Pediatric Surgery International

https://doi.org/10.1007/s00383-018-4312-7

ORIGINAL ARTICLE

Serial intralesional triamcinolone acetonide injections for acquired

subglottic stenosis in premature infants
Akinori Sekioka1 · Koji Fukumoto1 · Masaya Yamoto1 · Toshiaki Takahashi1 · Kengo Nakaya1 · Akiyoshi Nomura1 ·
Yutaka Yamada1 · Naoto Urushihara1

Accepted: 26 July 2018

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
Purpose  Long-term intubation of premature infants sometimes induces acquired subglottic stenosis (SGS), causing glottic
or supraglottic problems. These kinds of SGS often require tracheostomy and subsequently make decannulation difficult.
The aim of our study was to clarify the efficacy of repeated intralesional steroid injections to the stenosis.
Methods  Six children with acquired SGS, who were treated with triamcinolone acetonide injections to the subglottic space
just below the vocal folds between September 2015 and December 2017 were retrospectively reviewed.
Results  The patients’ mean age was 4.3 (range 1.3–4.4) years, the mean gestational age at birth was 25 (23–28) weeks, and
the mean birth weight was 591 (456–734) g. The degree of SGS was grade II in one patient and III in five patients, with
both tracheostoma and glottic or supraglottic abnormalities. They generally underwent ten procedures, every 3–4 weeks. In
most cases, the patency of the injected space improved by 25–220%, and the symptoms were relieved. One patient achieved
decannulation, and another one underwent laryngotracheal reconstruction and decannulation. Two patients started using a
speech cannula. There were no severe complications.
Conclusion  Serial intralesional steroid injections are likely to be effective in improving the patency of acquired SGS.

Keywords  Premature infants · Acquired subglottic stenosis · Steroid injection · Adrenal function

Introduction injections seem to have potential benefits, there are few

Acquired subglottic stenosis (SGS) is often associated with
endotracheal intubation. In children, there are various kinds
of treatments for acquired SGS, including non-operative
approaches or surgical interventions. However, there is
still no consensus on which treatment is the best option for
acquired SGS. This is partly because the severity of the ste-
nosis varies from one localized at the cricoid cartilage to the
other extending between the supraglottis and the cricoid car-
tilage. Acquired SGS with glottic or supraglottic problems
is particularly challenging for treatment [1, 2].
Recent studies have shown the efficacy of steroid injec-
tions to SGS, being combined with balloon dilation or
electro-surgery knife treatment [3–9]. Although the steroid
* Akinori Sekioka
akinori‑sekioka@i.shizuoka‑pho.jp
1
Department of Pediatric Surgery, Shizuoka Children’s
Hospital, 860 Urushiyama, Aoi‑ku, Shizuoka City,
Shizuoka Prefecture 420‑8660, Japan
reports of steroid treatment alone [3–5].
The present study was performed to examine the out-
comes of serial intralesional steroid (triamcinolone aceto-
nide: TA) injections to the stenosis just below the glottis in
pediatric patients dependent on tracheostoma.
Materials and methods
This study was approved by the institutional review board
(IRB #2016006) and complied with the Helsinki Declaration
of 1964 (revised 2013). The medical records of patients with
acquired SGS between September 2015 and November 2017
were retrospectively reviewed.
All bronchoscopic procedures were performed in the
operating room under general anesthesia. In all cases, a
4-mm flexible bronchoscope (BF TYPE P ­ 260F®, Olym-
pus, Tokyo, Japan) was used. The dose of the TA injec-
tion at one procedure was controlled to 1 mg/kg in total
and divided into 2 or 3 points around the subglottis (Fig. 1),

13
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Fig. 1  The steroid injection site just below glottis in patient 3
using an injection needle ­(Varixer®, Top, Tokyo, Japan).
The approach required just 10–20 min. In most procedures,
patients left the hospital on the day the treatment was per-
formed. All patients usually received ten injections, with
intervals of 3–4 weeks.
In this study, there were two main purposes of the TA
injections. First, the aim was to decannulate or help to
Fig. 2  The measurement of areas X and Y on the bronchoscopic images. a A bronchoscopic image of patient 3. b Drawing lines on the image.
c Area X, the area surrounded by the vocal cords and posterior commissure. Area Y, where airway patency was sustained just above the glottis
Fig. 3  Bronchoscopic images
of patient 5, each captured from
almost the same angle. a At the
first injection, b after treatment
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Pediatric Surgery International
decrease the invasiveness of additional surgery to decan-
nulate by reducing the stenosis just below the subglot-
tis. Second, in small children who were under 10 kg or
younger than 4 years old, they were encouraged to pro-
duce sounds and to acquire the ability to use language
more effectively. In our department, surgical treatment for
SGS is not indicated for small children less than 10 kg or
younger than 4 years old.
The patency of the subglottic space was evaluated by
the patient’s symptoms and the bronchoscopic images. On
the images, using an image software package ­(Photoshop®,
Adobe Systems, California, USA), the area surrounded
by both vocal cords and the posterior commissure (Area
X) and the area where airway patency was sustained just
below the glottis (Area Y) were calculated (Fig. 2). The
measurement of these areas was done in each broncho-
scopic image from almost the same angle (Fig. 3).
During the procedures, some patients underwent adre-
nal function tests, including adrenocorticotropic hormone
(ACTH) and cortisol tests.
Pediatric Surgery International

Results

cheos-
tomy
Tra-

+
+
+
+
+
+
+
Six patients (three male, three female) with acquired
SGS presented for TA injections, and only one of them

Developmental delay

Developmental delay
received two cycles (Table 1). Their mean age was 4.3
(range 1.3–5.4) years. All patients were born extremely

Comorbidity
early preterm, and the mean gestational age at birth was 25
(range 23–28) weeks. They also had extremely low birth
weight, with a mean birth weight of 591 (range 456–734)

−
−
−

−
g. All patients had long-term intubation since the neona-
tal period (range 50–180 days), subsequently developed

stenosis extended
SGS, and required tracheotomy in infancy. According

Level to which

Supraglottis

Supraglottis
Supraglottis
to the Cotton-Myer SGS grading classification [10], one
patient had grade II, and five patients had grade III. In four

Glottis
Glottis

Glottis
Glottis
patients, the stenosis extended from the cricoid cartilage
to the glottis, and two patients had stenosis extending to
the supraglottis.

Grade**
Stenosis
The outcomes are shown in Table 2. In six of seven
cycles, the patency of the airway improved by 21–200%,

III
III

III
III
III
III
II
and the patients’ symptoms also improved. The change in
patency following the procedure is shown in the line chart

Weight (kg)
(Fig. 4). Five of the patients received ten injections, and
one patient received five injections, because the patient’s

13.8
13.5
10.4
11.9

13.9
7.7
SGS was improved, and there were no sites where TA

8
could be injected after just 5 injections.
Patients 1 and 5 were younger than the other patients
Height (cm)

(1–2 years old) and still small (body weight 8 and 7.7 kg,

respectively). Therefore, TA injection was performed for 74
102
93
90
94
66
95
them to develop language more effectively by improv-
ing the patency of the SGS and voice quality. Before TA
Age at therapy

injection, they could not make a sound during capping

of the tracheostoma. As the treatment progressed, their
voice came easier. After finishing one cycle, their cannula
2y1m
4y3m
4y2m
4y5m
5y5m
1y4m
4y3m

**The Cotton-Myer SGS grading classification was used for stenotic grade
was changed to a speech cannula, and they went through
speech therapy more effectively.
For patients 2, 3, 4, and 6, TA injections were performed
period (days)
Intubation

to help decannulation. The degree of SGS in these patients

was improved by 21–76%. Patient 3 achieved decannula-
50
180
120
110
110
70
100

tion with only the TA injections. In patient 2 with grade III

SGS extending to the glottis, extended-partial cricotracheal
weight (g)

resection (PCTR) was first considered as initial treatment.

Birth

However, TA injections improved his stenosis just below the

456
548
588
660
660
593
734

glottis by 21%. The patient then underwent laryngotracheal

reconstruction (LTR) after the TA injections and was finally
Gestational age at

decannulated. Only in the second cycle of patient 4, the ste-

Table 1  Patients’ demographics

birth (weeks)

nosis could not be decreased.

Around the procedure, there were no severe complica-
tions. Patient 4 had subacute thyroiditis after the 7th injec-
26
23
24
27
27
23
28

tion in the first cycle, but it was not obviously proven to be

*Second cycle

associated with TA injection.

Sex

M
M

Adrenal function was also examined in patients 4, 5,

F
F
F

and 6 (Table  3). During the procedure, the values for

No

4*
1
2
3
4

5
6

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Table 2  Patients’ results
No Rate of subglottic Injection Additional treatment Complication Results Follow-
patency (times) up
(months)
Before After Effect Status

1 0.26 0.33 (+ 27%) 10 − − + Speech cannula 24

2 0.58 0.7 (+ 21%) 10 Laryngotracheal reconstruction − + Decannulated 23
3 0.38 0.67 (+ 76%) 10 − − + Decannulated 20
4 0.16 0.27 (+ 69%) 10 Additional TA injection (6 months later) Subacute thyroiditis + Better voice −
4* 0.36 0.31 (− 14%) 10 − − − No change 4
5 0.06 0.18 (+ 200%) 10 − − + Speech cannula 4
6 0.26 0.4 (+ 54%) 5 APC to granulation at tracheostoma − + Capping trial 9

APC argon plasma coagulation

*Second cycle

Fig. 4  Change of airway
patency in the subglottis

ACTH or cortisol became slightly lower than in the pre-
treatment condition, but they were not quite abnormal. A
few months after the TA injections, the laboratory data
came back to the same level as that before TA treatment.
Discussion
Airway complications associated with intubation, such as
SGS, have long been observed in neonatal intensive care
units. Though more attention to subglottic trauma in venti-
lated neonates has reduced the incidence of acquired SGS,
it still sometimes occurs and requires tracheostomy, espe-
cially in premature babies [7, 11]. Such cases of acquired
SGS often have glottic or supraglottic problems, and the
stenosis tends to extend from the cricoid cartilage to the
glottis. Probably because of the small size of the larynx in
premature babies, the wide range of damage from the glottis
or supraglottis to the cricoid cartilage could occur and result
in the extensive stenosis. Extended SGS has proven to be a
challenging situation to treat [12].
Acquired SGS depending on tracheostoma is not likely to
improve spontaneously, and it often requires surgical inter-
vention for decannulation [11]. LTR or partial cricotracheal
resection (PCTR) has been shown to be an effective surgical
procedure for severe SGS, but if the stenosis extends to the
glottis, it decreases the rate of successful decannulation and
requires more invasive surgery, such as extended-PCTR [1,

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Pediatric Surgery International
Table 3  Laboratory analysis of adrenal function during triamcinolone
acetonide injection therapy
No Before After 5 times After the
therapy
ACTH (pg/ml)
 4* 15.1 6.9 6.8
 5 18.5 8.7 25.2
 6 16.3 11.8 16.1
Cortisol (µg/dl)
 4* 9.9 2.4 2.2
 5 8.1 4.1 7.1
 6 8 2.4 7.6
ACTH adrenocorticotropic hormone
*Second cycle
2, 7]. Therefore, we introduced intralesional steroid injection
to reduce the stenosis just above the glottis, to consequently
decrease the degree of surgical invasion, and if possible, to
accomplish decannulation.
The secondary purpose of TA injection is to help small
children with SGS to produce a sound by diminishing the
stenosis. In our institution, invasive therapy for laryngotra-
cheal stenosis is planned at around 5 years of age and over
10 kg. Certainly, some previous reports showed the efficacy
of the surgical approach in children weighing less than 10 kg
or younger than 2 years of age [13, 14]. However, there is
still a risk in performing invasive laryngotracheal surgery
in small children, except in limited and experienced institu-
tions. Although serial treatments may need some time, they
are less invasive than open surgery, and they are worth try-
ing, especially in small children.
In the present study, the degree of improvement of the
stenosis was not always remarkable and constant. However,
Pouiseuille’s law states that even an obviously small increase
in airway caliber reduces airway resistance by a power of
four (laminar airflow) or five (turbulent airflow) [9, 15]. In
fact, through the TA injections, the volume of airflow in
the larynx was likely to increase, and patients consequently
became able to breathe during capping the tracheostoma and
utter speech more easily.
The mechanism of action of intralesional steroid injec-
tion is not completely clear. Managing SGS with intrale-
sional steroid injections was first reported in the 1970s [8].
Intralesional steroid injection is known to decrease colla-
gen synthesis and fibrosis. Several reports have not proven
significant efficacy, but it seems that the steroid should
reduce inflammation and subsequent scarring [7]. Some
reports have shown the role of steroid injection to SGS,
combined with balloon dilation, ­CO 2 laser, or debride-
ment, and in some cases avoiding more invasive proce-
dures [6, 7]. In the present study, SGS was so extended to
the glottis that we avoided combining TA injection with
other described treatments, which may damage the vocal
cords. Recently, in adult patients, serial intralesional ster-
oid injections have been solely performed for idiopathic
SGS as a conservative treatment [4, 5].
During the study period, there was no apparent sup-
pression in adrenal function and no complications associ-
ated with intralesional corticosteroid injection. None of
the patients in the present study developed a Cushingoid
state. Some previous reports, however, showed a few com-
plications with TA used for keloids or arthritis [16–19]
mainly referring to secondary Cushing’s syndrome. Since
there is still little evidence in the pediatric age group about
TA injections, close monitoring for a Cushingoid appear-
ance and adrenal function is needed. In addition, subacute
thyroiditis occurred in patient 4. Generally, steroid itself
has never been proven to cause subacute thyroiditis. The
injection site was slightly far from the thyroid, and the thy-
roiditis would be less likely to be related to the procedure
of injection, in which the length of injection needle was
only 5 mm. During the thyroiditis, probably incidental, the
supraglottic space became edematous, and the condition
interfered with the treatment.
Although patient 4 only had two cycles of treatment,
she eventually did not have a good outcome. Several rea-
sons may explain her poor results. First, she had more
severe supraglottic stenosis than SGS. We expected that
even small increase in the patency of the SGS would
increase the volume of airflow through the larynx, but
this did not occur. Severe supraglottic stenosis would not
be influenced by the small increasing amount of airflow
through the SGS. Second, there is a limit in how TA injec-
tions can improve stenosis. In most cases, SGS patency
became a steady condition at the 7th or 8th injection.
Therefore, we suppose that it might be better to determine
the effect of this therapy at around the 8th injection, or at
least within 10 times.
There are several limitations in the present study. First,
this study included only a small number of patients and
lacked a comparator group. Second, the method of measur-
ing the degree of airway stenosis was different from that in
previous reports. The traditional method of evaluating SGS
was to measure by the diameter of the endotracheal tube. In
the present study, however, the shape of the airway around
the glottis was distorted and difficult to evaluate precisely by
the endotracheal tube, which has a round shape. Therefore,
the level of stenosis was evaluated with the original method.
As an alternative, three-dimensional multidetector computed
tomography (3D-CT) may be a useful method for evalua-
tion. Although none of our patients underwent 3D-CT before
or after treatment, there is a possibility that it may more
effectively measure the patency of subglottic space, includ-
ing the length of stenosis. Finally, this was a single-center,
13

retrospective, observational study. Further study is needed to
confirm the effectiveness of TA injections for acquired SGS.
Conclusion
This is the first report of sole serial intralesional steroid
injections for acquired SGS in pediatric patients who were
born prematurely. The patency of SGS improved to some
extent, and the patients’ symptoms were relieved. Although
many questions remain, we believe that these TA injections
can be an alternative treatment option for acquired SGS.
Compliance with ethical standards  12. Morita K, Yokoi A, Bitoh Y et al (2015) Severe acquired sub-
Conflict of interest  Akinori Sekioka, Koji Fukumoto, Masaya Yamoto,
Toshiaki Takahashi, Kengo Nakaya, Akiyoshi Nomura, Yutaka Yam-
ada, Naoto Urushihara have no conflicts of interest or financial ties to
disclose.
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