The authors are grateful to Philipp Grundtner for his help with the statistical analyses.

The protocol follows the guidelines of the local ethics committee of the Friedrich-Alexander University Erlangen-N&#252;rnberg (FAU).
1. DISE-TCI-Bispectral Analysis Procedure
<ol>
	<li>Perform venipuncture and place an IV catheter in the patients left back of the hand or median cubital vein to obtain intravenous access to administer the sedative.</li>
	<li>Carry out the investigation at room temperature (22 &#176;C).</li>
	<li>Bring the awake patient into the operating theater. Place the patient in the supine position on the operating table.</li>
	<li>Following this, have the anesthesiologist connect the monitoring system of vital signs. Monitor the patient during the whole procedure by peripheral pulse oximetry, 3-channel ECG and non-invasive blood pressure measurement at 3-min intervals.</li>
	<li>Ensure that both the anesthesiologist and the anesthetic equipment are on the left side of the patient.</li>
	<li>Have the anesthesiologist place and fix the single-use sensor for bispectral analysis.
	<ol>
		<li>To do this, wipe skin with disinfectant and let it dry.</li>
		<li>Position sensor (4 interconnected and adhesive electrodes) diagonally on the patient&#39;s forehead: one electrode (number 1) at center of forehead, electrodes 2 and 3 directly above eyebrow and electrode 4 on temple between corner of eye and hairline.</li>
		<li>Connect sensor via interface cable to the bispectral analysis-monitor. Press electrodes firmly and ensure that the automatic sensor test is passed.</li>
	</ol>
	</li>
	<li>Have the anesthesiologist enter patients&#39; individual sex, age, height, weight and plasma target concentration of propofol into the data manager with the pre-programmed pharmacokinetic model of Marsh17. 
	NOTE: According to this model, the TCI-data manager calculates the infusion rates of propofol and operates the connected TCI-infusion pump to establish and automatically maintain the set target plasma concentration.</li>
	<li>Dim the light in the operating room.</li>
	<li>Induce sleep solely by the intravenous infusion of propofol with the TCI-infusion pump with an initial target plasma level of 2.0 &#181;g/ml.</li>
	<li>Under continuous monitoring of the patient&#39;s respiration, state of consciousness and value of the bispectral analysis, raise the target plasma propofol level in steps of 0.2 &#181;g/ml/2 min until the desired depth of sedation is reached. 
	NOTE: The target depth of sedation is a sleeping patient (eyes closed), with maintained spontaneous breathing and / or starting to snore and / or obstructive apnea observed by the examiner with the endoscope or the anesthesiologist.</li>
	<li>Record manually the mean value of the bispectral analysis at the target depth of sedation.</li>
	<li>Have the examiner with the endoscope stand at head level on the right side next to the patient.</li>
	<li>At the target depth of sedation insert a flexible fiber endoscope transnasally via the inferior nasal meatus.</li>
	<li>Film the endoscopic examination and store digitally. Use the image acquisition system according to manufacturer&#39;s instructions. 
	NOTE: In case of nasal septal deviation or hypertrophy of the inferior turbinates, the inferior meatus with the larger diameter should be chosen.</li>
	<li>Examine the upper airways by videoendoscopy in a proximal to distal direction from the nasopharynx as far as the hypopharyngeal entrance.</li>
	<li>Classify the obstruction site(s) (velum, oropharynx, tongue base, epiglottis) and configuration/obstruction pattern (anterior-posterior, lateral, concentric) and the degree/severity (no obstruction/no vibration, partial obstruction/vibration, complete obstruction/collapse) according to the VOTE system at the target depth of sedation15.</li>
	<li>In the case of isolated sleep endoscopy, terminate sedation of the patient by stopping the propofol infusion after completing the endoscopic examination.</li>
	<li>In the case of sleep endoscopy as part of a planned surgical procedure, let the anesthesiologist perform total intravenous anesthesia by starting infusion of opioids (e.g., using remifentanil in TCI mode) and increasing infusion of propofol (e.g., set TCI level to 4 &#181;g/ml) until loss of consciousness. Inject muscle relaxant (e.g., rocuronium) and intubate the patient.</li>
</ol>

<ol>
	<li>Punjabi, N. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+epidemiology+of+adult+obstructive+sleep+apnea.">The epidemiology of adult obstructive sleep apnea.</a> Proc Am Thorac Soc. 5 (2), 136-143 (2008).</li><li>Giles, L. T., Lasserson, T. J., Smith, B., White, J., Wright, J. J., Cates, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+positive+airways+pressure+for+obstructive+sleep+apnoea+in+adults.">Continuous positive airways pressure for obstructive sleep apnoea in adults.</a> Cochrane Database Syst Rev. 19 (3), (2006).</li><li>Mayer, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deutsche+Gesellschaft+f&#252;r+Schlafforschung+und+Schlafmedizin+(DGSM),+S3-Leitlinie.+Nicht+erholsamer+Schlaf/Schlafst&#246;rungen.">Deutsche Gesellschaft f&#252;r Schlafforschung und Schlafmedizin (DGSM), S3-Leitlinie. Nicht erholsamer Schlaf/Schlafst&#246;rungen.</a> Somnologie. 13, 1-160 (2009).</li><li>McArdle, N., Devereux, G., Heidarnejad, H., Engleman, H. M., Mackay, T. W., Douglas, N. 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B., Pringle, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+nasendoscopy:+a+technique+of+assessment+in+snoring+and+obstructive+sleep+apnoea.">Sleep nasendoscopy: a technique of assessment in snoring and obstructive sleep apnoea.</a> Clin Otolaryngol Allied Sci. 16 (5), 504-509 (1991).</li><li>De Vito, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug-induced+sleep+endoscopy:+conventional+versus+target+controlled+infusion+techniques--a+randomized+controlled+study.">Drug-induced sleep endoscopy: conventional versus target controlled infusion techniques--a randomized controlled study.</a> Eur Arch Otorhinolaryngol. 268 (3), 457-462 (2011).</li><li>Kezirian, E. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrater+reliability+of+drug-induced+sleep+endoscopy.">Interrater reliability of drug-induced sleep endoscopy.</a> Arch Otolaryngol Head Neck Surg. 136 (4), 393-397 (2010).</li><li>Rodriguez-Bruno, K., Goldberg, A. N., McCulloch, C. E., Kezirian, E. 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The Report of an American Academy of Sleep Medicine Task Force.</a> Sleep. 22 (5), 667-689 (1999).</li><li>Iber, C., Ancoli-Israel, S., Chesson, A., Quan, S. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 1st ed. , (2007).</li><li>Berry, R. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rules+for+scoring+respiratory+events+in+sleep:+update+of+the+2007+AASM+Manual+for+the+Scoring+of+Sleep+and+Associated+Events.+Deliberations+of+the+Sleep+Apnea+Definitions+Task+Force+of+the+American+Academy+of+Sleep+Medicine.">Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine.</a> J Clin Sleep Med. 8 (5), 597-619 (2012).</li><li>Kezirian, E. J., Hohenhorst, W., de Vries, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug-induced+sleep+endoscopy:+the+VOTE+classification.">Drug-induced sleep endoscopy: the VOTE classification.</a> Eur Arch Otorhinolaryngol. 268 (8), 1233-1236 (2011).</li><li>Ihmsen, H., Schraag, S., Kreuer, S., Bruhn, J., Albrecht, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Target-controlled+infusion.+Clinical+relevance+and+special+features+when+using+pharmacokinetic+models.">Target-controlled infusion. Clinical relevance and special features when using pharmacokinetic models.</a> Anaesthesist. 58 (7), 708-715 (2009).</li><li>Marsh, B., White, M., Morton, N., Kenny, G. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacokinetic+model+driven+infusion+of+propofol+in+children.">Pharmacokinetic model driven infusion of propofol in children.</a> Brit J Anaesth. 67 (1), 41-48 (1991).</li><li>Schnider, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+method+of+administration+and+covariates+on+the+pharmacokinetics+of+propofol+in+adult+volunteers.">The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.</a> Anesthesiology. 88 (5), 1170-1182 (1998).</li><li>Sigl, J. C., Chamoun, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+introduction+to+bispectral+analysis+for+the+electroencephalogram.">An introduction to bispectral analysis for the electroencephalogram.</a> J Clin Monitor. 10 (6), 392-404 (1994).</li><li>Avidan, M. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anesthesia+awareness+and+the+bispectral+index.">Anesthesia awareness and the bispectral index.</a> New Engl J Med. 358 (11), 1097-1108 (2008).</li><li>Kissin, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Depth+of+anesthesia+and+bispectral+index+monitoring.">Depth of anesthesia and bispectral index monitoring.</a> Anesth Analg. 90 (5), 1114-1117 (2000).</li><li>Borowiecki, B., Pollak, C. P., Weitzman, E. D., Rakoff, S., Imperato, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fibro-optic+study+of+pharyngeal+airway+during+sleep+in+patients+with+hypersomnia+obstructive+sleep-apnea+syndrome.">Fibro-optic study of pharyngeal airway during sleep in patients with hypersomnia obstructive sleep-apnea syndrome.</a> Laryngoscope. 88 (8), 1310-1313 (1978).</li><li>Fujita, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+the+effectiveness+of+uvulopalatopharyngoplasty.">Evaluation of the effectiveness of uvulopalatopharyngoplasty.</a> Laryngoscope. 95 (1), 70-74 (1985).</li><li>Zerpa Zerpa, ., Carrasco Llatas, M., Agostini Porras, G., Dalmau Galofre, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug-induced+sedation+endoscopy+versus+clinical+exploration+for+the+diagnosis+of+severe+upper+airway+obstruction+in+OSAHS+patients.">Drug-induced sedation endoscopy versus clinical exploration for the diagnosis of severe upper airway obstruction in OSAHS patients.</a> Sleep Breath. 19 (4), 1367-1372 (2015).</li><li>Fernandez-Julian, E., Garcia-Perez, M. 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The authors have no funding, financial relationships, or conflicts of interest to disclose.

The first experiments using flexible fiber optic rhinopharyngolaryngoscopy during spontaneous sleep to detect the site of obstruction was described as early as the 1970s22. However, the roots of this investigative technique were initially of a purely descriptive pathophysiological nature. During the establishment of surgical techniques to treat OSA, such as uvulopalatopharyngoplasty (UPPP) by Fujita, it was, however, shown that the success of the operation was apparently dependent on a careful preoperative sel...

Obstructive sleep apnea (OSA) is characterized by repetitive phases of complete (apnea) or partial (hypopnea) collapse of the upper airways during sleep. These phases are often associated with arterial oxygen desaturation and a fragmentation of sleep caused by arousals. The reported prevalence of OSA with accompanying daytime symptoms in the general population is 3 - 7% in men and 2 - 5% in women1. The gold standard in the treatment of moderate to severe OSA is nasal continuous positive airway pressure (nCPAP), for which compliance is internationally reported as about 40 - 60%2. This treatment is used by 29 - 83% of OSA patients on a regular basis for less than 4 hr3. Both positive and negative predictors regarding long-term compliance of CPAP-use are well known nowadays4. In addition, emotional and clinical side effects often considerably reduce compliance. Alternative treatment options such as upper airway surgery therefore play an important role in OSA therapy. However, the fact that the success rate of surgery (responder rate) is relatively low in comparison with ventilation therapy is problematic 5,6.
It was hoped that the introduction of sleep endoscopy by Croft and Pringle in 1991 would not only provide further insights into the pathophysiology of OSA but also might improve the responder rate through individualized surgical treatment7. As early as 2011, studies by De Vito et al. demonstrated the advantage of using investigative techniques based on target-controlled infusion (TCI) and bispectral analysis with respect to safety, stability and accuracy8. In the meantime, the validity and reliability of sleep endoscopy have been established and, ever since the 2014 European Position Paper, it is on the road to standardization9-11. The aim of the present study is to establish a standardized protocol for sleep endoscopy by target-controlled infusion of the sedative propofol, combined with real-time monitoring of the depth of sedation using bispectral analysis, in order to differentiate obstruction patterns according to OSA-severity.
CASE PRESENTATION:
Study Design:
The retrospective study was conducted in the Department of Otorhinolaryngology, Head &#38; Neck Surgery of the Friedrich-Alexander University Erlangen-N&#252;rnberg between September 2012 and November 2014, following approval by the local Ethics Committee. All 57 participating patients, aged 20 to 73 years, were recruited by the Department of Otorhinolaryngology, Head and Neck Surgery. 52 patients were men and 5 women. In addition to a standardized interview, they were examined by an otorhinolaryngologist and underwent an awake endoscopy to assess the upper airways. Cardiorespiratory polysomnography was then undertaken in the Department&#39;s sleep laboratory to enable an exact classification of their sleep-related breathing disorder. The OSA severity was classified as mild (AHI 5 - 15/hr), moderate (AHI &#62; 15 &#60; 30/hr) or severe (AHI &#62; 30/hr), according to the criteria of the American Academy of Sleep Medicine Task Force12. The indication for sleep endoscopy was established in the context of a planned surgical intervention of the upper airways (primary indication) or in the case of nCPAP non-compliance (secondary or adjuvant indication).
Inclusion criteria for this study were men and women aged 18 - 75 years with mild, moderate or severe OSA diagnosed by polysomnography. Exclusion criteria were an American Society of Anesthesiologists Classification (ASA) IV/V, central sleep apnea, positive history of misuse of sedatives, alcohol or addictive drugs, allergy to propofol, pregnant women.
Diagnosis, Assessment, and Plan:
Cardiorespiratory polysomnography (PSG):
Polysomnography was carried out with a 33-channel cardiorespiratory diagnostic system. The technical procedure for the polysomnographic diagnostics followed the recommendations of the American Academy of Sleep Medicine (AASM) in the standardized technique using an electroencephalogram (EEG; F4-M1, C4-M1, O2-M1), right and left electro-oculogram, electromyogram of the mentalis and tibialis muscles, nasal pressure cannula, thoracic and abdominal respiratory effort sensors (inductive plethysmographs), body position sensors, pulse oximetry, snoring microphone, a one-channel ECG and an infrared video recording13. The evaluation was performed according to the AASM Criteria (Version 2.0, 2012) and was undertaken by an accredited medical sleep specialist of the German Sleep Society (DGSM)13, 14. After polysomnography had confirmed OSA, all 57 patients underwent a standardized propofol-based Drug-Induced Sleep Endoscopy (DISE) with TCI and bispectral analysis (DISE-TCI-bispectral analysis).
Preoperative preparations:
Due to the muscle relaxant effect, no premedication with benzodiazepines was given in the case of sleep endoscopies undertaken solely for diagnostic purposes. If the sleep endoscopy was performed during a planned surgical procedure, clonidine was used for premedication as an alternative for benzodiazepines, taking the corresponding contraindications into account.
Classification of the obstruction:
The VOTE system was used for classification purposes15. The following sites of obstruction were considered: velum, oropharynx (lateral oropharyngeal walls, tonsils), tongue base and epiglottis. Obstruction severity was divided into three grades (no obstruction; partial and complete obstruction). The configuration of the obstruction was divided into anterior-posterior, lateral and concentric.
Target-controlled infusion (TCI):
Target-Controlled Infusion (TCI) describes the infusion of drugs using microchip-controlled infusion pumps to achieve a target concentration in the blood. The aim of this method is the rapid achievement and maintenance of a certain effect (e.g., sedation) based on a specified (defined) plasma level or an effect level in the case of effect-site TCI. Calculation of the plasma level or effect-site level is based on pharmacokinetic 3-compartment models (according to Marsh or Schnider) that use the pharmacological half-life values and distribution coefficients determined in a volunteer population16-18. The infusion rates needed to rapidly achieve and maintain the specified target level of propofol in plasma are then automatically calculated and controlled by the infusion pump. The present study used a system consisting of an infusion pump and a data manager together with the pre-programmed pharmacokinetic model of Marsh. The objective depth of sedation was simultaneously monitored by bispectral analysis.
Bispectral analysis:
The bispectral analysis/index is correlated with electrical activity in the brain. The monitor of bispectral analysis records frontal EEG signals and, with the help of various proprietary algorithms, analyzes the distribution of the EEG power spectrum. The bispectral index is a dimensionless number between 0 and 100 19. In general, a value around 90 reflects a preponderance of high-frequency beta-waves and indicates that the patient is awake. Bispectral analysis values below 10 are indicative of EEG suppression 20, 21. This scale therefore provides an indirect measurement of the effect of sedatives on the brain. In order to maintain an adequate depth of anesthesia and avoid an undesirable intraoperative awakeness of the patient, a bispectral index of &#60; 60 is recommended. On the other hand, values of the bispectral index of &#60; 40 should be avoided, in order to prevent unnecessarily deep anesthesia.
All sleep endoscopies were performed by two experienced otorhinolaryngology consultants with additional qualifications in sleep medicine (T. M. 59.6% (34/57), A. F. 40.4% (23/57).

<table><tbody><tr><td>&lt;strong&gt;Cardiorespiratory polysomnography&amp;nbsp;&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>&lt;em&gt;SOMNOscreen&amp;nbsp;&lt;/em&gt;</td><td>SOMNOmedics, Randersacker, Germany</td><td>SBT202</td><td></td></tr><tr><td>&lt;strong&gt;Sedation&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>&lt;em&gt;Propofol-Lipuro&lt;/em&gt; 20 mg/ml; 2,6-diisopropylphenol</td><td>B. Braun Melsungen AG, Melsungen, Germany</td><td></td><td></td></tr><tr><td>&lt;strong&gt;Target-controlled infusion (TCI)&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Infusion pump &lt;em&gt;Orchestra Module DPS Visio&lt;/em&gt;</td><td>Fresenius Kabi, Germany GmbH&amp;nbsp;</td><td>Z082420</td><td></td></tr><tr><td>Data manager &lt;em&gt;Orchestra Base Primea&lt;/em&gt;</td><td>Fresenius Kabi Germany GmbH</td><td>Z081320</td><td></td></tr><tr><td>&lt;strong&gt;Bispectral analysis (BIS)&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>BIS single-use electrode &lt;em&gt;BIS Quatro Sensor&lt;/em&gt;</td><td>Covidien, Neustadt/Donau, Germany GmbH</td><td>186-0106</td><td></td></tr><tr><td>BIS monitor&lt;em&gt; BIS VISTA&lt;/em&gt;</td><td>Covidien, Neustadt/Donau, Germany GmbH</td><td>186-0210</td><td></td></tr><tr><td>&lt;strong&gt;Endoscope&amp;nbsp;&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Laryngo fiberscope, length 30 cm, diameter 3.5 mm</td><td>KARL STORZ GmbH &amp;amp; Co. KG, Tuttlingen, Germany</td><td>11101RP</td><td></td></tr><tr><td>&lt;strong&gt;Picture Archiving&amp;nbsp; System&amp;nbsp;&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>AIDA</td><td>Karl STORZ GmbH &amp;amp; Co. KG, Tuttlingen, Germany</td><td>WD 200-XX</td><td></td></tr><tr><td>&lt;strong&gt;Premedication&amp;nbsp;&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>&lt;em&gt;Catapresan;&lt;/em&gt; Clonidin-HCl 0.075 mg/0.15 mg/0.3 mg</td><td>Boehringer Ingelheim Pharma, GmbH &amp;amp; Co. KG, Ingelheim am Rhein, Germany</td><td></td><td></td></tr></tbody></table>

drug-induced sleep endoscopy (dise) with target controlled infusion (tci) and bispectral analysis in obstructive sleep apnea

The aim of this study was to establish a standardized protocol for drug-induced sleep endoscopy (DISE) to differentiate obstruction patterns in obstructive sleep apnea (OSA). Target-controlled infusion (TCI) of the sedative propofol was combined with real-time monitoring of the depth of sedation using bispectral analysis.
In an observational study 57 patients (mean age 44.8 years, &#177; SD 10.5; mean apnea hypopnea Index (AHI) 30.8/hr, &#177; SD 21.6, mean BMI 28.2 kg/m2, &#177; SD 5.3) underwent cardiorespiratory polysomnography followed by DISE with TCI and bispectral analysis. Sleep was induced solely by the intravenous infusion of propofol with a TCI-pump, with an initial target plasma level of 2.0 &#181;g/ml. Under continuous monitoring of the patient&#39;s respiration, state of consciousness and value of the bispectral analysis, the target plasma propofol level was raised in steps of 0.2 &#181;g/ml/2 min until the desired depth of sedation was reached. The mean value of the bispectral analysis at the target depth of sedation was determined and the obstruction patterns during DISE-TCI-bispectral analysis then classified according to the VOTE-system. Subsequently the results were analyzed according to polysomnographic and anthropometric data. The occurrence of multilevel obstruction sites across all degrees of severity of OSA clarifies the need for sleep endoscopy prior to upper airway surgery.
The advantage of this technique is the reproducibility of the protocol even for heterogeneous groups of patients. In addition, the gradual controlled and standardized increase of the plasma level of propofol with real-time control of the bispectral index leads to a precisely controllable depth of sedation. The DISE-TCI-bispectral analysis procedure is a step towards a required reproducible protocol of sleep endoscopy &#8212; capable of standardization. However it is not yet known whether these observed obstruction patterns also correspond to findings in natural sleep.

Characteristics of the patients are shown in Table 1. The mean value of the bispectral analysis at the desired depth of sedation was 60 (&#177; SD 10.4, range 35 - 80; 95% confidence interval 42.0 - 47.6). Single or multiple combined sites of obstruction were found across all levels of OSA severity. The identified sites of obstruction, in decreasing order of frequency, were: velar 59.6% (34/57), tongue base 43.9% (25/57), oropharynx 42.1% (24/57) or at the level of the ep...

Watch this Scientific Journal Video about Drug-Induced Sleep Endoscopy DISE with Target Controlled Infusion TCI and Bispectral Analysis in Obstructive Sleep Apnea at JoVE.com

Drug-Induced Sleep Endoscopy DISE with Target Controlled Infusion TCI and Bispectral Analysis in Obstructive Sleep Apnea

The aim of this study was to establish a standardized protocol for sleep endoscopy to differentiate obstruction patterns in obstructive sleep apnea (OSA). Target-controlled infusion (TCI) of the sedative was combined with real-time monitoring of the depth of sedation using bispectral analysis.

Drug-Induced Sleep Endoscopy (DISE) with Target Controlled Infusion (TCI) and Bispectral Analysis in Obstructive Sleep Apnea

The aim of this study was to establish a standardized protocol for drug-induced sleep endoscopy (DISE) to differentiate obstruction patterns in ...

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Research

JoVE Journal

Medicine

19.5K Views.  Friedrich-Alexander University Erlangen-Nürnberg (FAU). The aim of this study was to establish a standardized protocol for sleep endoscopy to differentiate obstruction patterns in obstructive sleep apnea (OSA). Target-controlled infusion (TCI) of the sedative was combined with real-time monitoring of the depth of sedation using bispectral analysis.

Video: Drug-Induced Sleep Endoscopy DISE with Target Controlled Infusion TCI and Bispectral Analysis in Obstructive Sleep Apnea

Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a long recovery period. To perform an EEG recording, the animal is connected to a receiver, creating an unnatural tether to the head-mount. EEG monitoring is time consuming, carries risk to the animal, and is not a completely natural setting for the measurement of sleep. Alternative methods to detect sleep, particularly in a high-throughput fashion, would greatly advance the field of sleep research. Here, we describe a validated method for detecting sleep via activity-based home-cage monitoring. Previous studies have shown that sleep assessed via this method has a high degree of agreement with sleep defined by traditional EEG-based measures. Whereas this method is validated for total sleep time, it is important to note that sleep bout duration should be assessed by an EEG which has better temporal resolution. The EEG can also differentiate rapid eye movement (REM) and non-REM sleep, giving more detail about the exact nature of sleep. Nevertheless, activity-based sleep determination can be used to analyze multiple days of undisturbed sleep and to assess sleep as a response to an acute event (like stress). Here, we show the power of this system to detect the response of mice to daily intraperitoneal injections.

We describe a high-throughput method of measuring sleep by means of activity-based home-cage monitoring. This method offers advantages over traditional EEG-based methods. It is well validated for the determination of total sleep duration and can be a powerful tool to monitor sleep in rodent models of human disease.

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a ...

Behavior

Topical Airway Anesthesia for Awake-endoscopic Intubation Using the Spray-as-you-go Technique with High Oxygen Flow

A patient&#39;s willingness to cooperate is an absolute precondition for successful awake intubation of the trachea. Whilst drug-sedation of patients can jeopardize their spontaneous breathing, topical anesthesia of the airway is a popular technique. The spray-as-you-go technique represents one of the simplest opportunities to anesthetize the airway mucosa. The application of local anesthetic through the working channel of the flexible endoscope is a widespread practice for anesthetists as well as pulmonologists. There is neither need for additional devices nor special training as a pre-requisite to perform this technique. However, a known clinical problem is the coughing and gagging reflex that may occur when the liquid anesthetic strikes the airway mucosa and other sensitive structures like the vocal cords. This can be avoided by the use of oxygen applied through the working channel with the aim of fogging the local anesthetic into finer particles. Furthermore, the oxygen flow provides a higher oxygen supply and contributes to a better view, dispersing mucus secretions and blood away from the lens. Using an atomizer with a high oxygen flow of 10 L/min we maximized these benefits, caused less coughing and had more satisfied and therefore cooperative patients. Possible, but very rare complications of using oxygen flow including gastric insufflation, organ rupture or barotrauma did not arise. We attribute the complication-free use of high oxygen flow to the design of the set, which permits flow and pressure release.

The topical anesthetic lidocaine was atomized using a high oxygen flow through the working channel of a flexible intubating endoscope to achieve topical airway anesthesia for awake endotracheal intubation. We prefer this modified spray-as-you-go technique for endoscopic intubation to classical bolus application because of higher patient satisfaction and better compliance.

A patient&#39;s willingness to cooperate is an absolute precondition for successful awake intubation of the trachea. Whilst drug-sedation of patients can ...

Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most neuroimaging or neurophysiological investigations in humans have been confined to the study of &#947;-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anesthetics, while the effects of dissociative N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthetics ketamine, nitrous oxide (N2O) and xenon (Xe) are largely unknown. This paper describes the methods underlying the simultaneous recording of magnetoencephalography (MEG) and electroencephalography (EEG) from healthy males during inhalation of the gaseous anesthetic agents N2O and Xe. Combining MEG and EEG data enables the assessment of electromagnetic brain activity during anesthesia at high temporal, and moderate spatial, resolution. Here we describe a detailed protocol, refined over multiple recording sessions, that includes subject recruitment, anesthesia equipment setup in the MEG scanner room, data collection and basic data analysis. In this protocol each participant is exposed to varying levels of Xe and N2O in a repeated measures cross-over design. Following relevant baseline recordings participants are exposed to step-wise increasing inspired concentrations of Xe and N2O of 8, 16, 24 and 42%, and 16, 32 and 47% respectively, during which their level of responsiveness is tracked with an auditory continuous performance task (aCPT). Results are presented for a number of recordings to highlight the sensor-level properties of the raw data, the spectral topography, the minimization of head movements, and the unequivocal level dependent effects on the auditory evoked responses. This paradigm describes a general approach to the recording of electromagnetic signals associated with the action of different kinds of gaseous anesthetics, which can be readily adapted to be used with volatile and intravenous anesthetic agents. It is expected that the method outlined can contribute to the understanding of the macro-scale mechanisms of anesthesia by enabling methodological extensions involving source space imaging and functional network analysis.

Simultaneous magnetoencephalography and electroencephalography provides a useful tool to search for common and distinct macro-scale mechanisms of reductions in consciousness induced by different anesthetics. This paper illustrates the empirical methods underlying the recording of such data from healthy humans during N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthesia during inhalation of nitrous oxide and xenon.

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most ...

Neuroscience

Computer-based Multitaper Spectrogram Program for Electroencephalographic Data

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. This paper describes a Windows-based, open source code for creating EEG multitaper spectrograms. The compiled program is accessible to Windows users without software licensing. For Macintosh users, the program is limited to those with a MATLAB software license. The program is illustrated via EEG spectrograms that vary as a function of states of sleep and wakefulness, and opiate-induced alterations in those states. The EEGs of C57BL/6J mice were wirelessly recorded for 4 h after intraperitoneal injection of saline (vehicle control) and antinociceptive doses of morphine, buprenorphine, and fentanyl. Spectrograms showed that buprenorphine and morphine caused similar changes in EEG power at 1&#8722;3 Hz and 8&#8722;9 Hz. Spectrograms after administration of fentanyl revealed maximal average power bands at 3 Hz and 7 Hz. The spectrograms unmasked differential opiate effects on EEG frequency and power. These computer-based methods are generalizable across drug classes and can be readily modified to quantify and display a wide range of rhythmic biological signals.

This protocol provides an open source, compiled MATLAB program that generates multitaper spectrograms for electroencephalographic data.

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. ...

Multi-Modal Home Sleep Monitoring in Older Adults

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and research participants. Home sleep testing has gained momentum in the field of sleep medicine due to its convenience and lower cost, as well as being more naturalistic. The accuracy and quality of home sleep testing, however, may be variable because studies are not monitored by sleep technologists. There has been some success in improving the accuracy of home sleep studies by having trained sleep technicians assist participants inside their homes with putting on the devices, but this can be intrusive and time-consuming for those involved. In this protocol, participants undergo at-home sleep monitoring with multiple devices: 1) a single-channel EEG device; 2) a home sleep test for sleep-disordered breathing and periodic limb movements; 3) actigraphy; and 4) sleep logs. A major challenge of this study is obtaining high-quality sleep monitoring data on the first attempt in order to minimize participant burden. This protocol describes the implementation of educational manuals with step-by-step instructions and photos. The goal is to improve the quality of home sleep testing.

Here, we present a protocol to improve the quality of data from home sleep testing by providing a method to enhance instructions through a structured participant visit. This protocol includes the implementation of a step-by-step educational manual with photos to ensure proper placement of equipment.

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and ...

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease and arrhythmias in people with epilepsy (i.e., epileptic heart.) Additionally, cardiac and autonomic disturbances have been reported surrounding seizures. 1:1,000 epilepsy patients/year die of sudden unexpected death in epilepsy (SUDEP). The mechanisms for SUDEP remain incompletely understood. Electroencephalograms (EEG) and electrocardiograms (ECG) are two techniques routinely used in the clinical setting to detect and study the substrates/triggers for seizures and arrhythmias. While many studies and descriptions of this methodology are in rodents, their cardiac electrical activity differs significantly from humans. This article provides a description of a non-invasive method for recording simultaneous video-EEG-ECG-oximetry-capnography in conscious rabbits. As cardiac electrical function is similar in rabbits and humans, rabbits provide an excellent model of translational diagnostic and therapeutic studies. In addition to outlining the methodology for data acquisition, we discuss the analytical approaches for examining neuro-cardiac electrical function and pathology in rabbits. This includes arrhythmia detection, spectral analysis of EEG and a seizure scale developed for restrained rabbits.

Using simultaneous video-EEG-ECG-oximetry-capnography, we developed a methodology to evaluate the susceptibility of rabbit models to develop provoked arrhythmias and seizures. This novel recording system establishes a platform to test the efficacy and safety of therapeutics and can capture the complex cascade of multi-system events that culminate in sudden death.

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease ...

Image Acquisition using Portable Sonography for Emergency Airway Management

With its increasing popularity and accessibility, portable ultrasonography has been rapidly adapted not only to improve the perioperative care of patients, but also to address the potential benefits of employing ultrasound in airway management. The benefits of point of care ultrasound (POCUS) include its portability, the speed at which it can be utilized, and its lack of invasiveness or exposure of the patient to radiation of other imaging modalities.
Two primary indications for airway POCUS include confirmation of endotracheal intubation and identification of the cricothyroid membrane in the event a surgical airway is required. In this article, the technique of using ultrasound to confirm endotracheal intubation and the relevant anatomy is described, along with the associated ultrasonographic images. In addition, identification of the anatomy of the cricothyroid membrane and the ultrasonographic acquisition of appropriate images to perform this procedure are reviewed.
Future advances include utilizing airway POCUS to identify patient characteristics that might indicate difficult airway management. Traditional bedside clinical exams have, at best, fair predictive values. The addition of ultrasonographic airway assessment has the potential to improve this predictive accuracy. This article describes the use of POCUS for airway management, and initial evidence suggests that this has improved the diagnostic accuracy of predicting a difficult airway. Given that one of the limitations of airway POCUS is that it requires a skilled sonographer, and image analysis can be operator dependent, this paper will provide recommendations to standardize the technical aspects of airway ultrasonography and promote further research utilizing sonography in airway management. The goal of this protocol is to educate researchers and medical health professionals and to advance the research in the field of airway POCUS.

Point of care ultrasound (POCUS) is increasingly being utilized in airway management. Presented here are some clinical utilities of POCUS, including differentiating endotracheal and esophageal intubation, identification of the cricothyroid membrane in the event a surgical airway is required, and measuring anterior neck soft tissue to predict difficult airway management.

With its increasing popularity and accessibility, portable ultrasonography has been rapidly adapted not only to improve the perioperative care of ...

A Non-Intubation Protocol for Video-Assisted Thoracoscopic Surgery with Preserved Autonomic Breathing

Non-Intubated Video-Assisted Thoracoscopic Surgery

Double-lumen intubation under general anesthesia is currently the most commonly performed intubation technique for pneumonectomy, wedge resection of the lung, and lobectomy. However, there is a high incidence of pulmonary complications arising from general anesthesia with tracheal intubation. Non-intubation with the preservation of voluntary breathing is an alternative to anesthesia. Non-intubation procedures minimize the adverse effects of tracheal intubation and general anesthesia, such as intubation-related airway trauma, ventilation-induced lung injury, residual neuromuscular blockade, and post-operative nausea and vomiting. However, the steps for non-intubation procedures are not detailed in many studies. Here, we present a concise non-intubated protocol for the performance of video-assisted thoracoscopic surgery with preserved autonomic breathing. This article identifies the conditions necessary to convert from non-intubated to intubated anesthesia and also discusses the advantages and limitations of non-intubated anesthesia. In this work, this intervention was performed on 58 patients. In addition, the results of a retrospective study are presented. Compared with intubated general anesthesia, patients in the non-intubated video-assisted thoracic surgery group had lower rates of post-operative pulmonary complications, shorter operative times, less intraoperative blood loss, shorter PACU stays, a lower number of days to chest drain removal, less post-operative drainage, and shorter hospital stays.

Author Spotlight: A Non-Intubated Video-Assisted Thoracoscopic Surgery with Multimodal Analgesia and Sevoflurane Inhalation Anesthesia 

Here, we present a non-intubated protocol for performing video-assisted thoracoscopic surgery with preserved autonomic breathing.

Double-lumen intubation under general anesthesia is currently the most commonly performed intubation technique for pneumonectomy, wedge resection of the ...

Acupoint and Ear Plaster Therapy for Treating Sleep Disorders in AECOPD Patients

Acupoint Application Combined with Ear Plaster Therapy for Treating Sleep Disorders with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a lung disease characterized by persistent airflow limitation, which is not fully reversible and progressive. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) refers to acute changes in respiratory distress, cough, and sputum in COPD patients at baseline levels. Sleep disorders are a very common complication in patients with AECOPD. At present, long-term use of sedative-hypnotics alone has many side effects, such as mental and physical dependence and cognitive impairment. While the efficacy of other special intervention methods is not clear, and the cost is high, there is an urgent need for effective and safe treatment in clinics. Acupoint application and ear plaster therapy are considered the characteristic therapies of traditional Chinese medicine. They have the advantages of small side effects, high safety, and simple procedure. This study will elucidate in detail the specific process and efficacy of the two treatment methods for AECOPD complicated with sleep disorders, including medical devices used, selection of acupoints, procedure, and posttreatment care. This study is intended to provide a new reference for the clinical treatment modality of this type of disease.

Author Spotlight: Traditional Chinese Medicine for Sleep Disorders in Acute COPD &#8212; A Safe, Cost-Effective Approach

The present protocol describes the specific process and efficacy of the acupoint application combined with ear plaster therapy for sleep disorders in a patient with acute exacerbation of chronic obstructive pulmonary disease, including medical devices, selection of acupoints, operating methods, and posttreatment care.

Chronic Obstructive Pulmonary Disease (COPD) is a lung disease characterized by persistent airflow limitation, which is not fully reversible and ...

Management of Insomnia

The sleep cycle, an integral part of human health, consists of several stages with distinct characteristics and functions. It begins with a transition from wakefulness to sleep, known as the light sleep phase, followed by the restorative deep sleep phase, essential for physical recovery and growth. The cycle concludes with the Rapid Eye Movement (REM) phase, characterized by high brain activity and vivid dreaming. Insomnia, a prevalent sleep disorder, involves difficulty falling asleep, staying asleep, or both. These disruptions result in sleepiness, mood disturbances, and impaired performance. Insomnia can be transient (lasting a few days), short-term (a few weeks), or chronic (more than three months).
&#160;Management of insomnia involves a combination of cognitive-behavioral therapy (CBT), lifestyle modifications, and pharmacotherapy if needed. Good sleep hygiene includes maintaining a regular sleep schedule and avoiding certain activities close to bedtime, such as exercise and caffeine intake. CBT for insomnia aims to reshape thoughts, feelings, and behaviors that contribute to insomnia. Techniques include stimulus control to establish strong sleep cues, sleep restriction to improve sleep efficiency, and relaxation training to reduce anxiety and promote restfulness.
In addition, sedative-hypnotics may be used to manage severe insomnia under medical supervision. These are a class of drugs that induce or maintain sleep. Sedative-hypnotics are further categorized into benzodiazepines (BZDs), barbiturates, and non-benzodiazepines (also known as &#34;Z-drugs&#34;). These drugs all act on different allosteric sites on the GABAA channel.
BZDs increase the inhibitory actions of gamma-aminobutyric acid (GABAA), a neurotransmitter that reduces neuronal excitability and induces sleep. However, BZDs have potential side effects, including dependency and withdrawal symptoms, and their long-term use for insomnia is discouraged. Barbiturates, another class of sedative-hypnotics, should be avoided where possible, due to their high risk of addiction and overdose. Z-drugs and melatonin receptor agonists are newer classes of sleep-inducing drugs. Z-drugs (e.g., zolpidem, zaleplon, and eszopiclone) are non-benzodiazepine hypnotics that selectively act on GABAA receptors, promoting sedation and effectively treating insomnia. In contrast, melatonin receptor agonists (e.g., ramelteon) mimic the action of melatonin by targeting melatonin receptors in the brain&#39;s suprachiasmatic nucleus, aiding in the regulation of circadian rhythms and improving sleep onset, especially in patients with delayed sleep phase disorder or chronic insomnia. They are therapeutically effective and preferred over BZDs and barbiturates because they have a lower risk of abuse and risk of dependence with fewer side effects than conventional hypnotics.
In conclusion, understanding the sleep cycle and the complexities of insomnia is crucial for effective management. This involves a comprehensive approach, combining lifestyle modifications, cognitive-behavioral therapy, and carefully monitored pharmacotherapy when necessary.

Leczenie bezsenności

The sleep cycle comprises multiple stages, progressing from wakefulness to light sleep and finally into deep sleep, concluding with the Rapid Eye Movement ...