Drug-induced sleep endoscopy while administering CPAP therapy in patients with CPAP failure

This study was designed as a retrospective, single-center descriptive cohort study including 30 consecutive patients diagnosed with CPAP failure due to an insufficient decrease in AHI above 5 apneas per hour. All patients were previously diagnosed with OSA which was either confirmed by polysomnography (PSG) or respiratory polygraphy (home sleep apnea test or PG) and were initially treated with CPAP. During follow-up, all patients experienced persistent OSA-related complaints and repeatedly measured an AHI above 5 apneas per hour despite intensive support and additional CPAP titration. Patients were extensively discussed in the multidisciplinary sleep team, composed of ENT-surgeons, neurologists, oral and maxillofacial surgeons, and pulmonologists and were diagnosed with CPAP failure. Drug-induced sleep endoscopy with and without administering CPAP therapy was carried out in order to identify the cause of CPAP failure. Subjects with and without previous nasal and/or pharyngeal surgery were included.

Drug-induced sleep endoscopy was carried out in a quiet operating room with dimmed lights. All procedures were carried out by the same experienced ENT-surgeon (MC) with an anesthesiologist to manage sedation. Sleep was induced by an initial bolus of 1 mg/kg propofol followed by manual titration of propofol. The optimal depth of sedation was reached when the patient began to snore and/or no awakening from vocal or tactile stimuli was achieved. Once a proper level of sedation was approached, the upper airway was thoroughly observed by flexible fiberoptic laryngoscopy. The upper airway was assessed in supine position using the VOTE classification earlier described by Kezirian et al. (Table 1) [16, 17]. This classification system is commonly used to assess levels and structures that may contribute to upper airway obstruction, namely velum (V), oropharynx (O), tongue base (T), and epiglottis (E). For each anatomical level, the configuration (anteroposterior, lateral, or concentric) and severity (no obstruction, partial obstruction, or complete obstruction) of the upper airway collapse were described. Subsequently, an adapted CPAP mask—allowing an endoscope to enter the nose, while permitting to increase CPAP pressures without air leakage—was adjusted (Fig. 1). After the flexible laryngoscope was introduced into the nasal cavity via the adapted CPAP mask, CPAP therapy was started at a pressure of 6 cm H₂O and gradually enhanced until the potential obstruction was discontinued or a pressure of 16 cm H₂O was reached. Again, the upper airway was assessed by using the VOTE classification while administering CPAP therapy. Additionally, a jaw thrust maneuver was performed, in order to mimic the effect of mandibular advancement device (MAD) in combination with CPAP therapy. The jaw thrust maneuver was called positive if the obstruction was discontinued on all levels. The jaw thrust maneuver was called negative if the obstruction was still present on one (or more) levels.

The statistical analysis was performed by using Statistical Package for Social Studies (IBM SPSS Statistics version 24 for Windows, New York, NY, USA). Descriptive statistics were accomplished to create the baseline characteristics. Continuous variables are presented as means with standard deviations. Categorical variables are presented as frequencies with percentages. Comparisons between groups were performed using chi-square test for categorical variables, Student’s t test, and univariate analysis of variance (ANOVA) for continuous variables. For all analyses, a two-tailed p value of < 0.05 was considered statistically significant.

The study population consisted of 30 patients. Patients were predominantly men (80%), with a mean age of 56.8 ± 13.0 years and a mean BMI of 28.6 ± 4.5 kg/m². Previous nasal/or pharyngeal surgery was performed in 13 patients (43%). In two patients (7%), uvulopalatopharyngoplasty was performed as previous OSA treatment. Nine patients (30%) underwent previous tonsillectomy. However, in all patients, the tonsillectomy was not OSA related. Two patients (7%) underwent previous closure of a cleft palate. The mean pretreatment AHI was 42.1 ± 22.4 (7.0–96.0); the mean central breathing events per hour were 4.4 ± 6.9. The mean AHI with CPAP therapy was 26.0 ± 16.3 (5.7–69.4) (Table 2). The initial AHI and AHI with CPAP therapy are presented for each subject individually in Fig. 2. A significant decrease in AHI after CPAP therapy with an average of 16.1 events per hour was found (95% CI, 10.0–22.3; p < 0.0005). However, all patients experienced persistent OSA-related complaints and measured a residual AHI above 5 apneas per hour.

All patients underwent DISE, while CPAP was administered, during which no complications occurred. Table 3 shows DISE findings while administering CPAP therapy utilizing the VOTE classification. Figure 3 shows the distribution of the main outcomes. Eleven patients (37%) had a persistent anteroposterior (AP) collapse, including a collapse at velum, tongue base, or epiglottis level and a multilevel collapse. Eight patients (27%) had a floppy epiglottis. Five patients (17%) had a persistent complete concentric collapse (CCC) and three patients showed a laryngeal collapse (10%). In three patients (10%), no airway collapse was found after CPAP administration; in two patients, air leakage via the mouth was objectified, when closing the mouth CPAP therapy was effective. While administering CPAP therapy, a jaw thrust maneuver was performed. The obstruction was discontinued on all levels in 22 cases, two cases showed a persistent obstruction on one (or more) levels. In the three patients who did not have any upper airway collapse while administering CPAP, the jaw thrust maneuver was not performed. In the remaining three patients a jaw thrust maneuver was not reported.

The mean age, BMI, and AHI with CPAP therapy were compared between the different DISE outcomes. All variables were statistically significantly different for the different outcomes of DISE (p = 0.060, p = 0.019, and p = 0.017 respectively). An LSD post hoc test was done to specify between which groups the underlying difference was statistically significant. Firstly, patients with a persistent CCC were significantly younger than patients with a floppy epiglottis (p = 0.043) or a laryngeal collapse (p = 0.027). Patients with a laryngeal collapse were significantly older than patients encountering mask problems (p = 0.031). Secondly, patients with a persistent CCC had a significantly higher BMI than patients with a persistent AP collapse (p = 0.011) or floppy epiglottis (p = 0.002). Lastly, comparing the groups based on their mean AHI with CPAP therapy, we found that patients with a persistent AP collapse had a significantly lower AHI than patients with a persistent CCC (p = 0.015) or laryngeal collapse (p = 0.026). Patients with mask problems had a significantly lower AHI compared to patients with persistent CCC (p = 0.007) or laryngeal collapse (p = 0.010).

The distribution of different treatment options advised on account of the DISE outcome is shown in Fig. 4. In 21 of the 22 patients with a positive effect of the jaw thrust maneuver, either a MAD or a MAD combined with CPAP therapy was advised. In the other patient, a therapy including a MAD was impossible due to an edentate mandible. In four patients, a different CPAP mask was advised. One patient was advised to lose weight. In four patients, other treatment options were advised, including soft palate surgery, referral to a plastic surgeon because of CPAP failure due to an earlier unsuccessful operation of a cleft palate, and tracheotomy because of CPAP failure due to a laryngeal collapse at the level of the arytenoid cartilages.

This study has several limitations. It is obvious that assessment of the upper airway during DISE is based on subjective findings and therefore, prone to experience bias. However, previous studies have shown a moderate to substantial interrater reliability depending on the experience of the surgeon [23, 24]. Furthermore, the degree of anesthetic depth and body position can alter the upper airway collapse [25, 26]. Opponents of DISE argue that pharmacologically induced sleep, e.g., by propofol as in this study, is characterized by changing sleep patterns. Conversely, Rabelo et al. have shown that the AHI and other respiratory parameters remain unaffected [27]. It is nevertheless important not to oversedate [25]. Patients respond differently to propofol; therefore, it is stressed that the technique to elicit sleep must be standardized rather than to establish a universal concentration for all patients [27]. In this context, we used a consistent method of sedation in all patients by administering an initial bolus of 1 mg/kg. However, after the initial bolus, titration of propofol was administered manually until the patient began to snore and/or no awakening from vocal or tactile stimuli was achieved. In order to aim for a standardized technique, in future measuring sedation depth and the use of target-controlled infusion pumps should be considered. It may also be discussed that the jaw thrust maneuver to mimic the effect of a MAD is a very imprecise maneuver as it lacks reproducibility and standardization. However, despite its limitations, performing a jaw thrust maneuver can easily and routinely be implemented during DISE and might improve patient selection for (additional) MAD treatment [28]. Undoubtedly, the retrospective nature and the small sample size of this study are the limitating factors. Testing for possible associations between the outcome of DISE and the befitting treatment was not applicable due to this small sample size. Additionally, the correlations found between DISE results and age, BMI, and AHI with CPAP therapy are based on a small sample size and therefore only tentative conclusions can be drawn. Studies with a larger sample size need to be conducted in the future in order to validate these results.