to
be significantly more sensitive, specific, and accurate in predicting
post-extubation stridor.5
A Cochrane Systematic Review published in 2009 evaluated the effects of
corticosteroids at reducing the risk for stridor and extubation failure
in patients of all ages.7 No difference in the rates
of reintubation was observed when analyzing neonates and children
separately. However, they did find a significant reduction in stridor
when the neonatal and pediatric patients were analyzed together. The
authors of this review concluded that based on the studies available at
the time, there was no evidence for the effectiveness of corticosteroids
in reducing stridor or extubation failure in neonates and children and
therefore there was no consensus for their use in this population. In
contrast, a more recently systematic review and meta-analysis of 10
pediatric studies was published in 2020, evaluating the effectiveness of
corticosteroids in reducing post-extubation stridor and extubation
failure in pediatric patients.1 Among this larger
cohort the investigators noted that, despite a wide range of doses used,
corticosteroids did significantly reduce the rates of stridor and
reintubation in patients who had – or were at risk of – laryngeal
edema. In contrast to the less clear data in pediatrics, there is a
larger body of adult data to support the use of corticosteroids for this
purpose. A systematic review and meta-analysis of 11 adult trials showed
that prophylactic corticosteroids prior to extubation were effective at
reducing rates of post-extubation airway obstruction and reintubation in
high-risk patients.8 These patients were defined as
being at-risk based on an air leak test, though the definitions of a
positive air leak test varied across the studies.
It is important to note that across all of these studies, in both the
pediatric and adult literature, there was no consistency in which
corticosteroid was used, dose, frequency, or how much time elapsed
between the first dose and timing of extubation. While difficult to draw
direct conclusions from these varying regimens regarding optimal dosing,
there does seem to be an indication that a single dose of steroids one
hour prior to extubation is not effective, but that multiple doses in
the 24 hours prior to extubation may have more
benefit.3 In an effort to answer some of the remaining
questions, a multi-center, prospective, double-blind, randomized,
placebo-controlled, phase IV clinical trial is now underway in Spain
designed to evaluate the effectiveness of steroids versus placebo at
preventing upper airway obstruction after extubation in 200
children.9 In this study, the investigators plan to
use a steroid regimen of dexamethasone at 0.25 mg/kg/dose every six
hours for a total of four doses, which would fall into line with the LD
regimen used in the study by Parajuli et al.
While there currently remain more questions than answers with regard to
the use of prophylactic corticosteroids prior to extubation in pediatric
patients, a careful review of the literature certainly provides some
insight into how to best care for our patients. Based on the current
published literature, it appears that the use of corticosteroids prior
to a planned extubation is likely beneficial for a select group of
at-risk pediatric patients.1 While no definitive
algorithm for identifying these high risk patients presently exists, in
our institution, we combine a careful consideration of any risk factors
with an air leak test, in line with what many other institutions
presently utilize.10 While the choice of
corticosteroid is likely of lesser consequence, there seems to be no
benefit to support the use of HD over LD steroids. However, it does
appear to be important to plan ahead and administer the first dose at
least six hours prior to extubation, with more benefit likely occurring
with multiple doses given in the 24 hours prior to
extubation.3 Given the associated increase in
healthcare costs and morbidities associated with unanticipated PAEO in
children, the present study by Parajuli et al. ultimately draws
attention to an important need for continued investigation to better
inform the development of evidence-based extubation protocols as well as
further mitigation of underlying predisposing factors.