Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02693977 |
| Other study ID # |
IRB00009825 |
| Secondary ID |
1K23HL127132-01A |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2015 |
| Est. completion date |
March 31, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
Oregon Health and Science University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Pediatric obstructive sleep apnea (OSA) is associated with heavy snoring and brief pauses in
breathing during sleep. It affects at least 1-3% of the general pediatric population with
greater prevalence among certain high risk groups such as children with obesity, Down
syndrome, craniofacial anomalies, or neuromuscular disorders. Several studies have shown
that, even after having adenotonsillectomy (AT), approximately 30% of children continue to
struggle with OSA. They further found that older children (age > 7 yrs), obesity, and high
pre-operative OSA severity were all risk factors contributing to residual OSA. Despite these
known risk factors, the ability to predict each individual patient's risk of residual OSA
after tonsil surgery is difficult. Determining what tool will best predict residual OSA is an
important step towards more effective post-surgery OSA management.
The purpose of this study is to determine whether sleep endoscopy can predict whether their
AT will be successful as a treatment for OSA. Our hypothesis is that subjects with multiple
areas of obstruction in addition to large tonsils will be more likely to have residual OSA
after AT. Sleep endoscopy is a procedure performed during drug-induced sleep that involves
passing a flexible endoscope through the subject's nose into the back of the throat to look
for sources of obstruction while breathing spontaneously.
This will be a prospective cohort study examining subjects between the ages of 2 and 18 who
are having AT for treatment of obstructive sleep apnea (OSA) and are considered high risk for
residual OSA after surgery. High risk will be defined based on the following criteria:
obesity, Down syndrome, African American race, severe baseline OSA, and age > 7 yrs. Eligible
subjects will be recruited from the pediatric otolaryngology clinic at the time of initial
evaluation for AT. Subjects will undergo a sleep endoscopy under moderate sedation at the
time of AT. All patients will be asked to complete a preoperative sleep study to confirm the
diagnosis of OSA and a postoperative sleep study to determine the impact of AT and the
presence of residual OSA. Secondary outcome measures will include several questionnaires
assessing generic and OSA-specific quality of life as well as subjective measures of
cognitive/executive functioning and daytime sleepiness.
Description:
The purpose of this study is to determine whether sleep endoscopy performed in high-risk
pediatric patients with obstructive sleep apnea (OSA) at the time of adenotonsillectomy (AT)
can predict whether the AT will be successful as an initial treatment for OSA. We hypothesize
that patients with multiple sites of obstruction in addition to adenotonsillar hypertrophy
(e.g. the nasal airway, velum, base of tongue, supraglottis) will be more likely to have
residual sleep apnea on postoperative sleep testing.
Obstructive sleep apnea syndrome OSAS is defined as the symptomatic repetitive obstruction of
the upper airway during sleep and has been estimated to affect 1-6% of the general pediatric
population. Untreated OSAS in children has been associated with childhood hypertension,
autonomic dysfunction, attention deficit/hyperactivity disorder, neurobehavioral impairment,
and poor quality of life. These sequelae contribute to a 226% increase in health care
utilization among children with OSAS compared to controls, primarily in the form of increased
hospitalizations, emergency department visits, and medication use. Adenotonsillar hypertrophy
is considered the most common risk factor for OSAS in children, therefore unlike in adult
OSAS, adenotonsillectomy (AT) is the recommended first line treatment. In large part due to
the increasing awareness and diagnosis of pediatric OSAS, the incidence of AT increased
dramatically from 1980 to 2005. With more than 500,000 procedures performed per year, AT is
now the second-most common procedure performed in children in the US, and 77% of these have
OSAS as the primary indication.
Current guidelines recommend AT as a first line treatment for pediatric OSAS even for those
patients who may have significant risk of post-AT OSAS. Estimates of the prevalence of
persistent OSAS after AT vary widely due to use of different polysomnographic criteria for
diagnosis. Studies that assessed the risk of post-AT OSAS using a conservative adult
threshold for diagnosis demonstrated that even with this high threshold at least 13-29% of
children undergoing AT for pediatric OSAS will have significant residual disease and
approximately 75% of children will fail to achieve normalization on polysomnography. Specific
populations of patients that have been recognized to be particularly at risk for post-AT OSAS
include those with severe baseline OSAS, Down syndrome, obesity, and age > 7 years. In obese
patients, the prevalence of post-AT OSAS has been reported as high as 73-88%. Since obesity
has tripled over the last three decades and now affects approximately 8% of children aged 2-5
years, 18% of children aged 6-11 and 21% of adolescents aged 12-19 years, the problem of
persistent OSAS after AT is likely to continue to grow.
Even within populations at risk for AT failure, there is a wide variation in treatment
response. One study of morbidly obese children undergoing AT demonstrated only a 37% cure
rate while 53% had sufficient residual OSAS to require further treatment with continuous
positive airway pressure (CPAP). However, no significant baseline differences were identified
between surgical responders and non-responders. The mechanism for failure in this population
is unclear, but it is presumed that increased generalized adiposity leads to multilevel
obstruction similar to obese adults, thus decreasing the likelihood of success with AT.
Similarly a poor but still variable response to AT was observed in children with Down
syndrome with post-AT success varying between 18% and 55% depending on the specific criteria
used. There are no studies that have clearly identified predictors of AT outcome within the
Down syndrome population, however, some studies of Down syndrome patients who failed AT have
suggested that multilevel obstruction is common. Thus, although specific populations of
patients are known to have greater risk of post-AT OSAS on average, the individual
characteristics causing persistent disease remain unclear. Accurate prognostication of the
risk of residual OSA after AT for any individual patient remains a challenge. Studies of
patients with persistent post-AT OSAS have suggested that multilevel obstruction at locations
besides the tonsils or adenoids are likely contributors, but this has not been clearly
demonstrated. In this study, we present a novel concept for building a composite model to
predict the outcome of AT in children with OSAS. This model will include not just baseline
features of history and physical exam but also the findings of dynamic sleep-related collapse
at specific anatomic sites in the pharynx observed during sleep endoscopy. This model will
give further insight into the mechanisms of airway obstruction as well as the possible
reasons for persistent OSAS after AT.
A rating scale for DISE has previously been described in an attempt to standardize the
reporting of endoscopic findings in adults with OSAS. This rating scale evaluates the degree
and pattern of obstruction at four levels of the pharynx: the Velum (soft palate), Oropharynx
(including the tonsils), Tongue base, and Epiglottis (VOTE). The VOTE rating scale has been
demonstrated to have moderate to substantial inter-rater reliability with kappa values
ranging from 0.4-0.8 depending on the specific structures being compared. Other investigators
have utilized modified versions of the VOTE rating scale in children, including other levels
of the airway such as the nasal airway, nasopharynx, and supraglottis. One recent study
demonstrated that sleep endoscopy findings in children were more reliable than during awake
endoscopy and noted a strong correlation between polysomnography results and the overall
impression of OSA severity during endoscopy.
Dexmedetomidine, which will be used in this study, is a highly selective α2-adrenoceptor
agonist that has been demonstrated to result in a sedated sleep similar to natural sleep
without causing respiratory depression. Though there have been some reports of transient
bradycardia and blood pressure changes in response to dexmedetomidine infusion (usually
transient hypotension of 10% with slow infusion) these cardiovascular effects are mitigated
by co-administration of a bolus of ketamine. These patients would already have been using
dexmedetomidine or a different anesthesia for their tonsil surgery. The dexmedetomidine is
not an intervention or part of this study.
In a preliminary retrospective review of our patient population and surgical volume, we
examined the electronic medical record of all patients who underwent AT over a 12 month
period. 498 patients were identified, operated on by the four pediatric otolaryngologists in
the group. Approximately 200 (40%) of these were performed for OSAS in patients that could be
considered high risk for residual post-AT OSAS and would meet inclusion/exclusion criteria
described below.
Untreated OSA in children has been associated with childhood hypertension, autonomic
dysfunction, attention-deficit/hyperactivity disorder, poor school performance, and poor
quality of life. These sequelae contribute to a 226% increase in health care utilization
among children with OSA compared to controls. Residual OSA after AT in the pediatric
population remains a serious concern; as the patient grows and changes, their airway
physiology also changes. Although there is a growing body of research suggesting demographic
and comorbidity risk factors for post-AT residual OSA, the ability to accurately predict the
likelihood or severity of residual OSA for any given individual remains elusive. Possible
tools for the evaluation of post-AT OSA in pediatric populations include radiologic
examinations, cine MRI scanning, and endoscopic evaluation, along with polysomnography,
validated questionnaires, and physical examinations. Determining what instruments best
predict residual OSA after surgical intervention is an important step towards more effective
OSA management.
