Primary pOsterioR TRacheopexy prevents collapse of the trachea in newborns with esophageal AtresIa and Tracheomalacia

A blind-ending esophagus, or Esophageal Atresia (EA), is very often accompanied
by a weakened windpipe (trachea). This is known as tracheomalacia (TM) and
entails that the windpipe collapses during expiration. Severe TM can cause
increased respiratory morbidity, including frequent respiratory tract
infections and blue spells, that can potentially progress to respiratory
arrest. Respiratory morbidity poses a significant burden on EA patients, both
in the short term and over the course of long-term follow-up. When severe TM is
identified, surgical intervention may be necessary. This surgical procedure
involves widening the trachea (using sutures) to prevent its collapse, known
as posterior tracheopexy (PT). Prior to performing this PT, complications and
sequelae of TM may have already manifested. Additionally, performing this PT as
a secondary operation after correcting the EA is a complex surgical procedure
in newborns, and poses a significant risk of damaging the recently performed EA
anastomosis. This separate, secondary PT also requires several hours of
surgery, due to the presence of extensive adhesions. As a result, there has
been a growing trend to carry out the PT concurrently with the initial
correction of EA, known as a primary posterior tracheopexy (PPT). Previous
studies have shown a decrease in respiratory tract infections (RTI*s) and brief
respiratory unexplained events (BRUE*s) following the implementation of a PPT,
when compared to patients who did not undergo PPT. However, it's important to
note that these studies were predominantly conducted at a single medical center
and relied mostly on retrospective data analysis To address several sources of
bias, such as center-specific factors, selection-bias and information bias, a
double-blind randomized controlled trial should be conducted.
To accurately evaluate the effects of PPT versus no-PPT (i.e. the tracheal
diameter) a bronchoscopy needs to be performed, as it is the only objective
measure for this purpose. Bronchoscopy allows for a direct visual examination
of the trachea, ensuring a reliable and unbiased evaluation of the impact of
PPT on tracheal diameter.

The aim of this study is to evaluate if a PPT can significantly decrease - or
possibly prevent - the collapse of the trachea in newborns with EA and moderate
or severe TM. Additionally, the study aims to determine whether the observed
effect of PPT on tracheal stability is sustained over time.

A double-blind randomized controlled trial

randomization between performing a PPT or no-PPT

Burden:
To determine whether PPT is superior in preventing or reducing tracheal
collapse, and subsequently respiratory morbidity, compared to no-PPT, a
randomized double-blind trial is necessary.
This trial will eliminate dependence on other factors specific to individual
centers and provide generalizable results. Importantly, since EA correction
with PPT (more recently implemented in centers of expertise) and without PPT
are both accepted and safe treatment options, participating in the trial does
not pose an increased risk or burden for the participants with regards to the
treatment. However, randomization of patients in this trial can be burdensome
as it involves assigning them to either the PPT or no-PPT group based on
chance. Parents/caretakers may have preferences or expectations regarding
treatment, and being randomized to a specific group may not align with those
preferences.
To address this burden, it is important to carefully explain the rationale and
significance of randomization to the parents/caretakers. Providing clear and
comprehensive information about the trial design, objectives, potential
benefits, and the importance of unbiased evaluation can help alleviate concerns
and ensure informed decision-making. Maintaining open communication channels
and offering support throughout the trial can also help alleviate any emotional
or psychological burden associated with the randomization process.

Performing intra- and postoperative bronchoscopies may pose a potential burden
in the trial. However, a bronchoscopy is a routine diagnostic procedure
commonly used to safely assess the condition of the trachea, even in newborns.
Complications arising from bronchoscopy are rare. An intra-operative
bronchoscopy through the ventilation tube is always performed in patients with
a PPT as routine care. In patients with ventilatory problems, even without PPT,
bronchoscopy can also be routinely performed. In this double-blind randomized
trial, all patients will undergo the intra-operative flexible bronchoscopy
through the ventilation tube. However, considering the controlled
circumstances, there is negliglible burden and negliglible risk.
After the correction of esophageal atresia (EA), newborns are typically
extubated in the neonatal or pediatric intensive care unit (ICU) within a few
days. During this extubation process, the first postoperative bronchoscopy is
conducted through the ventilation tube by a pediatric otorhinolaryngologist,
with the presence of either the ICU specialist and ICU nurse. Therefore, the
burden and risk associated with the bronchoscopy procedure are considered
negligible, given the controlled and supervised environment it is performed.
The duration of this bronchoscopy is 15 seconds.
The second postoperative bronchoscopy may present a burden due to the need for
readmission and administration of general anesthesia in the operating theatre.
However, a routine bronchoscopy in the surgical theatre is often performed in
all (Karolinska Institutet and Great Ormond Street Hospital) or half
(Wilhelmina and Sophia Children*s Hospital) of the EA patients, depending on
the treating center. Thus, only in a small percentage of the trial participants
an extra bronchoscopy is needed. Especially since the majority of these latter
patients undergo a esophagogastroscopy under general anesthesia for clinical
reasons (eg dilatation/eosinophilic esophagitis). In these patients the 2nd
postoperative bronchoscopy will be performed during this planned
esophagogastroscopy.The general anesthesia is administered to safely and
effectively perform the bronchoscopy in a controlled and supervised
environment. The bronchoscopy is the only objective measure to evaluate the
degree of collapse in these patients. This second postoperative bronchoscopy
will determine if the observed effect of the PPT on tracheal stability is
sustained over time. Also, this burden is justifiable due to the potential
deterioration of tracheal collapse that can occur in the first months following
the initial EA correction. Conducting a second postoperative bronchoscopy
allows for the identification of patients whose condition has worsened. The
ability to identify such patients may outweigh the associated risks or added
burden of the procedure in a small percentage of the trial participants.
Moreover, if there is no difference between the intra-operative bronchoscopy
and the first and second bronchoscopies, this could mean that in the future, we
could sustain with only the (less burdensome) intra- (or first post-) operative
bronchoscopy. The respiratory complaints will be evaluated to research if the
degree of TM corresponds with the severity of the symptoms.

Group relatedness:
The advantage of conducting the primary posterior tracheopexy (PPT) earlier in
the treatment process will become evident through the results of this
randomized controlled trial (RCT). If PPT demonstrates superior outcomes, it
could lead to a reduction in postoperative complications and interventions,
including bronchoscopies under general anesthesia and additional extensive
surgeries for secondary PPT. Conversely, if the secondary posterior tracheopexy
(PT) yields better results, it could mean fewer babies having to undergo an
unnecessary PPT procedure. The trial will provide valuable insights to guide
the optimal timing for tracheopexy and approach of tracheomalacia in improving
patient outcomes/symptoms.
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