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. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+use+of+CPAP+therapy+for+sleep+apnea/hypopnea+syndrome.">Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome.</a> Am J Respir Crit Care Med. 159 (4), 1108-1114 (1999).</li><li>Verse, T., 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=HNO-spezifische+Therapie+der+obstruktiven+Schlafapnoe+bei+Erwachsenen.">HNO-spezifische Therapie der obstruktiven Schlafapnoe bei Erwachsenen.</a> AWMF. , (2015).</li><li>Sher, A. E., Schechtman, K. B., Piccirillo, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+efficacy+of+surgical+modifications+of+the+upper+airway+in+adults+with+obstructive+sleep+apnea+syndrome.">The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome.</a> Sleep. 19 (2), 156-177 (1996).</li><li>Croft, C. 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. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Test-retest+reliability+of+drug-induced+sleep+endoscopy.">Test-retest reliability of drug-induced sleep endoscopy.</a> Otolaryngol Head Neck Surg. 140 (5), 646-651 (2009).</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=European+position+paper+on+drug-induced+sedation+endoscopy+(DISE).">European position paper on drug-induced sedation endoscopy (DISE).</a> Sleep Breath. 18 (3), 453-465 (2014).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep-related+breathing+disorders+in+adults:+recommendations+for+syndrome+definition+and+measurement+techniques+in+clinical+research.+The+Report+of+an+American+Academy+of+Sleep+Medicine+Task+Force.">Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. 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. A., Garcia-Callejo, J., Ferrer, F., Marti, F., Marco, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+planning+after+sleep+versus+awake+techniques+in+patients+with+obstructive+sleep+apnea.">Surgical planning after sleep versus awake techniques in patients with obstructive sleep apnea.</a> Laryngoscope. 124 (8), 1970-1974 (2014).</li><li>Vroegop, A. V., 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+in+sleep-disordered+breathing:+report+on+1,249+cases.">Drug-induced sleep endoscopy in sleep-disordered breathing: report on 1,249 cases.</a> Laryngoscope. 124 (3), 797-802 (2014).</li></ol>

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 selection of patients23. The introduction of drug-induced sleep endoscopy (DISE) by Pringle and Croft in 1991 led to the first-ever objective method of patient selection and the resulting individualized treatment concept in OSA patients7. In subsequent years, the world-wide popularity of DISE increased and numerous sleep endoscopy protocols were published. Due to numerous controversial discussions over the years about patient selection, choice of sedative, classification of the obstruction, validity, reliability, applicability of the results to spontaneous sleep, etc., it has been impossible to establish a standard protocol for the procedure. One small milestone was the publication in 2014 of the European Position Paper on DISE, which is supposed to serve as the first approach to the standardization of this examination technique11.
The DISE procedure described in this study goes one step further in the standardization process, in that it combines the two standardizable techniques of TCI and bispectral analysis. The patient-individualized pharmacokinetic and dynamic monitoring of the sedative (propofol) as part of TCI enables the desired depth of sedation to be achieved with the help of bispectral monitoring. Our mean results of the bispectral analysis (60 &#177; 10.4) correspond to the already described target corridor of 50 - 70 11. A standardized TCI protocol that is based on a population pharmacokinetic model for propofol, also enables sedation specific to a patient&#39;s weight, height, sex and age. That is the fundamental requirement in order for results to be reproducible and hence comparable with future investigations of different centers.
Alternatively to monitoring of the bispectral index, EEG-analysis could be performed to control for depth of sedation. However, raw EEG data is difficult to interpret and prone to bias by inter- and intra-individual variations. The advantage of the bispectral index is the fact that it is a dimensionless number between 0 and 100 and independent of any examiner&#39;s interpretation. Moreover, processed parameters obtained by EEG power spectrum analysis like median or spectral edge frequency, are much less used and evaluated in intraoperative settings as compared to monitoring of the bispectral index. Therefore, bispectral analysis is currently the best clinically evaluated and easily obtainable parameter to judge depth of sedation and allow for comparability of study results.
As an alternative to plasma TCI mode of propofol infusion, effect-site (brain) TCI may be used. However, using this mode and the same intended target concentration, the patient would most likely be confronted with more negative side effects such as hypotension, unintentional deep sedation and apnea. This is due to exceedingly high and overshooting propofol plasma levels as a result of the implemented pharmacokinetic protocol to quickly achieve the set effect-site concentration. To avoid critical hypoxia during sleep endoscopy, a nasal oxygen catheter can be placed in the contralateral nostril and oxygen flow (3 - 5 L/min) can be adjusted to maintain adequate peripheral oxygen saturation. Unnecessary interruptions of the examination with re-oxygenation of the patient can be prevented in this way.
The value of preoperative sleep endoscopy can be indirectly measured from the success rates of UPPP &#8212; which is widely performed as the classical soft palate operation &#8212; and also that of multilevel surgery. In the current literature, the average reported success rate of UPPP in non-selected patients is between 33% and 50% 5. In the selected group with clinically suspected obstruction exclusively at the level of the soft palate, the reported success rate is 52.3% 5. In our investigation, across all levels of OSA severity we observed 49.1% (28/57) obstructions at the level of the velum or oropharynx or both. This would confirm the UPPP responder rate in the literature, both in selected and non-selected patient groups of &#60; 50%.
In terms of invasive, multilevel surgery, the surgical success rate (according to Sher) described in the German S2e-guideline is approximately 53.8% 5,6. The results of this meta-analysis are based on a total of 66 retrospective studies and prospective case series with a mean AHI 40.17. The most interesting fact is that a sleep endoscopy was performed only in three of the 66 studies (4.5%). In the remaining studies, the only technique to detect the sites of obstruction was a rigid optic or flexible rhinopharyngolaryngoscopy in wake and sometimes seated patients although it could be shown in various studies that the investigation in wake patients underestimates the obstruction pattern, particularly at the level of the tongue base, epiglottis and hypopharynx 24, 25. Applying the results of our study on the patients treated with multi-level surgery in the German S2e-guideline, at least one obstruction site at the epiglottis should be expected in 52% of patients with severe OSA. The poor responder-rate of 53.8% in multi-level surgery may therefore suggest that the potential obstruction site &#34;epiglottis&#34; might sometimes have been underdiagnosed and consecutively undertreated. In conclusion this is another argument in favor of a pre-interventional sleep endoscopy, especially in patients with severe OSA.
The limiting factor of the VOTE-classification, however, is the fact that it does not differentiate between a primary (epiglottis collapsing independently) or a secondary (epiglottis is pushed posteriorly by the tongue base with consecutive airway obstruction due to the epiglottal suction phenomenon) epiglottal collapse. In our population we could find an increasing prevalence of primary and secondary epiglottal collapse in mild (0%; 7.7%), moderate (5.3%; 10.5%) and severe OSA (12%; 40.0%).
If the results of our investigations are compared with those of a Belgian study of 1,249 sleep endoscopies, it is clear that despite our comparatively small group, both the distribution and the frequencies of the obstruction sites appear reproducible (palatal/velar: 81% Vroegop et al. vs. 59.6%; tongue base: 46.6% Vroegop et al. vs. 43.9%; hypopharyngeal/epiglottis: 38.7% Vroegop et al. vs. 29.8%, multi-level: 68.2% Vroegop et al. vs. 61.4%)26. However, the transferability of the results still remains problematic, because sedation in the Belgian study was achieved with midazolam (a muscle-relaxing benzodiazepine with respiration-depressant effects) and propofol. In addition, the depth of sedation was not measured objectively &#8212; which further limits the comparability of the results. This is another reason for advocating further standardization of sleep endoscopy. Furthermore, it still has to be shown that the results obtained with sleep endoscopy and their influence on the treatment decision, ultimately also lead to an improvement in the surgical outcome. A limiting factor of our protocol is the fact that there exists no data comparing obstruction patterns in DISE with obstruction patterns in natural sleep. This should be subject of future investigations, for example, by means of comparing obstruction patterns during DISE with obstruction patterns during magnetic resonance imaging in natural sleep.
The fact that a multilevel obstruction is present in 80% of cases of severe OSA, with over half of the cases (52%) showing epiglottal involvement, illustrates the need for sleep endoscopy prior to planned upper airway surgery. This is also true in terms of improving the postoperative outcome. 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.

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).

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	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:387px;">Cardiorespiratory polysomnography&#160;</td>
			<td style="width:544px;"></td>
			<td style="width:313px;"></td>
			<td style="width:179px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">SOMNOscreen&#160;</td>
			<td>SOMNOmedics, Randersacker, Germany</td>
			<td>SBT202</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Sedation</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Propofol-Lipuro 20 mg/mL; 2,6-diisopropylphenol</td>
			<td>B. Braun Melsungen AG, Melsungen, Germany</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Target-controlled infusion (TCI)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Infusion pump Orchestra Module DPS Visio</td>
			<td>Fresenius Kabi, Germany GmbH&#160;</td>
			<td>Z082420</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Data manager Orchestra Base Primea</td>
			<td>Fresenius Kabi Germany GmbH</td>
			<td>Z081320</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Bispectral analysis (BIS)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">BIS single-use electrode BIS Quatro Sensor</td>
			<td>Covidien, Neustadt/Donau, Germany GmbH</td>
			<td>186-0106</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">BIS monitor BIS VISTA</td>
			<td>Covidien, Neustadt/Donau, Germany GmbH</td>
			<td>186-0210</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Endoscope&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Laryngo fiberscope, length 30 cm, diameter 3.5 mm</td>
			<td>KARL STORZ GmbH &#38; Co. KG, Tuttlingen, Germany</td>
			<td>11101RP</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Picture Archiving&#160; System&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:387px;">AIDA</td>
			<td>Karl STORZ GmbH &#38; Co. KG, Tuttlingen, Germany</td>
			<td>WD 200-XX</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:387px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:387px;">Premedication&#160;</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Catapresan; Clonidin-HCl 0.075 mg/0.15 mg/0.3 mg</td>
			<td>Boehringer Ingelheim Pharma, GmbH &#38; 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 epiglottis 29.8% (17/57). Velar or oropharyngeal obstructions, in each case isolated or in combination, were seen in 49.1% (28/57) of patients. 38.6% (22/57) of all OSA patients showed a single site of obstruction and 61.4% (35/57) at least two sites. The configuration of the obstruction sites differed depending on OSA severity (Figure 1).
Mild OSA
Characteristics of the patients are shown in Table 1. Among the patients with mild OSA, more than half (53.8% (7/13)) showed complete obstruction at a single site (Figure 2). Two or more obstruction sites were present in 46.2% (6/13).
Moderate OSA
Characteristics of the patients are shown in Table 1. Over half of the patients (52.6% (10/19)) with moderate OSA had a solitary complete obstruction (Figure 3), with 47.4% (9/19) showing obstruction at two or more sites.
Severe OSA
Characteristics of the patients are shown in Table 1. Only 20.0% (5/25) of the patients with severe OSA showed obstruction at a single site (Figure 4) and in marked contrast to the groups with mild or moderate OSA, obstructions at two or more sites were present in 80.0% (20/25) of the patients in the severe OSA group. A combination of velar and/or oropharyngeal obstruction was found in 40% (10/25) of the severe OSAS patients. In 44% (11/25) velar obstructions were combined with other obstruction sites (tonsils, tongue base, epiglottis). 48% (12/25) of the severe OSAS patients displayed obstruction at the level of the tongue base and this obstruction was combined with one at another site in 91.7% (11/12) of them. Likewise, oropharyngeal obstruction was combined in 91.7% (11/12) of cases with obstruction at another location. The epiglottis was the site of at least one obstruction in 52% (13/25) of cases. 40% (10/25) of the patients with severe OSA also showed coexistent obstructions at the level of the tongue base. Analysing solely velum obstruction patterns showed a marked decrease of anterior-posterior collapses from mild and moderate (90%) to severe OSA (50%). In contrast, a substantial increase of concentric obstructions emerges from mild (0%) to moderate (10%) to severe OSA (36%) whereas the ratio of partial and complete velum obstruction seems to be independent of OSA severity (mild OSA: 60%/40%; moderate OSA: 60%/40%; severe OSA: 57%/43%) (Figure 5).
<img alt="Figure 1" src="/files/ftp_upload/54739/54739fig1.jpg" /> 
Figure 1: Prevalence (in %) of Obstruction Patterns (x-axis) According to OSA Severity. Due to the fact that every single obstruction site can occur multiple times within a multi-level collapse, more than 100% can be achieved cumulatively according to each grade of OSA. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54739/54739fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/54739/54739fig2.jpg" /> 
Figure 2: Mild OSA. Venn diagram showing all possible relations of upper airway obstruction sites (prevalence in % and ratio of upper airway obstruction sites). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54739/54739fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/54739/54739fig3.jpg" /> 
Figure 3: Moderate OSA. Venn diagram showing all possible relations of upper airway obstruction sites (prevalence in % and ratio of upper airway obstruction sites). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54739/54739fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" src="/files/ftp_upload/54739/54739fig4.jpg" /> 
Figure 4: Severe OSA. Venn diagram showing all possible relations of upper airway obstruction sites (prevalence in % and ratio of upper airway obstruction sites). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54739/54739fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" src="/files/ftp_upload/54739/54739fig5.jpg" /> 
Figure 5: Prevalence (in %) of Velum Obstruction Patterns (x-axis) According to OSA Severity. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54739/54739fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Table 1" src="/files/ftp_upload/54739/54739table1.jpg" /> 
Table 1: Patient Characteristics. SD= standard deviation, BMI=Body Mass Index (kg/m2), AHI=Apnea Hypopnea Index (/hr).

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 ...

drug-induced-sleep-endoscopy-dise-with-target-controlled-infusion-tci

Nanyang Technological University

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

A Novel Capsulorhexis Technique Using Shearing Forces with Cystotome

Purpose:
To demonstrate a capsulorhexis technique using predominantly shearing forces with a cystotome on a virtual reality simulator and on a human eye.
Method:
Our technique involves creating the initial anterior capsular tear with a cystotome to raise a flap. The flap left unfolded on the lens surface. The cystotome tip is tilted horizontally and is engaged on the flap near the leading edge of the tear. The cystotome is moved in a circular fashion to direct the vector forces. The loose flap is constantly swept towards the centre so that it does not obscure the view on the tearing edge.
Results:
Our technique has the advantage of reducing corneal wound distortion and subsequent anterior chamber collapse. The capsulorhexis flap is moved away from the tear leading edge allowing better visualisation of the direction of tear. This technique offers superior control of the capsulorhexis by allowing the surgeon to change the direction of the tear to achieve the desired capsulorhexis size.
Conclusions:
The EYESI Surgical Simulator is a realistic training platform for surgeons to practice complex capsulorhexis techniques. The shearing forces technique is a suitable alternative and in some cases a far better technique in achieving the desired capsulorhexis.

This video demonstrates a novel capsulorhexis technique in modern cataract surgery. Capsulorhexis is the most difficult and important part of phacoemulsification surgery.

Purpose:
To demonstrate a capsulorhexis technique using predominantly shearing forces with a cystotome on a virtual reality simulator and on a human eye....

A Novel Technique of Rescuing Capsulorhexis Radial Tear-out using a Cystotome

Part 1 : Purpose: To demonstrate a capsulorhexis radial tear out rescue technique using a cystotome on a virtual reality cataract surgery simulator and in a human eye. Part 2 : Method: Steps: When a capsulorhexis begins to veer radially towards the periphery beyond the pupillary margin the following steps should be applied without delay. 2.1) Stop further capsulorhexis manoeuvre and reassess the situation. 2.2) Fill the anterior chamber with ophthalmic viscosurgical device (OVD). We recommend mounting the cystotome to a syringe containing OVD so that the anterior chamber can be reinflated rapidly. 2.3) The capsulorhexis flap is then left unfolded on the lens surface. 2.4) The cystotome tip is tilted horizontally to avoid cutting or puncturing the flap and is engaged on the flap near the leading edge of the tear but not too close to the point of tear. 2.5) Gently push or pull the leading edge of tear opposite to the direction of tear. 2.6) The leading tearing edge will start to do a 'U-Turn'. Maintain the tension on the flap until the tearing edge returns to the desired trajectory. Part 3 : Results: Using our technique, a surgeon can respond instantly to radial tear out without having to change surgical instruments. Changing surgical instruments at this critical stage runs a risk of further radial tear due to sudden shallowing of anterior chamber as a result of forward pressure from the vitreous. Our technique also has the advantage of reducing corneal wound distortion and subsequent anterior chamber collapse. Part 4 : Discussion The EYESI Surgical Simulator is a realistic training platform for surgeons to practice complex capsulorhexis tear-out techniques. Capsulorhexis is the most important and complex part of phacoemulsification and endocapsular intraocular lens implantation procedure. A successful cataract surgery depends on achieving a good capsulorhexis. During capsulorhexis, surgeons may face a challenging situation like a capsulorhexis radial tear-out. A surgeon must learn to tackle the problem promptly without making the situation worse. Some other methods of rescuing the situation have been described using a capsulorhexis forceps. However, we believe our method is quicker, more effective and easier to manipulate as demonstrated on the EYESi surgical simulator and on a human eye. Acknowledgments: List acknowledgements and funding sources. We would like to thank Dr. Wael El Gendy, for video clip. Disclosures: describe potential conflicting interests or state We have nothing to disclose. References: 1. Brian C. Little, Jennifer H. Smith, Mark Packer. J Cataract Refract Surg 2006; 32:1420 1422, Issue-9. 2. Neuhann T. Theorie und Operationstechnik der Kapsulorhexis. Klin Monatsbl Augenheilkd. 1987; 1990: 542-545. 3. Gimbel HV, Neuhann T. Development, advantages and methods of the continuous circular capsulorhexis technique. J Cataract Refract Surg. 1990; 16: 31-37. 4. Gimbel HV, Neuhann T. Continuous curvilinear capsulorhexis. (letter) J Cataract Refract Sur. 1991; 17: 110-111.

Capsulorhexis is an important step in phacoemulsification surgery. A surgeon creates a continous curvilinear tear on the anterior lens capsule by controlling the tearing vector forces. A peripherally extended tear is a serious complication. This video demonstrates a novel technique of rescuing capsular radial tear out using a cystotome.

Part 1 : Purpose:   To demonstrate a capsulorhexis radial tear out rescue technique using a cystotome on a virtual reality cataract surgery simulator and ...

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI3. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax)4,5. These values provide indirect measurements of respiratory muscle performance6. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function6. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles7, known as the voluntary response index (VRI)8, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)9. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity9-11. We showed previously9 that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

The purpose of this publication is to present our original work on a multi-muscle surface electromyographic approach to quantitatively characterize respiratory muscle activation patterns in individuals with chronic spinal cord injury using vector-based analysis.

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies

Biomarkers are directly-measured biological indicators of disease, health, exposures, or other biological information. In population and social sciences, biomarkers need to be easy to obtain, transport, and analyze. Dried Blood Spots meet this need, and can be collected in the field with high response rates. These elements are particularly important in longitudinal study designs including interventions where attrition is critical to avoid, and high response rates improve the interpretation of results. Dried Blood Spot sample collection is simple, quick, relatively painless, less invasive then venipuncture, and requires minimal field storage requirements (i.e.&#160;samples do not need to be immediately frozen and can be stored for a long period of time in a stable freezer environment before assay). The samples can be analyzed for a variety of different analytes, including cholesterol, C-reactive protein, glycosylated hemoglobin, numerous cytokines, and other analytes, as well as provide genetic material. DBS collection is depicted as employed in several recent studies.

Biomarkers are directly-measured biological indicators of disease or health. In population and social sciences, biomarkers need to be easy to obtain, transport, and analyze. Dried Blood Spot (DBS) collection meets this need, can be collected in the field with high response rates&#160;and analyzed for a variety of biomarkers.

Biomarkers are directly-measured biological indicators of disease, health, exposures, or other biological information. In population and social sciences, ...

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention

One desirable endpoint of general anesthesia is the state of unconsciousness, also known as hypnosis. Defining the hypnotic state in animals is less straightforward than it is in human patients. A widely used behavioral surrogate for hypnosis in rodents is the loss of righting reflex (LORR), or the point at which the animal no longer responds to their innate instinct to avoid the vulnerability of dorsal recumbency. We have developed a system to assess LORR in 24 mice simultaneously while carefully controlling for potential confounds, including temperature fluctuations and varying gas flows. These chambers permit reliable assessment of anesthetic sensitivity as measured by latency to return of the righting reflex (RORR) following a fixed anesthetic exposure. Alternatively, using stepwise increases (or decreases) in anesthetic concentration, the chambers also enable determination of a population's sensitivity to induction (or emergence) as measured by EC50 and Hill slope. Finally, the controlled environmental chambers described here can be adapted for a variety of alternative uses, including inhaled delivery of other drugs, toxicology studies, and simultaneous real-time monitoring of vital signs.

Loss of the righting reflex has long served as a standard behavioral surrogate for unconsciousness, also called hypnosis, in laboratory animals. Alterations in volatile anesthetic sensitivity caused by pharmacological interventions can be detected with a carefully controlled high-throughput assessment system, which may be adapted for delivery of any inhaled therapeutic.

One desirable endpoint of general anesthesia is  the state of unconsciousness, also known as hypnosis. Defining the hypnotic state in animals is  less ...

Murine Echocardiography of Left Atrium, Aorta, and Pulmonary Artery

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic pressure through echocardiography, as well as to obtain measurements of the Aorta and PA diameter in mice.
Mice older than 10 d of age can be analyzed using the present technique. The technique is composed of 3 main steps: set-up, image acquisition, and image analysis. The set-up step consists of getting the mouse anesthetized with 1% isoflurane, shaving it, and taping it in a supine position to a heated EKG board where the image acquisition will take place. The image acquisition step consists of learning to identify the cardiac structures and obtaining all the required images with its correspondent probe and axis in order to be able to calculate volumes and diameters. The image analysis step consists of measuring the previously acquired images with the aid of computer software.
Advantages of the proposed technique include a fast (15 min) procedure that would allow the researcher to evaluate interventions in a non-invasive, non-terminal approach and therefore follow the same mouse over time; each mouse can be used as its own control. This fact plus having the same operator perform all the acquisition and analysis for the entire experiment minimizes the limitation of operator-dependency. The present methodology is useful for mouse researchers in cardiovascular and pulmonary medicine.

The following protocol describes the methodology for the acquisition and analysis of echocardiographic images used to obtain the Left Atrial Volume (LAV), Aorta (Ao) diameter, and Pulmonary Artery (PA) diameter in mice. This technique is a non-invasive, non-terminal procedure that allows assessment of the cardiopulmonary function.

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic ...

In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue

The tongue is a highly innervated and vascularized muscle hydrostat on the floor of the mouth of most vertebrates. Its primary functions include supporting mastication and deglutition, as well as taste-sensing and phonetics. Accordingly, the strength and volume of the tongue can impact the ability of vertebrates to accomplish basic activities such as feeding, communicating, and breathing. Human patients with sleep apnea have enlarged tongues, characterized by reduced muscle tone and increased intramuscular fat that can be visualized and quantified by magnetic resonance imaging (MRI). The abilities to measure force generation and viscoelastic properties of the tongue constitute important tools for obtaining functional information to correlate with imaging data. Here, we present techniques for measuring tongue force production in anesthetized Zucker rats via electrical stimulation of the hypoglossal nerves and for determining the viscoelastic properties of the tongue by applying passive Lissajous force/deformation curves.

In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue

We describe a surgical procedure in an anesthetized rat model for determining the muscle tone and viscoelastic properties of the tongue. The procedure involves specific stimulation of the hypoglossal nerves and application of passive Lissajous force/deformation curves to the muscle.

The tongue is a highly innervated and vascularized muscle hydrostat on the floor of the mouth of most vertebrates. Its primary functions include ...

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 ...

Culture and Imaging of Human Nasal Epithelial Organoids

Individualized therapy for cystic fibrosis (CF) patients can be achieved with an in vitro disease model to understand baseline Cystic Fibrosis Transmembrane conductance Regulator (CFTR) activity and restoration from small molecule compounds. Our group recently focused on establishing a well-differentiated organoid model directly derived from primary human nasal epithelial cells (HNE). Histology of sectioned organoids, whole-mount immunofluorescent staining, and imaging (using confocal microscopy, immunofluorescent microscopy, and bright field) are essential to characterize organoids and confirm epithelial differentiation in preparation for functional assays. Furthermore, HNE organoids produce lumens of varying sizes that correlate with CFTR activity, distinguishing between CF and non-CF organoids. In this manuscript, the methodology for culturing HNE organoids are described in detail, focusing on the assessment of differentiation using the imaging modalities, including the measurement of baseline lumen area (a method of CFTR activity measurement in organoids that any laboratory with a microscope can employ) as well as the developed automated approach to a functional assay (which requires more specialized equipment).

A detailed protocol is presented here to describe an in vitro organoid model from human nasal epithelial cells. The protocol has options for measurements requiring standard laboratory equipment, with additional possibilities for specialized equipment and software.

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

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In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue

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Culture and Imaging of Human Nasal Epithelial Organoids