Name: drug-induced sleep endoscopy (dise) with target controlled infusion (tci) and bispectral analysis in obstructive sleep apnea
Uploaded: 2016-12-06T12:30:00
Description: 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

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 p...

<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. 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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. 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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 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).

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			<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>
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			<td height="20" style="height:20px;">SOMNOscreen&#160;</td>
			<td>SOMNOmedics, Randersacker, Germany</td>
			<td>SBT202</td>
			<td></td>
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			<td></td>
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			<td height="20" style="height:20px;">Sedation</td>
			<td></td>
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			<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>
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			<td height="20" style="height:20px;">Target-controlled infusion (TCI)</td>
			<td></td>
			<td></td>
			<td></td>
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			<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>
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			<td height="20" style="height:20px;">Data manager Orchestra Base Primea</td>
			<td>Fresenius Kabi Germany GmbH</td>
			<td>Z081320</td>
			<td></td>
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			<td height="20" style="height:20px;">Bispectral analysis (BIS)</td>
			<td></td>
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			<td></td>
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			<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>
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			<td height="20" style="height:20px;">BIS monitor BIS VISTA</td>
			<td>Covidien, Neustadt/Donau, Germany GmbH</td>
			<td>186-0210</td>
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			<td height="20" style="height:20px;">Endoscope&#160;</td>
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			<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>
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			<td height="20" style="height:20px;">Picture Archiving&#160; System&#160;</td>
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			<td></td>
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			<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>
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			<td height="20" style="height:20px;width:387px;"></td>
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			<td height="20" style="height:20px;width:387px;">Premedication&#160;</td>
			<td></td>
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			<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>
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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 ...

The overall goal of this procedure is to establish a standardized and reproducible protocol for drug-induced sleep endoscopy for heterogeneous groups of patients with obstructive sleep apnea to differentiate obstruction patterns to enable and improve individualized treatment. This method can help to differentiate obstruction patterns even in heterogeneous groups of patients with obstructive sleep apnea by using a standardized, and reproducible protocol. The main advantage of this technique is the target controlled infusion, or TCI of the sedative can be combined with real-time bispectral analysis to precisely control patient sedation.Generally, examiners knew the drug induce sleep endoscopy would struggle. With inducing the desired depth of sedation, leading to an unintentional deep sedation, followed by consecutive apnea, hypoxia, or hypertension. Begin by helping the patient into the supine position on the operating table.Then have the anesthesiologist connect the vital sign monitoring system on the left side of the patient, and wipe the patient's forehead with disinfectant. When the skin is dry, position a sensor with four interconnected and adhesive electrodes diagonally on the patient's forehead with one electrode at the center of the forehead, one directly above each eyebrow, and one on the temple between the corner of one eye and hairline. When all of the electrodes are in place, connect the sensor interface cable to the bispectral analysis monitor, pressing the electrodes firmly to confirm that the automatic test is passed.Have the anesthesiologist enter the patient's individual age, height, weight, gender, and Propofol plasma target concentration into the data manager with the pre-programmed pharmacokinetic model of Marsh. Now dim the lights in the operating room and use the TCI infusion pump to infuse an initial target plasma level of two micrograms per milliliter of Propofol, inducing sleep. Under continuous monitoring, raise the target plasma Propofol level 0.2 micrograms per milliliter every two minutes.The most critical step is identifying the target sedation depth. What can be identified as a sleeping patient with closed eyes and spontaneous breathing, accompanied by snoring or an observed obstructive apnea at a target bispectral analysis corridor of 50 to 70. Once the target depth of sedation is reached, stand at the head on the right side of the patient and insert a flexible fiber endoscope transnasally via the inferior nasal meatus.When the endoscope is in place, using the image acquisition system according to the manufacturers instructions, begin the endoscopic examination of the upper airways by video endoscopy in approximal to distal direction from the nasofarinks as far as the hypopharyngeal entrance. At the target depth of sedation, classify the obstruction sites, obstruction configuration patterns, and degrees of the obstruction severity according to the VOTE system. In the case of isolated sleep endoscopy, after completing the endoscopic examination, stop the Propofol infusion to terminate the patient's sedation.In the case of sleep endoscopy as part of a planned surgical procedure, have the anesthesiologist start the opioid infusion to induce a total intravenous anaesthesia while increasing the infusion of the Propofol until a loss of consciousness is observed. Then inject a muscle relaxant and intubate the patient prior to beginning the surgical procedure. The identified sites of obstruction are, in decreasing order of frequency, velum, tongue base, oropharynx, and at the level of the epiglottis.Among the patients with mild obstructive sleep apnea, more than half demonstrate a complete obstruction at a single site, with two or more obstructions sites present in nearly half of the patients. Over half of the patients with moderate obstructive sleep apnea, present a solitary complete obstruction with again, almost half of the patients showing obstruction at two or more sites. Only 20%of patients with sever obstructive sleep apnea exhibit an obstruction at a single site with two or more sites of obstruction observed in 80%of patients with severe obstructive sleep apnea.48%of the severe obstructive sleep apnea patients display obstruction at the tongue base, which is combined with one other site in 91.7%of cases. The epiglottis is typically the site of at least one obstruction in 52%of cases with 40%of severe obstructive sleep apnea patients also demonstrating coexistent obstructions at the tongue base. The analysis of velum obstruction patterns only reveals a market decrease in anterior posterior collapses from mild and moderate to severe obstructive sleep apnea.In contrast, a substantial increase of concentric obstructions emerges from mild to moderate to severe obstructive sleep apnea, whereas the ratio of partial and complete velum obstruction appears to be independent of obstructive sleep apnea severity. Drug induced sleep endoscopy provides further insights into the pathophysiology of obstructive sleep apnea and may improve individualized surgical treatment. Whereas investigations in awake patients frequently underestimate the obstruction patterns, particularly at the level of the tongue base and epiglottis.Once mastered, this procedure can be completed in ten to fifty minutes. Using microchip controlled syringe pumps and pharmacokinetics models, target controlled infusion is a patient individualized drug application method suitable to gradually achieve and maintain certain degrees of sedation by producing and sustaining constant plasma levels of a sedative. Bispectral analysis, which provides a dimensionless number between zero and one hundred, independent of an examiner's interpretation, is currently the best clinically evaluated and easily obtainable parameter for charting sedation depth.The multilevel obstruction is present in 80%of cases of sever obstructive sleep apnea, with over half of the cases demonstrating epiglottic movement and illustrating the need for the pre-interventional sleep endoscopy. After watching this video, you should have a good understanding of how to preform a standardized and reproducible drug induced sleep endoscopy for the differentiation of individual obstruction patterns in heterogeneous groups of patients with obstructive sleep apnea.

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Research

JoVE Journal

Medicine

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....

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 ...

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.

Individualized therapy for cystic fibrosis (CF) patients can be achieved with an in vitro disease model to understand baseline Cystic Fibrosis ...

Acupuncture Stimulation of Ears to Alleviate Sleeping Disorders in COPD Patients

Auricular Acupuncture as a Traditional Chinese Medicine Therapy for Chronic Obstructive Pulmonary Disease Combined with Sleep Disorders

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome characterized by persistent and irreversible airflow limitation and chronic respiratory symptoms. It has a wide spectrum of complications, and sleep disorders, as part of it, are common in severe cases, especially in elderly patients. Long-term lack of sleep may lead to the aggravation of the original disease, reducing patients' quality of life. Benzodiazepines are mainly used for symptomatic treatment of COPD combined with sleep disorders. However, such drugs have the side effect of respiratory central inhibition and could probably aggravate hypoxia symptoms. Auricular acupuncture is a special method of treating physical and psychosomatic dysfunctions by stimulating specific points in the ear. This article explains the specific methods of clinical operation of auricular acupuncture in detail, including assessment of patient eligibility, medical devices used, acupuncture points, course of treatment, post-treatment care, responses to emergencies, etc. The Pittsburgh sleep quality index (PSQI) and chronic obstructive pulmonary disease assessment scale (CAT) were used as the observational index of this method. So far, clinical reports have proved that auricular acupuncture has a definite curative effect in the treatment of COPD combined with sleep disorders, and its advantages of simple operation, few adverse reactions are worthy of further study and promotion, which provide a reference for the clinical treatment of such diseases.

Author Spotlight: Utilizing Traditional Chinese Acupuncture of the Ear to Improve Sleep Disorders 

This protocol introduces an effective method to improve the sleep condition of patients with chronic obstructive pulmonary disease and alleviate cough symptoms by using auricular acupuncture techniques to percutaneously stimulate specific acupoints in the patients' ears.

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome characterized by persistent and irreversible airflow limitation and chronic ...

Establishing a Device for Sleep Deprivation in Mice

Circadian rhythm disruption refers to the desynchronization between the external environment or behavior and the endogenous molecular clock, which significantly impairs health. Sleep deprivation is one of the most common causes of circadian rhythm disruption. Various modalities (e.g., platforms on the water, gentle handling, sliding bar chambers, rotating drums, orbital shakers, etc.) have been reported for inducing sleep deprivation in mice to investigate its effects on health. The current study introduces an alternative method for sleep deprivation in mice. An automated rocker platform-based device was designed that is cost-effective and efficiently disrupts sleep in group-housed mice at adjustable time intervals. This device induces characteristic changes of sleep deprivation with minimal stress response. Consequently, this method may prove useful for investigators interested in studying the effects and underlying mechanisms of sleep deprivation on the pathogenesis of multiple diseases. Moreover, it offers a cost-effective solution, particularly when multiple sleep deprivation devices are required to run in parallel.

The present protocol outlines a method for setting up a cost-effective rocker platform-based device used for inducing sleep deprivation in mice. This device has proven to be effective in causing disruptions in electroencephalogram (EEG)-evidenced sleep patterns, as well as inducing metabolic and molecular changes associated with sleep deprivation.

Circadian rhythm disruption refers to the desynchronization between the external environment or behavior and the endogenous molecular clock, which ...

Assessing Sleep Quality and Cognitive Function in Patients with Major Depressive Disorder

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (&plusmn;2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Author Spotlight: Unveiling the Connection Between Sleep Disorders and Cognitive Symptoms in Depression

Here, we present a protocol that investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. The THINC-integrated tool and polysomnography were used to evaluate cognitive symptoms and sleep quality.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both ...

Polysomnography Procedure to Assess Sleep Quality in Patients with MDD

To begin, collect the participant's demographics and instruct them to complete the Epworth Sleeping Scale. Lead the participant to the sleep monitoring room. Next, connect 15 electrodes of the electroencephalogram according to the International 1020 system of electrode placement.Also, connect the two derivations of Electrogram near the participant's eyes. Three derivations of Chin electromyogram, and two derivations of electrocardiogram. To acquire data, start the software by double clicking on device manager.Double click the room option, add the personal information of the participant and click OK.Click start recording, followed by the calibration button. Instruct the participant to perform according to the step-by-step calibration procedure. Keep the derivations in the correct position and collect the data for the entire night.On the next day, wake the participant by turning on the light of the sleep monitoring room. For post calibration, click the calibration button and instruct the participant to repeat the step-by-Step calibration procedure. Then click the close button to stop recording.After recording, remove all the derivations, avoiding skin damage. Next, start the scoring system by double clicking the profusion PSG four button. Select the participant and click the scoring button.Select the scoring automatically option to score sleep phases and arousals. Click the create button and lay out the results. Review the variables like time in bed, total sleep time, sleep latency, wake after sleep onset, sleep efficiency, and REM latency according to the PSG data and waves.