A single-center pilot study comparing dexmedetomidine continuous infusion versus propofol TCI for drug-induced sleep endoscopy (DISE) : Journal of Head and Neck Anesthesia

Secondary Logo

Journal Logo

Original Study

A single-center pilot study comparing dexmedetomidine continuous infusion versus propofol TCI for drug-induced sleep endoscopy (DISE)

Alicino, Ilaria MDa; Corso, Ruggero MDb,; Barbara, Michele MDc; Dibenedetto, Valentina I. MDd; Barbara, Francesco MDc; De Benedetto, Michele MD, PhDd; Fossati, Nicoletta MD, PhDe; Cattano, Davide MD, PhDf

Author Information
Journal of Head & Neck Anesthesia 5(1):p e40, May 2021. | DOI: 10.1097/HN9.0000000000000040
  • Open

Abstract

Drug-induced sleep endoscopy (DISE) has established itself as a diagnostic procedure to identify the pattern of airway obstruction in obstructive sleep apnea (OSA) patients, thus driving the therapeutic decision making process1,2. Choosing the right drug and its administration protocol are crucial in this setting: the aim is to reproduce natural sleep as closely as possible, avoiding or minimizing the effect of the drug on upper airway muscle tone. Among the various drugs used, propofol is the gold standard for its pharmacokinetic profile, allowing a rapid onset and an equally rapid emergence from sedation3. Nevertheless, propofol can cause muscle tone loss, decrease ventilatory drive, and induce respiratory depression in OSA patients. Importantly, sedation induced by propofol does not reproduce physiological sleep4. In the last decade dexmedetomidine, a selective alpha-2 adrenergic receptor agonist reproducing the EEG pattern of physiological sleep without causing respiratory depression, has been considered as possible pharmacological alternative for DISE5,6. Several studies have confirmed the favorable properties of propofol for this procedure, yet there is relative paucity of studies comparing propofol to dexmedetomidine7. Importantly, procedural conditions may vary depending on the type of sedation regimen. We conducted a pilot real-life study comparing procedural conditions under dexmedetomidine continuous infusion with propofol target-controlled infusion (TCI). The primary aim of the study was to compare the effects of dexmedetomidine and propofol on lowest oxygen saturation (SpO2), as this is potentially the most relevant aspect of DISE in terms of safety; the secondary aim was to compare other DISE procedural conditions, namely time to obtain optimal observation, recovery time after sedation, overall procedure time, cardiovascular variables and DISE obstruction sites and grading.

Methods

Approval for this pilot real-life randomized prospective trial was obtained from the Institutional Review Board of R. Dimiccoli Hospital, Barletta, Italy (ClinicalTrials.gov NCT 03892122). From March to December 2019, 32 adults undergoing DISE at the Department of Otorhinolaryngology, Head and Neck Surgery of R. Dimiccoli Hospital were screened and 28 were eventually enrolled in the study. The patients were recruited as part of the evaluation and diagnostic decision-making process before sleep apnea surgery. Patients with a history of upper airway surgery for OSA, severe comorbidity (ASA physical status ≥3), allergy or contraindications to dexmedetomidine or propofol, and severe predicted difficult airway were excluded from the trial. After obtaining written informed consent patients were allocated to either group P (propofol-TCI; n=14) or group D (dexmedetomidine; n=14) through computer-based randomization. Airway assessment, age, body mass index, neck circumference, apnea-hypopnea index, oxygen desaturation index, peripheral oxygen saturation (SpO2) nadir (lowest SpO2 during total sleep time), mean SpO2 and percentage of total sleep time spent with SpO2<90% (CT90%) had been recorded for all patients during preprocedural polysomnography (PSG). During DISE, time to reach the observation window and overall DISE duration were recorded and ECG, pulse oximetry, noninvasive blood pressure, and bispectral index (BIS) monitored; the BIS value was kept in the 60–80 range, ideally corresponding to a Ramsay Sedation Scale (RSS) score of 5. Cardiorespiratory and clinical variables were recorded at 5-minute intervals from the beginning of sedation (T0-sedation) up to 20 minutes (T4-sedation). Group P received sedation via propofol infusion by a TCI pump (B. Braun Perfusor Space Target Controlled Infusion Device, B. Braun Medical Ltd, UK) with initial propofol effect-site target concentration of 2.0 µg/mL, increased by 0.3 µg/mL every 2 minutes (Schnider model). Group D received sedation via a dexmedetomidine bolus of 1 µg/kg given over 10 minutes, followed by infusion at 0.7 µg/kg/h. The induction of sleep state was titrated to a clinically defined end point of (1) absent response to verbal commands, (2) audible snoring present, and (3) upper airway obstruction observed during endoscopy. At this point, the assessment of the upper airway obstruction during DISE was performed after the first cycle of snoring and obstruction had been completed and at least 2 cycles of obstructed breathing had been observed for each subsite, as recommended by the European position paper on DISE8. The optimal observation was determined by the endoscopist, who was blinded to treatment arm. The grade and patterns of upper airway collapse were recorded with the VOTE classification system8. After the completion of DISE, drug infusion was stopped (T0-recovery) and patients were taken to the recovery room (RR), where they were observed at regular intervals (10 min) from T0 up to an hour (T6-recovery). At these intervals, Aldrete and RSS scores were recorded. STATA MP (StataCorp LLC, Texas) was used for the statistical analysis. Parametric and nonparametric variables (mean, SD, median, and interval) were analyzed (t test; Wilcoxon rank-aggregate; analysis of variance, χ2) accordingly. A P-value of <0.05 was considered statistically significant. No power analysis was provided due to the nature and sample size of the pilot study.

Results

A total of 28 patients were enrolled and completed the study (Fig. 1): the cohort included 26 males (92.85%) and 2 females (7.14%). The mean age was 45.4±11.1 [interquartile (IQ), 25.0–65.0] years, body mass index 30.5±3.4 kg/m2 (IQ, 21.0–36.0), and apnea-hypopnea index 36.9±21.1 events/hour (IQ, 7.8–95.0) (Table 1). There were no intraprocedural complications and no patient required airway rescue interventions (including use of supplemental oxygen). No significant differences were identified in the presedation physiological variables between the 2 groups (T0-sedation). However, few differences were identified during the observation window (procedural phase) for heart rate (P<0.001), SpO2 (P<0.001), and RSS (P<0.001; Fig. 2) while mean arterial pressure (P=0.08; Table 2) was not found to be significantly different.

F1
Figure 1:
Consolidated standards of reporting trials flowchart.
Table 1 - Patient characteristics.
Variables Group P (n=14) Group D (n=14) Total (n=28) P
Age (y) 46.9±11.6 (25.0–65.0) 43.9±10.8 (30.0–63.0) 45.4±11.1 (25.0–65.0) 0.486
Males 12 (85.7) 14 (100.0) 26 (92.9) 0.481
BMI 31.4±3.2 (25.4–36.0) 29.7±3.5 (21.0–34.0) 30.5±3.4 (21.0–36.0) 0.183
ESS 11.9±4.8 (5.0–20.0) 12.4±6.1 (4.0–24.0) 12.1±5.4 (4.0–24.0) 0.811
NC 43.4±3.1 (38.0–51.0) 43.4±1.7 (41.0–47.0) 43.4±2.5 (38.0–51.0) 0.970
AHI 41.1±23.2 (10.3–95.0) 32.7±18.6 (7.8–60.0) 36.9±21.1 (7.8–95.0) 0.300
ODI 32.0±17.7 (9.8–61.6) 24.1±15.7 (1.6–50.3) 28.1±16.9 (1.6–61.6) 0.218
SpO2 91.2±3.0 (85.0–95.5) 92.5±2.8 (84.4–95.4) 91.9±2.9 (84.4–95.5) 0.182
SpO2 nadir (PSG) 73.8±10.1 (51.0–89.0) 76.6±7.9 (57.0–89.0) 75.8±9.4 (51.0–89.0) 0.667
CT 90% 11.0±12.4 (0.0–30.0) 9.1±9.4 (0.0–28.0) 10.1±10.8 (0.0–30.0) 0.658
All variables expressed as mean±SD (range), except age and males (% vs. females) as numbers.
AHI indicates apnea-hypopnea index (average events/hour); BMI, body mass index (kg/m2); CT90%, percentage of time spent below 90% saturation (%); D, dexmedetomidine; ESS, Epworth sleepiness scale; NC, neck circumference (cm); ODI, oxygen desaturation index (average events/hour); SpO2, peripheral oxygen saturation (%); SpO2 nadir, lowest peripheral oxygen saturation (%).

F2
Figure 2:
Nadir SpO2 between propofol and dexmedetomidine. The comparison includes the SpO2 values obtained during natural-induced sleep (spontaneous) or drug-induced sleep polysomnography. Nadir SpO2=lowest peripheral oxygen saturation during DISE=P<0.001. DISE indicates drug-induced sleep endoscopy.
Table 2 - Hemodynamic and SpO2 variations during DISE sedation.
T0 (0 min) T1 (5 min) T2 (10 min) T3 (15 min) T4 (20 min)
MAP group P 93.8±7.9 90.3±6.2 89.1±5.7 90.4±4.7 91.4±4.7
MAP group D 93.7±3.8 94.0±6.2 93.2±9.7 92.3±8.4 91.1±7.3
HR group P 77.5±10.9 79.3±10.9 79.3±11.6* 79.6±9.9* 80.4±8.9*
HR group D 72.1±10.9 67.6±9.4 60.4±6.5* 62.2±6.2* 62.8±6.6*
SpO2 group P 97.9±0.9 90.6±4.8 81.4±7.7* 79.9±6.7* 80.3±7.3*
SpO2 group D 97.9±1.0 95.8±2.7 93.0±4.9* 89.5±4.4* 89.6±4.1*
*P<0.001, when comparing the 2 groups.
HR indicates heart rate (b/m); MAP, mean arterial pressure (mm Hg); SpO2, peripheral oxygen saturation (%).

During DISE, patients in group D had lower heart rate at T2, T3, and T4-sedation (P<0.001; Table 2) than those in group P; however, no pharmacological treatment for bradycardia was required. As for peripheral oxygenation, whereas group P and D were comparable for SpO2 nadir in pre-DISE PSG studies (73.8±10.1% vs. 76.6±7.9%, respectively), group P SpO2 nadir during DISE (75.0±11.0%) was significantly lower than group D (87.09±5.4%; P<0.001; Fig. 2). When comparing preprocedural PSG versus intraprocedural DISE SpO2 levels within the same group, group P nadirs were similar (73.8±10.1% vs. 75.0±11.0%; P>0.5), whereas group D had a less pronounced SpO2 nadir during DISE, that is a higher SpO2 (87.09±5.4%), when compared with PSG levels (76.6±7.9%; P<0.001; Fig. 2). The time to ideal sedation and observation window was faster in group P than group D; recovery time was also faster in group P with a significantly shorter time to Aldrete score ≥9 (9.1±1.9 vs. 40.4±9.0 min, P<0.001; Table 3). The RSS (≤2) mirrored the Aldrete sedation score (Fig. 3). As regards obstruction site findings, no significant differences were identified between the 2 groups (Table 4). In the RR, all patients were monitored continuously for recurrent respiratory events for 60 minutes: for all cases the observation periods in RR and on the general ward were both uneventful.

Table 3 - Intraexamination and postexamination DISE variables.
Variable Group P (n=14) Group D (n=14) Total (n=28) P
Time to observation window (min) 8.1±1.6 (6.0–12.0) 14.7±2.8 (10.0–20.0) 11.4±4.0 (6.0–20.0) 0.001
SpO2 nadir during DISE (%) 75±11 (51.0–89.0) 87.9±5.4 (78.9–94.0) 80.8±10.7 (50.0–94.0) 0.001
Time to Aldrete score ≥9 (min) 9.1±1.9 (5.0–12.0) 40.4±9.0 (27.0–50.0) 24.7±17.2 (5.0–50.0) 0.001
Overall DISE time (from DISE beginning to Aldrete ≥9) (min) 26.5±4.0 (19.0–33.0) 65.5±10.7 (48.0–80.0) 46.0±21.4 (19.0–80.0) 0.001
Data expressed as mean±SD.
D indicates dexmedetomidine; DISE, drug-induced sleep endoscopy; P, propofol TCI; SpO2 nadir, lowest peripheral oxygen saturation during DISE.

F3
Figure 3:
Sedation scores during and post drug-induced sleep endoscopy (DISE). A, Ramsay Sedation Score (RSS) variation during DISE. B, RSS variation post-DISE. C, Aldrete score variation post-DISE.
Table 4 - VOTE classification findings of upper airway obstruction in propofol-based and dexmedetomidine-based drug-induced sleep endoscopies (N=28).
Group P Obstruction N=14 Group D Obstruction N=14
Site of Obstruction Complete (Collapse) Partial (Vibration) None (No Vibration) Complete (Collapse) Partial (Vibration) None (No Vibration) P<0.05
Velum
 AP 9 0 0 5 3 0 NS
 Lateral 0 0 0 0 0 0
 Concentric 0 0 0 0 0 0
Oropharynx: lateral 5 5 6 5 0 NS
Tongue base: AP 6 0 0 4 2 0 NS
Epiglottis
 AP 2 0 0 1 0 0 NS
 Lateral 0 0 0 0 0 0
Values in n (%). Levels of obstruction were evaluated with the VOTE classification system: velum, oropharyngeal-lateral walls, tongue base, and epiglottis.
Pearson χ2 test.
AP indicates anterior-posterior; NS, nonsignificant.

Discussion

The present pilot study offers a small-scale but clinically interesting opportunity to evaluate the efficacy of dexmedetomidine in a real-life scenario, highlighting some of the strengths and shortcomings of a drug that has received attention in several settings (operative sedations, intraoperative use, critical care): in the context of DISE, dexmedetomidine continues to attract some interest, especially by nonexperts, as an agent hypothetically preventing deeper and longer desaturations. Therefore, we aimed to assess whether dexmedetomidine, in light of its pharmacodynamic properties, could replace propofol for DISE if needed or preferred, and with the main purpose to assess the timing and quality of peripheral oxygen desaturations, in respect of the procedure goals, that is the reproduction of airway obstruction patterns for the identification of the ideal surgical intervention9,10. Propofol has consistently established itself as the gold standard for sedation in this setting as it combines overall safety and time effectiveness. Moreover, several studies have shown that findings in DISE tests conducted under propofol sedation led to appropriate surgical outcomes11,12. Propofol can be administered in boluses or as an infusion. TCI technology, the most reliable and reproducible infusion device, is not available in the United States despite the large number of sleep apnea surgery procedures, stimulating the search for alternative solutions2. In the probability ramp approach the distribution is determined by infusing propofol in the defined manner while observing for airway collapse; the total amount of propofol used to achieve this condition is noted, and the effect site concentration estimated using the pharmacokinetic model of Cortínez et al13. The validity of this approach has been demonstrated by a recent study on >400 procedures of DISE14. However, some of the pharmacological effects of dexmedetomidine (little or no influence on upper airway tone, a more physiological sleep, less pronounced desaturation) could make it a valid alternative for DISE sedation in selected cases15. In the present study no propofol rescue boluses were needed for group D, nor were they included in the protocol: dexmedetomidine dosage was somewhat higher than in most published studies, which also utilize hybrid pharmacological models. In a study using low-dose dexmedetomidine (1 µg/kg for 10 min, followed by 0.2–1.4 µg/kg/h) Cho et al16 had reported inadequate sedation in one-half of the patients requiring an additional administration of propofol. Similarly, Elkalla and El Mourad17 have recently reported about the need for propofol rescue doses with low-dose dexmedetomidine. As expected from dexmedetomidine effective dosage our results showed a tendency of dexemdetomidine to slow heart rate: there were no significant bradycardias though, and considering our adult patient population, we would not have implicated interventions due to hemodynamic instabilities often more precariuos in pediatric patients and nevertheless majority still considerably benign18. However, in another study by Viana et al15, atropine had to be administered, albeit in only 1 case. We are rather in support of deferring pharmacological treatment of bradycardia as recommended by current guidelines (altered mental status, hypotension, syncope, myocardial ischemia, or heart failure)19. While anatomic obstructions were similar in group P and group D, oxygenation levels were higher in group D. In the study by Viana et al15, the SpO2 nadir observed with dexmedetomidine DISE sedation was significantly higher than in PSG. Moreover, dexmedetomidine did not cause any significant respiratory depressive effects. These findings suggest that respiratory drive, and possibly upper airway collapse, during dexmedetomidine DISE is less pronounced than with propofol and, interestingly, even less pronounced than during physiological sleep. According to Capasso et al20 propofol induced far more tongue based collapsed during DISE than dexmedetomidine. It cannot be excluded that the reported differences and operative observation assessments might have been affected by the nonblinding of the operator, as well as the limited number of observations. However, in our opinion, the influence of the type of sedative on the sites of obstruction remains a point for debate. There are contradictory results in the literature, which pose significant challenges to clinicians:

  • There is currently no universal consensus about the protocol for DISE sedation. The use of sedatives that influence upper airway muscle tone may lead to overestimating or underestimating the severity of the collapse.
  • There is a plethora of DISE classification systems, all of which are based on limited evidence21.
  • Sleep position is not always stated in DISE studies, and this may affect obstruction site visualization, making comparisons between studies inappropriate.
  • DISE results can be influenced by patient physical status before the test. Park and Kim22 compared DISE findings in a group of patients after a treadmill stress test with another group without pre-DISE exercise and found significant changes in obstruction levels between the 2 groups.

The discrepancies in desaturation and anatomic findings between dexmedetomidine and propofol DISE studies published so far need to be addressed with larger randomized trials23. One of the main limitations of our study was the lack of blinding in the intraprocedural and postprocedural data collection, which may have skewed the clinical observations for the operative views. Moreover, BIS use is still in its validation phase for dexmedetomidine. Finally, the 2 groups were not homogeneous as to the OSA phenotype (eg, positional vs. nonpositional). Operator-dependent and patient-dependent variability can partially explain the differences between the 2 groups. Dexmedetomidine can be an alternative to propofol for DISE especially in situations where the degree of desaturation linked to propofol-mediated upper airway hypotonia may represent an excessive risk for the patient (eg, craniofacial malformations, predicted severe difficult airway); however, the significant increase in the time needed to carry out the procedure and the consequent impact on operating room efficiency has to be taken into consideration, limiting its universal adoption.

Conclusion

In this clinical “real-life,” randomized nonblinded pilot study, dexmedetomidine continuous infusion and propofol infused as TCI both provided adequate sedation during DISE. Whereas propofol TCI seems to remain the gold standard for this procedure, dexmedetomidine may represent an alternative, albeit with limitations, if propofol is absolutely contraindicated or not available; studies with greater patient numbers are warranted to further confirm dexmedetomidine effects on cardiorespiratory variables and recovery profiles during DISE.

Clinical endpoints

  • Propofol TCI infusion for DISE achieves appropriate levels of sedation and recovery faster than dexmedetomidine continuous infusion, while causing lower SpO2 nadirs.
  • Dexmedetomidine as single high dose agent for DISE may achieve some endoscopic views of airway sites of obstruction similar to propofol, while maintaining higher SpO2 levels with prolonged sedation times. The effect on endoscopic view is a topic for debate and our results need to be confirmed in a larger series.

Sources of funding

None.

Conflict of interest disclosures

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Acknowledgments

The authors thanks Luana Conte, Roberto Lomaistro, and Daniela Paolillo for their contribution to the study.

References

1. Chong KB, De Vito A, Vicini C. Drug-induced sleep endoscopy in treatment options selection. Sleep Med Clin 2019;14:33–40.
2. Atkins JH, Mandel JE. Drug-induced sleep endoscopy: from obscure technique to diagnostic tool for assessment of obstructive sleep apnea for surgical interventions. Curr Opin Anaesthesiol 2018;31:120–6.
3. De Vito A, Agnoletti V, Berrettini S, et al. Drug-induced sleep endoscopy: conventional versus target-controlled infusion techniques—a randomized controlled study. Eur Arch Otorhinolaryngol 2011;268:457–62.
4. Shteamer JW, Dedhia RC. Sedative choice in drug‐induced sleep endoscopy: a neuropharmacology‐based review. Laryngoscope 2017;127:273–9.
5. Chang ET, Certal V, Song SA, et al. Dexmedetomidine versus propofol during drug-induced sleep endoscopy and sedation: a systematic review. Sleep Breath 2017;21:727–35.
6. Cattano D, Lam NC, Ferrario L, et al. Dexmedetomidine versus remifentanil for sedation during awake fiberoptic intubation. Anesthesiol Res Pract 2012;2012:753107.
7. Padiyara TV, Bansal S, Jain D, et al. Dexmedetomidine versus propofol at different sedation depths during drug-induced sleep endoscopy: a randomized trial. Laryngoscope 2020;130:257–62.
8. De Vito A, Carrasco Llatas M, Ravesloot MJ, et al. European position paper on drug-induced sleep endoscopy: 2017 update. Clin Otolaryngol 2018;43:1541–52.
9. Albdah AA, Alkusayer MM, Al-Kadi M, et al. The impact of drug-induced sleep endoscopy on therapeutic decisions in obstructive sleep apnea: a systematic review and meta-analysis. Cureus 2019;11:e6041.
10. Certal VF, Pratas R, Guimarães L, et al. Awake examination versus DISE for surgical decision making in patients with OSA: a systematic review. Laryngoscope 2016;126:768–74.
11. De Vito A, Agnoletti V, Zani G, et al. The importance of drug-induced sedation endoscopy (D.I.S.E.) techniques in surgical decision making: conventional versus target controlled infusion techniques—a scheduled randomized controlled study and a retrospective surgical outcomes analysis. Eur Arch Otorhinolaryngol 2017;274:2307–17.
12. Carrasco-Llatas M, Matarredona-Quiles S, De Vito A, et al. Drug-induced sleep endoscopy: technique, indications, tips and pitfalls. Healthcare (Basel) 2019;7:93.
13. Cortínez LI, Anderson BJ, Penna A, et al. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth 2010;105:448–56.
14. Mandel JE, Atkins JH. Results from 404 drug-induced sleep endoscopies with probability ramp control: lessons for pharmacokinetic design of DISE protocols. J Head Neck Anesth 2020;4:e27.
15. Viana A, Zhao C, Rosa T, et al. The effect of sedating agents on drug-induced sleep endoscopy findings. Laryngoscope 2019;129:506–13.
16. Cho JS, Soh S, Kim EJ, et al. Comparison of three sedation regimens for drug-induced sleep endoscopy. Sleep Breath 2015;19:711–7.
17. Elkalla RS, El Mourad MB. Respiratory and hemodynamic effects of three different sedative regimens for drug induced sleep endoscopy in sleep apnea patients. A prospective randomized study. Minerva Anestesiol 2020;86:132–40.
18. Mason KP, Lönnqvist PA. Bradycardia in perspective-not all reductions in heart rate need immediate intervention. Paediatr Anaesth 2015;25:44–51.
19. Sidhu S, Marine JE. Evaluating and managing bradycardia. Trends Cardiovasc Med 2020;30:265–72.
20. Capasso R, Rosa T, Tsou DY, et al. Variable findings for drug-induced sleep endoscopy in obstructive sleep apnea with propofol versus dexmedetomidine. Otolaryngol Head Neck Surg 2016;154:765–70.
21. Dijemeni E, D’Amone G, Gbati I. Drug-induced sedation endoscopy (DISE) classification systems: a systematic review and meta-analysis. Sleep Breath 2017;21:983–94.
22. Park SM, Kim DK. Effect of physical stress on drug-induced sleep endoscopy for obstructive sleep apnea. Eur Arch Otorhinolaryngol 2017;274:3115–20.
23. Yoon BW, Hong JM, Hong SL, et al. A comparison of dexmedetomidine versus propofol during drug-induced sleep endoscopy in sleep apnea patients. Laryngoscope 2016;126:763–7.
Keywords:

Obstructive sleep apnea (OSA); Drug-induced sleep endoscopy (DISE); Dexmedetomidine; Propofol

Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Society for Head and Neck Anesthesia.