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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 29-39

Review findings of drug-induced sleep endoscopy (DISE) in children with obstructive sleep apnea (OSA)


Department of Paediatrics and Adolescent Medicine, Kwong Wah Hospital, Hong Kong SAR, China

Date of Submission20-Apr-2022
Date of Decision27-May-2022
Date of Acceptance13-Jun-2022
Date of Web Publication20-Jul-2022

Correspondence Address:
Gerry Man-Fung Yeung
Department of Paediatrics and Adolescent, Kwong Wah Hospital, 25 Waterloo Road, Hong Kong SAR
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/prcm.prcm_5_22

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  Abstract 

Background: Drug-induced sleep endoscopy (DISE) is an objective assessment and diagnostic procedure of the upper airway obstruction (UAO) under sedation. Findings of DISE in Hong Kong pediatric group patients with obstructive sleep apnea (OSA) are limited. Materials and Methods: This is a single-center retrospective chart review study on DISE findings in pediatric patients with OSA documented by polysomnography (PSG). We used the DISE scoring system proposed by Chan 2014, Fishman 2013 together as our internal practice. A standard sedation protocol was conducted. Endoscopic findings were recorded and evaluated the level of obstruction, severity, and correlation with PSG parameters. Results: A total of 124 patients who underwent DISE were reviewed in our study. Multiple levels of obstruction had been observed in all patients. Forty-five (36.6%) patients suffered from severe obstruction in more than one level. Tongue base was the most common level being severely obstructed. DISE total score is positively correlated with obstructive apnea-hypopnea index (oAHI, r = 0.35, P = <0.001), negatively correlated with oxygen nadir (SpO2 nadir, r = –0.32, P = <0.001), and positively correlated with desaturation index (DI, r = 0.34, P < 0.001). In the subgroup analysis of the post-adenotonsillectomy (AT) group, scores in nostrils, tongue base, and supraglottic showed significantly increased. None of the subjects had complications from sedation or the endoscopy procedure. Conclusion: In our study, DISE was shown to be a safe, feasible, and informative assessment tool for pediatric OSA patients. In particular, multiple levels of obstruction were common in children and we observed a significant correlation between the severity of UAO measured by DISE in children with OSA and PSG parameters. Changes in UAO sites were observed when preoperative patients underwent surgical treatment.

Keywords: DISE, drug-induced sleep endoscopy, obstructive sleep apnea, pediatric


How to cite this article:
Yeung GM, Leung SY, Kwok KL. Review findings of drug-induced sleep endoscopy (DISE) in children with obstructive sleep apnea (OSA). Pediatr Respirol Crit Care Med 2021;5:29-39

How to cite this URL:
Yeung GM, Leung SY, Kwok KL. Review findings of drug-induced sleep endoscopy (DISE) in children with obstructive sleep apnea (OSA). Pediatr Respirol Crit Care Med [serial online] 2021 [cited 2022 Oct 3];5:29-39. Available from: https://www.prccm.org/text.asp?2021/5/2/29/351529




  Introduction Top


Obstructive sleep apnea (OSA) affects up to 6% of children worldwide.[1],[2] This is a sleep-related breathing disorder caused by upper airway obstruction (UAO) characterized by snoring and/or increased respiratory effort. Evidence has demonstrated that left untreated cases are associated with long-term comorbidities including neurocognitive, behavioral disturbances, and cardiovascular dysfunction.[3] The American Academy of Pediatrics (AAP) suggested adenotonsillectomy (AT) as the first-line treatment for OSA children with adenotonsillar hypertrophy.[4] However, persistent OSA after AT was common. Data on OSA improvement following AT remain inconclusive, with a variable success rate between 12% and 83% observed depending on the characteristics of the study population.[5]

Drug-induced sleep endoscopy (DISE) provides a direct evaluation of the dynamics of upper airway using flexible endoscopy while patients are put under sedation.[6] It can be used as a first-line assessment tool to guide subsequent management to optimize outcomes and minimize unnecessary operations like AT, and for children with persistent OSA after AT. It is also a recommended investigation for those children with significant symptoms of sleep-disordered breathing (SDB) with relatively small tonsils and adenoids, and for occult or sleep state-dependent laryngomalacia. DISE has the potential to guide the surgical decision and improve the outcome. In recent studies based on UAO findings during DISE, a non-surgical treatment was proposed for 11% of children. A 91% success rate was obtained in those treated with AT.[7]

‘Sleep naso-endoscopy’ was first described by Croft and Pringle et al. for use with adults and children in early 1990.[8],[9] Further study by Myatt and Beckenham in children with complex UAO disorders in 2000.[10] The name was changed to ‘drug-induced sleep endoscopy’ (DISE) by Kezirian and Hohenhorst in 2005 to better reflect the key elements of the procedure.[11] However, there is no universally accepted consensus on the DISE scoring system. Six different scoring systems (VOTE, SERS, Chan, Bachar, Fishman, Boudewyns) have been used to report pediatric DISE findings. VOTE is the most frequent and well published one both for adults and children but lacks scoring in the nasopharyngeal and supraglottic region.[6]

The choice of anesthetic agents for DISE remains controversial. The challenge is to find an agent that can provide analgesia to simulate a natural sleep state without causing respiratory depression, cardiovascular effects, or airway collapse beyond those seen during natural sleep.[12] The combination of anesthetic agents using dexmedetomidine (DEX) and ketamine is commonly used, because it carries lower risk of respiratory depression and UAO in children as compared with other agents like inhalational agents.

Data on DISE findings in Hong Kong children with OSA are limited. A better understanding of multiple-level airway obstructions in OSA children is crucial to directing a precise and effective treatment plan.


  Materials and Methods Top


We conducted a retrospective chart review study in the Department of Pediatrics, Kwong Wah Hospital. Patients aged from 2 years old to less than 18 years old, confirmed with OSA by polysomnography (PSG) undergoing DISE between December 1, 2016 and December 31, 2019 were included. Significant medical illnesses, such as cardiac, respiratory, or renal insufficiency, or dysmorphic syndrome, would be excluded. The primary outcome includes the DISE score in different levels of UAO (nasal obstruction, adenoids, velum, lateral pharyngeal wall (LPW), tongue base, and supraglottis); whereas the secondary outcome includes a correlation between DISE findings with PSG parameters, and the safety of our DISE protocol.

The obstructive apnea–hypopnea index (oAHI) was defined as the number of obstructive apneas and hypopneas per hour of sleep. OSAS was defined as an oAHI ≥ 1/h. OSAS was classified as mild (oAHI between 1 and 5/h), moderate (oAHI 5–10/h), or severe (oAHI ≥ 10/h).

Pediatric sleep questionnaire (PSQ) is one of the most popular parent-report scales for screening sleep problems in children with good validity and reliability.[13] Selected 22 question-items scale (PSQ: SRBD, Pediatric Sleep Questionnaire: Sleep-Related Breathing Disorder Scale) contains 22 symptom items that ask about snoring frequency, loud snoring, observed apneas, difficulty breathing during sleep, daytime sleepiness, inattentive or hyperactive behavior, and other pediatric OSA features. Score 8 or more positive answers to the 22 question-items were considered abnormal with a sensitivity of 0.85 and a specificity of 0.87. We obtained PSQ results in most of our study populations (n = 114).

We developed a standardized DISE sedation protocol with a combination of midazolam (dose range from 0.05 mg/kg/dose to 0.1 mg/kg/dose) and fentanyl (0.5 µg/kg/dose to 2 µg/kg/dose). Lignocaine (2%) was used to topically anesthetize the nasal mucosa. The level of sedation was assessed by UMSS (The University of Michigan Sedation Scale [Figure 1]),[14] which provided the level of alertness on a 5-point scale ranging from 1 to 5. It is a simple, valid, and reliable tool for rapid and frequent assessment on the depth of sedation in children
Figure 1: Level of sedation during endoscopy (University of Michigan sedation scale, UMSS)

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Digital records of all endoscopies were maintained sequentially and were available for review. In our unit, we combined the Chan and Fishman[15],[16] scores to better assess UAO. It included nasal, adenoids, velum, LPW, tongue base, and supraglottis, a total of 6 levels (see [Figure 2] for detailed information on the scoring system). Multiple level obstruction was defined as the presence of obstruction on more than one level.
Figure 2: Drug-induced sleep endoscopy (DISE) scoring system

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The study was approved by the Research Ethics Committee of the Kowloon Central/Kowloon East Clusters of the Hospital Authority in Hong Kong.

Statistical analysis

The normality of data was assessed by the Shapiro–Wilk test. Continuous variables were presented as the mean ± standard deviation (SD). Non-normal variables were reported as median (interquartile range [IQR]). Categorical variables are summarized as frequencies and percentages. Pearson’s correlation coefficient analysis was used for assessing the association between DISE findings and PSG parameters. Parametric and non-parametric data were compared using Student’s t test or Mann–Whitney U test, respectively. The chi-square or Fisher’s exact tests were used to compare proportions. Paired t test or Wilcoxon signed ranks test was used for comparing continuous variables such as DISE findings, PSG parameters, mESS score, OSA-18 score, and PSQ: SRBD score before and after operation. McNecmar test was used for paired nominal data. A p-value <0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM, Armonk, New York).


  Result Top


A total of 161 DISE were conducted during the study period. Thirty-seven were excluded (30 were syndromal cases and 7 were missing prior PSG reports). Finally, 124 sleep endoscopies met the inclusion criteria and were eligible for analysis. Ninety-seven of them were surgical naïve patients, whereas 27 were post-adenotonsillectomy (post-AT) cases [Figure 3]. Demographic data are shown in [Table 1].
Figure 3: Flow chart of study population

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Table 1: Demographic, anthropometric, and PSG parameters

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The median age at the time of endoscopy was 12.7 years old (IQR 9.4–15.3), with a slight male preponderance (95, 76.6%). Obesity, defined as body mass index (BMI) with z score >1.645 (i.e., 95th percentile), was noted in 35 patients (28.2%). The median of sleep efficiency (SE) was 90.3% (IQR 84.7–94.1%), whereas the median of total sleep time (TST) was 432.8 min (IQR 385.6–476.8 min). Over half of the patients (65, 52.4%) in the study population had mild OSAS. 17.7% and 29.8% of them had moderate and severe OSAS, respectively. The median oxygen saturation nadir was 90% (SpO2 nadir, IQR 86–92%). The median desaturation index (DI) was 1.8/h (IQR 0.3–6.8/h). One-third of them have obstructive hypoventilation defined as 25% of total sleeping time with PaCO2 >= 50 mm Hg. PSQ:SRBD score was obtained in 114 patients with a median score of 7.5 (IQR 5.0–11.0). The number of patients with obesity was more in the surgical naive group compared to the post-AT group (n = 32 vs n = 3, P = 0.025). Lower PSQ: SRBD score was found in post-AT groups (n = 88, 8.5 vs n = 26, 6.5, P = 0.043).

Based on the grade of obstruction sites observed during DISE, their prevalence could be determined. All study populations (N = 124) had multiple levels of obstruction, defined as mild obstruction or obstruction score >=1 in more than one level. Forty-five patients (36.3%) had severe obstructions or obstruction score=3 in more than one level. For severe obstruction or obstruction score =3, tongue base was the most common level of obstruction (n = 54, 43.5%), followed by lateral pharyngeal wall (LPW) (n = 30, 24.2%), velum (n = 18, 14.5%), nasal, adenoid and supraglottic were comparable (n = 17, 13.7%).

The median of the total obstruction score, defined as the sum of the obstruction score in all six levels, was 10 (IQR 8–11) (DISE results are shown in [Table 2]). There was no difference in total score between surgical naive and post-AT group.
Table 2: DISE findings

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There were significantly higher scores in the tongue base obstruction in the post-AT group (3 vs. 2, P = 0.005) than in the surgically naive group. The post-AT group had significantly lower LPW obstruction (0 vs. 2, P < 0.001). The obstruction scores at the nostril, adenoid, and supraglottis level did not differ significantly between the two groups.

Based on the correlation analysis, oAHI was significantly correlated to the total obstruction score (r = 0.352, P < 0.001). In a similar way, DI was significantly associated with total obstruction score (r = 0.342, P < 0.001). SpO2 nadir was negatively correlated with the total obstruction score (r = –0.315, P = < 0.001) [Figure 4]. Using our DISE scoring system, we have demonstrated that oAHI, DI and SpO2 nadir on pre-procedural PSG correlate with severity of UAO in pediatric patients with OSA.
Figure 4: Correlation between total obstruction score and oAHI, DI, and SpO2 nadir

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The level of sedation was assessed by UMSS (University of Michigan Sedation Scale), and the median is 1 (1 = Minimally sedated: tired/sleepy, appropriate response to verbal conversation and/or sound).

There were no complications nor adverse events during sedation and procedure of DISE.

For the post-AT group (n = 27), we performed a subgroup analysis to determine if ther e was a difference in their demographic and UAO status between pre and post-surgery. For comparison, 23 out of 27 patients had both pre- and post-AT PSGs. Seven of the pre-AT endoscopy records fell within our study period. We retrospectively scored 16 pre-AT endoscopy records using our updated DISE scoring system.

Regarding their demographic data, oAHI, DI and SpO2 nadir showed no difference before and after surgery. PSQ:SRBD showed lower after surgery [Table 3].
Table 3: Subgroup analysis of the post-AT group: demographic, anthropometric, and PSG parameters (n = 23)

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Compared to the pre-AT group, the total obstruction score was significantly lower (10 vs. 9, P = 0.034) in the post-AT group. LPW and adenoid scores were also significantly lower in the post-AT group. There was, however, a significant increase in obstruction scores in the post-AT group in the nasal, tongue base, and supraglottis scores. Velum scores showed no significant change [Table 4].
Table 4: Subgroup analysis of the post-AT group: DISE findings (n = 23)

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  Discussion Top


This is the first study in Hong Kong children aged from 2 to 18 years old with OSA, without syndromic condition nor comorbidity, to report on DISE findings and to establish the correlation between severity of anatomic obstruction measured by DISE and PSG parameters. According to our data, DISE is a feasible and safe way to assess dynamic airway obstruction in children with OSA. It is worth noting that our DISE procedures and PSG were done by pediatricians specialized in respiratory and sleep medicine, whereas most of the literature about DISE is written by otolaryngologists.[6]

We found that multiple-level obstructions, defined as mild obstruction or obstruction score >= 1 in more than one level, are very common among OSA children regardless of their surgical status, and 71.8% of our study participants were not obese (n = 89). This was consistent with many previous studies. As reported by Boudewyns A et al.[7] and Park et al.,[17] 56% and 49% of their study populations were found to have multilevel obstructions. Megan et al.[18] investigated DISE findings in post-AT children with persistent OSA, showing multilevel obstructions contribute to persistent sleep disorder breathing after T&A. Seckin O. Ulualp et al.[19] found that the majority of children with OSA had obstruction at multiple sites of the airway. Combination of the oropharynx/lateral walls and velum obstruction were the most common sites of obstruction.

It is beyond our expectation that 36.3% of them had severe obstructions or obstruction score=3 in more than one level. Tongue base obstruction score was significantly higher in post-AT patients while comparing to surgical naïve group. Myatt et al.[10] published a series of pediatric DISE findings in 2000 demonstrating similar findings, which common site of obstructions in surgical naive and complex disease (i.e., background with severe OSA, syndromal or cerebral palsy), was tongue base (30%), followed by velopharyngeal and tonsillar obstruction, both present in 20% of subjects. Park et al.[17] performed a similar study with one-third of them being Down Syndrome and found that the tongue base was the most common site of persistent airway obstruction. A meta-analysis by Manickam et al.[20] concluded the most common sites of obstruction were the tongue base, adenoids (secondary to regrowth), inferior turbinates, velum, and the lateral oropharyngeal walls.

In the subgroup analysis focusing comparison on pre and post-AT DISE findings, we noted that obstruction scores increased in nostrils, tongue base, and supraglottis in post-AT compared to their pre-AT status. It could be postulated that these changes were primarily responsible for persistent OSA in post-AT patients. Megan et al.[18] reported that tongue base was the most common cause (85%), followed by adenoid regrowth and inferior turbinate hypertrophy in post-AT patients.

In our unit, we routinely use DISE for airway obstruction evaluation for all children with OSA before tailor-made subsequent management. It is known that there is no consensus on the indication of DISE in children, but at least there is no strong objection to have DISE in OSA patients before surgery. A. Boudewyns[7] suggested DISE could be a routine examination in all pediatric OSAS patients prior to surgery to improve outcome. Review article[6] proposed in an update review article that the indications include persistent OSA after AT, prior to surgery for those high-risk persistent OSA cases (obesity, Down syndrome, craniofacial abnormalities and neurological impairment), significant symptoms of SDB children with small tonsil and adenoid, occult or sleep state-dependent laryngomalacia, and prior hypoglossal nerve stimulator treatment. A retrospective cohort study[21] mentioned that DISE changed surgical decisions for 30% of children with OSA and allowed the management plan to address multiple obstruction levels, although whether it provides additional benefit on treatment outcomes remains uncertain.

It is our limitation that we did not include the DISE-guided management and their surgical outcome in data analysis. Medical treatment like nasal medications, CPAP or ventilation support, oral myofunctional therapy, multidisciplinary surgical assessment with dentist and ENT, and weight reduction programs are common treatment modalities provided in our unit. Recent systematic review suggested that outcome is better with DISE-directed surgery in a small subset of population, that is, children with underlying comorbidity or syndrome.[22] But whether DISE-guided management would provide a better outcome among non-syndromic or surgical naive patients remains doubtful and requires further research.

We developed a standardized scoring system combining Chan[15] and Fishman[16] together based on the suggestion published in the APPS paper,[3] which includes six levels for more comprehensive information on obstruction status. We take into account both structural and dynamic upper airway abnormalities in combination with a quantification of the degree of obstruction. But it’s clear that there are no standardized protocols and validated grading scales in children under DISE. Inter-observer variability should be addressed providing that data from DISE is performed by up to eight different attending pediatricians. Williamson et al.[23] propose a standardized method of scoring and performing DISE in children with refractory OSA by adding lingual tonsil, epiglottis, aryepiglottic fold, and arytenoids into the scoring system making it a total of 10 levels to be scored. Further validation study should be followed to see if it could be applied in future clinical work.

This is the first time reported that using a combination of scoring systems, a weak to moderate correlation is obtained between total score and PSG parameters. John P. Dahl et al.[24] first reported that Chan 2014 DISE score correlated with PSG parameters including AHI and SpO2 nadir in children. De Corso et al.[25] demonstrated in an adult study that there was a good correlation between DISE obstructions severity and AHI and Epworth Sleepiness Scale scores (ESS score). Observational bias, test–retest reliability among different physicians would be generated as they were not blinded to pre-endoscopy PSG parameters.

One major controversy is about sedation, whether a drug-induced sleep state is comparable with natural sleep, especially in children whose sleep obstructive events happen frequently in rapid eye movement (REM) sleep. Updated review suggested no anesthetic agents are currently able to replicate REM sleep, and the use of DISE in children with REM obstructive disease requires cautious interpretation.[6],[12] Our sedation agents were intravenous midazolam and fentanyl. Some authors[26],[27] suggested that the majority of the dynamic airway obstruction occurred during N1 and N2 sleep while benzodiazepine causing no REM sleep and less N3 sleep duration making midazolam to be a good option for sleep endoscopy. But they also mentioned the UAO was commonly seen with an increase in nasal airway resistance and decreased airway cross-sectional area. For fentanyl, opioids are known to depress both the ventilatory and pharyngeal neuromotor drive, therefore decreasing airway patency.[12] Both of the sedation agents are so far safe and effective according to our experience with no patient suffering from sedation adverse effects. But if their sedation effect worsens the upper airway condition leading more obstructions observed in study subjects remains debatable. Dexmedetomidine and ketamine are reported to be commonly used agents in previous studies. Both of them do not lead to respiratory depression with less muscular relaxation, and with a more sustained respiratory effort. Dexmedetomidine can also replicate non-rapid eye movement (non-REM) and has been preferred for its overall safer profile based upon hemodynamic stability.[28] Moreover, this is the first study using an objective score (i.e., UMSS) to document sedation level in children under DISE. This serves as an objective measurement to see if medications are given to induce a sleep-like state in patients.

The retrospective study design, as well as the fact that this represented a single-center experience, remains the major limitation of our study. We propose to use the results from the present study as a basis for a multicenter prospective study, to evaluate the association between PSG parameters and the level of obstruction on pediatric DISE, to set up a standard or validated DISE scoring and sedation system for children, and finally to improve the outcome with DISE guided management.

Financial support and sponsorship

This study was supported by the Tung Wah Group of Hospitals Research Fund 2018/2019.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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