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Critical Care Medicine and the World
ediatric extubation failure is associated with increased duration of in- Federation of Pediatric Intensive and
vasive mechanical ventilation, ICU length of stay, and mortality (1, 2). Critical Care Societies
Upper airway obstruction (UAO) is the primary etiology of extubation DOI: 10.1097/PCC.0000000000003377
• Cuff leak testing lacks sensitivity and specificity on age and size. The LACWD measures the difference
in pediatric patients for identification of potential between a patient’s LACW with the balloon cuff of the
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development of PES. Laryngeal ultrasound is a ETT inflated and deflated and is comparable in chil-
promising predictive tool. dren, from patient to patient. In this study, we aimed to
• This clinical investigation evaluated the fea- evaluate the feasibility and the diagnostic performance
sibility and potential diagnostic performance of LACWD measured by an intensivist using point-of-
of intensivist-performed, laryngeal ultrasound care laryngeal ultrasound.
measurement of laryngeal air column width
difference (LACWD) in relation to subsequent
PES. METHODS
Study Setting, Design, and Ethics
failure among children, causing 41–51% of pediatric This prospective, observational cohort study was per-
extubation failure in two single-center reports (3, 4). formed in the PICU at a quaternary care children’s
Post-extubation UAO is difficult to predict as the prox- hospital. The study, under the title “Laryngeal ultra-
imal airway cannot be reliably assessed before extuba- sound and air column width as a predictor of post
tion with the endotracheal tube (ETT) in place (5, 6). extubation stridor,” was approved by the University of
While UAO can occur along the entire airway axis, most Alabama at Birmingham Institutional Review Board
attention is focused on subglottic UAO, manifesting as (IRB-300006847) on May 28, 2021. Informed consent
stridor because it is treatable before and after extubation was obtained from legal guardians at the time of en-
(7–9). Clinical assessment of the subglottic airway be- rollment. All procedures were followed in accordance
fore extubation traditionally relies on the airway leak with the ethical standards of the IRB on human exper-
test (ALT) which is neither sensitive (27–55%) nor spe- imentation and with the Helsinki Declaration of 1975.
cific (35–81%) for identifying post-extubation UAO in Between July 19, 2021, and October 31, 2022, we
pediatric patients (10). Treatment of patients at high risk screened for enrollment all patients in our PICU, every
for subglottic UAO with glucocorticoids can decrease day. Inclusion criteria were as follows: younger than 5
post-extubation stridor (PES) (8, 9). At the same time, years old, invasive mechanical ventilation for greater
the administration of glucocorticoids can be spared in than or equal to 24 hours with a cuffed ETT, and eli-
patients at low risk for developing PES. Therefore, there gibility for spontaneous breathing trials based on the
is a need to develop and evaluate other bedside tests fo- institutional eligibility screen. We restricted the pop-
cusing on feasibility, reproducibility, and diagnostic ac- ulation to younger than 5 years old because this age
curacy for this important outcome. group is at greater risk of post-extubation UAO or
Laryngeal ultrasound can visualize the column of PES, and the LACWD ultrasound measurement is
air passing through the vocal cords. The width of this only capable of evaluating the subglottic airway (3, 17).
column of air is referred to as laryngeal air column Exclusion criteria included a predisposition to supra-
width (LACW). This measurement has been studied glottic airway obstruction (i.e., severe traumatic brain
as a tool for identifying potential PES in adults. In a injury, hypoxic-ischemic encephalopathy, craniofacial
2001–2002 pilot study of 51 adults, LACW meas- syndromes, midface hypoplasia), known supraglottic
ured with the ETT balloon cuff deflated had “poten- obstruction, surgical intervention to the airway dur-
tial ability to predict PES in intubated patients” (11). ing admission, presence of an uncuffed ETT, and the
Subsequent laryngeal ultrasound studies in adults presence of a device obstructing laryngeal ultrasound
have demonstrated varying test characteristics in the performance (e.g., cervical collar). The clinical team
prediction of PES (12–15). In a PICU population, a was blinded to the results of the laryngeal ultrasound.
Laryngeal Ultrasound Procedure cricoid cartilage, and a clear air-mucosal interface. The
laryngeal air column was depicted as the width of air
The principal investigator (L.B.) performed all ultra- passing through the vocal cords. Three separate clips of
sound studies. Having no previous training in diag- the images in the appropriate field of view were saved
nostic airway point-of-care ultrasound, the principal with the ETT balloon cuff inflated. The patients’ res-
investigator gained proficiency in performing laryn- piratory therapist (RT) then completely deflated the
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geal ultrasound after completing and reviewing 25 balloon cuff. The same field of view was reimaged, and
examinations curated by a credentialed diagnostic three more clips were stored. LACW was measured
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ultrasonographer within the division of pediatric along the most superficial hyperechoic line depict-
critical care (V.B.) over the course of 3 months. Each ing the air-tissue interface, as described above, with
image and measurement was compared with published the ETT cuff inflated and deflated. The average of the
images and descriptions of LACW (11, 16). three measurements was taken. LACWD (LACWcuff
The LACW represents the functional airway size de- –LACWcuff inflated) was calculated. The LACWdeflated
deflated
termined using ultrasound. It is the width of the air is greater than LACWinflated since deflation of the cuff
column passing through the vocal cords. On an ul- creates a larger column of air through the vocal cords.
trasound image, it is depicted with a hyperechoic line A smaller LACWD suggests airway narrowing, pre-
at the air-tissue interface with reverberation artifacts sumably from soft tissue edema, and a higher likeli-
beneath (Fig. 1). The air column appears rectangular hood of developing PES. While the cuff was deflated,
when the ETT cuff is inflated. The air column becomes the RT performed an ALT by attaching a self-inflating
trapezoid in shape, and the width increases as it con- bag with a positive end-expiratory pressure valve to
forms to the subglottic area, which is the narrowest part the ETT and delivering a pressure of 25 cm H2O. The
of the airway when the cuff is deflated. Laryngeal ultra- neck was auscultated to evaluate for the presence or
sound was performed as originally described by Ding absence of a leak. Based on auscultation, the result was
et al (11). The scans were done within 6 hours before a recorded as either leak present or leak absent. The RT
planned extubation attempt. Patients were positioned then reinflated the balloon cuff of the ETT to the pre-
supine with the neck in a neutral to a hyperextended vious level.
position. A high-frequency, linear ultrasound probe
was used with a laryngeal preset applied with 2.5 cm
Extubation Timing and Post-Extubation Stridor
of depth, optimal gain, and a frequency of 12 MHz.
Definition
The probe was placed over the cricothyroid membrane
in a transverse plane of cut to facilitate visualization The timing of extubation was determined by the clin-
of the appropriate field of view. For quality control, ical team, which was blinded to the results of the la-
we ensured that the image included the vocal cords, ryngeal ultrasound. After extubation, the clinical team
Figure 1. Ultrasound image at the level of cricoid cartilage (CC) showing (arrow) air column width. Note the rectangular shape of
air column (left) with cuff inflated and trapezoid shape (right) with cuff deflated. Probe placement is depicted in the center. A-M = air
mucosal interface, TG = thyroid gland.
evaluated subjects for the presence of stridor. The and means with sds for parametric continuous variables.
principal investigator did not enroll or perform any ul- As appropriate, the stridor and nonstridor groups were
trasound studies while serving in a clinical role to min- compared using the two-sample t tests, the Kruskal-
imize conflict of interest. PES, for the purposes of this Wallis test, and chi-square tests. Correction was made
study, was defined as a high-pitched inspiratory res- to the p value for multiple comparisons. The bivariate
piratory noise suspected to be from a subglottic focus Pearson’s correlation coefficient was used to evaluate
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and received medical intervention (i.e., racemic epi- test-retest reliability between the repeated measures
nephrine, glucocorticoids, or heliox). The study team of LACWD. In the “diagnostic test” evaluation, we
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had no role in determining the presence of stridor or used receiver operating characteristic (ROC) curves to
the need for intervention. evaluate the potential utility of LACWD in its identi-
The following data were collected from the medical fication of subsequent PES and extubation failure. A
record of each subject: age, height, weight, sex, primary cutoff for LACWD was determined with priority for a
diagnosis, ETT size, length of invasive mechanical ven- balance between maximal sensitivity and specificity. A
tilation for the screened ventilator encounter, neuro- STrengthening the Reporting of Observational Studies
logic or pulmonary comorbidity, ETT cuff pressure, the in Epidemiology (STROBE) statement was completed
presence or absence of glucocorticoids administered in and can be found in the supplemental content (http://
the 24 hours before extubation, history of difficult in- links.lww.com/PCC/C436).
tubation, the laryngoscopic view grade as reported by
the clinician performing intubation, and the number RESULTS
of intubation attempts. Neurologic and pulmonary co-
morbidity was defined as any coexisting, neurologic During the study period, our PICU had 588 patients
or pulmonary condition not otherwise encompassed needing mechanical ventilation, with 199 patients eli-
by the primary admission diagnosis. ETT cuff pres- gible for enrollment. Fifty-three patients were included
sure was measured by the RT at the time of extubation in the study (Fig. 2). The mean interval from laryngeal
and reported as less than 20 mm Hg, 20–30 mm Hg, or ultrasound to extubation was 2.54 ± 1.97 hours. The
greater than 30 mm Hg. mean duration of the laryngeal ultrasonography scan
was 73 ± 14 seconds. Repeated measures of the LACWD
were correlated, reflecting acceptable test-retest relia-
Statistical Methods
bility (Pearson’s correlation coefficient 0.983; p = 0.01).
The 2015–2017 PICU study of 400 patients found that No patient decompensations, unplanned tube move-
mean LACWD among those with stridor was 50% ments, or extubations were associated with the study
smaller than patients without stridor (16). For a power protocol. None of the subjects received any additional
of 80% and α level of 0.05, a sample size of 17 patients sedation for the laryngeal ultrasound. Additionally,
in each group, with and without stridor, would allow a images of sufficient quality to measure LACW were
t-test to detect a difference of 25% of the mean LACWD obtained in 100% of the subjects enrolled.
value between the two groups with an expected sd of Descriptive statistics of the 53 patients are shown in
25% of the mean. Table 1. On inspection of the data, PES was observed
We report the mean observed to estimated ETT in 18 of 53 patients (34%). Of note, median (IQR)
inner diameter ratio in the results, a measure of appro- LACWD was lower in PES patients vs. those with
priate ETT size selection. The predicted ETT inner di- no stridor, even using the p value for multiple com-
ameter was calculated using the equation: (age in yr/4) parisons (p < 0.004) (PES, 0.37 mm [0.23–0.46 mm]
+ 3.5 for cuffed ETTs. All results were rounded to the vs. no stridor, 0.78 mm [0.56–1.07 mm]; p < 0.001).
nearest 0.5 mm inner diameter. For infants younger None of the other comparisons reached this level of
than 6 months old, 3.0 mm was predicted, whereas significance.
3.5 mm was predicted for infants 7–12 months old. The The ROC curve analysis evaluated the diagnostic
ratio of actual to expected ETT size is reported. utility of LACWD as a potential identifier of subse-
Descriptive statistics included counts/percentages quent PES (Fig. 3). It yielded an area under the ROC
for categorical variables, medians with interquartile curve (AUROC) of 0.94 (95% CI, 0.89–1.00; p < 0.001).
ranges (IQRs) for nonparametric continuous variables The AUROC-determined cutoff value for LACWD for
Pediatric Critical Care Medicine www.pccmjournal.org 225
Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
Burton et al
determined diagnostic
cutoff value in LACWD
for extubation failure was
0.32 mm, which provides a
sensitivity of 88.0%, speci-
ficity of 66.7%, positive pre-
dictive value of 13.7%, and
negative predictive value of
98.9%. The pre-to-post-test
change in probability of
extubation failure is 0.06 to
0.14 for LACWD less than
or equal to 0.32 mm.
DISCUSSION
In this single-center pilot
study of pre-extubation ul-
Figure 2. Consort diagram of enrollment. trasound measurement of
in situ cuffed ETT LACWD
diagnosis of was 0.47 mm, which provides a sensitivity in subjects younger than 5 years old, we have two main
of 91.4%, specificity of 88.9%, positive predictive value observations. First, point-of-care ultrasound assess-
80.9%, and negative predictive value 95.4%. The sim- ment of the larynx is feasible by PICU personnel after
ilar analysis for absence of leak on the ALT and PES a short period of training. Second, we have hypothesis-
provides sensitivity 44.4% and specificity 77.1%, with generating data regarding the diagnostic utility of
positive predictive value 50% and negative predictive
value 73%. In our population, the pre-test probability
of PES was 18 of 53, or 0.34. That is, the pre-to-post- AT THE BEDSIDE
test change in probability of PES is 0.34 to 0.81 for
LACWD less than or equal to 0.47 mm, and 0.34 to • LACWD in pre-extubation subjects younger
0.50 for absence of air leak on ALT. than 5 years old is a skill that is feasible and
Among the 53 cases in our study, with respect to the easy to learn with equipment already available
AUROC-determined cutoff point for PES less than or in most PICUs.
equal to 0.47 mm, LACWD was measured above the • As a potential pre-extubation diagnostic test of
cutoff in 34 patients and below in 19. Of the 34 patients subsequent PES, LACWD may be suited to as
with LACWD above the cutoff, 2 (6%) had PES. Among part of a pre-extubation readiness testing bundle.
the 19 cases with LACWD measured below the cutoff, • Our hypothesis-generating data suggests that
16 (84%) had PES. a LACWD cutoff around 0.47 mm needs valida-
Extubation failure due to subglottic UAO was tion in other studies.
evaluated as an exploratory outcome (Table 2). There
TABLE 1.
Study Population Description by Variable
Variable Whole Cohort Stridor No Stridor
LACWD in identifying subsequent risk of PES. Taken These features, if incorporated into a protocol for
together, these data may help to develop work toward a extubation, would allow clinicians to make decisions
pre-extubation bundle of assessment. with the most current information at the bedside.
Laryngeal ultrasound is well-suited to pediatric Furthermore, avoiding additional sedation also pro-
patients. The lack of maturity of thyroid, cricoid and motes the possibility of timely extubation.
laryngeal cartilages, and bony structures, in addition Our LACWD data are hypothesis-generating and so,
to the low depth of penetration required to visualize at this stage, are preliminary to diagnostic testing of po-
airway structures allows easy acquisition of high- tential PES. For example, we measured LACWD in our
resolution images. In our experience, the laryngeal 53 patients, then used an AUROC analysis to identify a
ultrasound skills involved in this study were readily cutoff that was optimal for the diagnosis of subsequent
acquired over a three-week period of training. Our PES, or extubation failure. As expected, the LACWD
patients younger than five years old tolerated the pro- cutoff value yielded for extubation failure (0.32 mm)
cedure without difficulty, the need for additional se- was lower than the value for PES (0.47 mm). However,
dation, or adverse or unexpected events. However, the we have not validated these cutoffs in a population sep-
upper limit of the 95% CI for no adverse events in 53 arate to the one in which we have generated the cutoff.
patients is 6%, and so such events should be expected Also, at present, all we have is the diagnostic uncertainty
with wider experience. That said, the intensivist- evident in the change in pre-to-post-test probability of
performed point-of-care diagnostic evaluation could PES (0.34–0.81), and of extubation failure (0.06–0.14),
be performed very quickly and close to the time of and the question is whether such performance would
extubation. The measurement was also reproducible. influence practice. Here, we should discuss the prior
Figure 3. Receiver operating characteristic (ROC) curve. A, Laryngeal air column width difference (LACWD) as a predictor for post-
extubation stridor. B, LACWD as a predictor for extubation failure. AUROC = area under the receiver operating characteristic curve.
pediatric study of LACWD (16). Of note, this popula- accuracy and low sensitivity of the ALT in young chil-
tion of 400 cases, 0–18 years old, included 400 patients dren. In our study, we did not quantify air leak as origi-
with a pre-test probability of PES 44 of 400 (0.11). The nally defined in 1996 (19); instead, we used a pragmatic
authors’ hypothesis-generating data for the diagnosis of “yes or no” approach to applied pressure of 25 cm H2O,
PES identified a LACWD cutoff of 0.80 mm, which is which is also described in the PALISI network CPG (5).
higher that the cutoff of 0.47 mm in our younger than Our pilot study in subjects younger than 5 years old
5-year-old population. Using this higher cutoff across shows considerable diagnostic uncertainty of using ab-
the whole pediatric age range, the change in pre-to- sent air leak on ALT for subsequent development of PES;
post-test probability of PES (0.11–0.44) considerable di- the pre-to-post-test change in probability of PES is 0.34–
agnostic uncertainty is evident, which is no better than 0.50, again no better than a coin-flip. Taking this infor-
tossing-a-coin. Taken together, there are two points mation together with our LACWD findings, we wonder
that will need to be clarified in future study: 1) what are about an alternative approach to airway assessment at
the normal expected measurements in LACWD by age the time of extubation. Perhaps a tiered approach could
and 2) what degree of diagnostic certainty in change in be used in patient evaluation and intervention.
pre-to-post-test probability of PES at the time of extu- Recent evidence supports the early administration
bation would influence practitioners responsible for of glucocorticoids to prevent post-extubation UAO
decision-making. (8, 9). A pragmatic approach based on our results in
In 2022, there were two key reports on pediatric ven- subjects younger than 5 years old could be, at the time
tilation liberation (5, 18). The Pediatric Acute Lung of extubation readiness, as follows. First, use laryngeal
Injury and Sepsis Investigators (PALISI) network clin- ultrasound to measure LACWD. If the measurement
ical practice guideline (CPG) suggests “using the ALT, falls above the cutoff value reported above, then con-
in children with cuffed ETT, as part of the extubation sider that there is no utility in waiting for a cuff leak
readiness bundle, to assess the risk for the development before extubation or treating with steroids. However,
of post-extubation UAO” (strength of recommenda- if the LACWD is below the threshold value, then this
tion, conditional; certainty of evidence, very low) (5). finding could be indication for delaying extubation ir-
However, there are concerns regarding the diagnostic respective of the presence of air leak and administering
TABLE 2.
Description of Variables
Variable Extubation Failure Extubation Success
n 3 50
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Male sex 2 31
Diagnosis category
Pulmonary 2 25
Neurologic 1 10
Airway 0 2
Other 0 13
Length of ventilation (hr), median (IQR) 73 (54–79) 100.5 (52.3–169)
Median observed: expected ETT inner diameter ± (sd) 1.2 (1–1.2) 1 (1–1.2)
Neurologic comorbidity 1 18
Pulmonary comorbidity 3 28
ETT cuff pressure at scan time
Low 1 12
Recommended 2 37
Steroids 24 hr before extubation 3 29
Laryngeal air column width difference (mm), median (IQR) 0.30 (0.1–0.37) 0.6 (0.45–0.94)
Air leak
Present 1 36
Absent 2 14
ETT = endotracheal tube, IQR = interquartile range.
glucocorticoids. However, these assumptions—not this technical limitation can induce unwanted errors,
least the threshold in LACWD—need testing in future but we mitigated against this potential problem by tak-
work. ing three measurements and demonstrating that there
There are limitations in our study. It was powered was excellent test-retest reliability in LACW measure-
for clinically significant UAO, but clinicians are not ment. Other limitations are the single-center design
consistent in making this diagnosis (3, 6, 20). Often, and the lack of inter-rater reliability due to a single
obstruction is at multiple levels leading to serial airway ultrasonographer. Additionally, this test is only valid
resistance, which added together increases overall re- for subjects with cuffed ETT as the LACWD value
sistance and increased risk of extubation failure (3). relies on inflated and deflated LACW measurements.
Therefore, a more clinically relevant outcome is extu- In conclusion, measurement of LACWD in patients
bation failure due to subglottic UAO, which is a rare being considered for extubation is a novel, feasible point-
event and our study was underpowered for this out- of-care laryngeal ultrasound technique that can be learned
come. The ability to predict who will require reintu- and applied by PICU practitioners. However, there re-
bation due to subglottic UAO is a research priority in mains diagnostic uncertainty in the utility of LACWD as a
pediatric ventilation liberation (5). Regarding poten- test of PES. Therefore, future multicenter studies will need
tial limits to the laryngeal ultrasound measurement, to focus on: 1) investigation of normal LACWD meas-
the difference in LACWD between the groups with and urement by age; 2) diagnostic utility of LACWD below
without PES is of the order of the axial resolution of the threshold in relation to PES and/or to subglottic UAO-
12 MHz ultrasound transducer (0.06 mm). However, mediated extubation failure; and 3) a tiered approach to
extubation readiness including ALT, LACWD measure- 6. Khemani RG, Schneider JB, Morzov R, et al: Pediatric upper
airway obstruction: Interobserver variability is the road to per-
ment, and intervention with glucocorticoids.
dition. J Crit Care 2013; 28:490–497
7. Kimura S, Ahn JB, Takahashi M, et al: Effectiveness of corti-
ACKNOWLEDGMENTS costeroids for post-extubation stridor and extubation failure in
pediatric patients: A systematic review and meta-analysis. Ann
We thank Dr. James Odum, MD for article review and Intensive Care 2020; 10:155
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suggestions during the revision process. We also ac- 8. Iyer NP, López-Fernández YM, González-Dambrauskas S, et
knowledge and thank the Respiratory Therapists in the al: A network meta-analysis of dexamethasone for preventing
ywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 04/12/2024